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Sample records for blood diagnostic microfluidic

  1. A novel passive microfluidic device for preprocessing whole blood for point of care diagnostics

    DEFF Research Database (Denmark)

    Shah, Pranjul Jaykumar; Dimaki, Maria; Svendsen, Winnie Edith

    2009-01-01

    A novel strategy to sort the cells of interest (White Blood Cells (leukocytes)) by selectively lysing the Red Blood Cells (erythrocytes) in a miniaturized microfluidic device is presented. Various methods to lyse cells on a chip exist i.e. electrical, mechanical, chemical and thermal but they need...... integration of electrodes, traps, reservoirs, heaters, etc which is often difficult at microscale [1 – 4]. On the other hand, FACSlyse protocol uses only osmotic pressure to lyse erythrocytes allowing further isolation of leukocytes. This motivated us to develop a novel herringbone based lyser which works...

  2. [Recent development of microfluidic diagnostic technologies].

    Science.gov (United States)

    Li, Haifang; Zhang, Qianyun; Lin, Jin-Ming

    2011-04-01

    Microfluidic devices exhibit a great promising development in clinical diagnosis and disease screening due to their advantages of precise controlling of fluid flow, requirement of miniamount sample, rapid reaction speed and convenient integration. In this paper, the improvements of microfluidic diagnostic technologies in recent years are reviewed. The applications and developments of on-chip disease marker detection, microfluidic cell selection and cell drug metabolism, and diagnostic micro-devices are discussed.

  3. Overview of the microfluidic diagnostics commercial landscape.

    Science.gov (United States)

    Kim, Lily

    2013-01-01

    Since its birth in the late 1980s, the field of microfluidics has continued to mature, with a growing number of companies pursuing diagnostic applications. In 2009 the worldwide in vitro diagnostics market was estimated at >$40 billion USD, and microfluidic diagnostics are poised to reap a significant part of this market across a range of areas including laboratory diagnostics, point-of-care diagnostics, cancer diagnostics, and others. The potential economic advantages of microfluidics are numerous and compelling: lower reagent and/or sample volumes, lower equipment costs, improved portability, increased automation, and increased measurement speed. All of these factors may help put more information in the hands of doctors and patients sooner, enabling earlier disease detection and more tailored, effective treatments. This chapter reviews the microfluidic diagnostics commercial landscape and discusses potential commercialization challenges and opportunities.

  4. Microfluidic Devices for Blood Fractionation

    Directory of Open Access Journals (Sweden)

    Chwee Teck Lim

    2011-07-01

    Full Text Available Blood, a complex biological fluid, comprises 45% cellular components suspended in protein rich plasma. These different hematologic components perform distinct functions in vivo and thus the ability to efficiently fractionate blood into its individual components has innumerable applications in both clinical diagnosis and biological research. Yet, processing blood is not trivial. In the past decade, a flurry of new microfluidic based technologies has emerged to address this compelling problem. Microfluidics is an attractive solution for this application leveraging its numerous advantages to process clinical blood samples. This paper reviews the various microfluidic approaches realized to successfully fractionate one or more blood components. Techniques to separate plasma from hematologic cellular components as well as isolating blood cells of interest including certain rare cells are discussed. Comparisons based on common separation metrics including efficiency (sensitivity, purity (selectivity, and throughput will be presented. Finally, we will provide insights into the challenges associated with blood-based separation systems towards realizing true point-of-care (POC devices and provide future perspectives.

  5. Microfluidic Sensing Platforms for Medicine and Diagnostics

    DEFF Research Database (Denmark)

    Kiilerich-Pedersen, Katrine

    the specialized laboratory. Microfluidic cell migration devices, imitating in vivo conditions were developed with success, improving the in vitro experimental setup for basic research and drug discovery. Polymer biosensors have reached a new level of maturity, and pathogen detection could benefit from...... the integration of electrical sensors into low cost plastic microdevices pioneering point of care testing. The presented biosensing platforms have potential for scaling up towards high throughput screening, and are adaptable to other applications in medicine and diagnostics, and other fields....

  6. Droplet Microfluidics for Chip-Based Diagnostics

    Directory of Open Access Journals (Sweden)

    Karan V. I. S. Kaler

    2014-12-01

    Full Text Available Droplet microfluidics (DMF is a fluidic handling technology that enables precision control over dispensing and subsequent manipulation of droplets in the volume range of microliters to picoliters, on a micro-fabricated device. There are several different droplet actuation methods, all of which can generate external stimuli, to either actively or passively control the shape and positioning of fluidic droplets over patterned substrates. In this review article, we focus on the operation and utility of electro-actuation-based DMF devices, which utilize one or more micro-/nano-patterned substrates to facilitate electric field-based handling of chemical and/or biological samples. The underlying theory of DMF actuations, device fabrication methods and integration of optical and opto-electronic detectors is discussed in this review. Example applications of such electro-actuation-based DMF devices have also been included, illustrating the various actuation methods and their utility in conducting chip-based laboratory and clinical diagnostic assays.

  7. Handheld Microfluidic Blood Ananlyzer Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Nanohmics proposes to develop a handheld blood analyzer for micro- and hypo-gravity missions. The prototype instrument will combine impedance analysis with optical...

  8. Microfluidic Device for Continuous Magnetophoretic Separation of Red Blood Cells

    CERN Document Server

    Iliescu, Ciprian; Avram, Marioara; Xu, G; Avram, Andrei

    2008-01-01

    This paper presents a microfluidic device for magnetophoretic separation red blood cells from blood under contionous flow. The separation method consist of continous flow of a blood sample (diluted in PBS) through a microfluidic channel which presents on the bottom "dots" of feromagnetic layer. By appling a magnetic field perpendicular on the flowing direction, the feromagnetic "dots" generates a gradient of magnetic field which amplifies the magnetic force. As a result, the red blood cells are captured on the bottom of the microfluidic channel while the rest of the blood is collected at the outlet. Experimental results show that an average of 95 % of red blood cells are trapped in the device

  9. Teaching microfluidic diagnostics using Jell-O(®) chips.

    Science.gov (United States)

    Yang, Cheng Wei T; Lagally, Eric T

    2013-01-01

    Microfluidics has emerged as a versatile technology that has found many applications, including DNA chips, fuel cells, and diagnostics. As the field of microfluidic diagnostics grows, it is important to introduce the principles of this technology to young students and the general public. The objective of this project was to create a simple and effective method that could be used to teach key microfluidics concepts using easily accessible materials. Similar to the poly(dimethylsiloxane) soft lithography technique, a Jell-O(®) "chip" is produced by pouring a mixture of Jell-O(®) and gelatine solution into a mold, which is constructed using foam plate, coffee stirrers, and double-sided tape. The plate is transferred to a 4°C refrigerator for curing, and then the Jell-O(®) chip is peeled off for experimental demonstrations. Three types of chips have been fabricated with different molds: a JELLO mold, a Y-channel mold, and a pH-sensor mold. Using these devices, the basics of microfluidic diagnostics can be demonstrated in one or two class periods. The method described in this chapter provides teachers with a fast and inexpensive way to introduce this technology, and students with a fun and hands-on way to understand the basics of microfluidic diagnostics.

  10. MEMS and microfluidics for diagnostics devices.

    Science.gov (United States)

    Rosen, Y; Gurman, P

    2010-06-01

    There are conditions in clinical medicine demanding critical therapeutic decisions. These conditions necessitate accuracy, rapidity, accessibility, cost-effectiveness and mobility. New technologies have been developed in order to address these challenges. Microfluidics and Micro Electro-Mechanical Systems are two of such technologies. Microfluidics, a discipline that involves processing fluids at the microscale in etched microchannels, is being used to build lab- on-a-chip systems to run chemical and biological assays. These systems are being transformed into handheld devices designed to be used at remote settings or at the bedside. MEMS are microscale electromechanical elements integrated in lab chip systems or used as individual components. MEMS based sensors represents a highly developed field with successful commercialized products currently being incorporated into vitro,ex vivo and in vivo devices. In the present paper several examples of microfluidic devices and MEMS sensors are introduced together with some current examples of commercialized products. Future challenges and trends will be discussed.

  11. Microfluidic Cytometer for Complete Blood Count Analysis Project

    Data.gov (United States)

    National Aeronautics and Space Administration — RMD proposes to develop a MEMS based complete blood count (CBC) instrument that can be used aboard a spacecraft. We will produce a microfluidic scale combination...

  12. Microfluidic Cytometer for Complete Blood Count Analysis Project

    Data.gov (United States)

    National Aeronautics and Space Administration — We will fabricate and test microfluidic designs for a micro-electromechanical system based complete blood count (CBC) analysis in separate modules and integrate them...

  13. Smart Pipette and Microfluidic Pipette Tip for Blood Plasma Separation.

    Science.gov (United States)

    Kim, Byeongyeon; Choi, Sungyoung

    2016-01-13

    An integrated method for blood plasma separation is presented by combining a pneumatic device, which is referred to as a "smart pipette," and a hydrophoretic microchannel as a microfluidic pipette tip for whole-blood sample preparation. This method enables hemolysis-free, high-purity plasma separation through smart pipetting of whole blood, potentially providing the means for rapid, inexpensive blood sample preparation for point-of-care testing.

  14. Dynamics of blood flow in a microfluidic ladder network

    Science.gov (United States)

    Maddala, Jeevan; Zilberman-Rudenko, Jevgenia; McCarty, Owen

    The dynamics of a complex mixture of cells and proteins, such as blood, in perturbed shear flow remains ill-defined. Microfluidics is a promising technology for improving the understanding of blood flow under complex conditions of shear; as found in stent implants and in tortuous blood vessels. We model the fluid dynamics of blood flow in a microfluidic ladder network with dimensions mimicking venules. Interaction of blood cells was modeled using multiagent framework, where cells of different diameters were treated as spheres. This model served as the basis for predicting transition regions, collision pathways, re-circulation zones and residence times of cells dependent on their diameters and device architecture. Based on these insights from the model, we were able to predict the clot formation configurations at various locations in the device. These predictions were supported by the experiments using whole blood. To facilitate platelet aggregation, the devices were coated with fibrillar collagen and tissue factor. Blood was perfused through the microfluidic device for 9 min at a physiologically relevant venous shear rate of 600 s-1. Using fluorescent microscopy, we observed flow transitions near the channel intersections and at the areas of blood flow obstruction, which promoted larger thrombus formation. This study of integrating model predictions with experimental design, aids in defining the dynamics of blood flow in microvasculature and in development of novel biomedical devices.

  15. Integrated separation of blood plasma from whole blood for microfluidic paper-based analytical devices.

    Science.gov (United States)

    Yang, Xiaoxi; Forouzan, Omid; Brown, Theodore P; Shevkoplyas, Sergey S

    2012-01-21

    Many diagnostic tests in a conventional clinical laboratory are performed on blood plasma because changes in its composition often reflect the current status of pathological processes throughout the body. Recently, a significant research effort has been invested into the development of microfluidic paper-based analytical devices (μPADs) implementing these conventional laboratory tests for point-of-care diagnostics in resource-limited settings. This paper describes the use of red blood cell (RBC) agglutination for separating plasma from finger-prick volumes of whole blood directly in paper, and demonstrates the utility of this approach by integrating plasma separation and a colorimetric assay in a single μPAD. The μPAD was fabricated by printing its pattern onto chromatography paper with a solid ink (wax) printer and melting the ink to create hydrophobic barriers spanning through the entire thickness of the paper substrate. The μPAD was functionalized by spotting agglutinating antibodies onto the plasma separation zone in the center and the reagents of the colorimetric assay onto the test readout zones on the periphery of the device. To operate the μPAD, a drop of whole blood was placed directly onto the plasma separation zone of the device. RBCs in the whole blood sample agglutinated and remained in the central zone, while separated plasma wicked through the paper substrate into the test readout zones where analyte in plasma reacted with the reagents of the colorimetric assay to produce a visible color change. The color change was digitized with a portable scanner and converted to concentration values using a calibration curve. The purity and yield of separated plasma was sufficient for successful operation of the μPAD. This approach to plasma separation based on RBC agglutination will be particularly useful for designing fully integrated μPADs operating directly on small samples of whole blood.

  16. Microfluidic optoelectronic sensor for salivary diagnostics of stomach cancer.

    Science.gov (United States)

    Zilberman, Yael; Sonkusale, Sameer R

    2015-05-15

    We present a microfluidic optoelectronic sensor for saliva diagnostics with a potential application for non-invasive early diagnosis of stomach cancer. Stomach cancer is the second most common cause of cancer-related deaths in the world. The primary identified cause is infection by a gram-negative bacterium Helicobacter pylori. These bacteria secrete the enzyme urease that converts urea into carbon dioxide (CO2) and ammonia (NH3), leading to their elevated levels in breath and body fluids. The proposed optoelectronic sensor will detect clinically relevant levels of CO2 and NH3 in saliva that can potentially be used for early diagnosis of stomach cancer. The sensor is composed of the embedded in a microfluidic device array of microwells filled with ion-exchange polymer microbeads doped with various organic dyes. The optical response of this unique highly diverse sensor is monitored over a broad spectrum, which provides a platform for cross-reactive sensitivity and allows detection of CO2 and NH3 in saliva at ppm levels.

  17. Microfluidic filtration system to isolate extracellular vesicles from blood.

    Science.gov (United States)

    Davies, Ryan T; Kim, Junho; Jang, Su Chul; Choi, Eun-Jeong; Gho, Yong Song; Park, Jaesung

    2012-12-21

    Extracellular vesicles are released by various cell types, particularly tumor cells, and may be potential targets for blood-based cancer diagnosis. However, studies performed on blood-borne vesicles to date have been limited by lack of effective, standardized purification strategies. Using in situ prepared nanoporous membranes, we present a simple strategy employing a microfluidic filtration system to isolate vesicles from whole blood samples. This method can be applied to purify nano-sized particles from blood allowing isolation of intact extracellular vesicles, avoiding the need for laborious and potentially damaging centrifugation steps or overly specific antibody-based affinity purification. Porous polymer monoliths were integrated as membranes into poly(methyl methacrylate) microfluidic chips by benchtop UV photopolymerization through a mask, allowing precise positioning of membrane elements while preserving simplicity of device preparation. Pore size could be manipulated by changing the ratio of porogenic solvent to prepolymer solution, and was tuned to a size proper for extraction of vesicles. Using the membrane as a size exclusion filter, we separated vesicles from cells and large debris by injecting whole blood under pressure through the microfluidic device. To enhance isolation purity, DC electrophoresis was employed as an alternative driving force to propel particles across the filter and increase the separation efficiency of vesicles from proteins. From the whole blood of melanoma-grown mice, we isolated extracellular vesicles and performed RT-PCR to verify their contents of RNA. Melan A mRNA derived from melanoma tumor cells were found enriched in filtered samples, confirming the recovery of vesicles via their cargo. This filtration system can be incorporated into other on-chip processes enabling integrated sample preparation for the downstream analysis of blood-based extracellular vesicles.

  18. Microfluidic-integrated biosensors: prospects for point-of-care diagnostics.

    Science.gov (United States)

    Kumar, Suveen; Kumar, Saurabh; Ali, Md Azahar; Anand, Pinki; Agrawal, Ved Varun; John, Renu; Maji, Sagar; Malhotra, Bansi D

    2013-11-01

    There is a growing demand to integrate biosensors with microfluidics to provide miniaturized platforms with many favorable properties, such as reduced sample volume, decreased processing time, low cost analysis and low reagent consumption. These microfluidics-integrated biosensors would also have numerous advantages such as laminar flow, minimal handling of hazardous materials, multiple sample detection in parallel, portability and versatility in design. Microfluidics involves the science and technology of manipulation of fluids at the micro- to nano-liter level. It is predicted that combining biosensors with microfluidic chips will yield enhanced analytical capability, and widen the possibilities for applications in clinical diagnostics. The recent developments in microfluidics have helped researchers working in industries and educational institutes to adopt some of these platforms for point-of-care (POC) diagnostics. This review focuses on the latest advancements in the fields of microfluidic biosensing technologies, and on the challenges and possible solutions for translation of this technology for POC diagnostic applications. We also discuss the fabrication techniques required for developing microfluidic-integrated biosensors, recently reported biomarkers, and the prospects of POC diagnostics in the medical industry.

  19. Point-of-care technologies for molecular diagnostics using a drop of blood.

    Science.gov (United States)

    Song, Yujun; Huang, Yu-Yen; Liu, Xuewu; Zhang, Xiaojing; Ferrari, Mauro; Qin, Lidong

    2014-03-01

    Molecular diagnostics is crucial for prevention, identification, and treatment of disease. Traditional technologies for molecular diagnostics using blood are limited to laboratory use because they rely on sample purification and sophisticated instruments, are labor and time intensive, expensive, and require highly trained operators. This review discusses the frontiers of point-of-care (POC) diagnostic technologies using a drop of blood obtained from a finger prick. These technologies, including emerging biotechnologies, nanotechnologies, and microfluidics, hold the potential for rapid, accurate, and inexpensive disease diagnostics.

  20. Hydrodynamic blood plasma separation in microfluidic channels

    DEFF Research Database (Denmark)

    Jouvet, Lionel

    2010-01-01

    The separation of red blood cells from plasma flowing in microchannels is possible by biophysical effects such as the Zweifach–Fung bifurcation law. In the present study, daughter channels are placed alongside a main channel such that cells and plasma are collected separately. The device is aimed...

  1. Microfluidics-based diagnostics of infectious diseases in the developing world.

    Science.gov (United States)

    Chin, Curtis D; Laksanasopin, Tassaneewan; Cheung, Yuk Kee; Steinmiller, David; Linder, Vincent; Parsa, Hesam; Wang, Jennifer; Moore, Hannah; Rouse, Robert; Umviligihozo, Gisele; Karita, Etienne; Mwambarangwe, Lambert; Braunstein, Sarah L; van de Wijgert, Janneke; Sahabo, Ruben; Justman, Jessica E; El-Sadr, Wafaa; Sia, Samuel K

    2011-07-31

    One of the great challenges in science and engineering today is to develop technologies to improve the health of people in the poorest regions of the world. Here we integrated new procedures for manufacturing, fluid handling and signal detection in microfluidics into a single, easy-to-use point-of-care (POC) assay that faithfully replicates all steps of ELISA, at a lower total material cost. We performed this 'mChip' assay in Rwanda on hundreds of locally collected human samples. The chip had excellent performance in the diagnosis of HIV using only 1 μl of unprocessed whole blood and an ability to simultaneously diagnose HIV and syphilis with sensitivities and specificities that rival those of reference benchtop assays. Unlike most current rapid tests, the mChip test does not require user interpretation of the signal. Overall, we demonstrate an integrated strategy for miniaturizing complex laboratory assays using microfluidics and nanoparticles to enable POC diagnostics and early detection of infectious diseases in remote settings.

  2. Microfluidic strategy to investigate dynamics of small blood vessel function

    Science.gov (United States)

    Yasotharan, Sanjesh; Bolz, Steffen-Sebastian; Guenther, Axel

    2010-11-01

    Resistance arteries (RAs, 30-300 microns in diameter) that are located within the terminal part of the vascular tree regulate the laminar perfusion of tissue with blood, via the peripheral vascular resistance, and hence controls the systemic blood pressure. The structure of RAs is adapted to actively controlling flow resistance by dynamically changing their diameter, which is non-linearly dependent on the temporal variation of the transmural pressure, perfusion flow rate and spatiotemporal changes in the chemical environment. Increases in systemic blood pressure (hypertension) resulting from pathologic changes in the RA response represent the primary risk factor for cardiovascular diseases. We use a microfluidic strategy to investigate small blood vessels by quantifying structural variations within the arterial wall, RA outer contour and diameter over time. First, we document the artery response to vasomotor drugs that were homogeneously applied at step-wise increasing concentration. Second, we investigate the response in the presence of well-defined axial and circumferential heterogeneities. Artery per- and superfusion is discussed based on microscale PIV measurements of the fluid velocity on both sides of the arterial wall. Structural changes in the arterial wall are quantified using cross-correlation and proper orthogonal decomposition analyses of bright-field micrographs.

  3. Modular microfluidic cartridge-based universal diagnostic system for global health applications

    Science.gov (United States)

    Becker, Holger; Klemm, Richard; Dietze, William; White, Wallace; Hlawatsch, Nadine; Freyberg, Susanne; Moche, Christian; Dailey, Peter; Gärtner, Claudia

    2016-03-01

    Current microfluidics-enabled point-of-care diagnostic systems are typically designed specifically for one assay type, e.g. a molecular diagnostic assay for a single disease of a class of diseases. This approach often leads to high development cost and a significant training requirement for users of different instruments. We have developed an open platform diagnostic system which allows to run molecular, immunological and clinical assays on a single instrument platform with a standardized microfluidic cartridge architecture in an automated sample-in answer-out fashion. As examples, a molecular diagnostic assay for tuberculosis, an immunoassay for HIV p24 and a clinical chemistry assay for ALT liver function have been developed and results of their pre-clinical validation are presented.

  4. Continuous-flow microfluidic blood cell sorting for unprocessed whole blood using surface-micromachined microfiltration membranes.

    Science.gov (United States)

    Li, Xiang; Chen, Weiqiang; Liu, Guangyu; Lu, Wei; Fu, Jianping

    2014-07-21

    White blood cells (WBCs) constitute about 0.1% of the blood cells, yet they play a critical role in innate and adaptive immune responses against pathogenic infections, allergic conditions, and malignancies and thus contain rich information about the immune status of the body. Rapid isolation of WBCs directly from whole blood is a prerequisite for any integrated immunoassay platform designed for examining WBC phenotypes and functions; however, such functionality is still challenging for blood-on-a-chip systems, as existing microfluidic cell sorting techniques are inadequate for efficiently processing unprocessed whole blood on chip with concurrent high throughput and cell purity. Herein we report a microfluidic chip for continuous-flow isolation and sorting of WBCs from whole blood with high throughput and separation efficiency. The microfluidic cell sorting chip leveraged the crossflow filtration scheme in conjunction with a surface-micromachined poly(dimethylsiloxane) (PDMS) microfiltration membrane (PMM) with high porosity. With a sample throughput of 1 mL h(-1), the microfluidic cell sorting chip could recover 27.4 ± 4.9% WBCs with a purity of 93.5 ± 0.5%. By virtue of its separation efficiency, ease of sample recovery, and high throughput enabled by its continuous-flow operation, the microfluidic cell sorting chip holds promise as an upstream component for blood sample preparation and analysis in integrated blood-on-a-chip systems.

  5. Thermal Blood Clot Formation and use in Microfluidic Device Valving Applications

    Science.gov (United States)

    Tai, Yu-Chong (Inventor); Shi, Wendian (Inventor); Guo, Luke (Inventor)

    2014-01-01

    The present invention provides a method of forming a blood-clot microvalve by heating blood in a capillary tube of a microfluidic device. Also described are methods of modulating liquid flow in a capillary tube by forming and removing a blood-clot microvalve.

  6. Origami microfluidic paper-analytical-devices (omPAD) for sensing and diagnostics.

    Science.gov (United States)

    Punjiya, Meera; Chung Hee Moon; Yu Chen; Sonkusale, Sameer

    2016-08-01

    Recent research activities in the area of low-cost sensing and diagnostics that are realized on cellulosic paper substrate are presented. First a three-dimensional origami paper-based analytical device (omPAD) with multiple electrochemical sensors, an integrated sample reservoir and tight integration with a custom CMOS potentiostat is presented. Second, an optical sensor array with built-in microfluidic channel for sample delivery is presented. The sensors are fabricated using a combination of wax printing and screen-printing using a solution based approach in ambient conditions without the need for expensive fabrication equipment or a cleanroom. Readout is based on using existing consumer grade electronic devices like flatbed scanner (for optical sensor) or custom designed CMOS potentiostat (for electrochemical sensors). Together the 3D paper-based analytical device with integrated sensor, microfluidics and portable readout instrumentation demonstrates a low-cost, self-contained system suitable for sensing and point-of-care diagnostics.

  7. A micro-fluidic study of whole blood behaviour on PMMA topographical nanostructures

    Directory of Open Access Journals (Sweden)

    Tsud Nataliya

    2008-02-01

    Full Text Available Abstract Background Polymers are attractive materials for both biomedical engineering and cardiovascular applications. Although nano-topography has been found to influence cell behaviour, no established method exists to understand and evaluate the effects of nano-topography on polymer-blood interaction. Results We optimized a micro-fluidic set-up to study the interaction of whole blood with nano-structured polymer surfaces under flow conditions. Micro-fluidic chips were coated with polymethylmethacrylate films and structured by polymer demixing. Surface feature size varied from 40 nm to 400 nm and feature height from 5 nm to 50 nm. Whole blood flow rate through the micro-fluidic channels, platelet adhesion and von Willebrand factor and fibrinogen adsorption onto the structured polymer films were investigated. Whole blood flow rate through the micro-fluidic channels was found to decrease with increasing average surface feature size. Adhesion and spreading of platelets from whole blood and von Willebrand factor adsorption from platelet poor plasma were enhanced on the structured surfaces with larger feature, while fibrinogen adsorption followed the opposite trend. Conclusion We investigated whole blood behaviour and plasma protein adsorption on nano-structured polymer materials under flow conditions using a micro-fluidic set-up. We speculate that surface nano-topography of polymer films influences primarily plasma protein adsorption, which results in the control of platelet adhesion and thrombus formation.

  8. Design of a sedimentation hole in a microfluidic channel to remove blood cells from diluted whole blood

    Science.gov (United States)

    Kuroda, Chiaki; Ohki, Yoshimichi; Ashiba, Hiroki; Fujimaki, Makoto; Awazu, Koichi; Makishima, Makoto

    2017-03-01

    With the aim of developing a sensor for rapidly detecting viruses in a drop of blood, in this study, we analyze the shape of a hole in a microfluidic channel in relation to the efficiency of sedimentation of blood cells. The efficiency of sedimentation is examined on the basis of our calculation and experimental results for two types of sedimentation hole, cylindrical and truncated conical holes, focusing on the Boycott effect, which can promote the sedimentation of blood cells from a downward-facing wall. As a result, we demonstrated that blood cells can be eliminated with an efficiency of 99% or higher by retaining a diluted blood sample of about 30 µL in the conical hole for only 2 min. Moreover, we succeeded in detecting the anti-hepatitis B surface antigen antibody in blood using a waveguide-mode sensor equipped with a microfluidic channel having the conical sedimentation hole.

  9. A sample-to-result system for blood coagulation tests on a microfluidic disk analyzer.

    Science.gov (United States)

    Lin, Chia-Hui; Liu, Cheng-Yuan; Shih, Chih-Hsin; Lu, Chien-Hsing

    2014-09-01

    In this report, we describe in detail a microfluidic analyzer, which is able to conduct blood coagulation tests using whole blood samples. Sample preparation steps, such as whole blood aliquoting and metering, plasma separation, decanting, and mixing with reagents were performed in sequence through microfluidic functions integrated on a disk. Both prothrombin time (PT) and activated partial thromboplastin time (aPTT) were carried out on the same platform and the test results can be reported in 5 min. Fifty clinical samples were tested for both PT and aPTT utilizing the microfluidic disk analyzer and the instrument used in hospitals. The test results showed good correlation and agreement between the two instruments.

  10. Development of a microfluidic device for cell concentration and blood cell-plasma separation.

    Science.gov (United States)

    Maria, M Sneha; Kumar, B S; Chandra, T S; Sen, A K

    2015-12-01

    This work presents design, fabrication and test of a microfluidic device which employs Fahraeus-Lindqvist and Zweifach-Fung effects for cell concentration and blood cell-plasma separation. The device design comprises a straight main channel with a series of branched channels placed symmetrically on both sides of the main channel. The design implements constrictions before each junction (branching point) in order to direct cells that would have migrated closer to the wall (naturally or after liquid extraction at a junction) towards the centre of the main channel. Theoretical and numerical analysis are performed for design of the microchannel network to ensure that a minimum flow rate ratio (of 2.5:1, main channel-to-side channels) is maintained at each junction and predict flow rate at the plasma outlet. The dimensions and location of the constrictions were determined using numerical simulations. The effect of presence of constrictions before the junctions was demonstrated by comparing the performances of the device with and without constrictions. To demonstrate the performance of the device, initial experiments were performed with polystyrene microbeads (10 and 15 μm size) and droplets. Finally, the device was used for concentration of HL60 cells and separation of plasma and cells in diluted blood samples. The cell concentration and blood-plasma purification efficiency was quantified using Haemocytometer and Fluorescence-Activated Cell Sorter (FACS). A seven-fold cell concentration was obtained with HL60 cells and a purification efficiency of 70 % and plasma recovery of 80 % was observed for diluted (1:20) blood sample. FACS was used to identify cell lysis and the cell viability was checked using Trypan Blue test which showed that more than 99 % cells are alive indicating the suitability of the device for practical use. The proposed device has potential to be used as a sample preparation module in lab on chip based diagnostic platforms.

  11. Electrodiffusion Method of Near-Wall Flow Diagnostics in Microfluidic Systems

    Directory of Open Access Journals (Sweden)

    Tihona J.

    2015-01-01

    Full Text Available The electrodiffusion technique has been mostly used for the near-wall flow diagnostics on large scales. A novel technique for fabrication of plastic microfluidic systems with integrated metal microelectrodes (called technique of sacrificed substrate enables us to produce microfluidic devices with precisely shaped sensors for wall shear stress measurements. Several micrometer thick gold sensors, which are built-in a plastic substrate, exhibit good mechanical resistance and smoothness. Proper functioning of prepared chips with microsensors has been first tested in various calibration experiments (polarization curve, sensor response to polarization set-up, steady flow calibration, temperature dependence of diffusivity. Our first results obtained for separating/reattaching flow behind a backward-facing step and for gas-liquid Taylor flow in microchannels then demonstrate its applicability for the detection of near-wall flow reversal, the delimitation of flow - recirculation zones, and the determination of wall shear stress response to moving bubbles. Other applications of these sensors in microfluidics (e.g. characterization of liquid films, capillary waves, bubbles or drops can be also envisaged.

  12. Contact activation of blood coagulation on a defined kaolin/collagen surface in a microfluidic assay.

    Science.gov (United States)

    Zhu, Shu; Diamond, Scott L

    2014-12-01

    Generation of active Factor XII (FXIIa) triggers blood clotting on artificial surfaces and may also enhance intravascular thrombosis. We developed a patterned kaolin (0 to 0.3 pg/μm(2))/type 1 collagen fibril surface for controlled microfluidic clotting assays. Perfusion of whole blood (treated only with a low level of 4 μg/mL of the XIIa inhibitor, corn trypsin inhibitor) drove platelet deposition followed by fibrin formation. At venous wall shear rate (100 s(-1)), kaolin accelerated onset of fibrin formation by ~100 sec when compared to collagen alone (250 sec vs. 350 sec), with little effect on platelet deposition. Even with kaolin present, arterial wall shear rate (1000 s(-1)) delayed and suppressed fibrin formation compared to venous wall shear rate. A comparison of surfaces for extrinsic activation (tissue factor TF/collagen) versus contact activation (kaolin/collagen) that each generated equal platelet deposition at 100 s(-1) revealed: (1) TF surfaces promoted much faster fibrin onset (at 100 sec) and more endpoint fibrin at 600 sec at either 100 s(-1) or 1000 s(-1), and (2) kaolin and TF surfaces had a similar sensitivity for reduced fibrin deposition at 1000 s(-1) (compared to fibrin formed at 100 s(-1)) despite differing coagulation triggers. Anti-platelet drugs inhibiting P2Y1, P2Y12, cyclooxygenase-1 or activating IP-receptor or guanylate cyclase reduced platelet and fibrin deposition on kaolin/collagen. Since FXIIa or FXIa inhibition may offer safe antithrombotic therapy, especially for biomaterial thrombosis, these defined collagen/kaolin surfaces may prove useful in drug screening tests or in clinical diagnostic assays of blood under flow conditions.

  13. High-throughput blood cell focusing and plasma isolation using spiral inertial microfluidic devices.

    Science.gov (United States)

    Xiang, Nan; Ni, Zhonghua

    2015-12-01

    Herein, we explored the blood cell focusing and plasma isolation using a spiral inertial microfluidic device. First, the flow-rate and concentration effects on the migration dynamics of blood cells were systematically investigated to uncover the focusing mechanisms and steric crowding effects of cells in Dean-coupled inertial flows. A novel phenomenon that the focusing status of discoid red blood cells (RBCs) changes according to the channel height was discovered. These experimental data may provide valuable insights for the high-throughput processing of blood samples using inertial microfluidics. On the basis of the improved understandings on blood cell focusing, efficient isolation of plasma from whole blood with a 20-fold dilution was achieved at a throughput up to 700 μl/min. The purity of the isolated blood plasma was close to 100 %, and the plasma yield was calculated to be 38.5 %. As compared with previously-reported devices, our spiral inertial microfluidic device provides a balanced overall performance, and has overriding advantages in terms of processing throughput and operating efficiency.

  14. Microfluidic isolation of leukocytes from whole blood for phenotype and gene expression analysis.

    Science.gov (United States)

    Sethu, Palaniappan; Moldawer, Lyle L; Mindrinos, Michael N; Scumpia, Philip O; Tannahill, Cynthia L; Wilhelmy, Julie; Efron, Philip A; Brownstein, Bernard H; Tompkins, Ronald G; Toner, Mehmet

    2006-08-01

    Technologies that enable the isolation of cell subtypes from small samples of complex populations will greatly facilitate the implementation of proteomics and genomics to human diseases. Transcriptome analysis of blood requires the depletion of contaminating erythrocytes. We report an automated microfluidic device to rapidly deplete erythrocytes from whole blood via deionized water lysis and to collect enriched leukocytes for phenotype and genomic analyses. Starting with blood from healthy subjects, we demonstrate the utility of this microfluidic cassette and lysis protocol to prepare unstimulated leukocytes, and leukocytes stimulated ex vivo with Staphylococcal enterotoxin B, which mimics some of the cellular effects seen in patients with severe bacterial infections. Microarrays are used to assess the global gene expression response to enterotoxin B. The results demonstrate that this system can isolate unactivated leukocytes from small blood samples without any significant loss, which permits more information to be obtained from subsequent analysis, and will be readily applicable to clinical settings.

  15. Manufacturing routes for disposable polymer blood diagnostic microfluidic systems

    DEFF Research Database (Denmark)

    Tosello, Guido; Griffiths, Christian; Azcarate, Sabino;

    2008-01-01

    was applied to standardize the different tooling methods employed. The micro tools were then tested with different polymers on different injection moulding machines. The paper provides a comparison of these technologies with a particular focus on the obtainable feature sizes, surface finish, and aspect ratios...... enabling patient-friendly and comfortable control, e.g. for drug efficiency monitoring of chronic diseases. For such a bright vision there is a strong need for the realisation of new technologies. This article presents the results of the Polymer Technology Division of the European Network of Excellence 4M...... (Multi-Material Micro Manufacture) that are relevant to the technology for disposable polymer parts for Micro-Tele-BioChip (µTBC) medical platforms. Combining two separation mechanisms a novel micro channel design was developed. The separation unit is based on a micro channel bend structure where typical...

  16. Synergism between particle-based multiplexing and microfluidics technologies may bring diagnostics closer to the patient.

    Science.gov (United States)

    Derveaux, S; Stubbe, B G; Braeckmans, K; Roelant, C; Sato, K; Demeester, J; De Smedt, S C

    2008-08-01

    In the field of medical diagnostics there is a growing need for inexpensive, accurate, and quick high-throughput assays. On the one hand, recent progress in microfluidics technologies is expected to strongly support the development of miniaturized analytical devices, which will speed up (bio)analytical assays. On the other hand, a higher throughput can be obtained by the simultaneous screening of one sample for multiple targets (multiplexing) by means of encoded particle-based assays. Multiplexing at the macro level is now common in research labs and is expected to become part of clinical diagnostics. This review aims to debate on the "added value" we can expect from (bio)analysis with particles in microfluidic devices. Technologies to (a) decode, (b) analyze, and (c) manipulate the particles are described. Special emphasis is placed on the challenges of integrating currently existing detection platforms for encoded microparticles into microdevices and on promising microtechnologies that could be used to down-scale the detection units in order to obtain compact miniaturized particle-based multiplexing platforms.

  17. Fabrication of All Glass Bifurcation Microfluidic Chip for Blood Plasma Separation

    Directory of Open Access Journals (Sweden)

    Hyungjun Jang

    2017-02-01

    Full Text Available An all-glass bifurcation microfluidic chip for blood plasma separation was fabricated by a cost-effective glass molding process using an amorphous carbon (AC mold, which in turn was fabricated by the carbonization of a replicated furan precursor. To compensate for the shrinkage during AC mold fabrication, an enlarged photoresist pattern master was designed, and an AC mold with a dimensional error of 2.9% was achieved; the dimensional error of the master pattern was 1.6%. In the glass molding process, a glass microchannel plate with negligible shape errors (~1.5% compared to AC mold was replicated. Finally, an all-glass bifurcation microfluidic chip was realized by micro drilling and thermal fusion bonding processes. A separation efficiency of 74% was obtained using the fabricated all-glass bifurcation microfluidic chip.

  18. Blood Perfusion in Microfluidic Models of Pulmonary Capillary Networks: Role of Geometry and Hematocrit

    Science.gov (United States)

    Stauber, Hagit; Waisman, Dan; Sznitman, Josue; Technion-IIT Team; Department of Neonatology Carmel Medical Center; Faculty of Medicine-Technion IIT Collaboration

    2015-11-01

    Microfluidic platforms are increasingly used to study blood microflows at true physiological scale due to their ability to overcome manufacturing obstacle of complex anatomical morphologies, such as the organ-specific architectures of the microcirculation. In the present work, we utilize microfluidic platforms to devise in vitro models of the underlying pulmonary capillary networks (PCN), where capillary lengths and diameters are similar to the size of RBCs (~ 5-10 μm). To better understand flow characteristics and dispersion of red blood cells (RBCs) in PCNs, we have designed microfluidic models of alveolar capillary beds inspired by the seminal ``sheet flow'' model of Fung and Sobin (1969). Our microfluidic PCNs feature confined arrays of staggered pillars with diameters of ~ 5,7 and 10 μm, mimicking the dense structure of pulmonary capillary meshes. The devices are perfused with suspensions of RBCs at varying hematocrit levels under different flow rates. Whole-field velocity patterns using micro-PIV and single-cell tracking using PTV are obtained with fluorescently-labelled RBCs and discussed. Our experiments deliver a real-scale quantitative description of RBC perfusion characteristics across the pulmonary capillary microcirculation.

  19. Modeling of Shear-Induced Red Blood Cell Migration for Guiding Microfluidic Device Design

    Science.gov (United States)

    Durant, Eden; Higgins, Adam; Sharp, Kendra

    2014-11-01

    Through refinement and extension of a two-phase flow model previously reported for modeling blood in cylindrical flows (Gidaspow, 2009), we have developed a computational model for blood flow in complex microfluidic. Treating plasma as a Newtonian fluid and the Red Blood Cells (RBCs) as a granular phase, whose local concentrations are determined statistically, we have captured the migration of RBCs and concomitant formation of a cell free plasma layer at the channel walls. This model provides us with a three-dimensional distribution of RBCs and the development of the stead-state flow profile, and enables us to study the influence of complex microfluidic geometries, including flow obstacles and varying channel dimensions, on the rate and extent of RBC margination. Simulations on 50 and 100 micron square channels match observed trends including decreasing RBC margination rate in larger channels, increasing RBC margination rate with higher hematocrit, and decreasing cell free layer width with increasing hematocrit. This predictive capability will allow microfluidic devices to be tailored and optimized for specific biomedical applications such as separation of blood constituents.

  20. High-throughput and clogging-free microfluidic filtration platform for on-chip cell separation from undiluted whole blood

    OpenAIRE

    Cheng, Yinuo; Ye, Xiongying; Ma, Zengshuai; Xie, Shuai; Wang, Wenhui

    2016-01-01

    Rapid separation of white blood cells from whole blood sample is often required for their subsequent analyses of functions and phenotypes, and many advances have been made in this field. However, most current microfiltration-based cell separation microfluidic chips still suffer from low-throughput and membrane clogging. This paper reports on a high-throughput and clogging-free microfluidic filtration platform, which features with an integrated bidirectional micropump and commercially availabl...

  1. Microcirculation-on-a-Chip: A Microfluidic Platform for Assaying Blood- and Lymphatic-Vessel Permeability.

    Directory of Open Access Journals (Sweden)

    Miwa Sato

    Full Text Available We developed a microfluidic model of microcirculation containing both blood and lymphatic vessels for examining vascular permeability. The designed microfluidic device harbors upper and lower channels that are partly aligned and are separated by a porous membrane, and on this membrane, blood vascular endothelial cells (BECs and lymphatic endothelial cells (LECs were cocultured back-to-back. At cell-cell junctions of both BECs and LECs, claudin-5 and VE-cadherin were detected. The permeability coefficient measured here was lower than the value reported for isolated mammalian venules. Moreover, our results showed that the flow culture established in the device promoted the formation of endothelial cell-cell junctions, and that treatment with histamine, an inflammation-promoting substance, induced changes in the localization of tight and adherens junction-associated proteins and an increase in vascular permeability in the microdevice. These findings indicated that both BECs and LECs appeared to retain their functions in the microfluidic coculture platform. Using this microcirculation device, the vascular damage induced by habu snake venom was successfully assayed, and the assay time was reduced from 24 h to 30 min. This is the first report of a microcirculation model in which BECs and LECs were cocultured. Because the micromodel includes lymphatic vessels in addition to blood vessels, the model can be used to evaluate both vascular permeability and lymphatic return rate.

  2. Real-Time Electrical Impedimetric Monitoring of Blood Coagulation Process under Temperature and Hematocrit Variations Conducted in a Microfluidic Chip

    OpenAIRE

    Lei, Kin Fong; Chen, Kuan-Hao; Tsui, Po-Hsiang; Tsang, Ngan-Ming

    2013-01-01

    Blood coagulation is an extremely complicated and dynamic physiological process. Monitoring of blood coagulation is essential to predict the risk of hemorrhage and thrombosis during cardiac surgical procedures. In this study, a high throughput microfluidic chip has been developed for the investigation of the blood coagulation process under temperature and hematocrit variations. Electrical impedance of the whole blood was continuously recorded by on-chip electrodes in contact with the blood sa...

  3. Optimized acoustic biochip integrated with microfluidics for biomarkers detection in molecular diagnostics.

    Science.gov (United States)

    Papadakis, G; Friedt, J M; Eck, M; Rabus, D; Jobst, G; Gizeli, E

    2017-09-01

    The development of integrated platforms incorporating an acoustic device as the detection element requires addressing simultaneously several challenges of technological and scientific nature. The present work was focused on the design of a microfluidic module, which, combined with a dual or array type Love wave acoustic chip could be applied to biomedical applications and molecular diagnostics. Based on a systematic study we optimized the mechanics of the flow cell attachment and the sealing material so that fluidic interfacing/encapsulation would impose minimal losses to the acoustic wave. We have also investigated combinations of operating frequencies with waveguide materials and thicknesses for maximum sensitivity during the detection of protein and DNA biomarkers. Within our investigations neutravidin was used as a model protein biomarker and unpurified PCR amplified Salmonella DNA as the model genetic target. Our results clearly indicate the need for experimental verification of the optimum engineering and analytical parameters, in order to develop commercially viable systems for integrated analysis. The good reproducibility of the signal together with the ability of the array biochip to detect multiple samples hold promise for the future use of the integrated system in a Lab-on-a-Chip platform for application to molecular diagnostics.

  4. Fabrication and Characterization of a Microfluidic Device to Ultrapurify Blood Samples

    KAUST Repository

    Tallerico, Marco

    2015-05-04

    The improvement of blood cell sorting techniques in recent years have attracted the attention of many researchers due to the possible benefits that these methods can lead in biology, regenerative medicine, materials science and therapeutic area. In this work a cell sorting technique based on filtration is described. The separation occurs by means of a microfluidic device, suitably designed, manufactured and tested, that is connected to an external experimental set-up. The fabrication process can be divided in two parts: at first it is described the manufacturing process of a filtering membrane, with holes of specific size that allow the passage of only certain cell types. Following the microfluidic device is fabricated through the mechanical micromilling. The membrane and the microdevice are suitably bonded and tested by means of an external connection with syringe pumps that inject blood samples at specific flow rates. The device is designed to separate blood cells and tumor cells only by using differences in size and shape. In particular during the first experiments red blood cells and platelets are sorted from white blood cells; in the other experiments red blood cells and platelets are separated from white blood cells and tumor cells. The microdevice has proven to be very efficient, in fact a capture efficiency of 99% is achieved. For this reason it could be used in identification and isolation of circulating tumor cells, a very rare cancer cell type whose presence in the bloodstream could be symptom of future solid tumor formation. The various experiments have also demonstrated that tumor cells survive even after the separation treatment, and then the suffered stress during the sorting process does not harm the biological sample.

  5. 21 CFR 864.9275 - Blood bank centrifuge for in vitro diagnostic use.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Blood bank centrifuge for in vitro diagnostic use... Manufacture Blood and Blood Products § 864.9275 Blood bank centrifuge for in vitro diagnostic use. (a) Identification. A blood bank centrifuge for in vitro diagnostic use is a device used only to separate blood...

  6. Soft inertial microfluidics for high throughput separation of bacteria from human blood cells.

    Science.gov (United States)

    Wu, Zhigang; Willing, Ben; Bjerketorp, Joakim; Jansson, Janet K; Hjort, Klas

    2009-05-01

    We developed a new approach to separate bacteria from human blood cells based on soft inertial force induced migration with flow defined curved and focused sample flow inside a microfluidic device. This approach relies on a combination of an asymmetrical sheath flow and proper channel geometry to generate a soft inertial force on the sample fluid in the curved and focused sample flow segment to deflect larger particles away while the smaller ones are kept on or near the original flow streamline. The curved and focused sample flow and inertial effect were visualized and verified using a fluorescent dye primed in the device. First the particle behaviour was studied in detail using 9.9 and 1.0 microm particles with a polymer-based prototype. The prototype device is compact with an active size of 3 mm(2). The soft inertial effect and deflection distance were proportional to the fluid Reynolds number (Re) and particle Reynolds number (Re(p)), respectively. We successfully demonstrated separation of bacteria (Escherichia coli) from human red blood cells at high cell concentrations (above 10(8)/mL), using a sample flow rate of up to 18 microL/min. This resulted in at least a 300-fold enrichment of bacteria at a wide range of flow rates with a controlled flow spreading. The separated cells were proven to be viable. Proteins from fractions before and after cell separation were analyzed by gel electrophoresis and staining to verify the removal of red blood cell proteins from the bacterial cell fraction. This novel microfluidic process is robust, reproducible, simple to perform, and has a high throughput compared to other cell sorting systems. Microfluidic systems based on these principles could easily be manufactured for clinical laboratory and biomedical applications.

  7. Soft inertial microfluidics for high throughput separation of bacteria from human blood cells

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Zhigang; Willing, Ben; Bjerketorp, Joakim; Jansson, Janet K.; Hjort, Klas

    2009-01-05

    We developed a new approach to separate bacteria from human blood cells based on soft inertial force induced migration with flow defined curved and focused sample flow inside a microfluidic device. This approach relies on a combination of an asymmetrical sheath flow and proper channel geometry to generate a soft inertial force on the sample fluid in the curved and focused sample flow segment to deflect larger particles away while the smaller ones are kept on or near the original flow streamline. The curved and focused sample flow and inertial effect were visualized and verified using a fluorescent dye primed in the device. First the particle behavior was studied in detail using 9.9 and 1.0 {micro}m particles with a polymer-based prototype. The prototype device is compact with an active size of 3 mm{sup 2}. The soft inertial effect and deflection distance were proportional to the fluid Reynolds number (Re) and particle Reynolds number (Re{sub p}), respectively. We successfully demonstrated separation of bacteria (Escherichia coli) from human red blood cells at high cell concentrations (above 10{sup 8}/mL), using a sample flow rate of up to 18 {micro}L/min. This resulted in at least a 300-fold enrichment of bacteria at a wide range of flow rates with a controlled flow spreading. The separated cells were proven to be viable. Proteins from fractions before and after cell separation were analyzed by gel electrophoresis and staining to verify the removal of red blood cell proteins from the bacterial cell fraction. This novel microfluidic process is robust, reproducible, simple to perform, and has a high throughput compared to other cell sorting systems. Microfluidic systems based on these principles could easily be manufactured for clinical laboratory and biomedical applications.

  8. Sample pretreatment microfluidic chip for DNA extraction from rat peripheral blood

    Institute of Scientific and Technical Information of China (English)

    CHEN Xing; CUI Dafu; LIU Changchun; LI Hui; ZHAO Weixing

    2007-01-01

    A sample pretreatment microfluidic chip was described based on the principle of solid phase extraction and micro electro mechanical system technology.Oxidized porous silicon with the large surface area as the solid phase matrix for absorption of DNA from a biological sample can greatly improve the DNA yield.The factors that could affect the DNA yield were analyzed and the preparation technology and the experiment procedure were improved.The DNA purification process from the rat peripheral blood can be achieved and the DNA yield is 24 ng/(μL whole blood),which can reach the level of the commercial DNA purification kits.Furthermore,the DNA extracted from the whole blood can be amplified by polymerase chain reaction,which can achieve a high efficiency of the amplification.

  9. Development of Multiscale Materials in Microfluidic Devices: Case Study for Viral Separation from Whole Blood

    Science.gov (United States)

    Surawathanawises, Krissada

    such as blood cells, and the nanoscale pores promote permeation for affinity capture of bionanoparticles. Consequently, particles with a size difference of 3--4 orders of magnitude can be separated in a simple flow-through process. Computational analyses are employed to study the effect of micropattern shape and layout. A half-ring pattern is shown to reduce flow resistance and promote fluid permeation compared to a circular pattern. In the experiment, the micropatterned porous arrays yield around 4 times higher viral capture from whole blood compared with a micropatterned solid array. The micropatterned porous devices are capable of handling a large volume of fluid sample without clogging by cells. Therefore they can be used for nanoparticle concentration. Our study also indicates that the layout of micropatterns can be adjusted to improve the capture yield. For example, an increase in pattern radius, or a decrease in gap distance between each post and in width of half ring will enhance fluid permeation in the porous structure. When combined with downstream detection, these materials integrated into microfluidic platforms can be created as point-of-care diagnostics, as well as other applications for particle separation and analysis. (Abstract shortened by UMI.).

  10. Numerical Investigation of Cell Encapsulation for Multiplexing Diagnostic Assays Using Novel Centrifugal Microfluidic Emulsification and Separation Platform

    Directory of Open Access Journals (Sweden)

    Yong Ren

    2016-01-01

    Full Text Available In the present paper, we report a novel centrifugal microfluidic platform for emulsification and separation. Our design enables encapsulation and incubation of multiple types of cells by droplets, which can be generated at controlled high rotation speed modifying the transition between dripping-to-jetting regimes. The droplets can be separated from continuous phase using facile bifurcated junction design. A three dimensional (3D model was established to investigate the formation and sedimentation of droplets using the centrifugal microfluidic platform by computational fluid dynamics (CFD. The simulation results were compared to the reported experiments in terms of droplet shape and size to validate the accuracy of the model. The influence of the grid resolution was investigated and quantified. The physics associated with droplet formation and sedimentation is governed by the Bond number and Rossby number, respectively. Our investigation provides insight into the design criteria that can be used to establish centrifugal microfluidic platforms tailored to potential applications, such as multiplexing diagnostic assays, due to the unique capabilities of the device in handling multiple types of cells and biosamples with high throughput. This work can inspire new development of cell encapsulation and separation applications by centrifugal microfluidic technology.

  11. Blood coagulation screening using a paper-based microfluidic lateral flow device.

    Science.gov (United States)

    Li, H; Han, D; Pauletti, G M; Steckl, A J

    2014-10-21

    A simple approach to the evaluation of blood coagulation using a microfluidic paper-based lateral flow assay (LFA) device for point-of-care (POC) and self-monitoring screening is reported. The device utilizes whole blood, without the need for prior separation of plasma from red blood cells (RBC). Experiments were performed using animal (rabbit) blood treated with trisodium citrate to prevent coagulation. CaCl2 solutions of varying concentrations are added to citrated blood, producing Ca(2+) ions to re-establish the coagulation cascade and mimic different blood coagulation abilities in vitro. Blood samples are dispensed into a paper-based LFA device consisting of sample pad, analytical membrane and wicking pad. The porous nature of the cellulose membrane separates the aqueous plasma component from the large blood cells. Since the viscosity of blood changes with its coagulation ability, the distance RBCs travel in the membrane in a given time can be related to the blood clotting time. The distance of the RBC front is found to decrease linearly with increasing CaCl2 concentration, with a travel rate decreasing from 3.25 mm min(-1) for no added CaCl2 to 2.2 mm min(-1) for 500 mM solution. Compared to conventional plasma clotting analyzers, the LFA device is much simpler and it provides a significantly larger linear range of measurement. Using the red colour of RBCs as a visible marker, this approach can be utilized to produce a simple and clear indicator of whether the blood condition is within the appropriate range for the patient's condition.

  12. Permeability analysis of neuroactive drugs through a dynamic microfluidic in vitro blood-brain barrier model.

    Science.gov (United States)

    Booth, R; Kim, H

    2014-12-01

    This paper presents the permeability analysis of neuroactive drugs and correlation with in vivo brain/plasma ratios in a dynamic microfluidic blood-brain barrier (BBB) model. Permeability of seven neuroactive drugs (Ethosuximide, Gabapentin, Sertraline, Sunitinib, Traxoprodil, Varenicline, PF-304014) and trans-endothelial electrical resistance (TEER) were quantified in both dynamic (microfluidic) and static (transwell) BBB models, either with brain endothelial cells (bEnd.3) in monoculture, or in co-culture with glial cells (C6). Dynamic cultures were exposed to 15 dyn/cm(2) shear stress to mimic the in vivo environment. Dynamic models resulted in significantly higher average TEER (respective 5.9-fold and 8.9-fold increase for co-culture and monoculture models) and lower drug permeabilities (average respective decrease of 0.050 and 0.052 log(cm/s) for co-culture and monoculture) than static models; and co-culture models demonstrated higher average TEER (respective 90 and 25% increase for static and dynamic models) and lower drug permeability (average respective decrease of 0.063 and 0.061 log(cm/s) for static and dynamic models) than monoculture models. Correlation of the resultant logP e values [ranging from -4.06 to -3.63 log(cm/s)] with in vivo brain/plasma ratios (ranging from 0.42 to 26.8) showed highly linear correlation (R (2) > 0.85) for all model conditions, indicating the feasibility of the dynamic microfluidic BBB model for prediction of BBB clearance of pharmaceuticals.

  13. Polymeric nanoparticles assembled with microfluidics for drug delivery across the blood-brain barrier

    Science.gov (United States)

    Tavares, M. R.; de Menezes, L. R.; do Nascimento, D. F.; Souza, D. H. S.; Reynaud, F.; Marques, M. F. V.; Tavares, M. I. B.

    2016-07-01

    The blood-brain barrier (BBB) is a challenge in the treatment of some diseases, since it prevents many drugs from reaching therapeutic concentrations in the brain. In this context, there is a growing interest in nanoparticles for drug delivery, since they are able to cross this barrier and target the brain. The use of polymeric materials in the development of these nanoparticles has been extensively studied. It has already been demonstrated that these nanosystems have the ability to cross the BBB, which allows effective drug release into the brain. Biodegradable polymers provide a great advantage in the development of nanosystems, but modifications of the nanoparticles' surface is essential. The traditional batch methods lack precise control over the processes of nucleation and growth, resulting in poor control over final properties of the nanoparticles. Therefore, microfluidics could be used to achieve a better production environment for the fabrication of nano- structured drug delivery systems. This study provides a brief review of: the BBB, the polymeric nanoparticles with the ability to overcome the barrier, the properties of the most used polymeric matrices, and the nanostructured drug delivery systems assembled with microfluidics.

  14. Design of Smart Polymer-Protein Conjugates and Smart Magnetic Nanoparticles for Use in Microfluidic Diagnostic Assays

    Institute of Scientific and Technical Information of China (English)

    Allan; S.Hoffman

    2007-01-01

    1 Results In this talk,I will describe the design,synthesis and application of smart polymers for use in microfluidic diagnostic devices.We are synthesizing a variety of temperature- and pH-responsive polymers using RAFT living free radical polymerization techniques.This allows us to control molecular weight and to achieve a narrow MW distribution of the polymers. Furthermore,RAFT polymers have reactive end groups that are used to conjugate the polymers to proteins.We are also using those groups to bind...

  15. Real-time electrical impedimetric monitoring of blood coagulation process under temperature and hematocrit variations conducted in a microfluidic chip.

    Directory of Open Access Journals (Sweden)

    Kin Fong Lei

    Full Text Available Blood coagulation is an extremely complicated and dynamic physiological process. Monitoring of blood coagulation is essential to predict the risk of hemorrhage and thrombosis during cardiac surgical procedures. In this study, a high throughput microfluidic chip has been developed for the investigation of the blood coagulation process under temperature and hematocrit variations. Electrical impedance of the whole blood was continuously recorded by on-chip electrodes in contact with the blood sample during coagulation. Analysis of the impedance change of the blood was conducted to investigate the characteristics of blood coagulation process and the starting time of blood coagulation was defined. The study of blood coagulation time under temperature and hematocrit variations was shown a good agreement with results in the previous clinical reports. The electrical impedance measurement for the definition of blood coagulation process provides a fast and easy measurement technique. The microfluidic chip was shown to be a sensitive and promising device for monitoring blood coagulation process even in a variety of conditions. It is found valuable for the development of point-of-care coagulation testing devices that utilizes whole blood sample in microliter quantity.

  16. Design of microfluidic channels for magnetic separation of malaria-infected red blood cells

    Science.gov (United States)

    Wu, Wei-Tao; Martin, Andrea Blue; Gandini, Alberto; Aubry, Nadine; Massoudi, Mehrdad; Antaki, James F.

    2016-01-01

    This study is motivated by the development of a blood cell filtration device for removal of malaria-infected, parasitized red blood cells (pRBCs). The blood was modeled as a multi-component fluid using the computational fluid dynamics discrete element method (CFD-DEM), wherein plasma was treated as a Newtonian fluid and the red blood cells (RBCs) were modeled as soft-sphere solid particles which move under the influence of drag, collisions with other RBCs, and a magnetic force. The CFD-DEM model was first validated by a comparison with experimental data from Han et al. 2006 (Han and Frazier 2006) involving a microfluidic magnetophoretic separator for paramagnetic deoxygenated blood cells. The computational model was then applied to a parametric study of a parallel-plate separator having hematocrit of 40% with a 10% of the RBCs as pRBCs. Specifically, we investigated the hypothesis of introducing an upstream constriction to the channel to divert the magnetic cells within the near-wall layer where the magnetic force is greatest. Simulations compared the efficacy of various geometries upon the stratification efficiency of the pRBCs. For a channel with nominal height of 100 µm, the addition of an upstream constriction of 80% improved the proportion of pRBCs retained adjacent to the magnetic wall (separation efficiency) by almost 2 fold, from 26% to 49%. Further addition of a downstream diffuser reduced remixing, hence improved separation efficiency to 72%. The constriction introduced a greater pressure drop (from 17 to 495 Pa), which should be considered when scaling-up this design for a clinical-sized system. Overall, the advantages of this design include its ability to accommodate physiological hematocrit and high throughput – which is critical for clinical implementation as a blood-filtration system.

  17. Capillary flow-driven microfluidic device with wettability gradient and sedimentation effects for blood plasma separation

    Science.gov (United States)

    Maria, M. Sneha; Rakesh, P. E.; Chandra, T. S.; Sen, A. K.

    2017-01-01

    We report a capillary flow-driven microfluidic device for blood-plasma separation that comprises a cylindrical well between a pair of bottom and top channels. Exposure of the well to oxygen-plasma creates wettability gradient on its inner surface with its ends hydrophilic and middle portion hydrophobic. Due to capillary action, sample blood self-infuses into bottom channel and rises up the well. Separation of plasma occurs at the hydrophobic patch due to formation of a ‘self-built-in filter’ and sedimentation. Capillary velocity is predicted using a model and validated using experimental data. Sedimentation of RBCs is explained using modified Steinour’s model and correlation between settling velocity and liquid concentration is found. Variation of contact angle on inner surface of the well is characterized and effects of well diameter and height and dilution ratio on plasma separation rate are investigated. With a well of 1.0 mm diameter and 4.0 mm height, 2.0 μl of plasma was obtained (from <10 μl whole blood) in 15 min with a purification efficiency of 99.9%. Detection of glucose was demonstrated with the plasma obtained. Wetting property of channels was maintained by storing in DI water under vacuum and performance of the device was found to be unaffected over three weeks. PMID:28256564

  18. Performance study of microfluidic devices for blood plasma separation—a designer’s perspective

    Science.gov (United States)

    Tripathi, Siddhartha; Bala Varun Kumar, Y. V.; Prabhakar, Amit; Joshi, Suhas S.; Agrawal, Amit

    2015-08-01

    In this work, design and experiments on various blood plasma microdevices based on hydrodynamic flow separation techniques is carried out. We study their performance as a function of dependent governing parameters such as flow rate, feed hematocrit, and microchannel geometry. This work focuses on understanding separation phenomena in simple geometries; subsequently, individual simple geometrical parameters and biophysical effects are combined to fabricate hybridized designs, resulting in higher separation efficiencies. The distinctive features of our microfluidic devices are that they employ elevated dimensions (of the order of hundreds of microns), and thereby can be operated continuously over sufficient duration without clogging, while simplicity of fabrication makes them cost effective. The microdevices have been experimentally demonstrated over the entire range of hematocrit (i.e. from Hct 7% to Hct 45%). A high separation efficiency of about (78.34  ±  2.7)% with pure blood is achieved in our best hybrid design. We believe that the theory and experimental results presented in this study will aid designers and researchers working in the field of blood plasma separation microdevices.

  19. Capillary flow-driven microfluidic device with wettability gradient and sedimentation effects for blood plasma separation

    Science.gov (United States)

    Maria, M. Sneha; Rakesh, P. E.; Chandra, T. S.; Sen, A. K.

    2017-03-01

    We report a capillary flow-driven microfluidic device for blood-plasma separation that comprises a cylindrical well between a pair of bottom and top channels. Exposure of the well to oxygen-plasma creates wettability gradient on its inner surface with its ends hydrophilic and middle portion hydrophobic. Due to capillary action, sample blood self-infuses into bottom channel and rises up the well. Separation of plasma occurs at the hydrophobic patch due to formation of a ‘self-built-in filter’ and sedimentation. Capillary velocity is predicted using a model and validated using experimental data. Sedimentation of RBCs is explained using modified Steinour’s model and correlation between settling velocity and liquid concentration is found. Variation of contact angle on inner surface of the well is characterized and effects of well diameter and height and dilution ratio on plasma separation rate are investigated. With a well of 1.0 mm diameter and 4.0 mm height, 2.0 μl of plasma was obtained (from purification efficiency of 99.9%. Detection of glucose was demonstrated with the plasma obtained. Wetting property of channels was maintained by storing in DI water under vacuum and performance of the device was found to be unaffected over three weeks.

  20. Numerical study on the complete blood cell sorting using particle tracing and dielectrophoresis in a microfluidic device

    Science.gov (United States)

    Ali, Haider; Park, Cheol Woo

    2016-11-01

    In this study, a numerical model of a microfluidic device with particle tracing and dielectrophoresis field-flow fractionation was employed to perform a complete and continuous blood cell sorting. A low voltage was applied to electrodes to separate the red blood cells, white blood cells, and platelets based on their cell size. Blood cell sorting and counting were performed by evaluating the cell trajectories, displacements, residence times, and recovery rates in the device. A novel numerical technique was used to count the number of separated blood cells by estimating the displacement and residence time of the cells in a microfluidic device. For successful blood cell sorting, the value of cells displacement must be approximately equal to or higher than the corresponding maximum streamwise distance. The study also proposed different outlet designs to improve blood cell separation. The basic outlet design resulted in a higher cells recovery rate than the other outlets design. The recovery rate decreased as the number of inlet cells and flow rates increased because of the high particle-particle interactions and collisions with walls. The particle-particle interactions significantly affect blood cell sorting and must therefore be considered in future work.

  1. High-throughput and clogging-free microfluidic filtration platform for on-chip cell separation from undiluted whole blood.

    Science.gov (United States)

    Cheng, Yinuo; Ye, Xiongying; Ma, Zengshuai; Xie, Shuai; Wang, Wenhui

    2016-01-01

    Rapid separation of white blood cells from whole blood sample is often required for their subsequent analyses of functions and phenotypes, and many advances have been made in this field. However, most current microfiltration-based cell separation microfluidic chips still suffer from low-throughput and membrane clogging. This paper reports on a high-throughput and clogging-free microfluidic filtration platform, which features with an integrated bidirectional micropump and commercially available polycarbonate microporous membranes. The integrated bidirectional micropump enables the fluid to flush micropores back and forth, effectively avoiding membrane clogging. The microporous membrane allows red blood cells passing through high-density pores in a cross-flow mixed with dead-end filtration mode. All the separation processes, including blood and buffer loading, separation, and sample collection, are automatically controlled for easy operation and high throughput. Both microbead mixture and undiluted whole blood sample are separated by the platform effectively. In particular, for white blood cell separation, the chip recovered 72.1% white blood cells with an over 232-fold enrichment ratio at a throughput as high as 37.5 μl/min. This high-throughput, clogging-free, and highly integrated platform holds great promise for point-of-care blood pretreatment, analysis, and diagnosis applications.

  2. Paper-Origami-Based Multiplexed Malaria Diagnostics from Whole Blood.

    Science.gov (United States)

    Xu, Gaolian; Nolder, Debbie; Reboud, Julien; Oguike, Mary C; van Schalkwyk, Donelly A; Sutherland, Colin J; Cooper, Jonathan M

    2016-12-05

    We demonstrate, for the first time, the multiplexed determination of microbial species from whole blood using the paper-folding technique of origami to enable the sequential steps of DNA extraction, loop-mediated isothermal amplification (LAMP), and array-based fluorescence detection. A low-cost handheld flashlight reveals the presence of the final DNA amplicon to the naked eye, providing a "sample-to-answer" diagnosis from a finger-prick volume of human blood, within 45 min, with minimal user intervention. To demonstrate the method, we showed the identification of three species of Plasmodium, analyzing 80 patient samples benchmarked against the gold-standard polymerase chain reaction (PCR) assay in an operator-blinded study. We also show that the test retains its diagnostic accuracy when using stored or fixed reference samples.

  3. Dried blood spot analysis by digital microfluidics coupled to nanoelectrospray ionization mass spectrometry.

    Science.gov (United States)

    Shih, Steve C C; Yang, Hao; Jebrail, Mais J; Fobel, Ryan; McIntosh, Nathan; Al-Dirbashi, Osama Y; Chakraborty, Pranesh; Wheeler, Aaron R

    2012-04-17

    Dried blood spot (DBS) samples on filter paper are surging in popularity as a sampling and storage vehicle for a wide range of clinical and pharmaceutical applications. For example, a DBS sample is collected from every baby born in the province of Ontario, Canada, for quantification of approximately one hundred analytes that are used to screen for 28 conditions, including succinylacetone (SA), a marker for hepatorenal tyrosinemia. Unfortunately, the conventional methods used to evaluate DBS samples for newborn screening and other applications are tedious and slow, with limited options for automated analysis. In response to this challenge, we have developed a method to couple digital microfluidics (DMF) to nanoelectrospray ionization mass spectrometry (nESI-MS) for SA quantification in DBS samples. The new system is formed by sandwiching a pulled glass capillary emitter between the two DMF substrates such that the capillary emitter is immobilized without external seals or gaskets. Moreover, we introduce a new feedback control system that enables high-fidelity droplet manipulation across DBS samples without manual intervention. The system was validated by application to on-chip extraction, derivatization, and analysis of SA and other analytes from DBS samples, with comparable performance to gold-standard methods. We propose that the new methods described here can potentially contribute to a new generation of analytical techniques for quantifying analytes in DBS samples for a wide range of applications.

  4. Integrated Microfluidic Nucleic Acid Isolation, Isothermal Amplification, and Amplicon Quantification

    OpenAIRE

    Mauk, Michael G.; Changchun Liu; Jinzhao Song; Bau, Haim H.

    2015-01-01

    Microfluidic components and systems for rapid (<60 min), low-cost, convenient, field-deployable sequence-specific nucleic acid-based amplification tests (NAATs) are described. A microfluidic point-of-care (POC) diagnostics test to quantify HIV viral load from blood samples serves as a representative and instructive example to discuss the technical issues and capabilities of “lab on a chip” NAAT devices. A portable, miniaturized POC NAAT with performance comparable to conventional PCR (poly...

  5. 21 CFR 864.9160 - Blood group substances of nonhuman origin for in vitro diagnostic use.

    Science.gov (United States)

    2010-04-01

    ... vitro diagnostic use. 864.9160 Section 864.9160 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT... nonhuman origin for in vitro diagnostic use. (a) Identification. Blood group substances of nonhuman origin for in vitro diagnostic use are materials, such as blood group specific substances prepared...

  6. Blood-Mimicking Fluid for Testing Ultrasonic Diagnostic Instrument

    Science.gov (United States)

    Tanaka, Kouhei; Yoshida, Tomoji; Sato, Kazuishi; Kondo, Toshio; Yasukawa, Kazuhiro; Miyamoto, Nobuaki; Taniguchi, Masahiko

    2012-07-01

    We present a blood-mimicking fluid (BMF) for the Doppler test object of medical diagnostic instruments. Accurate measurement in a flow Doppler test requires a BMF that has the acoustic velocity and density defined in the International Electrotechnical Commission (IEC) standard, and furthermore, they must be stable over time. To formulate a fluid with the desired density and acoustic velocity, we have developed a new fluid made of glycerine and water-soluble silicone oil. The new BMF includes dispersed polystyrene particles as scatterers. The density of the liquid can be adjusted to maintain it at the same value as that of the polystyrene particles, thus ensuring neutral buoyancy of the particles. The MBF was stable over a period of 2 weeks, during which the density and acoustic velocity did not change.

  7. An integrated rotary microfluidic system with DNA extraction, loop-mediated isothermal amplification, and lateral flow strip based detection for point-of-care pathogen diagnostics.

    Science.gov (United States)

    Park, Byung Hyun; Oh, Seung Jun; Jung, Jae Hwan; Choi, Goro; Seo, Ji Hyun; Kim, Do Hyun; Lee, Eun Yeol; Seo, Tae Seok

    2017-05-15

    Point-of-care (POC) molecular diagnostics plays a pivotal role for the prevention and treatment of infectious diseases. In spite of recent advancement in microfluidic based POC devices, there are still rooms for development to realize rapid, automatic and cost-effective sample-to-result genetic analysis. In this study, we propose an integrated rotary microfluidic system that is capable of performing glass microbead based DNA extraction, loop mediated isothermal amplification (LAMP), and colorimetric lateral flow strip based detection in a sequential manner with an optimized microfluidic design and a rotational speed control. Rotation direction-dependent coriolis force and siphon valving structures enable us to perform the fluidic control and metering, and the use of the lateral flow strip as a detection method renders all the analytical processes for nucleic acid test simplified and integrated without the need of expensive instruments or human intervention. As a proof of concept for point-of-care DNA diagnostics, we identified the food-borne bacterial pathogen which was contaminated in water or milk. Not only monoplex Salmonella Typhimurium but also multiplex Salmonella Typhimurium and Vibrio parahaemolyticus were analysed on the integrated rotary genetic analysis microsystem with a limit of detection of 50 CFU in 80min. In addition, three multiple samples were simultaneously analysed on a single device. The sample-to-result capability of the proposed microdevice provides great usefulness in the fields of clinical diagnostics, food safety and environment monitoring.

  8. COMPARABLE CYTOLOGICAL DIAGNOSTIC OF BLOOD SMEARS ON BABESIA INFECTION

    Directory of Open Access Journals (Sweden)

    Pokhyl S.І.

    2015-05-01

    Full Text Available In last time Babesiosis as a tick-borne hemoprotozoans human disease have a very important role in differentil diagnostics of modern infectious medicine. It caused by protozon of the genus Babesia, which invade and destory erythrocytes. Babesiosis olso has been called tick fever. So, Babesia has been known by other genus names, including Nuttallia, Microbabesia, Babesialla, and Gonderia. Because all Babesia species are piroplasms, a more inclusive term for anthropozoonotic infections caused by these organisms would be piroplasmosis.They detective complicacy are bild that, tick-borne disease agents from prolongate life cycles involving arthropod and vertebrate host. The complexity is enhanced by the diversity of hosts in different biotopes, which depends on factors life type of vegetation, climate and/or human influence, such as restoration of former industrial sites, which leads to the development of new biotopes. So, on the one hand, new habitats for plants and animals including ticks, and nature are created. About the first case of babesiosis infection was reported as a cause of human sickness in 1969 in northeastern United State. Several hundred cases are now reported from this region each year. The disease is characterized by a grandual oncet of malaise with anorexia, fever, headaches, myalgia, and other vague symptoms, which may persist for long period. Occasionally dangerous fulminating infections occur particularly in immunocompromised or aged individuals. The purpose of the present research was to study of the cytological diagnostic of blood smears from object’s with the Babesia infection. Materials and methods. Blood smears (by Romanovsky- Gimze (standart, Wright’s standart and staining, the author’s modification, 2014 of domestic dogs (n = 31 of both sexes with Babesia infection at the age from 3 months to 6 years served as the material for the study. The preparations were fixed during 1-2 seconds with 96 % ethyl alcohol. Then

  9. Diagnostic Methods for Detection of Blood-Borne Candidiasis.

    Science.gov (United States)

    Clancy, Cornelius J; Nguyen, M Hong

    2016-01-01

    β-D-glucan (Fungitell) and polymerase chain reaction-based (T2Candida) assays of blood samples are FDA-approved adjuncts to cultures for diagnosing candidemia and other types of invasive candidiasis, but their clinical roles are unclear. In this chapter, we describe laboratory protocols for performing Fungitell and T2Candida assays. We then discuss step-by-step methods for interpreting test results at the bedside using a Bayesian framework, and for incorporating assays into rational patient management strategies. Prior to interpreting results, clinicians must recognize that test performance varies based on the type of invasive candidiasis being diagnosed. In general, the type of invasive candidiasis that is most likely in a given patient can be identified, and the pretest likelihood of disease estimated. From there, positive and negative predictive values (PPV, NPV) for an assay can be calculated. At a population level, tests can be incorporated into screening strategies for antifungal treatment. NPV and PPV thresholds can be defined for discontinuing antifungal prophylaxis or initiating preemptive treatment, respectively. Using the thresholds, it is possible to assign windows of pretest likelihood for invasive candidiasis (and corresponding patient populations) in which tests are most likely to valuable. At the individual patient level, tests may be useful outside of the windows proposed for screening populations. The interpretive and clinical decision-making processes we discuss will be applicable to other diagnostic assays as they enter the clinic, and to existing assays as more data emerge from various populations.

  10. A Review of Biomedical Centrifugal Microfluidic Platforms

    Directory of Open Access Journals (Sweden)

    Minghui Tang

    2016-02-01

    Full Text Available Centrifugal microfluidic or lab-on-a-disc platforms have many advantages over other microfluidic systems. These advantages include a minimal amount of instrumentation, the efficient removal of any disturbing bubbles or residual volumes, and inherently available density-based sample transportation and separation. Centrifugal microfluidic devices applied to biomedical analysis and point-of-care diagnostics have been extensively promoted recently. This paper presents an up-to-date overview of these devices. The development of biomedical centrifugal microfluidic platforms essentially covers two categories: (i unit operations that perform specific functionalities, and (ii systems that aim to address certain biomedical applications. With the aim to provide a comprehensive representation of current development in this field, this review summarizes progress in both categories. The advanced unit operations implemented for biological processing include mixing, valving, switching, metering and sequential loading. Depending on the type of sample to be used in the system, biomedical applications are classified into four groups: nucleic acid analysis, blood analysis, immunoassays, and other biomedical applications. Our overview of advanced unit operations also includes the basic concepts and mechanisms involved in centrifugal microfluidics, while on the other hand an outline on reported applications clarifies how an assembly of unit operations enables efficient implementation of various types of complex assays. Lastly, challenges and potential for future development of biomedical centrifugal microfluidic devices are discussed.

  11. A Turbidity Test Based Centrifugal Microfluidics Diagnostic System for Simultaneous Detection of HBV, HCV, and CMV

    Directory of Open Access Journals (Sweden)

    Hung-Cheng Chang

    2015-01-01

    Full Text Available This paper presents a LAMP- (loop-mediated isothermal amplification- based lab-on-disk optical system that allows the simultaneous detection of hepatitis B virus, hepatitis C virus, and cytomegalovirus. The various flow stages are controlled in the proposed system using different balance among centrifugal pumping, Coriolis pumping, and the capillary force. We have implemented a servo system for positioning and speed control for the heating and centrifugal pumping. We have also successfully employed a polymer light-emitting diode section for turbidity detection. The easy-to-use one-click system can perform diagnostics in less than 1 hour.

  12. 近期微流控芯片疾病诊断技术的研究进展%Recent development of microfluidic diagnostic technologies

    Institute of Scientific and Technical Information of China (English)

    李海芳; 张倩云; 林金明

    2011-01-01

    Microfluidic devices exhibit a great promising development in clinical diagnosis and disease screening due to their advantages of precise controlling of fluid flow, requirement of miniamount sample, rapid reaction speed and convenient integration. In this paper, the improvements of microfluidic diagnostic technologies in recent years are reviewed. The applications and developments of on-chip disease marker detection, microfluidic cell selection and cell drug metabolism, and diagnostic micro-devices are discussed.%微流控芯片具有液流可控、样品消耗量小、反应速度快、易于集成化等特点,在临床诊断和疾病筛查领域具有广阔的发展前景.本文针对近年来微流控芯片技术在疾病诊断方面的最新研究进展,从疾病标志物检测、细胞筛选和药物代谢研究及疾病诊断微流控芯片装置的发展现状等方面概述其在疾病诊断方面的应用和发展.

  13. Simulation and experimental determination of the online separation of blood components with the help of microfluidic cascading spirals.

    Science.gov (United States)

    Sprenger, Lisa; Dutz, Silvio; Schneider, Thomas; Odenbach, Stefan; Häfeli, Urs O

    2015-07-01

    Microfluidic spirals were used to successfully separate rare solid components from unpretreated human whole blood samples. The measured separation ratio of the spirals is the factor by which the concentration of the rare component is increased due to the Dean effect present in a flow profile in a curved duct. Different rates of dilution of the blood samples with a phosphate-buffered solution were investigated. The diameters of the spherical particles to separate ranged from 2 μm to 18 μm. It was found that diluting the blood to 20% is optimal leading to a separation ratio up to 1.97. Using two spirals continuously placed in a row led to an increase in separation efficacy in samples consisting of phosphate-buffered solution only from 1.86 to 3.79. Numerical investigations were carried out to display the flow profiles of Newtonian water samples and the shear-thinning blood samples in the cross-section of the experimentally handled channels. A macroscopic difference in velocity between the two rheologically different fluids could not be found. The macroscopic Dean flow is equally present and useful to help particles migrate to certain equilibrium positions in blood as well as lower viscous Newtonian fluids. The investigations highlight the potential for using highly concentrated, very heterogeneous, and non-Newtonian fluidic systems in known microsystems for screening applications.

  14. EDTA-treated cotton-thread microfluidic device used for one-step whole blood plasma separation and assay.

    Science.gov (United States)

    Ulum, Mokhamad Fakhrul; Maylina, Leni; Noviana, Deni; Wicaksono, Dedy Hermawan Bagus

    2016-04-21

    This study aims to observe the wicking and separation characteristics of blood plasma in a cotton thread matrix functioning as a microfluidic thread-based analytical device (μTAD). We investigated several cotton thread treatment methods using ethylenediaminetetraacetic acid (EDTA) anticoagulant solution for wicking whole blood samples and separating its plasma. The blood of healthy Indonesian thin tailed sheep was used in this study to understand the properties of horizontal wicking and separation on the EDTA-treated μTAD. The wicking distance and blood cell separation from its plasma was observed for 120 s and documented using a digital phone camera. The results show that untreated cotton-threads stopped the blood wicking process on the μTAD. On the other hand, the deposition of EDTA anticoagulant followed by its drying on the thread at room temperature for 10 s provides the longest blood wicking with gradual blood plasma separation. Furthermore, the best results in terms of the longest wicking and the clearest on-thread separation boundary between blood cells and its plasma were obtained using the μTAD treated with EDTA deposition followed by 60 min drying at refrigerated temperature (2-8 °C). The separation length of blood plasma in the μTADs treated with dried-EDTA at both room and refrigerated temperatures was not statistically different (P > 0.05). This separation occurs through the synergy of three factors, cotton fiber, EDTA anticoagulant and blood platelets, which induce the formation of a fibrin-filter via a partial coagulation process in the EDTA-treated μTAD. An albumin assay was employed to demonstrate the efficiency of this plasma separation method during a one-step assay on the μTAD. Albumin in blood is an important biomarker for kidney and heart disease. The μTAD has a slightly better limit of detection (LOD) than conventional blood analysis, with an LOD of 114 mg L(-1) compared to 133 mg L(-1), respectively. However, the μTAD performed

  15. Resonance Raman study of the oxygenation cycle of optically trapped single red blood cells in a microfluidic system

    Science.gov (United States)

    Ramser, Kerstin; Logg, Katarina; Enger, Jonas; Goksor, Mattias; Kall, Mikael; Hanstorp, Dag

    2004-10-01

    The average environmental response of red blood cells (RBCs) is routinely measured in ensemble studies, but in such investigations valuable information on the single cell level is obscured. In order to elucidate this hidden information is is important to enable the selection of single cells with certain properties while subsequent dynamics triggered by environmental stimulation are recorded in real time. It is also desirable to manipulate and control the cells under phsyiological conditions. As shown here, this can be achieved by combining optical tweezers with a confocal Raman set-up equipped with a microfluidic system. A micro-Raman set-up is combined with an optical trap with separate optical paths, lasers and objectives, which enables the acquisition of resonance Raman profils of single RBCs. The microfluidic system, giving full control over the media surrounding the cell, consists of a pattern of channels and reservoirs produced by electron beam lithography and moulded in PDMS. Fresh Hepes buffer or buffer containing sodium dithionite are transported through the channels using electro-osmotic flow, while the direct Raman response of the single optically trapped RBC is registered in another reservoir in the middle of the channel. Thus, it is possible to monitor the oxygenation cycle in a single cell and to study photo-induced chemistry. This experimental set-up has high potential for monitoring the drug response or conformational changes caused by other environmental stimuli for many types of single functional cells since "in vivo" conditions can be created.

  16. Microfluidic Device

    Science.gov (United States)

    Tai, Yu-Chong (Inventor); Zheng, Siyang (Inventor); Lin, Jeffrey Chun-Hui (Inventor); Kasdan, Harvey L. (Inventor)

    2017-01-01

    Described herein are particular embodiments relating to a microfluidic device that may be utilized for cell sensing, counting, and/or sorting. Particular aspects relate to a microfabricated device that is capable of differentiating single cell types from dense cell populations. One particular embodiment relates a device and methods of using the same for sensing, counting, and/or sorting leukocytes from whole, undiluted blood samples.

  17. Detection of ESKAPE Bacterial Pathogens at the Point of Care Using Isothermal DNA-Based Assays in a Portable Degas-Actuated Microfluidic Diagnostic Assay Platform.

    Science.gov (United States)

    Renner, Lars D; Zan, Jindong; Hu, Linda I; Martinez, Manuel; Resto, Pedro J; Siegel, Adam C; Torres, Clint; Hall, Sara B; Slezak, Tom R; Nguyen, Tuan H; Weibel, Douglas B

    2017-02-15

    An estimated 1.5 billion microbial infections occur globally each year and result in ∼4.6 million deaths. A technology gap associated with commercially available diagnostic tests in remote and underdeveloped regions prevents timely pathogen identification for effective antibiotic chemotherapies for infected patients. The result is a trial-and-error approach that is limited in effectiveness, increases risk for patients while contributing to antimicrobial drug resistance, and reduces the lifetime of antibiotics. This paper addresses this important diagnostic technology gap by describing a low-cost, portable, rapid, and easy-to-use microfluidic cartridge-based system for detecting the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) bacterial pathogens that are most commonly associated with antibiotic resistance. The point-of-care molecular diagnostic system consists of a vacuum-degassed microfluidic cartridge preloaded with lyophilized recombinase polymerase amplification (RPA) assays and a small portable battery-powered electronic incubator/reader. The isothermal RPA assays detect the targeted ESKAPE pathogens with high sensitivity (e.g., a limit of detection of ∼10 nucleic acid molecules) that is comparable to that of current PCR-based assays, and they offer advantages in power consumption, engineering, and robustness, which are three critical elements required for the point-of-care setting.

  18. Deformability measurement of red blood cells using a microfluidic channel array and an air cavity in a driving syringe with high throughput and precise detection of subpopulations.

    Science.gov (United States)

    Kang, Yang Jun; Ha, Young-Ran; Lee, Sang-Joon

    2016-01-07

    Red blood cell (RBC) deformability has been considered a potential biomarker for monitoring pathological disorders. High throughput and detection of subpopulations in RBCs are essential in the measurement of RBC deformability. In this paper, we propose a new method to measure RBC deformability by evaluating temporal variations in the average velocity of blood flow and image intensity of successively clogged RBCs in the microfluidic channel array for specific time durations. In addition, to effectively detect differences in subpopulations of RBCs, an air compliance effect is employed by adding an air cavity into a disposable syringe. The syringe was equally filled with a blood sample (V(blood) = 0.3 mL, hematocrit = 50%) and air (V(air) = 0.3 mL). Owing to the air compliance effect, blood flow in the microfluidic device behaved transiently depending on the fluidic resistance in the microfluidic device. Based on the transient behaviors of blood flows, the deformability of RBCs is quantified by evaluating three representative parameters, namely, minimum value of the average velocity of blood flow, clogging index, and delivered blood volume. The proposed method was applied to measure the deformability of blood samples consisting of homogeneous RBCs fixed with four different concentrations of glutaraldehyde solution (0%-0.23%). The proposed method was also employed to evaluate the deformability of blood samples partially mixed with normal RBCs and hardened RBCs. Thereafter, the deformability of RBCs infected by human malaria parasite Plasmodium falciparum was measured. As a result, the three parameters significantly varied, depending on the degree of deformability. In addition, the deformability measurement of blood samples was successfully completed in a short time (∼10 min). Therefore, the proposed method has significant potential in deformability measurement of blood samples containing hematological diseases with high throughput and precise detection of

  19. Real time observation and automated measurement of red blood cells agglutination inside a passive microfluidic biochip containing embedded reagents.

    Science.gov (United States)

    Huet, Maxime; Cubizolles, Myriam; Buhot, Arnaud

    2016-09-20

    The process of agglutination is commonly used for the detection of biomarkers like proteins or viruses. The multiple bindings between micrometer sized particles, either latex beads or red blood cells (RBCs), create aggregates that are easily detectable and give qualitative information about the presence of the biomarkers. In most cases, the detection is made by simple naked-eye observation of agglutinates without any access to the kinetics of agglutination. In this study, we address the development of a real-time time observation of RBCs agglutination. Using ABO blood typing as a proof-of-concept, we developed i) an integrated biological protocol suitable for further use as point-of-care (POC) analysis and ii) two dedicated image processing algorithms for the real-time and quantitative measurement of agglutination. Anti-A or anti-B typing reagents were dried inside the microchannel of a passive microfluidic chip designed to enhance capillary flow. A blood drop deposit at the tip of the biochip established a simple biological protocol. In situ agglutination of autologous RBCs was achieved by means of embedded reagents and real time agglutination process was monitored by video recording. Using a training set of 24 experiments, two real-time indicators based on correlation and variance of gray levels were optimized and then further confirmed on a validation set. 100% correct discrimination between positive and negative agglutinations was performed within less than 2min by measuring real-time evolution of both correlation and variance indicators.

  20. Comparison of roll-to-roll replication approaches for microfluidic and optical functions in lab-on-a-chip diagnostic devices

    Science.gov (United States)

    Brecher, Christian; Baum, Christoph; Bastuck, Thomas

    2015-03-01

    Economically advantageous microfabrication technologies for lab-on-a-chip diagnostic devices substituting commonly used glass etching or injection molding processes are one of the key enablers for the emerging market of microfluidic devices. On-site detection in fields of life sciences, point of care diagnostics and environmental analysis requires compact, disposable and highly functionalized systems. Roll-to-roll production as a high volume process has become the emerging fabrication technology for integrated, complex high technology products within recent years (e.g. fuel cells). Differently functionalized polymer films enable researchers to create a new generation of lab-on-a-chip devices by combining electronic, microfluidic and optical functions in multilayer architecture. For replication of microfluidic and optical functions via roll-to-roll production process competitive approaches are available. One of them is to imprint fluidic channels and optical structures of micro- or nanometer scale from embossing rollers into ultraviolet (UV) curable lacquers on polymer substrates. Depending on dimension, shape and quantity of those structures there are alternative manufacturing technologies for the embossing roller. Ultra-precise diamond turning, electroforming or casting polymer materials are used either for direct structuring or manufacturing of roller sleeves. Mastering methods are selected for application considering replication quality required and structure complexity. Criteria for the replication quality are surface roughness and contour accuracy. Structure complexity is evaluated by shapes producible (e.g. linear, circular) and aspect ratio. Costs for the mastering process and structure lifetime are major cost factors. The alternative replication approaches are introduced and analyzed corresponding to the criteria presented. Advantages and drawbacks of each technology are discussed and exemplary applications are presented.

  1. Challenges in the Use of Compact Disc-Based Centrifugal Microfluidics for Healthcare Diagnostics at the Extreme Point of Care

    Directory of Open Access Journals (Sweden)

    Jordon Gilmore

    2016-03-01

    Full Text Available Since its inception, Compact Disc (CD-based centrifugal microfluidic technology has drawn a great deal of interest within research communities due to its potential use in biomedical applications. The technology has been referred to by different names, including compact-disc microfluidics, lab-on-a-disk, lab-on-a-CD and bio-disk. This paper critically reviews the state-of-the-art in CD-based centrifugal microfluidics devices and attempts to identify the challenges that, if solved, would enable their use in the extreme point of care. Sample actuation, manufacturing, reagent storage and implementation, target multiplexing, bio-particle detection, required hardware and system disposal, and sustainability are the topics of focus.

  2. Going beyond 20 μm-sized channels for studying red blood cell phase separation in microfluidic bifurcations.

    Science.gov (United States)

    Roman, Sophie; Merlo, Adlan; Duru, Paul; Risso, Frédéric; Lorthois, Sylvie

    2016-05-01

    Despite the development of microfluidics, experimental challenges are considerable for achieving a quantitative study of phase separation, i.e., the non-proportional distribution of Red Blood Cells (RBCs) and suspending fluid, in microfluidic bifurcations with channels smaller than 20 μm. Yet, a basic understanding of phase separation in such small vessels is needed for understanding the coupling between microvascular network architecture and dynamics at larger scale. Here, we present the experimental methodologies and measurement techniques developed for that purpose for RBC concentrations (tube hematocrits) ranging between 2% and 20%. The maximal RBC velocity profile is directly measured by a temporal cross-correlation technique which enables to capture the RBC slip velocity at walls with high resolution, highlighting two different regimes (flat and more blunted ones) as a function of RBC confinement. The tube hematocrit is independently measured by a photometric technique. The RBC and suspending fluid flow rates are then deduced assuming the velocity profile of a Newtonian fluid with no slip at walls for the latter. The accuracy of this combination of techniques is demonstrated by comparison with reference measurements and verification of RBC and suspending fluid mass conservation at individual bifurcations. The present methodologies are much more accurate, with less than 15% relative errors, than the ones used in previous in vivo experiments. Their potential for studying steady state phase separation is demonstrated, highlighting an unexpected decrease of phase separation with increasing hematocrit in symmetrical, but not asymmetrical, bifurcations and providing new reference data in regimes where in vitro results were previously lacking.

  3. Hair: A Diagnostic Tool to Complement Blood Serum and Urine.

    Science.gov (United States)

    Maugh, Thomas H., II

    1978-01-01

    Trace elements and some drugs can be identified in hair and it seems likely that other organic chemicals will be identifiable in the future. Since hair is so easily collected, stored, and analyzed it promises to be an ideal complement to serum and urine analysis as a diagnostic tool. (BB)

  4. Lensless Imaging for Battlefield On-Chip Blood Diagnostics

    Science.gov (United States)

    2010-12-06

    our Related Achievements The needs and the requirements of medical diagnostics in resource limited settings such as the battlefield are significantly...different than advanced medical laboratories. On the battlefield, medical resources , as well as trained personnel capable of running advanced...which are especially important for immunity assesment ) and cytokines were printed in an array so as to juxtapose cell capture and cytokine

  5. Magnetic digital microfluidics - a review.

    Science.gov (United States)

    Zhang, Yi; Nguyen, Nam-Trung

    2017-03-14

    A digital microfluidic platform manipulates droplets on an open surface. Magnetic digital microfluidics utilizes magnetic forces for actuation and offers unique advantages compared to other digital microfluidic platforms. First, the magnetic particles used in magnetic digital microfluidics have multiple functions. In addition to serving as actuators, they also provide a functional solid substrate for molecule binding, which enables a wide range of applications in molecular diagnostics and immunodiagnostics. Second, magnetic digital microfluidics can be manually operated in a "power-free" manner, which allows for operation in low-resource environments for point-of-care diagnostics where even batteries are considered a luxury item. This review covers research areas related to magnetic digital microfluidics. This paper first summarizes the current development of magnetic digital microfluidics. Various methods of droplet manipulation using magnetic forces are discussed, ranging from conventional magnetic particle-based actuation to the recent development of ferrofluids and magnetic liquid marbles. This paper also discusses several new approaches that use magnetically controlled flexible substrates for droplet manipulation. In addition, we emphasize applications of magnetic digital microfluidics in biosensing and medical diagnostics, and identify the current limitations of magnetic digital microfluidics. We provide a perspective on possible solutions to close these gaps. Finally, the paper discusses the future improvement of magnetic digital microfluidics to explore potential new research directions.

  6. Development of an Automated and Sensitive Microfluidic Device for Capturing and Characterizing Circulating Tumor Cells (CTCs from Clinical Blood Samples.

    Directory of Open Access Journals (Sweden)

    Priya Gogoi

    Full Text Available Current analysis of circulating tumor cells (CTCs is hindered by sub-optimal sensitivity and specificity of devices or assays as well as lack of capability of characterization of CTCs with clinical biomarkers. Here, we validate a novel technology to enrich and characterize CTCs from blood samples of patients with metastatic breast, prostate and colorectal cancers using a microfluidic chip which is processed by using an automated staining and scanning system from sample preparation to image processing. The Celsee system allowed for the detection of CTCs with apparent high sensitivity and specificity (94% sensitivity and 100% specificity. Moreover, the system facilitated rapid capture of CTCs from blood samples and also allowed for downstream characterization of the captured cells by immunohistochemistry, DNA and mRNA fluorescence in-situ hybridization (FISH. In a subset of patients with prostate cancer we compared the technology with a FDA-approved CTC device, CellSearch and found a higher degree of sensitivity with the Celsee instrument. In conclusion, the integrated Celsee system represents a promising CTC technology for enumeration and molecular characterization.

  7. Density-Gradient Mediated Band Extraction of Leukocytes from Whole Blood Using Centrifugo-Pneumatic Siphon Valving on Centrifugal Microfluidic Discs.

    Directory of Open Access Journals (Sweden)

    David J Kinahan

    Full Text Available Here we present retrieval of Peripheral Blood Mononuclear Cells by density-gradient medium based centrifugation for subsequent analysis of the leukocytes on an integrated microfluidic "Lab-on-a-Disc" cartridge. Isolation of white blood cells constitutes a critical sample preparation step for many bioassays. Centrifugo-pneumatic siphon valves are particularly suited for blood processing as they function without need of surface treatment and are 'low-pass', i.e., holding at high centrifugation speeds and opening upon reduction of the spin rate. Both 'hydrostatically' and 'hydrodynamically' triggered centrifugo-pneumatic siphon valving schemes are presented. Firstly, the geometry of the pneumatic chamber of hydrostatically primed centrifugo-pneumatic siphon valves is optimised to enable smooth and uniform layering of blood on top of the density-gradient medium; this feature proves to be key for efficient Peripheral Blood Mononuclear Cell extraction. A theoretical analysis of hydrostatically primed valves is also presented which determines the optimum priming pressure for the individual valves. Next, 'dual siphon' configurations for both hydrostatically and hydrodynamically primed centrifugo-pneumatic siphon valves are introduced; here plasma and Peripheral Blood Mononuclear Cells are extracted through a distinct siphon valve. This work represents a first step towards enabling on disc multi-parameter analysis. Finally, the efficiency of Peripheral Blood Mononuclear Cells extraction in these structures is characterised using a simplified design. A microfluidic mechanism, which we termed phase switching, is identified which affects the efficiency of Peripheral Blood Mononuclear Cell extraction.

  8. Microfluidic bead-based multienzyme-nanoparticle amplification for detection of circulating tumor cells in the blood using quantum dots labels

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, He, E-mail: mzhang_he@126.com; Fu, Xin; Hu, Jiayi; Zhu, Zhenjun

    2013-05-24

    Graphical abstract: A microfluidic beads-based nucleic acid sensor for sensitive detection of circulating tumor cells (CTCs) in the blood using multienzyme-nanoparticle amplification and quantum dots labels was developed. The chip-based CTCs analysis could detect reverse transcription-polymerase chain reaction (RT-PCR) products of tumor cell as low as 1 tumor cell (e.g. CEA expressing cell) in 1 mL blood sample. This microfluidic beads-based nucleic acid sensor is a promising platform for disease-related nucleic acid molecules at the lowest level at their earliest incidence. -- Highlights: •Combination of microfluidic bead-based platform and enzyme–probe–AuNPs is proposed. •The developed nucleic acid sensor could respond to 5 fM of tumor associated DNA. •Microfluidic platform and multienzyme-labeled AuNPs greatly enhanced sensitivity. •The developed nucleic acid sensor could respond to RT-PCR products of tumor cell as low as 1 tumor cell in 1 mL blood sample. •We report a sensitive nucleic acid sensor for detection of circulating tumor cells. -- Abstract: This study reports the development of a microfluidic bead-based nucleic acid sensor for sensitive detection of circulating tumor cells in blood samples using multienzyme-nanoparticle amplification and quantum dot labels. In this method, the microbeads functionalized with the capture probes and modified electron rich proteins were arrayed within a microfluidic channel as sensing elements, and the gold nanoparticles (AuNPs) functionalized with the horseradish peroxidases (HRP) and DNA probes were used as labels. Hence, two signal amplification approaches are integrated for enhancing the detection sensitivity of circulating tumor cells. First, the large surface area of Au nanoparticle carrier allows several binding events of HRP on each nanosphere. Second, enhanced mass transport capability inherent from microfluidics leads to higher capture efficiency of targets because continuous flow within micro

  9. Punch Card Programmable Microfluidics

    OpenAIRE

    George Korir; Manu Prakash

    2014-01-01

    Small volume fluid handling in single and multiphase microfluidics provides a promising strategy for efficient bio-chemical assays, low-cost point-of-care diagnostics and new approaches to scientific discoveries. However multiple barriers exist towards low-cost field deployment of programmable microfluidics. Incorporating multiple pumps, mixers and discrete valve based control of nanoliter fluids and droplets in an integrated, programmable manner without additional required external component...

  10. Assessment of whole blood thrombosis in a microfluidic device lined by fixed human endothelium

    NARCIS (Netherlands)

    Jain, Abhishek; Meer, van der Andries D.; Papa, Anne-Laure; Barrile, Riccardo; Lai, Angela; Schlechter, Benjamin L.; Otieno, Monicah A.; Louden, Calvert S.; Hamilton, Geraldine A.; Michelson, Alan D.; Frelinger, Andrew L.; Ingber, Donald E.

    2016-01-01

    The vascular endothelium and shear stress are critical determinants of physiological hemostasis and platelet function in vivo, yet current diagnostic and monitoring devices do not fully incorporate endothelial function under flow in their assessment and, therefore, they can be unreliable and inaccur

  11. Diagnostic fetal umbilical blood sampling in the management of isoimmunization.

    Science.gov (United States)

    Reece, E A; Copel, J A; Scioscia, A L; Grannum, P A; DeGennaro, N; Hobbins, J C

    1988-11-01

    Current management of isoimmunization in pregnancy is predicted on the assumption that all sensitized women carry antigen-positive fetuses. In addition, management is based on indirect predictors of the magnitude of the fetal hemolytic disease. We present a preliminary report using a new approach of direct fetal blood sampling for the diagnosis and treatment of these patients. This form of evaluation provides specific information about fetal red blood cell antigen status and the degree of fetal anemia at an earlier gestational age than that validated by the Liley curves and eliminates empiricism from both the diagnosis and treatment of the isoimmunized pregnancy. The use of such a management protocol reduces the need for multiple invasive procedures in fetuses at little risk for disease and provides specific information about the status of those fetuses truly at risk.

  12. A microfluidic system enabling Raman measurements of the oxygenation cycle in single optically trapped red blood cells.

    Science.gov (United States)

    Ramser, Kerstin; Enger, Jonas; Goksör, Mattias; Hanstorp, Dag; Logg, Katarina; Käll, Mikael

    2005-04-01

    Using a lab-on-a-chip approach we demonstrate the possibility of selecting a single cell with certain properties and following its dynamics after an environmental stimulation in real time using Raman spectroscopy. This is accomplished by combining a micro Raman set-up with optical tweezers and a microfluidic system. The latter gives full control over the media surrounding the cell, and it consists of a pattern of channels and reservoirs defined by electron beam lithography that is moulded into rubber silicon (PDMS). Different buffers can be transported through the channels using electro-osmotic flow, while the resonance Raman response of an optically trapped red blood cell (RBC) is simultaneously registered. This makes it possible to monitor the oxygenation cycle of the cell in real time and to investigate effects like photo-induced chemistry caused by the illumination. The experimental set-up has high potential for in vivo monitoring of cellular drug response using a variety of spectroscopic probes.

  13. Microfluidic devices for cell cultivation and proliferation

    OpenAIRE

    Tehranirokh, Masoomeh; Kouzani, Abbas Z.; Francis, Paul S.; Kanwar, Jagat R.

    2013-01-01

    Microfluidic technology provides precise, controlled-environment, cost-effective, compact, integrated, and high-throughput microsystems that are promising substitutes for conventional biological laboratory methods. In recent years, microfluidic cell culture devices have been used for applications such as tissue engineering, diagnostics, drug screening, immunology, cancer studies, stem cell proliferation and differentiation, and neurite guidance. Microfluidic technology allows dynamic cell cul...

  14. Digital Microfluidics Sample Analyzer

    Science.gov (United States)

    Pollack, Michael G.; Srinivasan, Vijay; Eckhardt, Allen; Paik, Philip Y.; Sudarsan, Arjun; Shenderov, Alex; Hua, Zhishan; Pamula, Vamsee K.

    2010-01-01

    Three innovations address the needs of the medical world with regard to microfluidic manipulation and testing of physiological samples in ways that can benefit point-of-care needs for patients such as premature infants, for which drawing of blood for continuous tests can be life-threatening in their own right, and for expedited results. A chip with sample injection elements, reservoirs (and waste), droplet formation structures, fluidic pathways, mixing areas, and optical detection sites, was fabricated to test the various components of the microfluidic platform, both individually and in integrated fashion. The droplet control system permits a user to control droplet microactuator system functions, such as droplet operations and detector operations. Also, the programming system allows a user to develop software routines for controlling droplet microactuator system functions, such as droplet operations and detector operations. A chip is incorporated into the system with a controller, a detector, input and output devices, and software. A novel filler fluid formulation is used for the transport of droplets with high protein concentrations. Novel assemblies for detection of photons from an on-chip droplet are present, as well as novel systems for conducting various assays, such as immunoassays and PCR (polymerase chain reaction). The lab-on-a-chip (a.k.a., lab-on-a-printed-circuit board) processes physiological samples and comprises a system for automated, multi-analyte measurements using sub-microliter samples of human serum. The invention also relates to a diagnostic chip and system including the chip that performs many of the routine operations of a central labbased chemistry analyzer, integrating, for example, colorimetric assays (e.g., for proteins), chemiluminescence/fluorescence assays (e.g., for enzymes, electrolytes, and gases), and/or conductometric assays (e.g., for hematocrit on plasma and whole blood) on a single chip platform.

  15. BBB on chip: microfluidic platform to mechanically and biochemically modulate blood-brain barrier function

    NARCIS (Netherlands)

    Griep, L.M.; Wolbers, F.; Wagenaar, de B.; Braak, ter P.M.; Weksler, B.B.; Romero, A.; Couraud, P.O.; Vermes, I.; Meer, van der A.D.; Berg, van den A.

    2013-01-01

    The blood-brain barrier (BBB) is a unique feature of the human body, preserving brain homeostasis and preventing toxic substances to enter the brain. However, in various neurodegenerative diseases, the function of the BBB is disturbed. Mechanisms of the breakdown of the BBB are incompletely understo

  16. Investigations of significance of blood smear results in diagnostics of infectious and parasitic diseases in dogs

    Directory of Open Access Journals (Sweden)

    Potkonjak Aleksandar

    2010-01-01

    Full Text Available The microscopic examination of stained smears of peripheral blood is of vital significance in the speedy diagnostics of infectious and parasitic diseases, in particular during the stage of infection when the cause is present in the blood, or blood cells. It is sometimes possible to make a definitive diagnosis of an infectious or parasitic disease following an examination of a stained smear of the peripheral blood. Since microscopic examinations of a peripheral blood smear are applied increasingly rarely in clinical practice, due to the development of other methods for the diagnostics of infectious and parasitic diseases in dogs, as well as the lack of knowledge of the morphology of the numerous causes that can be present in the blood, we carried out an investigation into the presence and spread of infections whose causes can be present in dog blood. The investigations covered 100 dogs from which peripheral blood smears were taken and then stained with a Giemsa solution according to the standard protocol and examined under a microscope with an immersion lens. The examination of peripheral blood smears stained according to Giemsa resulted in the identification of the presence of an Ehrlichia spp. morula in a neutrophil granulocyte in one dog. The presence of hemotropic mycoplasmas was established in erythrocytes of eleven dogs, while the presence of the protozoa Babesia canis in erythrocytes was identified in five dogs included in the investigations. A microscopic examination of dog peripheral blood smears stained according to Giemsa was shown as a speedy, practical, simple, and inexpensive method for making a definitive etiological diagnosis of these infections, and it should be included regularly in standard protocols for the diagnostics of infectious and parasitic diseases.

  17. Microfluidics and microbial engineering.

    Science.gov (United States)

    Kou, Songzi; Cheng, Danhui; Sun, Fei; Hsing, I-Ming

    2016-02-01

    The combination of microbial engineering and microfluidics is synergistic in nature. For example, microfluidics is benefiting from the outcome of microbial engineering and many reported point-of-care microfluidic devices employ engineered microbes as functional parts for the microsystems. In addition, microbial engineering is facilitated by various microfluidic techniques, due to their inherent strength in high-throughput screening and miniaturization. In this review article, we firstly examine the applications of engineered microbes for toxicity detection, biosensing, and motion generation in microfluidic platforms. Secondly, we look into how microfluidic technologies facilitate the upstream and downstream processes of microbial engineering, including DNA recombination, transformation, target microbe selection, mutant characterization, and microbial function analysis. Thirdly, we highlight an emerging concept in microbial engineering, namely, microbial consortium engineering, where the behavior of a multicultural microbial community rather than that of a single cell/species is delineated. Integrating the disciplines of microfluidics and microbial engineering opens up many new opportunities, for example in diagnostics, engineering of microbial motors, development of portable devices for genetics, high throughput characterization of genetic mutants, isolation and identification of rare/unculturable microbial species, single-cell analysis with high spatio-temporal resolution, and exploration of natural microbial communities.

  18. The Diagnostic Value of Superb Microvascular Imaging (SMI) in Detecting Blood Flow Signals of Breast Lesions

    Science.gov (United States)

    Ma, Yan; Li, Gang; Li, Jing; Ren, Wei-dong

    2015-01-01

    Abstract The correlation between color Doppler flow imaging (CDFI) and Superb Microvascular Imaging (SMI) for detecting blood flow in breast lesions was investigated, as was the diagnostic value of SMI in differentiating benign from malignant breast lesions. These lesions were evaluated using both CDFI and SMI according to Adler's method. Pathologic examination showed 57 malignant lesions and 66 benign lesions. The number of blood vessels in a single mass was detected by 2 techniques (SMI and CDFI), and the difference between the 2 values (SMI-CDFI) was calculated. The optimal threshold for the diagnosis of malignant neoplasms and the diagnostic performances of SMI, CDFI, and SMI-CDFI were calculated. For the total lesions and malignant lesions alone, the difference between SMI and CDFI for detecting blood flow was significant (P < 0.01), but the difference was not significant for benign lesions (P = 0.15). The area under the receiver operating characteristic curve was 0.73 (95% confidence interval [CI]: 0.64–0.82) for CDFI; 0.81 (95% CI: 0.74–0.89) for SMI; and 0.89 (95% CI: 0.82–0.95) for SMI-CDFI. Furthermore, the modality of “SMI-CDFI” showed the best diagnostic performance. SMI provides further microvessel information in breast lesions. The diagnostic modality of “SMI-CDFI” can improve the diagnostic performance of ultrasound in the differentiation between benign and malignant masses. PMID:26356718

  19. Punch Card Programmable Microfluidics

    CERN Document Server

    Korir, George

    2014-01-01

    Small volume fluid handling in single and multiphase microfluidics provides a promising strategy for efficient bio-chemical assays, low-cost point-of-care diagnostics and new approaches to scientific discoveries. However multiple barriers exist towards low-cost field deployment of programmable microfluidics. Incorporating multiple pumps, mixers and discrete valve based control of nanoliter fluids and droplets in an integrated, programmable manner without additional required external components has remained elusive. Combining the idea of punch card programming with arbitrary fluid control, here we describe a self-contained, hand-crank powered, multiplex and robust programmable microfluidic platform. A paper tape encodes information as a series of punched holes. A mechanical reader/actuator reads these paper tapes and correspondingly executes a series of operations onto a microfluidic chip coupled to the platform in a plug-and-play fashion. Enabled by the complexity of codes that can be represented by a series ...

  20. System Design and Development of a Robotic Device for Automated Venipuncture and Diagnostic Blood Cell Analysis.

    Science.gov (United States)

    Balter, Max L; Chen, Alvin I; Fromholtz, Alex; Gorshkov, Alex; Maguire, Tim J; Yarmush, Martin L

    2016-10-01

    Diagnostic blood testing is the most prevalent medical procedure performed in the world and forms the cornerstone of modern health care delivery. Yet blood tests are still predominantly carried out in centralized labs using large-volume samples acquired by manual venipuncture, and no end-to-end solution from blood draw to sample analysis exists today. Our group is developing a platform device that merges robotic phlebotomy with automated diagnostics to rapidly deliver patient information at the site of the blood draw. The system couples an image-guided venipuncture robot, designed to address the challenges of routine venous access, with a centrifuge-based blood analyzer to obtain quantitative measurements of hematology. In this paper, we first present the system design and architecture of the integrated device. We then perform a series of in vitro experiments to evaluate the cannulation accuracy of the system on blood vessel phantoms. Next, we assess the effects of vessel diameter, needle gauge, flow rate, and viscosity on the rate of sample collection. Finally, we demonstrate proof-of-concept of a white cell assay on the blood analyzer using in vitro human samples spiked with fluorescently labeled microbeads.

  1. A cyclic-olefin-copolymer microfluidic immobilized-enzyme reactor for rapid digestion of proteins from dried blood spots.

    Science.gov (United States)

    Wouters, Bert; Dapic, Irena; Valkenburg, Thalassa S E; Wouters, Sam; Niezen, Leon; Eeltink, Sebastiaan; Corthals, Garry L; Schoenmakers, Peter J

    2017-03-31

    A critical step in the bottom-up characterization of proteomes is the conversion of proteins to peptides, by means of endoprotease digestion. Nowadays this method typically uses overnight digestion and as such represents a considerable bottleneck for high-throughput analysis. This report describes protein digestion using an immobilized-enzyme reactor (IMER), which enables accelerated digestion times that are completed within seconds to minutes. For rapid digestion to occur, a cyclic-olefin-copolymer microfluidic reactor was constructed containing trypsin immobilized on a polymer monolithic material through a 2-vinyl-4,4-dimethylazlactone linker. The IMER was applied for the rapid offline digestion of both singular protein standards and a complex protein mixture prior to liquid chromatography-electrospray ionisation-tandem mass spectrometry (LC-ESI-MS/MS) analysis. The effects of protein concentration and residence time in the IMER were assessed for protein standards of varying molecular weight between 11 and 240kDa. Compared to traditional in-solution digestion, IMER-facilitated protein digestion at room temperature for 5min yielded similar results in terms of sequence coverage and number of identified peptides. Good repeatability was demonstrated with a relative standard deviation of 6% for protein-sequence coverage. The potential of the IMER was also demonstrated for a complex protein mixture in the analysis of dried blood spots. Compared to a traditional workflow a similar number of proteins could be identified, while reducing the total analysis time from 22.5h to 4h and importantly omitting the sample-pre-treatment steps (denaturation, reduction, and alkylation). The identified proteins from two workflows showed similar distributions in terms of molecular weight and hydrophobic character.

  2. 3D printed microfluidic mixer for point-of-care diagnosis of anemia.

    Science.gov (United States)

    Plevniak, Kimberly; Campbell, Matthew; Mei He

    2016-08-01

    3D printing has been an emerging fabrication tool in prototyping and manufacturing. We demonstrated a 3D microfluidic simulation guided computer design and 3D printer prototyping for quick turnaround development of microfluidic 3D mixers, which allows fast self-mixing of reagents with blood through capillary force. Combined with smartphone, the point-of-care diagnosis of anemia from finger-prick blood has been successfully implemented and showed consistent results with clinical measurements. Capable of 3D fabrication flexibility and smartphone compatibility, this work presents a novel diagnostic strategy for advancing personalized medicine and mobile healthcare.

  3. Portable microfluidic chip for detection of Escherichia coli in produce and blood

    Directory of Open Access Journals (Sweden)

    Wang S

    2012-05-01

    Full Text Available ShuQi Wang,1* Fatih Inci,1* Tafadzwa L Chaunzwa,1 Ajay Ramanujam,1 Aishwarya Vasudevan,1 Sathya Subramanian,1 Alexander Chi Fai Ip,1 Banupriya Sridharan,1 Umut Atakan Gurkan,1 Utkan Demirci,1,21Bio-Acoustic-MEMS in Medicine (BAMM Laboratory, Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02139, 2Harvard-MIT Health Sciences and Technology, Cambridge, MA, USA, *These authors contributed equally to this workAbstract: Pathogenic agents can lead to severe clinical outcomes such as food poisoning, infection of open wounds, particularly in burn injuries and sepsis. Rapid detection of these pathogens can monitor these infections in a timely manner improving clinical outcomes. Conventional bacterial detection methods, such as agar plate culture or polymerase chain reaction, are time-consuming and dependent on complex and expensive instruments, which are not suitable for point-of-care (POC settings. Therefore, there is an unmet need to develop a simple, rapid method for detection of pathogens such as Escherichia coli. Here, we present an immunobased microchip technology that can rapidly detect and quantify bacterial presence in various sources including physiologically relevant buffer solution (phosphate buffered saline [PBS], blood, milk, and spinach. The microchip showed reliable capture of E. coli in PBS with an efficiency of 71.8% ± 5% at concentrations ranging from 50 to 4,000 CFUs/mL via lipopolysaccharide binding protein. The limits of detection of the microchip for PBS, blood, milk, and spinach samples were 50, 50, 50, and 500 CFUs/mL, respectively. The presented technology can be broadly applied to other pathogens at the POC, enabling various applications including surveillance of food supply and monitoring of bacteriology in patients with burn wounds.Keywords: Escherichia coli, microchip, sepsis, food safety, point-of-care

  4. An assessment of various blood collection and transfer methods used for malaria rapid diagnostic tests

    Directory of Open Access Journals (Sweden)

    Baik Fred

    2007-11-01

    Full Text Available Abstract Background Four blood collection and transfer devices commonly used for malaria rapid diagnostic tests (RDTs were assessed for their consistency, accuracy and ease of use in the hands of laboratory technicians and village health workers. Methods Laboratory technicians and village health workers collected blood from a finger prick using each device in random order, and deposited the blood either on filter paper or into a suitable casette-type RDT. Consistency and accuracy of volume delivered was determined by comparing the measurements of the resulting blood spots/heights with the measurements of laboratory-prepared pipetted standard volumes. The effect of varying blood volumes on RDT sensitivity and ease of use was also observed. Results There was high variability in blood volume collected by the devices, with the straw and the loop, the most preferred devices, usually transferring volumes greater than intended, while the glass capillary tube and the plastic pipette transferring less volume than intended or none at all. Varying the blood volume delivered to RDTs indicated that this variation is critical to RDT sensitivity only when the transferred volume is very low. Conclusion None of the blood transfer devices assessed performed consistently well. Adequate training on their use is clearly necessary, with more development efforts for improved designs to be used by remote health workers, in mind.

  5. Development of class model based on blood biochemical parameters as a diagnostic tool of PSE meat.

    Science.gov (United States)

    Qu, Daofeng; Zhou, Xu; Yang, Feng; Tian, Shiyi; Zhang, Xiaojun; Ma, Lin; Han, Jianzhong

    2017-06-01

    A fast, sensitive and effective method based on the blood biochemical parameters for the detection of PSE meat was developed in this study. A total of 200 pigs were slaughtered in the same slaughterhouse. Meat quality was evaluated by measuring pH, electrical conductivity and color at 45min, 2h and 24h after slaughtering in M. longissimus thoracis et lumborum (LD). Blood biochemical parameters were determined in blood samples collected during carcass bleeding. Principal component analysis (PCA) biplot showed that high levels of exsanguination Creatine Kinase, Lactate Dehydrogenase, Aspertate aminotransferase, blood glucose and lactate were associated with the PSE meat, and the five biochemical parameters were found to be good indicators of PSE meat Discriminant function analysis (DFA) was able to clearly identify PSE meat using the five biochemical parameters as input data, and the class model is an effective diagnostic tool in pigs which can be used to detect the PSE meat and reduce economic loss for the company.

  6. Centrifugal microfluidics for biomedical applications.

    Science.gov (United States)

    Gorkin, Robert; Park, Jiwoon; Siegrist, Jonathan; Amasia, Mary; Lee, Beom Seok; Park, Jong-Myeon; Kim, Jintae; Kim, Hanshin; Madou, Marc; Cho, Yoon-Kyoung

    2010-07-21

    The centrifugal microfluidic platform has been a focus of academic and industrial research efforts for almost 40 years. Primarily targeting biomedical applications, a range of assays have been adapted on the system; however, the platform has found limited commercial success as a research or clinical tool. Nonetheless, new developments in centrifugal microfluidic technologies have the potential to establish wide-spread utilization of the platform. This paper presents an in-depth review of the centrifugal microfluidic platform, while highlighting recent progress in the field and outlining the potential for future applications. An overview of centrifugal microfluidic technologies is presented, including descriptions of advantages of the platform as a microfluidic handling system and the principles behind centrifugal fluidic manipulation. The paper also discusses a history of significant centrifugal microfluidic platform developments with an explanation of the evolution of the platform as it pertains to academia and industry. Lastly, we review the few centrifugal microfluidic-based sample-to-answer analysis systems shown to date and examine the challenges to be tackled before the centrifugal platform can be more broadly accepted as a new diagnostic platform. In particular, fully integrated, easy to operate, inexpensive and accurate microfluidic tools in the area of in vitro nucleic acid diagnostics are discussed.

  7. Statistical analysis of polarizing maps of blood plasma laser images for the diagnostics of malignant formations

    Science.gov (United States)

    Ungurian, V. P.; Ivashchuk, O. I.; Ushenko, V. O.

    2012-01-01

    This work is aimed at searching the interconnections between the statistic structure of blood plasma microscopic images and manifestations of optical anisotropy of liquid crystal protein network. The model of linear birefringence of albumin and globulin crystals underlies in the ground of this work. The results of investigating the interrelation between statistical moments of the 1st-4th order are presented that characterize the coordinate distributions of polarization ellipticity of laser images of blood plasma smears and pathological changes in human organism. The diagnostic criteria of breast cancer nascency and its severity degree differentiation are determined.

  8. Auxiliary diagnostic value of monocyte chemoattractant protein-1 of whole blood in active tuberculosis.

    Science.gov (United States)

    Wang, Ying; Li, Hang; Bao, Hong; Jin, Yufen; Liu, Xiaoju; Wu, Xueqiong; Yu, Ting

    2015-01-01

    The aim of this study was to study the expression level of interferon-γ (IFN-γ) and monocyte chemoattractant protein-1 (MCP-1) in peripheral blood and its auxiliary diagnostic value in active tuberculosis. A chemiluminescence enzyme immunoassay method was used to detect the levels of IFN-γ and MCP-1 in peripheral blood. Then the receiver operating characteristic curve were drawn to determine the threshold of IFN-γ and MCP-1 for diagnosis of active tuberculosis and to evaluate their diagnostic performance. The specific IFN-γ and MCP-1 levels in the active tuberculosis group were significantly higher than those in the non-tuberculous pulmonary disease group (P 0.05), but the MCP-1 levels in the non-tuberculous respiratory disease group were significantly higher than those of the healthy control group (P < 0.05). The specific IFN-γ and MCP-1 level cut off values were 256 pg/ml and 389 pg/ml as an active tuberculosis diagnostic standard. The sensitivities of IFN-γ and MCP-1 were 57.3% and 92.8%, respectively; specificities were 80% and 80.7%, respectively; the positive predictive values were 76.9% and 84.9%, respectively; negative predictive values were 61.7% and 78.7%, respectively; and accuracy rates were 76.9% and 84.9%, respectively. Compared with the detection of IFN-γ, we observed a better diagnostic performance of MCP-1 in peripheral blood in active tuberculosis. MCP-1 may become one of the active tuberculosis auxiliary diagnostic targets.

  9. Hydrodynamic lift of vesicles and red blood cells in flow--from Fåhræus & Lindqvist to microfluidic cell sorting.

    Science.gov (United States)

    Geislinger, Thomas M; Franke, Thomas

    2014-06-01

    Hydrodynamic lift forces acting on cells and particles in fluid flow receive ongoing attention from medicine, mathematics, physics and engineering. The early findings of Fåhræus & Lindqvist on the viscosity change of blood with the diameter of capillaries motivated extensive studies both experimentally and theoretically to illuminate the underlying physics. We review this historical development that led to the discovery of the inertial and non-inertial lift forces and elucidate the origins of these forces that are still not entirely clear. Exploiting microfluidic techniques induced a tremendous amount of new insights especially into the more complex interactions between the flow field and deformable objects like vesicles or red blood cells. We trace the way from the investigation of single cell dynamics to the recent developments of microfluidic techniques for particle and cell sorting using hydrodynamic forces. Such continuous and label-free on-chip cell sorting devices promise to revolutionize medical analyses for personalized point-of-care diagnosis. We present the state-of-the-art of different hydrodynamic lift-based techniques and discuss their advantages and limitations.

  10. Evaluation of three rapid diagnostic methods for direct identification of microorganisms in positive blood cultures.

    Science.gov (United States)

    Martinez, Raquel M; Bauerle, Elizabeth R; Fang, Ferric C; Butler-Wu, Susan M

    2014-07-01

    The identification of organisms from positive blood cultures generally takes several days. However, recently developed rapid diagnostic methods offer the potential for organism identification within only a few hours of blood culture positivity. In this study, we evaluated the performance of three commercial methods to rapidly identify organisms directly from positive blood cultures: QuickFISH (AdvanDx, Wolburn, MA), Verigene Gram-Positive Blood Culture (BC-GP; Nanosphere, Northbrook, IL), and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) with Sepsityper processing (Bruker Daltonics, Billerica, MA). A total of 159 blood cultures (VersaTREK Trek Diagnostic Systems, Cleveland, OH) positive for Gram-positive and Gram-negative bacteria as well as yeast were analyzed with QuickFISH and MALDI-TOF MS. In all, 102 blood cultures were analyzed using the BC-GP assay. For monomicrobial cultures, we observed 98.0% concordance with routine methods for both QuickFISH (143/146) and the BC-GP assay (93/95). MALDI-TOF MS demonstrated 80.1% (117/146) and 87.7% (128/146) concordance with routine methods to the genus and species levels, respectively. None of the methods tested were capable of consistently identifying polymicrobial cultures in their entirety or reliably differentiating Streptococcus pneumoniae from viridans streptococci. Nevertheless, the methods evaluated in this study are convenient and accurate for the most commonly encountered pathogens and have the potential to dramatically reduce turnaround time for the provision of results to the treating physician.

  11. Microfluidic electronics.

    Science.gov (United States)

    Cheng, Shi; Wu, Zhigang

    2012-08-21

    Microfluidics, a field that has been well-established for several decades, has seen extensive applications in the areas of biology, chemistry, and medicine. However, it might be very hard to imagine how such soft microfluidic devices would be used in other areas, such as electronics, in which stiff, solid metals, insulators, and semiconductors have previously dominated. Very recently, things have radically changed. Taking advantage of native properties of microfluidics, advances in microfluidics-based electronics have shown great potential in numerous new appealing applications, e.g. bio-inspired devices, body-worn healthcare and medical sensing systems, and ergonomic units, in which conventional rigid, bulky electronics are facing insurmountable obstacles to fulfil the demand on comfortable user experience. Not only would the birth of microfluidic electronics contribute to both the microfluidics and electronics fields, but it may also shape the future of our daily life. Nevertheless, microfluidic electronics are still at a very early stage, and significant efforts in research and development are needed to advance this emerging field. The intention of this article is to review recent research outcomes in the field of microfluidic electronics, and address current technical challenges and issues. The outlook of future development in microfluidic electronic devices and systems, as well as new fabrication techniques, is also discussed. Moreover, the authors would like to inspire both the microfluidics and electronics communities to further exploit this newly-established field.

  12. Unilateral Opening of Rat Blood-Brain Barrier Assisted by Diagnostic Ultrasound Targeted Microbubbles Destruction

    Directory of Open Access Journals (Sweden)

    Yali Xu

    2016-01-01

    Full Text Available Objective. Blood-brain barrier (BBB is a key obstacle that prevents the medication from blood to the brain. Microbubble-enhanced cavitation by focused ultrasound can open the BBB and proves to be valuable in the brain drug delivery. The study aimed to explore the feasibility, efficacy, and safety of unilateral opening of BBB using diagnostic ultrasound targeted microbubbles destruction in rats. Methods. A transtemporal bone irradiation of diagnostic ultrasound and intravenous injection of lipid-coated microbubbles were performed at unilateral hemisphere. Pathological changes were monitored. Evans Blue extravasation grades, extraction from brain tissue, and fluorescence optical density were quantified. Lanthanum nitrate was traced by transmission electron microscopy. Results. After diagnostic ultrasound mediated microbubbles destruction, Evans Blue extravasation and fluorescence integrated optical density were significantly higher in the irradiated hemisphere than the contralateral side (all p<0.01. Erythrocytes extravasations were demonstrated in the ultrasound-exposed hemisphere (4±1, grade 2 while being invisible in the control side. Lanthanum nitrate tracers leaked through interendothelial cleft and spread to the nerve fiber existed in the irradiation side. Conclusions. Transtemporal bone irradiation under DUS mediated microbubble destruction provides us with a more accessible, safer, and higher selective BBB opening approach in rats, which is advantageous in brain targeted drugs delivery.

  13. Punch card programmable microfluidics.

    Science.gov (United States)

    Korir, George; Prakash, Manu

    2015-01-01

    Small volume fluid handling in single and multiphase microfluidics provides a promising strategy for efficient bio-chemical assays, low-cost point-of-care diagnostics and new approaches to scientific discoveries. However multiple barriers exist towards low-cost field deployment of programmable microfluidics. Incorporating multiple pumps, mixers and discrete valve based control of nanoliter fluids and droplets in an integrated, programmable manner without additional required external components has remained elusive. Combining the idea of punch card programming with arbitrary fluid control, here we describe a self-contained, hand-crank powered, multiplex and robust programmable microfluidic platform. A paper tape encodes information as a series of punched holes. A mechanical reader/actuator reads these paper tapes and correspondingly executes operations onto a microfluidic chip coupled to the platform in a plug-and-play fashion. Enabled by the complexity of codes that can be represented by a series of holes in punched paper tapes, we demonstrate independent control of 15 on-chip pumps with enhanced mixing, normally-closed valves and a novel on-demand impact-based droplet generator. We demonstrate robustness of operation by encoding a string of characters representing the word "PUNCHCARD MICROFLUIDICS" using the droplet generator. Multiplexing is demonstrated by implementing an example colorimetric water quality assays for pH, ammonia, nitrite and nitrate content in different water samples. With its portable and robust design, low cost and ease-of-use, we envision punch card programmable microfluidics will bring complex control of microfluidic chips into field-based applications in low-resource settings and in the hands of children around the world.

  14. Punch card programmable microfluidics.

    Directory of Open Access Journals (Sweden)

    George Korir

    Full Text Available Small volume fluid handling in single and multiphase microfluidics provides a promising strategy for efficient bio-chemical assays, low-cost point-of-care diagnostics and new approaches to scientific discoveries. However multiple barriers exist towards low-cost field deployment of programmable microfluidics. Incorporating multiple pumps, mixers and discrete valve based control of nanoliter fluids and droplets in an integrated, programmable manner without additional required external components has remained elusive. Combining the idea of punch card programming with arbitrary fluid control, here we describe a self-contained, hand-crank powered, multiplex and robust programmable microfluidic platform. A paper tape encodes information as a series of punched holes. A mechanical reader/actuator reads these paper tapes and correspondingly executes operations onto a microfluidic chip coupled to the platform in a plug-and-play fashion. Enabled by the complexity of codes that can be represented by a series of holes in punched paper tapes, we demonstrate independent control of 15 on-chip pumps with enhanced mixing, normally-closed valves and a novel on-demand impact-based droplet generator. We demonstrate robustness of operation by encoding a string of characters representing the word "PUNCHCARD MICROFLUIDICS" using the droplet generator. Multiplexing is demonstrated by implementing an example colorimetric water quality assays for pH, ammonia, nitrite and nitrate content in different water samples. With its portable and robust design, low cost and ease-of-use, we envision punch card programmable microfluidics will bring complex control of microfluidic chips into field-based applications in low-resource settings and in the hands of children around the world.

  15. Perspective: microfluidic applications in microbiology.

    Science.gov (United States)

    Saleh-Lakha, Saleema; Trevors, Jack T

    2010-07-01

    The application of microfluidics technology to microbiology research is an excellent platform for the analysis of microorganisms and their nucleic acids. This technology combines engineering, physics, chemistry, biology and computing to control the devices. In this perspective we discuss how microfluidics can be applied to microbiological research and used in diagnostic applications. We also summarize advantages and limitations of this technology, as well as highlight some recent microbiological applications.

  16. Diagnostics And Treatment Of Patients With Blood Circulation Insufficiency In Vertebrobasilar Bed

    Directory of Open Access Journals (Sweden)

    A.M. Khachatryan

    2009-12-01

    Full Text Available For improvement of treatment results of patients with vertebrobasilar insufficiency we have analyzed data of medical examination and treatment of 182 patients stayed in clinics of Hospital Surgery and Nervous System Diseases from the 1st of January of 2005 till the 30th of June of 2009. Method of screening diagnostics, quantitative and qualitative blood flow estimation by means of Doppler ultrasonic investigation and angiography have been performed. The cause of blood circulation insufficiency in the vertebrobasilar bed at 87 patients was vertebral artery syndrome and in 95 cases there were the significant hemodynamical damages of blood flow in aorta arch branches and intracranial arteries. The neuroangiotropic therapy has been made for all patients, but the clinical improvement period was short in most cases, more prolonged effect was observed in addition of conservative therapy with plasmapheresis by indications. In the complex treatment of patients with vertebrobasilar insufficiency accompanied by degenerative diseases of spine chemical sympathectomy of vertebral artery in the III segment in the form of procaine and spirit-procaine blockades was made in 116 and 69 cases accordingly. The surgical sympathectomy was made in 15 patients. The surgical operations were made in 62 of 95 patients with significant hemodynamic pathology of blood flow in the vertebrobasilar region. In most cases isolative and combinative reconstructive surgery on carotid arteries was carried out. It played a significant role in blood flow correction. Favorable postoperative results were observed in most cases (93, 5%

  17. SPECT Myocardial Blood Flow Quantitation Concludes Equivocal Myocardial Perfusion SPECT Studies to Increase Diagnostic Benefits.

    Science.gov (United States)

    Chen, Lung-Ching; Lin, Chih-Yuan; Chen, Ing-Jou; Ku, Chi-Tai; Chen, Yen-Kung; Hsu, Bailing

    2016-01-01

    Recently, myocardial blood flow quantitation with dynamic SPECT/CT has been reported to enhance the detection of coronary artery disease in human. This advance has created important clinical applications to coronary artery disease diagnosis and management for areas where myocardial perfusion PET tracers are not available. We present 2 clinical cases that undergone a combined test of 1-day rest/dipyridamole-stress dynamic SPECT and ECG-gated myocardial perfusion SPECT scans using an integrated imaging protocol and demonstrate that flow parameters are capable to conclude equivocal myocardial perfusion SPECT studies, therefore increasing diagnostic benefits to add value in making clinical decisions.

  18. Sensitive KIT D816V mutation analysis of blood as a diagnostic test in mastocytosis

    DEFF Research Database (Denmark)

    Kielsgaard Kristensen, Thomas; Vestergaard, Hanne; Bindslev-Jensen, Carsten;

    2014-01-01

    The recent progress in sensitive KIT D816V mutation analysis suggests that mutation analysis of peripheral blood (PB) represents a promising diagnostic test in mastocytosis. However, there is a need for systematic assessment of the analytical sensitivity and specificity of the approach in order...... the mutation in PB in nearly all adult mastocytosis patients. The mutation was detected in PB in 78 of 83 systemic mastocytosis (94%) and 3 of 4 cutaneous mastocytosis patients (75%). The test was 100% specific as determined by analysis of clinically relevant control patients who all tested negative. Mutation...

  19. Diagnostic thresholds for ambulatory blood pressure moving lower: a review based on a meta-analysis-clinical implications

    DEFF Research Database (Denmark)

    Hansen, T.W.; Kikuya, M.; Thijs, L.;

    2008-01-01

    Upper limits of normal ambulatory blood pressure (ABP) have been a matter of debate in recent years. Current diagnostic thresholds for ABP rely mainly on statistical parameters derived from reference populations. Recent findings from the International Database of Ambulatory Blood Pressure....../75 mm Hg, 130/85 mm Hg, and 110/70 mm Hg, respectively, and those for ambulatory hypertension were 130/80 mm Hg, 140/85 mm Hg, and 120/70 mm Hg. However, in clinical practice, any diagnostic threshold for blood pressure needs to be assessed in the context of the patient's overall risk profile. The IDACO...

  20. Gold nanoparticles-coated magnetic microspheres as affinity matrix for detection of hemoglobin A1c in blood by microfluidic immunoassay.

    Science.gov (United States)

    Chen, Shao-Peng; Yu, Xiao-Dong; Xu, Jing-Juan; Chen, Hong-Yuan

    2011-08-15

    A novel microfluidic immunoassay system for specific detection of hemoglobin A1c (HbA1c) was developed based on a three-component shell/shell/core structured magnetic nanocomposite Au/chitosan/Fe(3)O(4), which was synthesized with easy handling feature of Fe(3)O(4) by magnet, high affinity for gold nanoparticles of chitosan and good immobilization ability for anti-human hemoglobin-A1c antibody (HbA1c mAb) of assembled colloidal gold nanoparticles. The resulting HbA1c mAb/Au/chitosan/Fe(3)O(4) magnetic nanoparticles were then introduced into microfluidic devices coupled with a gold nanoband microelectrode as electrochemical detector. After that, three-step rapid immunoreactions were carried out in the sequence of HbA1c, anti-human hemoglobin antibodies (Hb mAb) and the secondary alkaline phosphatase (AP)-conjugated antibody within 20 min. The current response of 1-naphtol obtained from the reaction between the secondary AP-conjugated antibody and 1-naphthyl phosphate (1-NP) increased proportionally to the HbA1c concentration. Under optimized electrophoresis and detection conditions, HbA1c responded linearly in the concentration of 0.05-1.5 μg mL(-1), with the detection limit of 0.025 μg mL(-1). This system was successfully employed for detection of HbA1c in blood with good accuracy and renewable ability. The proposed method proved its potential use in clinical immunoassay of HbA1c.

  1. A composite peripheral blood gene expression measure as a potential diagnostic biomarker in bipolar disorder

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Peijs, L; Vinberg, M

    2015-01-01

    as a diagnostic and state biomarker in bipolar disorder. First, messenger RNA levels of 19 candidate genes were assessed in peripheral blood mononuclear cells of 37 rapid cycling bipolar disorder patients in different affective states (depression, mania and euthymia) during a 6-12-month period and in 40 age......- and gender-matched healthy control subjects. Second, a composite gene expression measure was constructed in the first half study sample and independently validated in the second half of the sample. We found downregulation of POLG and OGG1 expression in bipolar disorder patients compared with healthy control...... subjects. In patients with bipolar disorder, upregulation of NDUFV2 was observed in a depressed state compared with a euthymic state. The composite gene expression measure for discrimination between patients and healthy control subjects on the basis of 19 genes generated an area under the receiver...

  2. [Mass spectrometry analysis of blood plasma lipidome as method of disease diagnostics, evuation of effectiveness and optimization of drug therapy].

    Science.gov (United States)

    Lokhov, P G; Maslov, D L; Balashova, E E; Trifonova, O P; Medvedeva, N V; Torkhovskaya, T I; Ipatova, O M; Archakov, A I; Malyshev, P P; Kukharchuk, V V; Shestakova, E A; Shestakova, M V; Dedov, I I

    2015-01-01

    A new method for the analysis of blood lipid based on direct mass spectrometry of lipophilic low molecular weight fraction of blood plasma has been considered. Such technique allows quantification of hundreds of various types of lipids and this changes existing concepts on diagnostics of lipid disorders and related diseases. The versatility and quickness of the method significantly simplify its wide use. This method is applicable for diagnostics of atherosclerosis, diabetes, cancer and other diseases. Detalization of plasma lipid composition at the molecular level by means of mass spectrometry allows to assess the effectiveness of therapy and to optimize the drug treatment of cardiovascular diseases by phospholipid preparations.

  3. Blood lactate concentration as diagnostic predictors of uterine necrosis and its outcome in dairy cows with uterine torsion

    Science.gov (United States)

    MURAKAMI, Takashi; NAKAO, Shigeru; SATO, Yohei; NAKADA, Satoshi; SATO, Akane; MUKAI, Shuhei; KOBAYASHI, Masanori; YAMADA, Yutaka; KAWAKAMI, Eiichi

    2017-01-01

    In order to determine blood lactate concentrations (bLac) and their validity as a diagnostic marker in bovine uterine torsion, blood samples were taken from 54 Holstein cows with uterine torsion before the correction of torsion. bLac in a group of cows with and without uterine necrosis were 15.0 and 3.0 mmol/l, respectively (P5.0 and >6.5 mmol/l, respectively. These findings suggest that in dairy cows with uterine torsion, an increase in bLac is a diagnostic predictor of uterine necrosis as well as poor prognosis in dams. PMID:28163266

  4. Integrated Microfluidic Nucleic Acid Isolation, Isothermal Amplification, and Amplicon Quantification

    Directory of Open Access Journals (Sweden)

    Michael G. Mauk

    2015-10-01

    Full Text Available Microfluidic components and systems for rapid (<60 min, low-cost, convenient, field-deployable sequence-specific nucleic acid-based amplification tests (NAATs are described. A microfluidic point-of-care (POC diagnostics test to quantify HIV viral load from blood samples serves as a representative and instructive example to discuss the technical issues and capabilities of “lab on a chip” NAAT devices. A portable, miniaturized POC NAAT with performance comparable to conventional PCR (polymerase-chain reaction-based tests in clinical laboratories can be realized with a disposable, palm-sized, plastic microfluidic chip in which: (1 nucleic acids (NAs are extracted from relatively large (~mL volume sample lysates using an embedded porous silica glass fiber or cellulose binding phase (“membrane” to capture sample NAs in a flow-through, filtration mode; (2 NAs captured on the membrane are isothermally (~65 °C amplified; (3 amplicon production is monitored by real-time fluorescence detection, such as with a smartphone CCD camera serving as a low-cost detector; and (4 paraffin-encapsulated, lyophilized reagents for temperature-activated release are pre-stored in the chip. Limits of Detection (LOD better than 103 virons/sample can be achieved. A modified chip with conduits hosting a diffusion-mode amplification process provides a simple visual indicator to readily quantify sample NA template. In addition, a companion microfluidic device for extracting plasma from whole blood without a centrifuge, generating cell-free plasma for chip-based molecular diagnostics, is described. Extensions to a myriad of related applications including, for example, food testing, cancer screening, and insect genotyping are briefly surveyed.

  5. Integrated Microfluidic Nucleic Acid Isolation, Isothermal Amplification, and Amplicon Quantification.

    Science.gov (United States)

    Mauk, Michael G; Liu, Changchun; Song, Jinzhao; Bau, Haim H

    2015-10-20

    Microfluidic components and systems for rapid (microfluidic point-of-care (POC) diagnostics test to quantify HIV viral load from blood samples serves as a representative and instructive example to discuss the technical issues and capabilities of "lab on a chip" NAAT devices. A portable, miniaturized POC NAAT with performance comparable to conventional PCR (polymerase-chain reaction)-based tests in clinical laboratories can be realized with a disposable, palm-sized, plastic microfluidic chip in which: (1) nucleic acids (NAs) are extracted from relatively large (~mL) volume sample lysates using an embedded porous silica glass fiber or cellulose binding phase ("membrane") to capture sample NAs in a flow-through, filtration mode; (2) NAs captured on the membrane are isothermally (~65 °C) amplified; (3) amplicon production is monitored by real-time fluorescence detection, such as with a smartphone CCD camera serving as a low-cost detector; and (4) paraffin-encapsulated, lyophilized reagents for temperature-activated release are pre-stored in the chip. Limits of Detection (LOD) better than 10³ virons/sample can be achieved. A modified chip with conduits hosting a diffusion-mode amplification process provides a simple visual indicator to readily quantify sample NA template. In addition, a companion microfluidic device for extracting plasma from whole blood without a centrifuge, generating cell-free plasma for chip-based molecular diagnostics, is described. Extensions to a myriad of related applications including, for example, food testing, cancer screening, and insect genotyping are briefly surveyed.

  6. Diagnostic prediction of renal failure from blood serum analysis by FTIR spectrometry and chemometrics

    Science.gov (United States)

    Khanmohammadi, Mohammdreza; Ghasemi, Keyvan; Garmarudi, Amir Bagheri; Ramin, Mehdi

    2015-02-01

    A new diagnostic approach based on Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) spectrometry and classification algorithm has been introduced which provides a rapid, reliable, and easy way to perform blood test for the diagnosis of renal failure. Blood serum samples from 35 renal failure patients and 40 healthy persons were analyzed by ATR-FTIR spectrometry. The resulting data was processed by Quadratic Discriminant Analysis (QDA) and QDA combined with simple filtered method. Spectroscopic studies were performed in 900-2000 cm-1 spectral region with 3.85 cm-1 data space. Results showed 93.33% and 100% of accuracy for QDA and filter-QDA models, respectively. In the first step, 30 samples were applied to construct the model. In order to modify the capability of QDA in prediction of test samples, filter-based feature selection methods were applied. It was found that the filtered spectra coupled with QDA could correctly predict the test samples in most of the cases.

  7. Diagnostic value of cancer-testis antigen mRNA in peripheral blood from hepatocellular carcinoma patients

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To evaluate the diagnostic value of cancer-testis antigen(CTA) mRNA in peripheral blood samples from hepatocellular carcinoma(HCC) patients.METHODS:Peripheral blood samples were taken from 90 patients with HCC before operation.Expression of melanoma antigen-1(MAGE-1),synovial sarcoma X breakpoint-1(SSX-1),and cancer-testis-associated protein of 11 kDa(CTp11) mRNA in peripheral blood mononuclear cells(PBMC) was tested by nested reverse transcriptspolymerase chain reaction(RT-PCR).Serum α-fetoprotein(AFP)...

  8. Bio-microfluidics: biomaterials and biomimetic designs.

    Science.gov (United States)

    Domachuk, Peter; Tsioris, Konstantinos; Omenetto, Fiorenzo G; Kaplan, David L

    2010-01-12

    Bio-microfluidics applies biomaterials and biologically inspired structural designs (biomimetics) to microfluidic devices. Microfluidics, the techniques for constraining fluids on the micrometer and sub-micrometer scale, offer applications ranging from lab-on-a-chip to optofluidics. Despite this wealth of applications, the design of typical microfluidic devices imparts relatively simple, laminar behavior on fluids and is realized using materials and techniques from silicon planar fabrication. On the other hand, highly complex microfluidic behavior is commonplace in nature, where fluids with nonlinear rheology flow through chaotic vasculature composed from a range of biopolymers. In this Review, the current state of bio-microfluidic materials, designs and applications are examined. Biopolymers enable bio-microfluidic devices with versatile functionalization chemistries, flexibility in fabrication, and biocompatibility in vitro and in vivo. Polymeric materials such as alginate, collagen, chitosan, and silk are being explored as bulk and film materials for bio-microfluidics. Hydrogels offer options for mechanically functional devices for microfluidic systems such as self-regulating valves, microlens arrays and drug release systems, vital for integrated bio-microfluidic devices. These devices including growth factor gradients to study cell responses, blood analysis, biomimetic capillary designs, and blood vessel tissue culture systems, as some recent examples of inroads in the field that should lead the way in a new generation of microfluidic devices for bio-related needs and applications. Perhaps one of the most intriguing directions for the future will be fully implantable microfluidic devices that will also integrate with existing vasculature and slowly degrade to fully recapitulate native tissue structure and function, yet serve critical interim functions, such as tissue maintenance, drug release, mechanical support, and cell delivery.

  9. Microfluidics' great promise for Biology - Microfluidics as a new engine for the molecular sciences

    KAUST Repository

    Kodzius, Rimantas

    2010-06-04

    History of the Life Sciences Origins of life Discoveries and instrumentation The power of genetic variation Diagnostics based on DNA/ protein variation Genomic scanning providers DNA sequencing companies Microfluidics story Commercial products available P

  10. A malaria diagnostic tool based on computer vision screening and visualization of Plasmodium falciparum candidate areas in digitized blood smears.

    Directory of Open Access Journals (Sweden)

    Nina Linder

    Full Text Available INTRODUCTION: Microscopy is the gold standard for diagnosis of malaria, however, manual evaluation of blood films is highly dependent on skilled personnel in a time-consuming, error-prone and repetitive process. In this study we propose a method using computer vision detection and visualization of only the diagnostically most relevant sample regions in digitized blood smears. METHODS: Giemsa-stained thin blood films with P. falciparum ring-stage trophozoites (n = 27 and uninfected controls (n = 20 were digitally scanned with an oil immersion objective (0.1 µm/pixel to capture approximately 50,000 erythrocytes per sample. Parasite candidate regions were identified based on color and object size, followed by extraction of image features (local binary patterns, local contrast and Scale-invariant feature transform descriptors used as input to a support vector machine classifier. The classifier was trained on digital slides from ten patients and validated on six samples. RESULTS: The diagnostic accuracy was tested on 31 samples (19 infected and 12 controls. From each digitized area of a blood smear, a panel with the 128 most probable parasite candidate regions was generated. Two expert microscopists were asked to visually inspect the panel on a tablet computer and to judge whether the patient was infected with P. falciparum. The method achieved a diagnostic sensitivity and specificity of 95% and 100% as well as 90% and 100% for the two readers respectively using the diagnostic tool. Parasitemia was separately calculated by the automated system and the correlation coefficient between manual and automated parasitemia counts was 0.97. CONCLUSION: We developed a decision support system for detecting malaria parasites using a computer vision algorithm combined with visualization of sample areas with the highest probability of malaria infection. The system provides a novel method for blood smear screening with a significantly reduced need for

  11. α-synuclein reactive antibodies as diagnostic biomarkers in blood sera of Parkinson's disease patients.

    Directory of Open Access Journals (Sweden)

    Kiran Yanamandra

    Full Text Available BACKGROUND: Auto-antibodies with specificity to self-antigens have been implicated in a wide variety of neurological diseases, including Parkinson's (PD and Alzheimer's diseases, being sensitive indicators of neurodegeneration and focus for disease prevention. Of particular interest are the studies focused on the auto-immune responses to amyloidogenic proteins associated with diseases and their applications in therapeutic treatments such as vaccination with amyloid antigens and antibodies in PD, Alzheimer's disease and potentially other neurodegeneration ailments. METHODOLOGY/PRINCIPAL FINDINGS: Generated auto-antibodies towards the major amyloidogenic protein involved in PD Lewy bodies--α-synuclein and its amyloid oligomers and fibrils were measured in the blood sera of early and late PD patients and controls by using ELISA, Western blot and Biacore surface plasmon resonance. We found significantly higher antibody levels towards monomeric α-synuclein in the blood sera of PD patients compared to controls, though the responses decreased with PD progression (P<0.0001. This indicates potential protective role of autoimmunity in maintaining the body homeostasis and clearing protein species whose disbalance may lead to amyloid assembly. There were no noticeable immune responses towards amyloid oligomers, but substantially increased levels of IgGs towards α-synuclein amyloid fibrils both in PD patients and controls, which subsided with the disease progression (P<0.0001. Pooled IgGs from PD patients and controls interacted also with the amyloid fibrils of Aβ (1-40 and hen lysozyme, however the latter were recognized with lower affinity. This suggests that IgGs bind to the generic amyloid conformational epitope, displaying higher specificity towards human amyloid species associated with neurodegeneration. CONCLUSIONS/SIGNIFICANCE: Our findings may suggest the protective role of autoimmunity in PD and therefore immune reactions towards PD major

  12. [Biochemical studies of blood serum use for diagnostics and efficacy of treatment evaluation of TMJ pain dysfunction].

    Science.gov (United States)

    Ibragimova, R S

    2007-01-01

    Study of biochemical indices of blood serum in patients with the pain disfunction of temporomandibular joint syndrome was performed. Analysis of biochemical studies of blood serum revealed the essential increase of adenozintriphosphate (ATPh) level on 17.5%, histamin--on 51.7%, stress hormones: adrenalin--on 76.9%, cortizol--on 51.4% in patients with the syndrome of pain disfunction of TMJ in comparison with the control group. Biochemical studies of blood revealed the more marked lowering of the level of histamin, adrenalin, cortizol in blood serum of patients after the treatment of alternative methods than after pharmaco- and physiotherapy. the high informative level of the studying of ATPh, histamin, kortisol of blood's serum for diagnostics and evaluation of the efficiency of treatment of the pain disfunction of temporomandibular joint syndrome was proved.

  13. Detection of malaria infection in blood transfusion: a comparative study among real-time PCR, rapid diagnostic test and microscopy: sensitivity of Malaria detection methods in blood transfusion.

    Science.gov (United States)

    Hassanpour, Gholamreza; Mohebali, Mehdi; Raeisi, Ahmad; Abolghasemi, Hassan; Zeraati, Hojjat; Alipour, Mohsen; Azizi, Ebrahim; Keshavarz, Hossein

    2011-06-01

    The transmission of malaria by blood transfusion was one of the first transfusion-transmitted infections recorded in the world. Transfusion-transmitted malaria may lead to serious problems because infection with Plasmodium falciparum may cause rapidly fatal death. This study aimed to compare real-time polymerase chain reaction (real-time PCR) with rapid diagnostic test (RDT) and light microscopy for the detection of Plasmodium spp. in blood transfusion, both in endemic and non-endemic areas of malaria disease in Iran. Two sets of 50 blood samples were randomly collected. One set was taken from blood samples donated in blood bank of Bandar Abbas, a city located in a malarious-endemic area, and the other set from Tehran, a non-endemic one. Light microscopic examination on both thin and thick smears, RDTs, and real-time PCR were performed on the blood samples and the results were compared. Thin and thick light microscopic examinations of all samples as well as RDT results were negative for Plasmodium spp. Two blood samples from endemic area were positive only with real-time PCR. It seems that real-time PCR as a highly sensitive method can be helpful for the confirmation of malaria infection in different units of blood transfusion organization especially in malaria-endemic areas where the majority of donors may be potentially infected with malaria parasites.

  14. Blood diagnostic biomarkers for major depressive disorder using multiplex DNA methylation profiles: discovery and validation.

    Science.gov (United States)

    Numata, Shusuke; Ishii, Kazuo; Tajima, Atsushi; Iga, Jun-ichi; Kinoshita, Makoto; Watanabe, Shinya; Umehara, Hidehiro; Fuchikami, Manabu; Okada, Satoshi; Boku, Shuken; Hishimoto, Akitoyo; Shimodera, Shinji; Imoto, Issei; Morinobu, Shigeru; Ohmori, Tetsuro

    2015-01-01

    Aberrant DNA methylation in the blood of patients with major depressive disorder (MDD) has been reported in several previous studies. However, no comprehensive studies using medication-free subjects with MDD have been conducted. Furthermore, the majority of these previous studies has been limited to the analysis of the CpG sites in CpG islands (CGIs) in the gene promoter regions. The main aim of the present study is to identify DNA methylation markers that distinguish patients with MDD from non-psychiatric controls. Genome-wide DNA methylation profiling of peripheral leukocytes was conducted in two set of samples, a discovery set (20 medication-free patients with MDD and 19 controls) and a replication set (12 medication-free patients with MDD and 12 controls), using Infinium HumanMethylation450 BeadChips. Significant diagnostic differences in DNA methylation were observed at 363 CpG sites in the discovery set. All of these loci demonstrated lower DNA methylation in patients with MDD than in the controls, and most of them (85.7%) were located in the CGIs in the gene promoter regions. We were able to distinguish patients with MDD from the control subjects with high accuracy in the discriminant analysis using the top DNA methylation markers. We also validated these selected DNA methylation markers in the replication set. Our results indicate that multiplex DNA methylation markers may be useful for distinguishing patients with MDD from non-psychiatric controls.

  15. Principles, Techniques, and Applications of Tissue Microfluidics

    Science.gov (United States)

    Wade, Lawrence A.; Kartalov, Emil P.; Shibata, Darryl; Taylor, Clive

    2011-01-01

    The principle of tissue microfluidics and its resultant techniques has been applied to cell analysis. Building microfluidics to suit a particular tissue sample would allow the rapid, reliable, inexpensive, highly parallelized, selective extraction of chosen regions of tissue for purposes of further biochemical analysis. Furthermore, the applicability of the techniques ranges beyond the described pathology application. For example, they would also allow the posing and successful answering of new sets of questions in many areas of fundamental research. The proposed integration of microfluidic techniques and tissue slice samples is called tissue microfluidics because it molds the microfluidic architectures in accordance with each particular structure of each specific tissue sample. Thus, microfluidics can be built around the tissues, following the tissue structure, or alternatively, the microfluidics can be adapted to the specific geometry of particular tissues. By contrast, the traditional approach is that microfluidic devices are structured in accordance with engineering considerations, while the biological components in applied devices are forced to comply with these engineering presets. The proposed principles represent a paradigm shift in microfluidic technology in three important ways: Microfluidic devices are to be directly integrated with, onto, or around tissue samples, in contrast to the conventional method of off-chip sample extraction followed by sample insertion in microfluidic devices. Architectural and operational principles of microfluidic devices are to be subordinated to suit specific tissue structure and needs, in contrast to the conventional method of building devices according to fluidic function alone and without regard to tissue structure. Sample acquisition from tissue is to be performed on-chip and is to be integrated with the diagnostic measurement within the same device, in contrast to the conventional method of off-chip sample prep and

  16. Microfluidic-chip platform for cell sorting

    Science.gov (United States)

    Malik, Sarul; Balyan, Prerna; Akhtar, J.; Agarwal, Ajay

    2016-04-01

    Cell sorting and separation are considered to be very crucial preparatory steps for numerous clinical diagnostics and therapeutics applications in cell biology research arena. Label free cell separation techniques acceptance rate has been increased to multifold by various research groups. Size based cell separation method focuses on the intrinsic properties of the cell which not only avoids clogging issues associated with mechanical and centrifugation filtration methods but also reduces the overall cost for the process. Consequentially flow based cell separation method for continuous flow has attracted the attention of millions. Due to the realization of structures close to particle size in micro dimensions, the microfluidic devices offer precise and rapid particle manipulation which ultimately leads to an extraordinary cell separation results. The proposed microfluidic device is fabricated to separate polystyrene beads of size 1 µm, 5 µm, 10 µm and 20 µm. The actual dimensions of blood corpuscles were kept in mind while deciding the particle size of polystyrene beads which are used as a model particles for study.

  17. Theoretical microfluidics

    DEFF Research Database (Denmark)

    Bruus, Henrik

    , complex flow patterns and acousto-fluidics, as well as the new fields of opto- and nano-fluidics. Throughout the book simple models with analytical solutions are presented to provide the student with a thorough physical understanding of order of magnitudes and various selected microfluidic phenomena...

  18. A lab-on-a-chip system for the development of complex assays using modular microfluidic components

    Science.gov (United States)

    Hlawatsch, Nadine; Klemm, Richard; Carstens, Cornelia; Brandst"tter, Thomas; Becker, Holger; Elbracht, Rudi; Gärtner, Claudia

    2012-03-01

    For complex biological or diagnostic assays, the development of an integrated microfluidic device can be difficult and error-prone. For this reason, a modular approach, using individual microfluidic functional modules for the different process steps, can be advantageous. However often the interconnection of the modules proves to be tedious and the peripheral instrumentation to drive the various modules is cumbersome and of large size. For this reason, we have developed an integrated instrument platform which has generic functionalities such as valves and pumps, heating zones for continuous-flow PCR, moveable magnets for bead-based assays and an optical detection unit build into the instrument. The instrument holds a titerplate-sized carrier in which up to four microscopy-slide sized microfluidic modules can be clipped in. This allows for developing and optimizing individual assay steps without the need to modify the instrument or generate a completely new microfluidic cartridge. As a proof-of-concept, the automated sample processing of liquor or blood culture in microfluidic structures for detection of currently occuring Neisseria meningitidis strains was carried out. This assay involves the extraction of bacterial DNA, the fluorescent labeling, amplification using PCR as well as the hybridization of the DNA molecules in three-dimensional capture sites spotted into a microchannel. To define the assay sensitivity, chip modules were tested with bacteria spiked samples of different origins and results were controlled by conventional techniques. For liquor or blood culture, the presence of 200 bacteria was detected within 1 hour.

  19. Electrical cell counting process characterization in a microfluidic impedance cytometer.

    Science.gov (United States)

    Hassan, Umer; Bashir, Rashid

    2014-10-01

    Particle counting in microfluidic devices with coulter principle finds many applications in health and medicine. Cell enumeration using microfluidic particle counters is fast and requires small volumes of sample, and is being used for disease diagnostics in humans and animals. A complete characterization of the cell counting process is critical for accurate cell counting especially in complex systems with samples of heterogeneous population interacting with different reagents in a microfluidic device. In this paper, we have characterized the electrical cell counting process using a microfluidic impedance cytometer. Erythrocytes were lysed on-chip from whole blood and the lysing was quenched to preserve leukocytes which subsequently pass through a 15 μm × 15 μm measurement channel used to electrically count the cells. We show that cell counting over time is a non-homogeneous Poisson process and that the electrical cell counts over time show the log-normal distribution, whose skewness can be attributed to diffusion of cells in the buffer that is used to meter the blood. We further found that the heterogeneous cell population (i.e. different cell types) shows different diffusion characteristics based on the cell size. Lymphocytes spatially diffuse more as compared to granulocytes and monocytes. The time difference between the cell occurrences follows an exponential distribution and when plotted over time verifies the cell diffusion characteristics. We also characterized the probability of occurrence of more than one cell at the counter within specified time intervals using Poisson counting statistics. For high cell concentration samples, we also derived the required sample dilution based on our particle counting characterization. Buffer characterization by considering the size based particle diffusion and estimating the required dilution are critical parameters for accurate counting results.

  20. Microfluidic MEMS hand-held flow cytometer

    Science.gov (United States)

    Grafton, Meggie M. G.; Maleki, Teimour; Zordan, Michael D.; Reece, Lisa M.; Byrnes, Ron; Jones, Alan; Todd, Paul; Leary, James F.

    2011-02-01

    Due to a number of recent technological advances, a hand-held flow cytometer can be achieved by use of semiconductor illuminators, optical sensors (all battery powered) and sensitive cell markers such as immuno-quantum dot (Qdot) labels. The specific application described is of a handheld blood analyzer that can quickly process a drop of whole, unfractionated human peripheral blood by real-time, on-chip magnetic separation of white blood cells (WBCs) and red blood cells (RBCs) and further fluorescence analysis of Qdot labeled WBC subsets. Various microfluidic patterns were fabricated in PDMS and used to characterize flow of single cells and magnetic deflection of magnetically labeled cells. An LED excitation, avalanche photodiode detection system (SensL Technologies, Ltd., Cork, Ireland) was used for immuno-Qdot detection of WBC subsets. A static optical setup was used to determine the sensitivity of the detection system. In this work we demonstrate: valve-less, on-chip magnetic sorting of immunomagnetically labeled white blood cells, bright Qdot labeling of lymphocytes, and counting of labeled white blood cells. Comparisons of these results with conventional flow cytometric analyses are reported. Sample preparation efficiency was determined by labeling of isolated white blood cells. Appropriate flow rates were determined for optical detection and confirmed with flowing particles. Several enabling technologies required for a truly portable, battery powered, hand-held flow cytometer for use in future point-of-care diagnostic devices have been demonstrated. The combining of these technologies into an integrated handheld instrument is in progress and results on whole blood cell analysis are to be reported in another paper.

  1. Evaluation of the effect of presence of blood in the stomach on endoscopic diagnostic tests for Helicobacter pylori infection

    Directory of Open Access Journals (Sweden)

    S Mittal

    2011-01-01

    Full Text Available Introduction: Presence of blood in the stomach has been thought to affect the performance of diagnostic tests used in detecting Helicobacter pylori (H. pylori in the stomach. This study evaluated the effect of blood on the efficacy of rapid urease test (RUT and microscopic appearance of the biopsy after staining with Giemsa stain. Materials and Methods: Patients with bleeding oesophageal varices who met the inclusion criteria were tested for H. pylori by RUT and microscopic examination of the biopsy. A repeat endoscopy, RUT and histology were done one month following initial presentation. The performance of the diagnostic tests was evaluated with and without the presence of intraluminal blood. A combined result of the two tests, RUT and histology, carried out in presence or absence of blood for the diagnosis of H. pylori, when considered together was considered as the gold standard. Results: Thirty six patients included in the study were in the ages ranging between 15-60 years (mean age = 44.14 years ±2.1. The combination of tests at both visits showed 20/36 (55.6% patients were positive for H. pylori. The decrease in H. pylori positivity in the presence of blood was significant for RUT (8.3% vs. 38.9%; P=0.005 and combined test (19.4% vs. 47.2%; P=0.02 but the decrease in positivity for histology (11.1% vs 30.6% was not significant (P=0.08. In the presence of blood, the sensitivity of RUT, histology and combined tests were 15%, 20% and 35%, respectively. In the absence of blood, the sensitivity of RUT, histology and combination of tests was 70%, 55% and 85%, respectively. Conclusion: Blood in the stomach significantly decreased the sensitivity of RUT, histology and the combination of both. Negative results of these tests in acute upper gastro intestinal (GI bleeding should therefore be interpreted carefully.

  2. Microfluidic systems for pathogen sensing: a review.

    Science.gov (United States)

    Mairhofer, Jürgen; Roppert, Kriemhilt; Ertl, Peter

    2009-01-01

    Rapid pathogen sensing remains a pressing issue today since conventional identification methodsare tedious, cost intensive and time consuming, typically requiring from 48 to 72 h. In turn, chip based technologies, such as microarrays and microfluidic biochips, offer real alternatives capable of filling this technological gap. In particular microfluidic biochips make the development of fast, sensitive and portable diagnostic tools possible, thus promising rapid and accurate detection of a variety of pathogens. This paper will provide a broad overview of the novel achievements in the field of pathogen sensing by focusing on methods and devices that compliment microfluidics.

  3. Microfluidic Systems for Pathogen Sensing: A Review

    Directory of Open Access Journals (Sweden)

    Peter Ertl

    2009-06-01

    Full Text Available Rapid pathogen sensing remains a pressing issue today since conventional identification methodsare tedious, cost intensive and time consuming, typically requiring from 48 to 72 h. In turn, chip based technologies, such as microarrays and microfluidic biochips, offer real alternatives capable of filling this technological gap. In particular microfluidic biochips make the development of fast, sensitive and portable diagnostic tools possible, thus promising rapid and accurate detection of a variety of pathogens. This paper will provide a broad overview of the novel achievements in the field of pathogen sensing by focusing on methods and devices that compliment microfluidics.

  4. Electroosmotic oscillatory flow of micropolar fluid in microchannels:application to dynamics of blood flow in microfluidic devices

    Institute of Scientific and Technical Information of China (English)

    JC MISRA; S CHANDRA; GC SHIT; PK KUNDU

    2014-01-01

    The electroosmotic flow of a micropolar fluid in a microchannel bounded by two parallel porous plates undergoing periodic vibration is studied. The equations for conservation of linear and angular momentums and Gauss’s law of charge distribution are solved within the framework of the Debye-H¨uckel approximation. The fluid velocity and microrotation are assumed to depend linearly on the Reynolds number. The study shows that the amplitude of microrotation is highly sensitive to the changes in the magnitude of the suction velocity and the width of the microchannel. An increase in the micropolar parameter gives rise to a decrease in the amplitude of microrotation. Numerical estimates reveal that the microrotation of the suspended microelements in blood also plays an important role in controlling the electro-osmotically actuated flow dynamics in micro-bio-fluidic devices.

  5. In Vitro Blood-Brain Barrier Models-An Overview of Established Models and New Microfluidic Approaches

    DEFF Research Database (Denmark)

    Wolff, Anette; Antfolk, Maria; Brodin, Birger;

    2015-01-01

    The societal need for new central nervous system (CNS) medicines is substantial, because of the global increase in life expectancy and the accompanying increase in age-related CNS diseases. Low blood-brain barrier (BBB) permeability has been one of the major causes of failure for new CNS drug...... candidates. There has therefore been a great interest in cell models, which mimic BBB permeation properties. In this review, we present an overview of the performance of monocultured, cocultured, and triple-cultured primary cells and immortalized cell lines, including key parameters such as transendothelial......-of-the-art models and it was noted that, although they show great promise, these systems have not yet reached beyond the proof-of-concept stage. In general, it was found that there were large variations in experimental protocols, BBB phenotype markers, and paracellular flux markers used. It is the author's opinion...

  6. Detection of Chlamydia trachomatis in blood samples as a diagnostic method for complicated and persistent forms of urogenital chlamydia infections

    Directory of Open Access Journals (Sweden)

    Sultanakhmedov E.S.

    2015-09-01

    Full Text Available Goal: the study of the effectiveness of the method for laboratory diagnostics of urogenital chlamydial infection in patients with chronic form of the disease. Material and methods. The presence of DNAof C. trachomatis was detected by PCR in either genital or extragenital (blood sites in eighth patients (four men and four women. Results. It is established that in biological material taken from extragenital (blood sites, C. trachomatis was detected in all patients examined (in 100% of cases, while in clinical samples obtained from genital sites, in seven patients only (87.5%. Conclusion. We found that specific chlamydial DNAcan be detected in extragenital (blood site, despite the negative reaction in the clinical material from the genital tract of patients with genital chlamydial infection.

  7. Gene Detection in Complex Biological Media Using Semiconductor Nanorods within an Integrated Microfluidic Device.

    Science.gov (United States)

    Bi, Xinyan; Adriani, Giulia; Xu, Yang; Chakrabortty, Sabyasachi; Pastorin, Giorgia; Ho, Han Kiat; Ang, Wee Han; Chan, Yinthai

    2015-10-20

    The salient optical properties of highly luminescent semiconductor nanocrystals render them ideal fluorophores for clinical diagnostics, therapeutics, and highly sensitive biochip applications. Microfluidic systems allow miniaturization and integration of multiple biochemical processes in a single device and do not require sophisticated diagnostic tools. Herein, we describe a microfluidic system that integrates RNA extraction, reverse transcription to cDNA, amplification and detection within one integrated device to detect histidine decarboxylase (HDC) gene directly from human white blood cells samples. When anisotropic semiconductor nanorods (NRs) were used as the fluorescent probes, the detection limit was found to be 0.4 ng of total RNA, which was much lower than that obtained using spherical quantum dots (QDs) or organic dyes. This was attributed to the large action cross-section of NRs and their high probability of target capture in a pull-down detection scheme. The combination of large scale integrated microfluidics with highly fluorescent semiconductor NRs may find widespread utility in point-of-care devices and multitarget diagnostics.

  8. Prognostic and diagnostic value of moderate intensity stress test with blood pressure control

    Directory of Open Access Journals (Sweden)

    V. N. Marchenko

    2014-01-01

    Full Text Available In spite of age and blood pressure values at rest,hypertensive response to moderate intensity stress testingis characterized by increasing ofprobable beginning of cardiac infarction, stroke or coronary disease in 1.36 times. The hypertensive response to stress test in people with normal blood pressure values at rest (independent of other risk factors is characterized by increasing risk of future hypertension more than in 2 times. Antihypertensive drugs affect blood pressure values differently during the stress testing. The prognosis of blood pressure values during daily physical activity is necessary for antihypertensive treatment. Low availability of convenient instruments and methodological tools for continuous measurement of blood pressure (similar to Spiroarteriocardiorhythmograph, Finapres duringthe dosed physical loads constrain wide use of stress tests with controlled blood pressure in medical practice.

  9. A brief review on microfluidic platforms for hormones detection.

    Science.gov (United States)

    Ozhikandathil, Jayan; Badilescu, Simona; Packirisamy, Muthukumaran

    2017-01-01

    Lab-on-chip technology is attracting great interest due to its potential as miniaturized devices that can automate and integrate many sample-handling steps, minimize consumption of reagent and samples, have short processing time and enable multiplexed analysis. Microfluidic devices have demonstrated their potential for a broad range of applications in life sciences, including point-of-care diagnostics and personalized medicine, based on the routine diagnosis of levels of hormones, cancer markers, and various metabolic products in blood, serum, etc. Microfluidics offers an adaptable platform that can facilitate cell culture as well as monitor their activity and control the cellular environment. Signaling molecules released from cells such as neurotransmitters and hormones are important in assessing the health of cells and the effect of drugs on their functions. In this review, we provide an insight into the state-of-art applications of microfluidics for monitoring of hormones released by cells. In our works, we have demonstrated efficient detection methods for bovine growth hormones using nano and microphotonics integrated microfluidics devices. The bovine growth hormone can be used as a growth promoter in dairy farming to enhance the milk and meat production. In the recent years, a few attempts have been reported on developing very sensitive, fast and low-cost methods of detection of bovine growth hormone using micro devices. This paper reviews the current state-of-art of detection and analysis of hormone using integrated optical micro and nanofluidics systems. In addition, the paper also focuses on various lab-on-a-chip technologies reported recently, and their benefits for screening growth hormones in milk.

  10. Concentration and Methylation of Cell-Free DNA from Blood Plasma as Diagnostic Markers of Renal Cancer.

    Science.gov (United States)

    Skrypkina, Inessa; Tsyba, Liudmyla; Onyshchenko, Kateryna; Morderer, Dmytro; Kashparova, Olena; Nikolaienko, Oleksii; Panasenko, Grigory; Vozianov, Sergii; Romanenko, Alina; Rynditch, Alla

    2016-01-01

    The critical point for successful treatment of cancer is diagnosis at early stages of tumor development. Cancer cell-specific methylated DNA has been found in the blood of cancer patients, indicating that cell-free DNA (cfDNA) circulating in the blood is a convenient tumor-associated DNA marker. Therefore methylated cfDNA can be used as a minimally invasive diagnostic marker. We analysed the concentration of plasma cfDNA and methylation of six tumor suppressor genes in samples of 27 patients with renal cancer and 15 healthy donors as controls. The cfDNA concentrations in samples from cancer patients and healthy donors was measured using two different methods, the SYBR Green I fluorescence test and quantitative real-time PCR. Both methods revealed a statistically significant increase of cfDNA concentrations in cancer patients. Hypermethylation on cfDNA was detected for the LRRC3B (74.1%), APC (51.9%), FHIT (55.6%), and RASSF1 (62.9%) genes in patients with renal cancer. Promoter methylation of VHL and ITGA9 genes was not found on cfDNA. Our results confirmed that the cfDNA level and methylation of CpG islands of RASSF1A, FHIT, and APC genes in blood plasma can be used as noninvasive diagnostic markers of cancer.

  11. Concentration and Methylation of Cell-Free DNA from Blood Plasma as Diagnostic Markers of Renal Cancer

    Science.gov (United States)

    Tsyba, Liudmyla; Onyshchenko, Kateryna; Kashparova, Olena; Nikolaienko, Oleksii; Panasenko, Grigory; Vozianov, Sergii; Romanenko, Alina; Rynditch, Alla

    2016-01-01

    The critical point for successful treatment of cancer is diagnosis at early stages of tumor development. Cancer cell-specific methylated DNA has been found in the blood of cancer patients, indicating that cell-free DNA (cfDNA) circulating in the blood is a convenient tumor-associated DNA marker. Therefore methylated cfDNA can be used as a minimally invasive diagnostic marker. We analysed the concentration of plasma cfDNA and methylation of six tumor suppressor genes in samples of 27 patients with renal cancer and 15 healthy donors as controls. The cfDNA concentrations in samples from cancer patients and healthy donors was measured using two different methods, the SYBR Green I fluorescence test and quantitative real-time PCR. Both methods revealed a statistically significant increase of cfDNA concentrations in cancer patients. Hypermethylation on cfDNA was detected for the LRRC3B (74.1%), APC (51.9%), FHIT (55.6%), and RASSF1 (62.9%) genes in patients with renal cancer. Promoter methylation of VHL and ITGA9 genes was not found on cfDNA. Our results confirmed that the cfDNA level and methylation of CpG islands of RASSF1A, FHIT, and APC genes in blood plasma can be used as noninvasive diagnostic markers of cancer.

  12. 核酸扩增及微流芯片技术在献血者HCV筛查中的应用%Application of HCV nucleic amplification and microfluidic chip technique in blood donors

    Institute of Scientific and Technical Information of China (English)

    姚仁南; 姚根宏; 栾建凤; 陈复兴; 陈玲; 陈娜云

    2011-01-01

    目的 应用核酸扩增和微流芯片分析方法,用于献血者血液标本丙型肝炎病毒(HCV)的检测.方法 选取80份疑似HCV感染的血液标本,分别采用2种ELISA法、胶体金法、化学发光免疫分析(CLIA)法和核酸扩增后微流芯片法分析.结果 经过核酸扩增的HCV阳性血液经分析后皆出现预期大小片段的特异性条带,而阴性血液缺少相应的条带.特异性巢式PCR扩增及微流芯片法检测的阳性率与CLIA法差异无统计学意义(P>0.05),与ELISA法和胶体金法差异有统计学意义(P<0.01).结论 特异性巢式PCR扩增及微流芯片法结果稳定、准确,灵敏度高于ELISA法,可用于血液筛查.%Objective To apply nucleic amplification and microfluidic chip technique for detection of hepatitis C Virus ( HCV) in blood donors. Methods The selected 80 blood samples,suspicious with HCV infection, were respectively analyzed with two different ELISA reagents , colloid gold reagent , chemiluminescence immunoassay ( CLIA) and reverse transcriptasepolymerase chain reaction combined with microfluidic chip assay. Results Specrfic DNA zone was shown in HCV positive samples with 210 bp fragment.However,there was no corresponding DNA zone in the negative samples. Compared with CLIA,the positive rates of nucleic amplification and microfluidic chip assay had no significant differences (P>O. 05). But compared with ELISA and colloid gold reagent,there are significant differences (P<O. 01). Conclusion The nucleic amplification and microfluidic chip assay were steady and reliable,and more sensitive than ELISA,qualified for the future blood screening for HCV.

  13. Rapid light transmittance measurements in paper-based microfluidic devices

    Directory of Open Access Journals (Sweden)

    Christina Swanson

    2015-09-01

    Full Text Available We developed methodology and built a portable reader to assess light transmittance in paper-based microfluidic devices in a highly sensitive, user-friendly and field-appropriate manner. By sandwiching the paper assay between micro-light-emitting diodes and micro-photodetectors, the reader quantifies light transmittance through the paper independent of ambient light conditions. To demonstrate the utility of the reader, we created a single-use paper-based microfluidic assay for measurement of alanine aminotransferase, an indicator of liver health in blood. The paper assay and reader system accurately differentiated alanine aminotransferase levels across the human reference range and demonstrated significant differences at clinically relevant cutoff values. Results were provided within 10 min and were automatically generated without complex image analysis. Performance of this point-of-care diagnostic rivals the accuracy of lab-based spectrometer tests at a fraction of the cost, while matching the timeliness of low-cost portable assays, which have historically shown lower accuracy. This combination of features allows flexible deployment of low cost and quantitative diagnostics to resource-poor settings.

  14. 3D-printed microfluidic devices.

    Science.gov (United States)

    Amin, Reza; Knowlton, Stephanie; Hart, Alexander; Yenilmez, Bekir; Ghaderinezhad, Fariba; Katebifar, Sara; Messina, Michael; Khademhosseini, Ali; Tasoglu, Savas

    2016-06-20

    Microfluidics is a flourishing field, enabling a wide range of biochemical and clinical applications such as cancer screening, micro-physiological system engineering, high-throughput drug testing, and point-of-care diagnostics. However, fabrication of microfluidic devices is often complicated, time consuming, and requires expensive equipment and sophisticated cleanroom facilities. Three-dimensional (3D) printing presents a promising alternative to traditional techniques such as lithography and PDMS-glass bonding, not only by enabling rapid design iterations in the development stage, but also by reducing the costs associated with institutional infrastructure, equipment installation, maintenance, and physical space. With the recent advancements in 3D printing technologies, highly complex microfluidic devices can be fabricated via single-step, rapid, and cost-effective protocols, making microfluidics more accessible to users. In this review, we discuss a broad range of approaches for the application of 3D printing technology to fabrication of micro-scale lab-on-a-chip devices.

  15. Electro-Microfluidic Packaging

    Science.gov (United States)

    Benavides, G. L.; Galambos, P. C.

    2002-06-01

    There are many examples of electro-microfluidic products that require cost effective packaging solutions. Industry has responded to a demand for products such as drop ejectors, chemical sensors, and biological sensors. Drop ejectors have consumer applications such as ink jet printing and scientific applications such as patterning self-assembled monolayers or ejecting picoliters of expensive analytes/reagents for chemical analysis. Drop ejectors can be used to perform chemical analysis, combinatorial chemistry, drug manufacture, drug discovery, drug delivery, and DNA sequencing. Chemical and biological micro-sensors can sniff the ambient environment for traces of dangerous materials such as explosives, toxins, or pathogens. Other biological sensors can be used to improve world health by providing timely diagnostics and applying corrective measures to the human body. Electro-microfluidic packaging can easily represent over fifty percent of the product cost and, as with Integrated Circuits (IC), the industry should evolve to standard packaging solutions. Standard packaging schemes will minimize cost and bring products to market sooner.

  16. Microfluidics for T- lymphocyte cell separation and inflammation monitoring in burn patients.

    Science.gov (United States)

    Rosenbach, Alan E; Koria, Piyush; Goverman, Jeremy; Kotz, Kenneth T; Gupta, Amit; Yu, Ming; Fagan, Shawn P; Irimia, Daniel; Tompkins, Ronald G

    2011-02-01

    Severe burns result in T lymphocyte specific immunologic changes. In addition to decreased levels of circulating lymphocytes, changes in cytokine secretion and receptor expression also take place. Our finer understanding of the inflammatory response has led to the development of immune-targeted therapeutics, requiring specialized gene-expression monitoring. The emerging field of bio-micro-electromechanical systems can be used to isolate highly pure T lymphocytes in a clinically relevant and timely manner for downstream genomic analysis. Blood samples from healthy volunteers and burn-injured patients were introduced into microfluidic devices developed in our laboratory. Utilizing cell-affinity chromatography for positive selection of T lymphocytes, the devices served as a platform for RNA extraction and downstream cytokine analysis via quantitative real-time polymerase chain reaction (PCR). From a 0.5-mL whole blood sample, the microfluidic devices captured highly pure T lymphocytes from healthy volunteers and burn-injured patients. Cell capture was of sufficient quantity, and extracted RNA was of sufficient quality, for evaluating the gene expression of cytokines: interferon-gamma, interleukin-2, interleukin-4, and interleukin-10. Microfluidics is a useful tool in processing blood from burn-injured patients. Though in its very early stages of development, cell-specific information obtained by this platform/technology will likely be an important component of near-patient molecular diagnostics and personalized medicine.

  17. Diagnostic Value of White Blood Cell and C-Reactive Protein in Pediatric Appendicitis

    Directory of Open Access Journals (Sweden)

    Sevgi Buyukbese Sarsu

    2016-01-01

    Full Text Available Background. Acute appendicitis (AA associated with acute phase reaction is the most prevalent disease which requires emergency surgery. Its delayed diagnosis and unnecessarily performed appendectomies lead to numerous complications. In our study, we aimed to detect the role of WBC and CRP in the exclusion of acute and complicated appendicitis and diagnostic accuracy in pediatric age group. Methods. Appendectomized patient groups were constructed based on the results of histological evaluation. The area under a receiver operating characteristic (ROC curve (AUC was performed to examine diagnostic accuracy. Results. When WBC and CRP were used in combination, based on cut-off values of ≥13.1 × 103/μL for WBC counts and ≥1.17 mg/dL for CRP level, diagnostic parameters were as follows: sensitivity, 98.7%; specificity, 71.3%; PPV, 50.6%; NPV, 99.5%; diagnostic accuracy, 77.6%; LR(+, 3.44; LR(−, 0.017. AUC values were 0.845 (95% CI 0.800–0.891 for WBC and 0.887 (95% CI 0.841–0.932 for CRP. Conclusions. For complicated appendicitis, CRP has the highest degree of diagnostic accuracy. The diagnosis of appendicitis should be made primarily based on clinical examination, and obviously more specific and systemic inflammatory markers are needed. Combined use of cut-off values of WBC (≥13100/μL and CRP (≥1.17 mg/L yields a higher sensitivity and NPV for the diagnosis of complicated appendicitis.

  18. PREFACE: Nano- and microfluidics Nano- and microfluidics

    Science.gov (United States)

    Jacobs, Karin

    2011-05-01

    The field of nano- and microfluidics emerged at the end of the 1990s parallel to the demand for smaller and smaller containers and channels for chemical, biochemical and medical applications such as blood and DNS analysis [1], gene sequencing or proteomics [2, 3]. Since then, new journals and conferences have been launched and meanwhile, about two decades later, a variety of microfluidic applications are on the market. Briefly, 'the small flow becomes mainstream' [4]. Nevertheless, research in nano- and microfluidics is more than downsizing the spatial dimensions. For liquids on the nanoscale, surface and interface phenomena grow in importance and may even dominate the behavior in some systems. The studies collected in this special issue all concentrate on these type of systems and were part ot the priority programme SPP1164 'Nano- and Microfluidics' of the German Science Foundation (Deutsche Forschungsgemeinschaft, DFG). The priority programme was initiated in 2002 by Hendrik Kuhlmann and myself and was launched in 2004. Friction between a moving liquid and a solid wall may, for instance, play an important role so that the usual assumption of a no-slip boundary condition is no longer valid. Likewise, the dynamic deformations of soft objects like polymers, vesicles or capsules in flow arise from the subtle interplay between the (visco-)elasticity of the object and the viscous stresses in the surrounding fluid and, potentially, the presence of structures confining the flow like channels. Consequently, new theories were developed ( see articles in this issue by Münch and Wagner, Falk and Mecke, Bonthuis et al, Finken et al, Almenar and Rauscher, Straube) and experiments were set up to unambiguously demonstrate deviations from bulk, or 'macro', behavior (see articles in this issue by Wolff et al, Vinogradova and Belyaev, Hahn et al, Seemann et al, Grüner and Huber, Müller-Buschbaum et al, Gutsche et al, Braunmüller et al, Laube et al, Brücker, Nottebrock et al

  19. Microfluidic electrochemical reactors

    Science.gov (United States)

    Nuzzo, Ralph G [Champaign, IL; Mitrovski, Svetlana M [Urbana, IL

    2011-03-22

    A microfluidic electrochemical reactor includes an electrode and one or more microfluidic channels on the electrode, where the microfluidic channels are covered with a membrane containing a gas permeable polymer. The distance between the electrode and the membrane is less than 500 micrometers. The microfluidic electrochemical reactor can provide for increased reaction rates in electrochemical reactions using a gaseous reactant, as compared to conventional electrochemical cells. Microfluidic electrochemical reactors can be incorporated into devices for applications such as fuel cells, electrochemical analysis, microfluidic actuation, pH gradient formation.

  20. Development of a diagnostic sensor for measuring blood cell concentrations during haemoconcentration

    Science.gov (United States)

    Robertson, Craig A.; Gourlay, Terence

    2016-01-01

    Background: HemoSep® is a commercial ultrafiltration and haemoconcentration device for the concentration of residual bypass blood following surgery. This technology is capable of reducing blood loss in cardiac and other types of “clean site” procedures, including paediatric surgery. Clinical feedback suggested that the device would be enhanced by including a sensor technology capable of discerning the concentration level of the processed blood product. We sought to develop a novel sensor that can, using light absorption, give an accurate estimate of packed cell volume (PCV). Materials and methods: A sensor-housing unit was 3D printed and the factors influencing the sensor’s effectiveness – supply voltage, sensitivity and emitter intensity - were optimised. We developed a smart system, using comparator circuitry capable of visually informing the user when adequate PCV levels (⩾35%) are attained by HemoSep® blood processing, which ultimately indicates that the blood is ready for autotransfusion. Results: Our data demonstrated that the device was capable of identifying blood concentration at and beyond the 35% PCV level. The device was found to be 100% accurate at identifying concentration levels of 35% from a starting level of 20%. Discussion: The sensory capability was integrated into HemoSep’s® current device and is designed to enhance the user’s clinical experience and to optimise the benefits of HemoSep® therapy. The present study focused on laboratory studies using bovine blood. Further studies are now planned in the clinical setting to confirm the efficacy of the device. PMID:27591743

  1. Raman Tweezers as a Diagnostic Tool of Hemoglobin-Related Blood Disorders

    Directory of Open Access Journals (Sweden)

    Giulia Rusciano

    2008-12-01

    Full Text Available This review presents the development of a Raman Tweezers system for detecting hemoglobin-related blood disorders at a single cell level. The study demonstrates that the molecular fingerprint insight provided by Raman analysis holds great promise for distinguishing between healthy and diseased cells in the field of biomedicine. Herein a Raman Tweezers system has been applied to investigate the effects of thalassemia, a blood disease quite diffuse in the Mediterranean Sea region. By resonant excitation of hemoglobin Raman bands, we examined the oxygenation capability of normal, alpha- and beta-thalassemic erythrocytes. A reduction of this fundamental red blood cell function, particularly severe for beta-thalassemia, has been found. Raman spectroscopy was also used to draw hemoglobin distribution inside single erythrocytes; the results confirmed the characteristic anomaly (target shape, occurring in thalassemia and some other blood disorders. The success of resonance Raman spectroscopy for thalassemia detection reported in this review provide an interesting starting point to explore the application of a Raman Tweezers system in the analysis of several blood disorders.

  2. Mass spectrometric signatures of the blood plasma metabolome for disease diagnostics.

    Science.gov (United States)

    Lokhov, Petr G; Balashova, Elena E; Voskresenskaya, Anna A; Trifonova, Oxana P; Maslov, Dmitry L; Archakov, Alexander I

    2016-01-01

    In metabolomics, a large number of small molecules can be detected in a single run. However, metabolomic data do not include the absolute concentrations of each metabolite. Generally, mass spectrometry analyses provide metabolite concentrations that are derived from mass peak intensities, and the peak intensities are strictly dependent on the type of mass spectrometer used, as well as the technical characteristics, options and protocols applied. To convert mass peak intensities to actual concentrations, calibration curves have to be generated for each metabolite, and this represents a significant challenge depending on the number of metabolites that are detected and involved in metabolome-based diagnostics. To overcome this limitation, and to facilitate the development of diagnostic tests based on metabolomics, mass peak intensities may be expressed in quintiles. The present study demonstrates the advantage of this approach. The examples of diagnostic signatures, which were designed in accordance to this approach, are provided for lung and prostate cancer (leading causes of mortality due to cancer in developed countries) and impaired glucose tolerance (which precedes type 2 diabetes, the most common endocrinology disease worldwide).

  3. Novel immunoassay formats for integrated microfluidic circuits: diffusion immunoassays (DIA)

    Science.gov (United States)

    Weigl, Bernhard H.; Hatch, Anson; Kamholz, Andrew E.; Yager, Paul

    2000-03-01

    Novel designs of integrated fluidic microchips allow separations, chemical reactions, and calibration-free analytical measurements to be performed directly in very small quantities of complex samples such as whole blood and contaminated environmental samples. This technology lends itself to applications such as clinical diagnostics, including tumor marker screening, and environmental sensing in remote locations. Lab-on-a-Chip based systems offer many *advantages over traditional analytical devices: They consume extremely low volumes of both samples and reagents. Each chip is inexpensive and small. The sampling-to-result time is extremely short. They perform all analytical functions, including sampling, sample pretreatment, separation, dilution, and mixing steps, chemical reactions, and detection in an integrated microfluidic circuit. Lab-on-a-Chip systems enable the design of small, portable, rugged, low-cost, easy to use, yet extremely versatile and capable diagnostic instruments. In addition, fluids flowing in microchannels exhibit unique characteristics ('microfluidics'), which allow the design of analytical devices and assay formats that would not function on a macroscale. Existing Lab-on-a-chip technologies work very well for highly predictable and homogeneous samples common in genetic testing and drug discovery processes. One of the biggest challenges for current Labs-on-a-chip, however, is to perform analysis in the presence of the complexity and heterogeneity of actual samples such as whole blood or contaminated environmental samples. Micronics has developed a variety of Lab-on-a-Chip assays that can overcome those shortcomings. We will now present various types of novel Lab- on-a-Chip-based immunoassays, including the so-called Diffusion Immunoassays (DIA) that are based on the competitive laminar diffusion of analyte molecules and tracer molecules into a region of the chip containing antibodies that target the analyte molecules. Advantages of this

  4. Self-powered integrated microfluidic point-of-care low-cost enabling (SIMPLE) chip

    Science.gov (United States)

    Yeh, Erh-Chia; Fu, Chi-Cheng; Hu, Lucy; Thakur, Rohan; Feng, Jeffrey; Lee, Luke P.

    2017-01-01

    Portable, low-cost, and quantitative nucleic acid detection is desirable for point-of-care diagnostics; however, current polymerase chain reaction testing often requires time-consuming multiple steps and costly equipment. We report an integrated microfluidic diagnostic device capable of on-site quantitative nucleic acid detection directly from the blood without separate sample preparation steps. First, we prepatterned the amplification initiator [magnesium acetate (MgOAc)] on the chip to enable digital nucleic acid amplification. Second, a simplified sample preparation step is demonstrated, where the plasma is separated autonomously into 224 microwells (100 nl per well) without any hemolysis. Furthermore, self-powered microfluidic pumping without any external pumps, controllers, or power sources is accomplished by an integrated vacuum battery on the chip. This simple chip allows rapid quantitative digital nucleic acid detection directly from human blood samples (10 to 105 copies of methicillin-resistant Staphylococcus aureus DNA per microliter, ~30 min, via isothermal recombinase polymerase amplification). These autonomous, portable, lab-on-chip technologies provide promising foundations for future low-cost molecular diagnostic assays. PMID:28345028

  5. Designing Polymeric Microfluidic Platforms for Biomedical Applications

    DEFF Research Database (Denmark)

    Vedarethinam, Indumathi

    Micro- and Nanotechnology have the potential to offer a smart solution for diagnostics and academia research with rapid, low cost, robust analysis systems to facilitate biological analyses. New, high throughput microfluidic platforms have the potential to surpass in performance the conventional a...

  6. Quantitative analysis of genomic DNA degradation in whole blood under various storage conditions for molecular diagnostic testing.

    Science.gov (United States)

    Permenter, Jessalyn; Ishwar, Arjun; Rounsavall, Angie; Smith, Maddie; Faske, Jennifer; Sailey, Charles J; Alfaro, Maria P

    2015-12-01

    Proper storage of whole blood is crucial for isolating nucleic acids from leukocytes and to ensure adequate performance of downstream assays in the molecular diagnostic laboratory. Short-term and long-term storage recommendations are lacking for successful isolation of genomic DNA (gDNA). Container type (EDTA or heparin), temperature (4 °C and room temperature) and time (1-130 days) were assessed as criterion for sample acceptance policies. The percentage of integrated area (%Ti) between 150 and 10,000 bp from the 2200 TapeStation electropherogram was calculated to measure gDNA degradation. Refrigerated EDTA samples yielded gDNA with low %Ti (high quality). Heparinized samples stored at room temperature yielded gDNA of worst quality. Downstream analysis demonstrated that the quality of the gDNA correlated with the quality of the data; samples with high %Ti generated significantly lower levels of high molecular weight amplicons. Recommendations from these analyses include storing blood samples intended for nucleic acid isolation in EDTA tubes at 4 °C for long term storage (>10 days). gDNA should be extracted within 3 days when blood is stored at room temperature regardless of the container. Finally, refrigerated heparinized samples should not be stored longer than 9 days if expecting high quality gDNA isolates. Laboratories should consider many factors, in addition to the results obtained herein, to update their policies for sample acceptance for gDNA extraction intended for molecular genetic testing.

  7. Isolation of plasma from whole blood using a microfludic chip in a continuous cross-flow

    Institute of Scientific and Technical Information of China (English)

    CHEN Xing; CUI DaFu; ZHANG LuLu

    2009-01-01

    A novel microfluidic chip is developed for crossflow filtration plasma from the whole blood which is carried out in a continuous manner. This microfluidic chip was made of a silicon substrate sealed with a compound cover. The silicon substrate fabricated by micro-electro-mechanical system (MEMS)technology consisted of microposts array, microchannels and reservoirs. Then the silicon substrate was characterized by Scaning Electron Microscopy (SEM). The performance of the microfiuidic chip was valued by the experiments of plasma isolation. During more than one hour of continuous blood infusion through the chip, there were no problems of jamming or clogging, and the plasma selectivity of 97.78% was achieved. Due to the chip's simple structure and control mechanism with a continuous,real time operating manner, this microfluidic chip is easily expected to be integrated into micro total analytical system (uTAS) which will create a microanalysis system for point-of-care diagnostics.

  8. Microfluidic single sperm analysis

    NARCIS (Netherlands)

    Wagenaar, de Bjorn

    2016-01-01

    Microfluidic technology has been occasionally used for in vitro analysis and separation of cells. The small dimensions of microfluidic chips are very suitable to study cells on the single cell level rather than in whole populations. Also sperm cells have been studied and manipulated using microfluid

  9. Microfluidic sieve valves

    Science.gov (United States)

    Quake, Stephen R; Marcus, Joshua S; Hansen, Carl L

    2015-01-13

    Sieve valves for use in microfluidic device are provided. The valves are useful for impeding the flow of particles, such as chromatography beads or cells, in a microfluidic channel while allowing liquid solution to pass through the valve. The valves find particular use in making microfluidic chromatography modules.

  10. Microfluidic Dye Lasers

    DEFF Research Database (Denmark)

    Kristensen, Anders; Balslev, Søren; Gersborg-Hansen, Morten

    2006-01-01

    A technology for miniaturized, polymer based lasers, suitable for integration with planar waveguides and microfluidic networks is presented. The microfluidic dye laser device consists of a microfluidic channel with an embedded optical resonator. The devices are fabricated in a thin polymer film...

  11. Predicting Droplet Formation on Centrifugal Microfluidic Platforms

    Science.gov (United States)

    Moebius, Jacob Alfred

    Centrifugal microfluidics is a widely known research tool for biological sample and water quality analysis. Currently, the standard equipment used for such diagnostic applications include slow, bulky machines controlled by multiple operators. These machines can be condensed into a smaller, faster benchtop sample-to-answer system. Sample processing is an important step taken to extract, isolate, and convert biological factors, such as nucleic acids or proteins, from a raw sample to an analyzable solution. Volume definition is one such step. The focus of this thesis is the development of a model predicting monodispersed droplet formation and the application of droplets as a technique for volume definition. First, a background of droplet microfluidic platforms is presented, along with current biological analysis technologies and the advantages of integrating such technologies onto microfluidic platforms. Second, background and theories of centrifugal microfluidics is given, followed by theories relevant to droplet emulsions. Third, fabrication techniques for centrifugal microfluidic designs are discussed. Finally, the development of a model for predicting droplet formation on the centrifugal microfluidic platform are presented for the rest of the thesis. Predicting droplet formation analytically based on the volumetric flow rates of the continuous and dispersed phases, the ratios of these two flow rates, and the interfacial tension between the continuous and dispersed phases presented many challenges, which will be discussed in this work. Experimental validation was completed using continuous phase solutions of different interfacial tensions. To conclude, prospective applications are discussed with expected challenges.

  12. Blood microRNAs as potential diagnostic and prognostic markers in cerebral ischemic injury

    Institute of Scientific and Technical Information of China (English)

    Bridget Martinez; Philip V Peplow

    2016-01-01

    MicroRNAs are a family of small, genome-encoded endogenous RNAs that are transcribed but are not translated into proteins. They serve essential roles in virtually every aspect of brain function, including neurogenesis, neural development, and cellular responses leading to changes in synaptic plasticity. They are also implicated in neurodegeneration and neurological disorders, in responses to hypoxia and ischemia, and in ischemic tolerance induced by ischemic preconditioning. In recent developments, miRNA expres-sion proifling has been examined in stroke, and these studies indicate that miRNAs have emerged as key mediators in ischemic stroke biology. Both increased and decreased miRNA levels may be needed either as prevention or treatment of stroke. Novel approaches are being developed to get miRNA related therapeu-tics into the brain across an intact blood-brain barrier, including chemical modiifcation, use of targeting molecules and methods to disrupt the blood-brain barrier.

  13. Raman spectroscopy of blood serum for Alzheimer's disease diagnostics: specificity relative to other types of dementia.

    Science.gov (United States)

    Ryzhikova, Elena; Kazakov, Oleksandr; Halamkova, Lenka; Celmins, Dzintra; Malone, Paula; Molho, Eric; Zimmerman, Earl A; Lednev, Igor K

    2015-07-01

    The key moment for efficiently and accurately diagnosing dementia occurs during the early stages. This is particularly true for Alzheimer's disease (AD). In this proof-of-concept study, we applied near infrared (NIR) Raman microspectroscopy of blood serum together with advanced multivariate statistics for the selective identification of AD. We analyzed data from 20 AD patients, 18 patients with other neurodegenerative dementias (OD) and 10 healthy control (HC) subjects. NIR Raman microspectroscopy differentiated patients with more than 95% sensitivity and specificity. We demonstrated the high discriminative power of artificial neural network (ANN) classification models, thus revealing the high potential of this developed methodology for the differential diagnosis of AD. Raman spectroscopic, blood-based tests may aid clinical assessments for the effective and accurate differential diagnosis of AD, decrease the labor, time and cost of diagnosis, and be useful for screening patient populations for AD development and progression. Multivariate data analysis of blood serum Raman spectra allows for the differentiation between patients with Alzheimer's disease, other types of dementia and healthy individuals.

  14. Diagnostic value of blood gene expression signatures in active tuberculosis in Thais: a pilot study.

    Science.gov (United States)

    Satproedprai, N; Wichukchinda, N; Suphankong, S; Inunchot, W; Kuntima, T; Kumpeerasart, S; Wattanapokayakit, S; Nedsuwan, S; Yanai, H; Higuchi, K; Harada, N; Mahasirimongkol, S

    2015-06-01

    Tuberculosis (TB) is a major global health problem. Routine laboratory tests or newly developed molecular detection are limited to the quality of sputum sample. Here we selected genes specific to TB by a minimum redundancy-maximum relevancy package using publicly available microarray data and determine level of selected genes in blood collected from a Thai TB cohort of 40 active TB patients, 38 healthy controls and 18 previous TB patients using quantitative real-time PCR. FCGR1A, FCGR1B variant 1, FCGR1B variant 2, APOL1, GBP5, PSTPIP2, STAT1, KCNJ15, MAFB and KAZN had significantly higher expression level in active TB individuals as compared with healthy controls and previous TB cases (P<0.01). A mathematical method was applied to calculate TB predictive score, which contains the level of expression of seven genes and this score can identify active TB cases with 82.5% sensitivity and 100% specificity as compared with conventional culture confirmation. In addition, TB predictive scores in active TB patients were reduced to normal after completion of standard short-course therapy, which was mostly in concordant with the disease outcome. These finding suggested that blood gene expression measurement and TB Sick Score could have potential value in terms of diagnosis of TB and anti-TB treatment monitoring.

  15. Recent Advances in Applications of Droplet Microfluidics

    Directory of Open Access Journals (Sweden)

    Wei-Lung Chou

    2015-09-01

    Full Text Available Droplet-based microfluidics is a colloidal and interfacial system that has rapidly progressed in the past decade because of the advantages of low fabrication costs, small sample volumes, reduced analysis durations, high-throughput analysis with exceptional sensitivity, enhanced operational flexibility, and facile automation. This technology has emerged as a new tool for many recently used applications in molecular detection, imaging, drug delivery, diagnostics, cell biology and other fields. Herein, we review recent applications of droplet microfluidics proposed since 2013.

  16. Blood pyrrole-protein adducts as a diagnostic and prognostic index in pyrrolizidine alkaloid-hepatic sinusoidal obstruction syndrome

    Directory of Open Access Journals (Sweden)

    Gao H

    2015-08-01

    Full Text Available Hong Gao,1,* Jianqing Q Ruan,2,* Jie Chen,1 Na Li,2 Changqiang Q Ke,3 Yang Ye,3–5 Ge Lin,2,4,5 Jiyao Y Wang1,61Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong; 3Shanghai Institute of Materia Medica, Shanghai, People’s Republic of China; 4Joint Research Laboratory for Promoting Globalization of Traditional Chinese Medicines, Shanghai Institute of Materia Medica, 5Chinese University of Hong Kong, Hong Kong; 6Center of Evidence-Based Medicine Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this work and share first authorship Background: The diagnosis of hepatic sinusoidal obstruction syndrome (HSOS induced by pyrrolizidine alkaloids is mainly based on clinical investigation. There is currently no prognostic index. This study evaluated the quantitative measurement of blood pyrrole-protein adducts (PPAs as a diagnostic and prognostic index for pyrrolizidine alkaloid-induced HSOS.Methods: Suspected drug-induced liver injury patients were prospectively recruited. Blood PPAs were quantitatively measured using ultra-performance liquid chromatography-tandem mass spectrometry. Patients’ age, sex, biochemistry test results, and a detailed drug history were recorded. The patients were divided into two groups, ie, those with HSOS induced by pyrrolizidine alkaloid-containing drugs and those with liver injury induced by drugs without pyrrolizidine alkaloids. The relationship between herb administration, clinical outcomes, blood sampling time, and blood PPA concentration in pyrrolizidine alkaloid-associated HSOS patients was analyzed using multiple linear regression analysis.Results: Forty patients met the entry criteria, among whom 23 had pyrrolizidine alkaloid-associated HSOS and 17 had liver injury caused by drugs without pyrrolizidine alkaloids. Among the 23

  17. Impact of uncontrolled blood pressure on diagnostic accuracy of coronary flow reserve for detecting significant coronary stenosis in hypertensive patients

    Institute of Scientific and Technical Information of China (English)

    LI Wei-hong; XU Wei-xian; LI Zhao-ping; LI Cui-ping; WANG Xin-yu; HE Li-yun; ZHAO Wei

    2013-01-01

    Baciground Impaired coronary flow reserve (CFR) in patients with hypertension may be caused by epicardial coronary stenosis or microvascular dysfunction.Antihypertensive treatment has been shown to improve coronary microvascular dysfunction.The aim of this study was to evaluate the impact of uncontrolled blood pressure (BP) on diagnostic accuracy of CFR for detecting significant coronary stenosis.Methods A total of 98 hypertensive patients scheduled for coronary angiography (CAG) due to chest pain were studied.Of them,45 patients had uncontrolled BP (defined as the office BP >140/90 mmHg (1 mmHg=0.133 kPa) in general hypertensive patients,or >130/80 mmHg in hypertensive individuals with diabetes mellitus),and the remaining 53 patients had well-controlled BP.CFR was measured in the left anterior descending coronary artery (LAD) during adenosine triphosphate-induced hyperemia by non-invasive transthoracic Doppler echocardiography (TTDE) within 48 hours prior to CAG.Significant LAD stenosis was defined as >70% luminal narrowing.Diagnostic accuracy of CFR for detecting significant coronary stenosis was analyzed with a receiver operating characteristic analysis.Results CFR was significantly lower in patients with uncontrolled BP than in those with well-controlled BP (2.1±0.6 vs.2.6±0.9,P <0.01).Multivariate linear regression analysis of the study showed that the value of CFR was independently associated with the angiographically determined degree of LAD stenosis (β=-0.445,P <0.0001) and the presence of uncontrolled BP (β=-0.272,P=0.014).With a receiver operating characteristic analysis,CFR <2.2 was the optimal cut-off value for detecting LAD stenosis in all hypertensive patients (AUC 0.83,95%C/0.75-0.91) with a sensitivity of 75%,a specificity of 78%,and an accuracy of 77%.A significant reduction of diagnostic specificity was observed in patients with uncontrolled BP compared with those with well-controlled BP (67% vs.93%,P=0

  18. The diagnostic utility of stabilized blood for detection of foot-and-mouth disease virus RNA by RT-qPCR

    DEFF Research Database (Denmark)

    S. Fontél, Kristina; Bøtner, Anette; Belsham, Graham

    In Europe, clinical signs indicative of foot-and-mouth disease (FMD), would immediately lead to collection of blood and relevant organ material for further laboratory examination for this vesicular disease virus. Today, the first line system for detection of virus in the sample material is real t...... time RT-PCR (RT-qPCR). The aim of this study was to investigate the diagnostic utility of stabilized blood for detection of FMDV RNA in this system....

  19. Translating silicon nanowire BioFET sensor-technology to embedded point-of-care medical diagnostics

    DEFF Research Database (Denmark)

    Pfreundt, Andrea; Zulfiqar, Azeem; Patou, François;

    2013-01-01

    Silicon nanowire and nanoribbon biosensors have shown great promise in the detection of biomarkers at very low concentrations. Their high sensitivity makes them ideal candidates for use in early-stage medical diagnostics and further disease monitoring where low amounts of biomarkers need......, should be addressed in an automated way. Here, we are presenting the concept of a polysilicon nanoribbon sensor array integrated with multiplexed microfluidic functionalization, automated calibration and sample handling for flexible diagnostics from finger prick blood samples. Functionalization...... of the sensor surface is performed in a controlled microfluidic environment and can be monitored in real-time to ensure reproducible results. In a simple temporary PDMS device, multiple parallel pathways enable straight-forward selective functionalization for different biomarkers. Common diagnostic essays...

  20. Regional cerebral blood flow in normal pressure hydrocephalus: diagnostic and prognostic aspects

    Energy Technology Data Exchange (ETDEWEB)

    Larsson, A. (Dept. of Neurology, Sahlgren Hospital, Goeteborg (Sweden)); Bergh, A.C. (Dept. of Clinical Physiology, Sahlgren Hospital, Goeteborg (Sweden)); Bilting, M. (Dept. of Neurosurgery, Sahlgren Hospital, Goeteborg (Sweden)); Aerlig, AA. (Dept. of Radiation Physics, Sahlgren Hospital, Goeteborg (Sweden)); Jacobsson, L. (Dept. of Radiation Physics, Sahlgren Hospital, Goeteborg (Sweden)); Stephensen, H. (Dept. of Neurosurgery, Sahlgren Hospital, Goeteborg (Sweden)); Wikkelsoe, C. (Dept. of Neurology, Sahlgren Hospital, Goeteborg (Sweden))

    1994-02-01

    Relative regional cerebral blood flow (rrCBF) was measured by SPET using [sup 99m]Tc-HMPAO as flow tracer, in 23 patients with normal pressure hydrocephalus (NPH). 1000 MBq [sup 99m]Tc-HMPAO was given intravenously and the rrCBF calculated as regional/cerebellar count level ratios. The patients were examined before and 3-12 months after ventriculoperitoneal shunt surgery. rrCBF was also determined in ten healthy aged matched volunteers who served as controls. The NPH patients had decreased rrCBF in the hippocampal regions and in the frontal and parietal white matter as compared to the controls. The frontal/parietal rrCBF ratio correlated with both psychiatric disability and the preoperative degree of incontinence. Decreased flow in frontal white matter, frontoparietal and hippocampal grey matter and a low frontalparietal grey matter flow ratio preoperatively correlated with improvement in both Mini Mental State score and psychiatric disability after shunt surgery. After shunt surgery the rrCBF increased in the mesencephalon, frontal grey and white matter, parietal white matter and hippocampus. The flow increase in hippocampal regions and frontal white matter correlated with improvement in psychiatric symptomatology. The results of this study regarding the frontal and hippocampal rrCBF patterns, and the clinical correlation, support the hypothesis that CBF changes in these regions are of patohphysiological and prognostic importance in NPH. (orig./MG)

  1. Infrared tomography for diagnostic imaging of port wine stain blood vessels

    Energy Technology Data Exchange (ETDEWEB)

    Goodman, D. [Lawrence Livermore National Lab., CA (United States)

    1994-11-15

    The objective of this work is the development of Infrared Tomography (IRT) for detecting and characterizing subsurface chromophores in human skin. Characterization of cutaneous chromophores is crucial for advances in the laser treatment of pigmented lesions (e.g., port wine stain birthmarks and tatoos). Infrared tomography (IRT) uses a fast infrared focal plane array (IR-FPA) to detect temperature rises in a substrate induced by pulsed radiation. A pulsed laser is used to produce transient heating of an object. The temperature rise, due to the optical absorption of the pulsed laser light, creates an increase in infrared emission which is measured by the IR-FPA. Although the application of IRT to image subsurface cracks due to metal fatigue is a topic of great interest in the aircraft industry, the application to image subsurface chromophores in biological materials is novel. We present an image recovery method based on a constrained conjugate gradient algorithm that has obtained the first ever high quality images of port wine blood vessels.

  2. Rapid, whole blood diagnostic test for detecting anti-hantavirus antibody in rats.

    Science.gov (United States)

    Amada, Takako; Yoshimatsu, Kumiko; Yasuda, Shumpei P; Shimizu, Kenta; Koma, Takaaki; Hayashimoto, Nobuhito; Gamage, Chandika D; Nishio, Sanae; Takakura, Akira; Arikawa, Jiro

    2013-10-01

    Hantavirus is a causative agent of rodent-borne viral zoonoses, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome. Seoul virus (SEOV) is a causative agent of urban and laboratory rat-associated HFRS worldwide. Surveillance of rodents has been done mainly by serological detection of hantavirus-specific antibodies by enzyme linked immunosorbent assay (ELISA) and immunofluorescent antibody assay (IFA). An immunochromatographic (ICG) test was developed with the N-terminal 103 amino acids of nucleocapsid protein of Hantaan virus expressed by Escherichia coli as an antigen to detect IgG antibody specific to hantavirus in sera from Rattus sp. animals. Antibody-detecting sensitivity of the ICG test was the same as that of ELISA and about 100-times higher than that of IFA. Overall sensitivities and specificities of the ICG test in comparison to ELISA and IFA for sera from 192 urban rats and 123 laboratory rats were 99.3% and 100%, respectively. Diluted whole blood samples without separation could be used for the ICG test. The ICG test enabled detection of antibodies to SEOV, Hantaan, Dobrava/Belgrade, and Thailand viruses, which are causative agents of HFRS throughout Eurasia. The ICG test is a rapid, simple and safe method for diagnosis of SEOV infection in rats.

  3. Direct blood dry LAMP: a rapid, stable, and easy diagnostic tool for Human African Trypanosomiasis.

    Directory of Open Access Journals (Sweden)

    Kyoko Hayashida

    2015-03-01

    Full Text Available Loop-mediated isothermal amplification (LAMP is a rapid and sensitive tool used for the diagnosis of a variety of infectious diseases. One of the advantages of this method over the polymerase chain reaction is that DNA amplification occurs at a constant temperature, usually between 60-65°C; therefore, expensive devices are unnecessary for this step. However, LAMP still requires complicated sample preparation steps and a well-equipped laboratory to produce reliable and reproducible results, which limits its use in resource-poor laboratories in most developing countries. In this study, we made several substantial modifications to the technique to carry out on-site diagnosis of Human African Trypanosomiasis (HAT in remote areas using LAMP. The first essential improvement was that LAMP reagents were dried and stabilized in a single tube by incorporating trehalose as a cryoprotectant to prolong shelf life at ambient temperature. The second technical improvement was achieved by simplifying the sample preparation step so that DNA or RNA could be amplified directly from detergent-lysed blood samples. With these modifications, diagnosis of HAT in local clinics or villages in endemic areas becomes a reality, which could greatly impact on the application of diagnosis not only for HAT but also for other tropical diseases.

  4. Diagnostic tool for red blood cell membrane disorders: Assessment of a new generation ektacytometer.

    Science.gov (United States)

    Da Costa, Lydie; Suner, Ludovic; Galimand, Julie; Bonnel, Amandine; Pascreau, Tiffany; Couque, Nathalie; Fenneteau, Odile; Mohandas, Narla

    2016-01-01

    Inherited red blood cell (RBC) membrane disorders, such as hereditary spherocytosis, elliptocytosis and hereditary ovalocytosis, result from mutations in genes encoding various RBC membrane and skeletal proteins. The RBC membrane, a composite structure composed of a lipid bilayer linked to a spectrin/actin-based membrane skeleton, confers upon the RBC unique features of deformability and mechanical stability. The disease severity is primarily dependent on the extent of membrane surface area loss. RBC membrane disorders can be readily diagnosed by various laboratory approaches that include RBC cytology, flow cytometry, ektacytometry, electrophoresis of RBC membrane proteins and genetics. The reference technique for diagnosis of RBC membrane disorders is the osmotic gradient ektacytometry. However, in spite of its recognition as the reference technique, this technique is rarely used as a routine diagnosis tool for RBC membrane disorders due to its limited availability. This may soon change as a new generation of ektacytometer has been recently engineered. In this review, we describe the workflow of the samples shipped to our Hematology laboratory for RBC membrane disorder analysis and the data obtained for a large cohort of French patients presenting with RBC membrane disorders using a newly available version of the ektacytomer.

  5. The Diagnostic Value of Superb Microvascular Imaging (SMI) in Detecting Blood Flow Signals of Breast Lesions: A Preliminary Study Comparing SMI to Color Doppler Flow Imaging.

    Science.gov (United States)

    Ma, Yan; Li, Gang; Li, Jing; Ren, Wei-dong

    2015-09-01

    The correlation between color Doppler flow imaging (CDFI) and Superb Microvascular Imaging (SMI) for detecting blood flow in breast lesions was investigated, as was the diagnostic value of SMI in differentiating benign from malignant breast lesions.These lesions were evaluated using both CDFI and SMI according to Adler's method. Pathologic examination showed 57 malignant lesions and 66 benign lesions. The number of blood vessels in a single mass was detected by 2 techniques (SMI and CDFI), and the difference between the 2 values (SMI-CDFI) was calculated. The optimal threshold for the diagnosis of malignant neoplasms and the diagnostic performances of SMI, CDFI, and SMI-CDFI were calculated.For the total lesions and malignant lesions alone, the difference between SMI and CDFI for detecting blood flow was significant (P < 0.01), but the difference was not significant for benign lesions (P = 0.15). The area under the receiver operating characteristic curve was 0.73 (95% confidence interval [CI]: 0.64-0.82) for CDFI; 0.81 (95% CI: 0.74-0.89) for SMI; and 0.89 (95% CI: 0.82-0.95) for SMI-CDFI. Furthermore, the modality of "SMI-CDFI" showed the best diagnostic performance.SMI provides further microvessel information in breast lesions. The diagnostic modality of "SMI-CDFI" can improve the diagnostic performance of ultrasound in the differentiation between benign and malignant masses.

  6. Planar microfluidics - liquid handling without walls

    CERN Document Server

    Rathgeber, A; Kutschera, H J; Wixforth, A

    2001-01-01

    The miniaturization and integration of electronic circuitry has not only made the enormous increase in performance of semiconductor devices possible but also spawned a myriad of new products and applications ranging from a cellular phone to a personal computer. Similarly, the miniaturization and integration of chemical and biological processes will revolutionize life sciences. Drug design and diagnostics in the genomic era require reliable and cost effective high throughput technologies which can be integrated and allow for a massive parallelization. Microfluidics is the core technology to realize such miniaturized laboratories with feature sizes on a submillimeter scale. Here, we report on a novel microfluidic technology meeting the basic requirements for a microfluidic processor analogous to those of its electronic counterpart: Cost effective production, modular design, high speed, scalability and programmability.

  7. Design and Testing of Digital Microfluidic Biochips

    CERN Document Server

    Zhao, Yang

    2013-01-01

    This book provides a comprehensive methodology for automated design, test and diagnosis, and use of robust, low-cost, and manufacturable digital microfluidic systems. It focuses on the development of a comprehensive CAD optimization framework for digital microfluidic biochips that unifies different design problems. With the increase in system complexity and integration levels, biochip designers can utilize the design methods described in this book to evaluate different design alternatives, and carry out design-space exploration to obtain the best design point. Describes practical design automation tools that address different design problems (e.g., synthesis, droplet routing, control-pin mapping, testing and diagnosis, and error recovery) in a unified manner; Applies test pattern generation and error-recovery techniques for digital microfluidics-based biochips; Uses real bioassays as evaluation examples, e.g., multiplexed in vitro human physiological fluids diagnostics, PCR, protein crystallization.  

  8. Transcriptional profiling of peripheral blood mononuclear cells in pancreatic cancer patients identifies novel genes with potential diagnostic utility.

    Directory of Open Access Journals (Sweden)

    Michael J Baine

    Full Text Available BACKGROUND: It is well known that many malignancies, including pancreatic cancer (PC, possess the ability to evade the immune system by indirectly downregulating the mononuclear cell machinery necessary to launch an effective immune response. This knowledge, in conjunction with the fact that the trancriptome of peripheral blood mononuclear cells has been shown to be altered in the context of many diseases, including renal cell carcinoma, lead us to study if any such alteration in gene expression exists in PC as it may have diagnostic utility. METHODS AND FINDINGS: PBMC samples from 26 PC patients and 33 matched healthy controls were analyzed by whole genome cDNA microarray. Three hundred eighty-three genes were found to be significantly different between PC and healthy controls, with 65 having at least a 1.5 fold change in expression. Pathway analysis revealed that many of these genes fell into pathways responsible for hematopoietic differentiation, cytokine signaling, and natural killer (NK cell and CD8+ T-cell cytotoxic response. Unsupervised hierarchical clustering analysis identified an eight-gene predictor set, consisting of SSBP2, Ube2b-rs1, CA5B, F5, TBC1D8, ANXA3, ARG1, and ADAMTS20, that could distinguish PC patients from healthy controls with an accuracy of 79% in a blinded subset of samples from treatment naïve patients, giving a sensitivity of 83% and a specificity of 75%. CONCLUSIONS: In summary, we report the first in-depth comparison of global gene expression profiles of PBMCs between PC patients and healthy controls. We have also identified a gene predictor set that can potentially be developed further for use in diagnostic algorithms in PC. Future directions of this research should include analysis of PBMC expression profiles in patients with chronic pancreatitis as well as increasing the number of early-stage patients to assess the utility of PBMCs in the early diagnosis of PC.

  9. Material Biocompatibility for PCR Microfluidic Chips

    KAUST Repository

    Kodzius, Rimantas

    2010-04-23

    As part of the current miniaturization trend, biological reactions and processes are being adapted to microfluidics devices. PCR is the primary method employed in DNA amplification, its miniaturization is central to efforts to develop portable devices for diagnostics and testing purposes. A problem is the PCR-inhibitory effect due to interaction between PCR reagents and the surrounding environment, which effect is increased in high-surface-are-to-volume ration microfluidics. In this study, we evaluated the biocompatibility of various common materials employed in the fabrication of microfluidic chips, including silicon, several kinds of silicon oxide, glasses, plastics, wax, and adhesives. Two-temperature PCR was performed with these materials to determine their PCR-inhibitory effect. In most of the cases, addition of bovine serum albumin effectively improved the reaction yield. We also studied the individual PCR components from the standpoint of adsorption. Most of the materials did not inhibit the DNA, whereas they did show noticeable interaction with the DNA polymerase. Our test, instead of using microfluidic devices, can be easily conducted in common PCR tubes using a standard bench thermocycler. Our data supports an overview of the means by which the materials most bio-friendly to microfluidics can be selected.

  10. Low-cost bioanalysis on paper-based and its hybrid microfluidic platforms.

    Science.gov (United States)

    Dou, Maowei; Sanjay, Sharma Timilsina; Benhabib, Merwan; Xu, Feng; Li, XiuJun

    2015-12-01

    Low-cost assays have broad applications ranging from human health diagnostics and food safety inspection to environmental analysis. Hence, low-cost assays are especially attractive for rural areas and developing countries, where financial resources are limited. Recently, paper-based microfluidic devices have emerged as a low-cost platform which greatly accelerates the point of care (POC) analysis in low-resource settings. This paper reviews recent advances of low-cost bioanalysis on paper-based microfluidic platforms, including fully paper-based and paper hybrid microfluidic platforms. In this review paper, we first summarized the fabrication techniques of fully paper-based microfluidic platforms, followed with their applications in human health diagnostics and food safety analysis. Then we highlighted paper hybrid microfluidic platforms and their applications, because hybrid platforms could draw benefits from multiple device substrates. Finally, we discussed the current limitations and perspective trends of paper-based microfluidic platforms for low-cost assays.

  11. Tunable Microfluidic Dye Laser

    DEFF Research Database (Denmark)

    Olsen, Brian Bilenberg; Helbo, Bjarne; Kutter, Jörg Peter

    2003-01-01

    We present a tunable microfluidic dye laser fabricated in SU-8. The tunability is enabled by integrating a microfluidic diffusion mixer with an existing microfluidic dye laser design by Helbo et al. By controlling the relative flows in the mixer between a dye solution and a solvent......, the concentration of dye in the laser cavity can be adjusted, allowing the wavelength to be tuned. Wavelength tuning controlled by the dye concentration was demonstrated with macroscopic dye lasers already in 1971, but this principle only becomes practically applicable by the use of microfluidic mixing...

  12. Diagnostic Accuracy of Methylated SEPT9 for Blood-based Colorectal Cancer Detection: A Systematic Review and Meta-Analysis

    Science.gov (United States)

    Nian, Jiayun; Sun, Xu; Ming, SuYang; Yan, Chen; Ma, Yunfei; Feng, Ying; Yang, Lin; Yu, Mingwei; Zhang, Ganlin; Wang, Xiaomin

    2017-01-01

    Objectives: More convenient and effective blood-based methods are believed to increase colorectal cancer (CRC) detection adoption. The effectiveness of methylated SPET9 for CRC detection has been reviewed in the newly published recommendation statement by US Preventive Services Task Force (USPSTF), while detailed instructions were not provided, which may be a result of insufficient evidence. Therefore, more evidence is needed to assist practitioners to thoroughly understand the utilization of this special maker. Methods: Based on the standard method, a systematic review and meta-analysis was performed. Quadas-2 was used to assess the methodological quality of studies. Relevant studies were searched and screened from PubMed, Embase and other literature databases up to June 1, 2016. Pooled sensitivity, specificity and diagnostic odds ratio were summarized by bivariate mixed effect model and area under the curve (AUC) was estimated by hierarchical summary receiver operator characteristic curve. Results: 25 studies were included for analysis. The pooled sensitivity, specificity and AUC were 0.71, 0.92 and 0.88, respectively. Among the various methods and assays, Epipro Colon 2.0 with 2/3 algorithm was the most effective in colorectal cancer detection. Positive ratio of mSEPT9 was higher in advanced CRC (45% in I, 70% in II, 76% in III, 79% in IV) and lower differentiation (31% in high, 73% in moderate, 90% in low) tissue. However, this marker has poor ability of identifying precancerous lesions according to current evidence. Conclusions: mSEPT9 is a reliable blood-based marker in CRC detection, particularly advanced CRC. Epipro Colon 2.0 with 2/3 algorithm is currently the optimal method and assay to detect CRC. PMID:28102859

  13. Microfluidic stretchable RF electronics.

    Science.gov (United States)

    Cheng, Shi; Wu, Zhigang

    2010-12-07

    Stretchable electronics is a revolutionary technology that will potentially create a world of radically different electronic devices and systems that open up an entirely new spectrum of possibilities. This article proposes a microfluidic based solution for stretchable radio frequency (RF) electronics, using hybrid integration of active circuits assembled on flex foils and liquid alloy passive structures embedded in elastic substrates, e.g. polydimethylsiloxane (PDMS). This concept was employed to implement a 900 MHz stretchable RF radiation sensor, consisting of a large area elastic antenna and a cluster of conventional rigid components for RF power detection. The integrated radiation sensor except the power supply was fully embedded in a thin elastomeric substrate. Good electrical performance of the standalone stretchable antenna as well as the RF power detection sub-module was verified by experiments. The sensor successfully detected the RF radiation over 5 m distance in the system demonstration. Experiments on two-dimensional (2D) stretching up to 15%, folding and twisting of the demonstrated sensor were also carried out. Despite the integrated device was severely deformed, no failure in RF radiation sensing was observed in the tests. This technique illuminates a promising route of realizing stretchable and foldable large area integrated RF electronics that are of great interest to a variety of applications like wearable computing, health monitoring, medical diagnostics, and curvilinear electronics.

  14. Rapid and label-free microfluidic neutrophil purification and phenotyping in diabetes mellitus

    Science.gov (United States)

    Hou, Han Wei; Petchakup, Chayakorn; Tay, Hui Min; Tam, Zhi Yang; Dalan, Rinkoo; Chew, Daniel Ek Kwang; Li, King Ho Holden; Boehm, Bernhard O.

    2016-07-01

    Advanced management of dysmetabolic syndromes such as diabetes will benefit from a timely mechanistic insight enabling personalized medicine approaches. Herein, we present a rapid microfluidic neutrophil sorting and functional phenotyping strategy for type 2 diabetes mellitus (T2DM) patients using small blood volumes (fingerprick ~100 μL). The developed inertial microfluidics technology enables single-step neutrophil isolation (>90% purity) without immuno-labeling and sorted neutrophils are used to characterize their rolling behavior on E-selectin, a critical step in leukocyte recruitment during inflammation. The integrated microfluidics testing methodology facilitates high throughput single-cell quantification of neutrophil rolling to detect subtle differences in speed distribution. Higher rolling speed was observed in T2DM patients (P < 0.01) which strongly correlated with neutrophil activation, rolling ligand P-selectin glycoprotein ligand 1 (PSGL-1) expression, as well as established cardiovascular risk factors (cholesterol, high-sensitive C-reactive protein (CRP) and HbA1c). Rolling phenotype can be modulated by common disease risk modifiers (metformin and pravastatin). Receiver operating characteristics (ROC) and principal component analysis (PCA) revealed neutrophil rolling as an important functional phenotype in T2DM diagnostics. These results suggest a new point-of-care testing methodology, and neutrophil rolling speed as a functional biomarker for rapid profiling of dysmetabolic subjects in clinical and patient-oriented settings.

  15. Agarose-based microfluidic device for point-of-care concentration and detection of pathogen.

    Science.gov (United States)

    Li, Yiwei; Yan, Xinghua; Feng, Xiaojun; Wang, Jie; Du, Wei; Wang, Yachao; Chen, Peng; Xiong, Liang; Liu, Bi-Feng

    2014-11-04

    Preconcentration of pathogens from patient samples represents a great challenge in point-of-care (POC) diagnostics. Here, a low-cost, rapid, and portable agarose-based microfluidic device was developed to concentrate biological fluid from micro- to picoliter volume. The microfluidic concentrator consisted of a glass slide simply covered by an agarose layer with a binary tree-shaped microchannel, in which pathogens could be concentrated at the end of the microchannel due to the capillary effect and the strong water permeability of the agarose gel. The fluorescent Escherichia coli strain OP50 was used to demonstrate the capacity of the agarose-based device. Results showed that 90% recovery efficiency could be achieved with a million-fold volume reduction from 400 μL to 400 pL. For concentration of 1 × 10(3) cells mL(-1) bacteria, approximately ten million-fold enrichment in cell density was realized with volume reduction from 100 μL to 1.6 pL. Urine and blood plasma samples were further tested to validate the developed method. In conjugation with fluorescence immunoassay, we successfully applied the method to the concentration and detection of infectious Staphylococcus aureus in clinics. The agarose-based microfluidic concentrator provided an efficient approach for POC detection of pathogens.

  16. Rapid and label-free microfluidic neutrophil purification and phenotyping in diabetes mellitus

    Science.gov (United States)

    Hou, Han Wei; Petchakup, Chayakorn; Tay, Hui Min; Tam, Zhi Yang; Dalan, Rinkoo; Chew, Daniel Ek Kwang; Li, King Ho Holden; Boehm, Bernhard O.

    2016-01-01

    Advanced management of dysmetabolic syndromes such as diabetes will benefit from a timely mechanistic insight enabling personalized medicine approaches. Herein, we present a rapid microfluidic neutrophil sorting and functional phenotyping strategy for type 2 diabetes mellitus (T2DM) patients using small blood volumes (fingerprick ~100 μL). The developed inertial microfluidics technology enables single-step neutrophil isolation (>90% purity) without immuno-labeling and sorted neutrophils are used to characterize their rolling behavior on E-selectin, a critical step in leukocyte recruitment during inflammation. The integrated microfluidics testing methodology facilitates high throughput single-cell quantification of neutrophil rolling to detect subtle differences in speed distribution. Higher rolling speed was observed in T2DM patients (P < 0.01) which strongly correlated with neutrophil activation, rolling ligand P-selectin glycoprotein ligand 1 (PSGL-1) expression, as well as established cardiovascular risk factors (cholesterol, high-sensitive C-reactive protein (CRP) and HbA1c). Rolling phenotype can be modulated by common disease risk modifiers (metformin and pravastatin). Receiver operating characteristics (ROC) and principal component analysis (PCA) revealed neutrophil rolling as an important functional phenotype in T2DM diagnostics. These results suggest a new point-of-care testing methodology, and neutrophil rolling speed as a functional biomarker for rapid profiling of dysmetabolic subjects in clinical and patient-oriented settings. PMID:27381673

  17. Blood

    Science.gov (United States)

    ... Also, blood is either Rh-positive or Rh-negative. So if you have type A blood, it's either A positive or A negative. Which type you are is important if you need a blood transfusion. And your Rh factor could be important ...

  18. 基于惯性微流原理的微流控芯片用于血浆分离%Separation of blood plasma by inertial focusing using microfluidic chins

    Institute of Scientific and Technical Information of China (English)

    黄炜东; 张何; 徐涛; 李卓荣; 周雷激; 杨梦甦

    2011-01-01

    Blood plasma is widely used in clinical and biochemical tests, and techniques for plasma separation are essential for biomedical research. The technique of inertial microfluidics provides the capability to focus microparticles or cells in microchannels without the need for active device components. Based on the theory of inertial focusing, we designed and fabricated microfluidic chips with asymmetrically curved channels. Focusing performance was evaluated using homemade fluorescent microspheres as models. We found that the flow velocities required for maintenance of stable inertial focusing varied significantly among microspheres of different sizes. The microdevice was further employed for the separation of plasma from diluted blood samples. We achieved a 90% separation efficiency when the sample was separated twice in the device. These data suggest that microdevices can separate plasma efficiently without damaging blood cells, and can be readily integrated with other analytical devices.%血浆是临床生化检验中一类广泛使用的样品,从全血中分离血桨是生命医学研究领域中一项非常重要的技术.惯性微流(inertial microfluidics)原理的主要特点是无需施加任何外力如电磁力等,仅依靠液体流动就可以在微通道内实现一定尺寸的微粒或细胞的聚焦流动.本研究基于惯性微流原理,设计并制备了具有不对称弯管结构通道的微流控芯片.采用制备的荧光微球作为模型样品考察了装置的性能,发现尺寸越大的微球保持惯性聚集流动的流速范围也越大.在此基础上,利用发展的芯片平台成功实现从稀释的血液样品中将血浆分离.使用芯片对样品进行两次分离,即二级分离后,血液中血红细胞的分离效率超过9o%.该装置具有结构简单、体积小巧、操作方便等特点,不仅可以快速分离血浆,而且对血细胞基本无损,易于作为功能模块与现有的一些芯片实验室(lab on a chip,LOC)系统集成结合.

  19. Direct detection and drug-resistance profiling of bacteremias using inertial microfluidics.

    Science.gov (United States)

    Hou, Han Wei; Bhattacharyya, Roby P; Hung, Deborah T; Han, Jongyoon

    2015-05-21

    Detection of bacteria in bloodstream infections and their antibiotic susceptibility patterns is critical to guide therapeutic decision-making for optimal patient care. Current culture-based assays are too slow (>48 h), leading to excessive up-front use of broad-spectrum antibiotics and/or incorrect antibiotic choices due to resistant bacteria, each with deleterious consequences for patient care and public health. To approach this problem, we describe a method to rapidly isolate bacteria from whole blood using inertial microfluidics and directly determine pathogen identity and antibiotic susceptibility with hybridization-based RNA detection. Using the principle of Dean flow fractionation, bacteria are separated from host blood cells in a label-free separation method with efficient recovery of even low abundance bacteria. Ribosomal RNA detection can then be applied for direct identification of low abundance pathogens (~100 per mL) from blood without culturing or enzymatic amplification. Messenger RNA detection of antibiotic-responsive transcripts after brief drug exposure permits rapid susceptibility determination from bacteria with minimal culturing (~10(5) per mL). This unique coupling of microfluidic cell separation with RNA-based molecular detection techniques represents significant progress towards faster diagnostics (~8 hours) to guide antibiotic therapy.

  20. Predicting Droplet Formation on Centrifugal Microfluidic Platforms

    OpenAIRE

    Moebius, Jacob Alfred

    2015-01-01

    Centrifugal microfluidics is a widely known research tool for biological sample and water quality analysis. Currently, the standard equipment used for such diagnostic applications include slow, bulky machines controlled by multiple operators. These machines can be condensed into a smaller, faster benchtop sample-to-answer system.Sample processing is an important step taken to extract, isolate, and convert biological factors, such as nucleic acids or proteins, from a raw sample to an analyzabl...

  1. Pulse Arrival Time Based Cuff-Less and 24-H Wearable Blood Pressure Monitoring and its Diagnostic Value in Hypertension.

    Science.gov (United States)

    Zheng, Yali; Poon, Carmen C Y; Yan, Bryan P; Lau, James Y W

    2016-09-01

    Ambulatory blood pressure monitoring (ABPM) has become an essential tool in the diagnosis and management of hypertension. Current standard ABPM devices use an oscillometric cuff-based method which can cause physical discomfort to the patients with repeated inflations and deflations, especially during nighttime leading to sleep disturbance. The ability to measure ambulatory BP accurately and comfortably without a cuff would be attractive. This study validated the accuracy of a cuff-less approach for ABPM using pulse arrival time (PAT) measurements on both healthy and hypertensive subjects for potential use in hypertensive management, which is the first of its kind. The wearable cuff-less device was evaluated against a standard cuff-based device on 24 subjects of which 15 have known hypertension. BP measurements were taken from each subject over a 24-h period by the cuff-less and cuff-based devices every 15 to 30 minutes during daily activities. Mean BP of each subject during daytime, nighttime and over 24-h were calculated. Agreement between mean nighttime systolic BP (SBP) and diastolic (DBP) measured by the two devices evaluated using Bland-Altman plot were -1.4 ± 6.6 and 0.4 ± 6.7 mmHg, respectively. Receiver operator characteristics (ROC) statistics was used to assess the diagnostic accuracy of the cuff-less approach in the detection of BP above the hypertension threshold during nighttime (>120/70 mmHg). The area under ROC curves were 0.975/0.79 for nighttime. The results suggest that PAT-based approach is accurate and promising for ABPM without the issue of sleep disturbances associated with cuff-based devices.

  2. Full blood count and haemozoin-containing leukocytes in children with malaria: diagnostic value and association with disease severity

    Directory of Open Access Journals (Sweden)

    Lell Bertrand

    2008-06-01

    Full Text Available Abstract Background Diligent and correct laboratory diagnosis and up-front identification of risk factors for progression to severe disease are the basis for optimal management of malaria. Methods Febrile children presenting to the Medical Research Unit at the Albert Schweitzer Hospital (HAS in Lambaréné, Gabon, were assessed for malaria. Giemsa-stained thick films for qualitative and quantitative diagnosis and enumeration of malaria pigment, or haemozoin (Hz-containing leukocytes (PCL were performed, and full blood counts (FBC were generated with a Cell Dyn 3000® instrument. Results Compared to standard light microscopy of Giemsa-stained thick films, diagnosis by platelet count only, by malaria pigment-containing monocytes (PCM only, or by pigment-containing granulocytes (PCN only yielded sensitivities/specificities of 92%/93%; 96%/96%; and 85%/96%, respectively. The platelet count was significantly lower in children with malaria compared to those without (p ® instrument detected significantly more patients with PCL (p Conclusion In the age group examined in the Lambaréné area, platelets are an excellent adjuvant tool to diagnose malaria. Pigment-containing leukocytes (PCL are more readily detected by automated scatter flow cytometry than by microscopy. Automated Hz detection by an instrument as used here is a reliable diagnostic tool and correlates with disease severity. However, clinical usefulness as a prognostic tool is limited due to an overlap of PCL numbers recorded in severe versus non-severe malaria. However, this is possibly because of the instrument detection algorithm was not geared towards this task, and data lost during processing; and thus adjusting the instrument's algorithm may allow to establish a meaningful cut-off value.

  3. Improving the screening of blood donors with syphilis rapid diagnostic test (RDT) and rapid plasma reagin (RPR) in low- and middle-income countries (LMIC)

    DEFF Research Database (Denmark)

    Sarkodie, F.; Hassall, O.; Owusu-Dabo, E.

    2017-01-01

    BACKGROUND: Syphilis testing conventionally relies on a combination of non-treponemal and treponemal tests. The primary objective of this study was to describe the positive predictive value (PPV) of a screening algorithm in a combination of a treponemal rapid diagnostic test (RDT) and rapid plasm...... of blood donors by combining syphilis RDT and RPR with relatively good PPV may provide a reasonable technology for LMIC that has a limited capacity for testing and can contribute to the improvement of blood safety with a minimal loss of donors....

  4. Rapid detection of hemagglutination using restrictive microfluidic channels equipped with waveguide-mode sensors

    Science.gov (United States)

    Ashiba, Hiroki; Fujimaki, Makoto; Awazu, Koichi; Fu, Mengying; Ohki, Yoshimichi; Tanaka, Torahiko; Makishima, Makoto

    2016-02-01

    Hemagglutination is utilized for various immunological assays, including blood typing and virus detection. Herein, we describe a method of rapid hemagglutination detection based on a microfluidic channel installed on an optical waveguide-mode sensor. Human blood samples mixed with hemagglutinating antibodies associated with different blood groups were injected into the microfluidic channel, and reflectance spectra of the samples were measured after stopping the flow. The agglutinated and nonagglutinated samples were distinguishable by the alterations in their reflectance spectra with time; the microfluidic channels worked as spatial restraints for agglutinated red blood cells. The demonstrated system allowed rapid hemagglutination detection within 1 min. The suitable height of the channels was also discussed.

  5. Measuring Post-Partum Haemorrhage in Low-Resource Settings: The Diagnostic Validity of Weighed Blood Loss versus Quantitative Changes in Hemoglobin.

    Directory of Open Access Journals (Sweden)

    Esther Cathyln Atukunda

    Full Text Available Accurate estimation of blood loss is central to prompt diagnosis and management of post-partum hemorrhage (PPH, which remains a leading cause of maternal mortality in low-resource countries. In such settings, blood loss is often estimated visually and subjectively by attending health workers, due to inconsistent availability of laboratory infrastructure. We evaluated the diagnostic accuracy of weighed blood loss (WBL versus changes in peri-partum hemoglobin to detect PPH.Data from this analysis were collected as part of a randomized controlled trial comparing oxytocin with misoprostol for PPH (NCT01866241. Blood samples for complete blood count were drawn on admission and again prior to hospital discharge or before blood transfusion. During delivery, women were placed on drapes and had pre-weighed sanitary towels placed around their perineum. Blood was then drained into a calibrated container and the sanitary towels were added to estimate WBL, where each gram of blood was estimated as a milliliter. Sensitivity, specificity, negative and positive predictive values (PPVs were calculated at various blood volume loss and time combinations, and we fit receiver-operator curves using blood loss at 1, 2, and 24 hours compared to a reference standard of haemoglobin decrease of >10%.A total of 1,140 women were enrolled in the study, of whom 258 (22.6% developed PPH, defined as a haemoglobin drop >10%, and 262 (23.0% had WBL ≥500mL. WBL generally had a poor sensitivity for detection of PPH (85% in high prevalence settings when WBL exceeds 750mL.WBL has poor sensitivity but high specificity compared to laboratory-based methods of PPH diagnosis. These characteristics correspond to a high PPV in areas with high PPH prevalence. Although WBL is not useful for excluding PPH, this low-cost, simple and reproducible method is promising as a reasonable method to identify significant PPH in such settings where quantifiable red cell indices are unavailable.

  6. Nanomaterials meet microfluidics.

    Science.gov (United States)

    Pumera, Martin

    2011-05-28

    Nanomaterials and lab-on-a-chip platforms have undergone enormous development during the past decade. Here, we present an overview of how microfluidics benefited from the use of nanomaterials for the enhanced separation and detection of analytes. We also discuss how nanomaterials benefit from microfluidics in terms of synthesis and in terms of the simulation of environments for nanomotors and nanorobots. In our opinion, the "marriage" of nanomaterials and microfluidics is highly beneficial and is expected to solve vital challenges in related fields.

  7. Opto-Microfluidic Immunosensors: From Colorimetric to Plasmonic

    Directory of Open Access Journals (Sweden)

    Jie-Long He

    2016-02-01

    Full Text Available Optical detection has long been the most popular technique in immunosensing. Recent developments in the synthesis of luminescent probes and the fabrication of novel nanostructures enable more sensitive and efficient optical detection, which can be miniaturized and integrated with microfluidics to realize compact lab-on-a-chip immunosensors. These immunosensors are portable, economical and automated, but their sensitivity is not compromised. This review focuses on the incorporation and implementation of optical detection and microfluidics in immunosensors; it introduces the working principles of each optical detection technique and how it can be exploited in immunosensing. The recent progress in various opto-microfluidic immunosensor designs is described. Instead of being comprehensive to include all opto-microfluidic platforms, the report centers on the designs that are promising for point-of-care immunosensing diagnostics, in which ease of use, stability and cost-effective fabrication are emphasized.

  8. Compact and controlled microfluidic mixing and biological particle capture

    Science.gov (United States)

    Ballard, Matthew; Owen, Drew; Mills, Zachary Grant; Hesketh, Peter J.; Alexeev, Alexander

    2016-11-01

    We use three-dimensional simulations and experiments to develop a multifunctional microfluidic device that performs rapid and controllable microfluidic mixing and specific particle capture. Our device uses a compact microfluidic channel decorated with magnetic features. A rotating magnetic field precisely controls individual magnetic microbeads orbiting around the features, enabling effective continuous-flow mixing of fluid streams over a compact mixing region. We use computer simulations to elucidate the underlying physical mechanisms that lead to effective mixing and compare them with experimental mixing results. We study the effect of various system parameters on microfluidic mixing to design an efficient micromixer. We also experimentally and numerically demonstrate that orbiting microbeads can effectively capture particles transported by the fluid, which has major implications in pre-concentration and detection of biological particles including various cells and bacteria, with applications in areas such as point-of-care diagnostics, biohazard detection, and food safety. Support from NSF and USDA is gratefully acknowledged.

  9. Centrifugal microfluidic platforms: advanced unit operations and applications.

    Science.gov (United States)

    Strohmeier, O; Keller, M; Schwemmer, F; Zehnle, S; Mark, D; von Stetten, F; Zengerle, R; Paust, N

    2015-10-01

    Centrifugal microfluidics has evolved into a mature technology. Several major diagnostic companies either have products on the market or are currently evaluating centrifugal microfluidics for product development. The fields of application are widespread and include clinical chemistry, immunodiagnostics and protein analysis, cell handling, molecular diagnostics, as well as food, water, and soil analysis. Nevertheless, new fluidic functions and applications that expand the possibilities of centrifugal microfluidics are being introduced at a high pace. In this review, we first present an up-to-date comprehensive overview of centrifugal microfluidic unit operations. Then, we introduce the term "process chain" to review how these unit operations can be combined for the automation of laboratory workflows. Such aggregation of basic functionalities enables efficient fluidic design at a higher level of integration. Furthermore, we analyze how novel, ground-breaking unit operations may foster the integration of more complex applications. Among these are the storage of pneumatic energy to realize complex switching sequences or to pump liquids radially inward, as well as the complete pre-storage and release of reagents. In this context, centrifugal microfluidics provides major advantages over other microfluidic actuation principles: the pulse-free inertial liquid propulsion provided by centrifugal microfluidics allows for closed fluidic systems that are free of any interfaces to external pumps. Processed volumes are easily scalable from nanoliters to milliliters. Volume forces can be adjusted by rotation and thus, even for very small volumes, surface forces may easily be overcome in the centrifugal gravity field which enables the efficient separation of nanoliter volumes from channels, chambers or sensor matrixes as well as the removal of any disturbing bubbles. In summary, centrifugal microfluidics takes advantage of a comprehensive set of fluidic unit operations such as

  10. Microfluidic chemical reaction circuits

    Science.gov (United States)

    Lee, Chung-cheng; Sui, Guodong; Elizarov, Arkadij; Kolb, Hartmuth C.; Huang, Jiang; Heath, James R.; Phelps, Michael E.; Quake, Stephen R.; Tseng, Hsian-rong; Wyatt, Paul; Daridon, Antoine

    2012-06-26

    New microfluidic devices, useful for carrying out chemical reactions, are provided. The devices are adapted for on-chip solvent exchange, chemical processes requiring multiple chemical reactions, and rapid concentration of reagents.

  11. Microfluidics in inorganic chemistry.

    Science.gov (United States)

    Abou-Hassan, Ali; Sandre, Olivier; Cabuil, Valérie

    2010-08-23

    The application of microfluidics in chemistry has gained significant importance in the recent years. Miniaturized chemistry platforms provide controlled fluid transport, rapid chemical reactions, and cost-saving advantages over conventional reactors. The advantages of microfluidics have been clearly established in the field of analytical and bioanalytical sciences and in the field of organic synthesis. It is less true in the field of inorganic chemistry and materials science; however in inorganic chemistry it has mostly been used for the separation and selective extraction of metal ions. Microfluidics has been used in materials science mainly for the improvement of nanoparticle synthesis, namely metal, metal oxide, and semiconductor nanoparticles. Microfluidic devices can also be used for the formulation of more advanced and sophisticated inorganic materials or hybrids.

  12. Microfluidic Bead Suspension Hopper

    OpenAIRE

    Price, Alexander K.; MacConnell, Andrew B.; Paegel, Brian M.

    2014-01-01

    Many high-throughput analytical platforms, from next-generation DNA sequencing to drug discovery, rely on beads as carriers of molecular diversity. Microfluidic systems are ideally suited to handle and analyze such bead libraries with high precision and at minute volume scales; however, the challenge of introducing bead suspensions into devices before they sediment usually confounds microfluidic handling and analysis. We developed a bead suspension hopper that exploits sedimentation to load b...

  13. Synthetic microfluidic paper: high surface area and high porosity polymer micropillar arrays.

    Science.gov (United States)

    Hansson, Jonas; Yasuga, Hiroki; Haraldsson, Tommy; van der Wijngaart, Wouter

    2016-01-21

    We introduce Synthetic Microfluidic Paper, a novel porous material for microfluidic applications that consists of an OSTE polymer that is photostructured in a well-controlled geometry of slanted and interlocked micropillars. We demonstrate the distinct benefits of Synthetic Microfluidic Paper over other porous microfluidic materials, such as nitrocellulose, traditional paper and straight micropillar arrays: in contrast to straight micropillar arrays, the geometry of Synthetic Microfluidic Paper was miniaturized without suffering capillary collapse during manufacturing and fluidic operation, resulting in a six-fold increased internal surface area and a three-fold increased porous fraction. Compared to commercial nitrocellulose materials for capillary assays, Synthetic Microfluidic Paper shows a wider range of capillary pumping speed and four times lower device-to-device variation. Compared to the surfaces of the other porous microfluidic materials that are modified by adsorption, Synthetic Microfluidic Paper contains free thiol groups and has been shown to be suitable for covalent surface chemistry, demonstrated here for increasing the material hydrophilicity. These results illustrate the potential of Synthetic Microfluidic Paper as a porous microfluidic material with improved performance characteristics, especially for bioassay applications such as diagnostic tests.

  14. MEMS in microfluidic channels.

    Energy Technology Data Exchange (ETDEWEB)

    Ashby, Carol Iris Hill; Okandan, Murat; Michalske, Terry A.; Sounart, Thomas L.; Matzke, Carolyn M.

    2004-03-01

    Microelectromechanical systems (MEMS) comprise a new class of devices that include various forms of sensors and actuators. Recent studies have shown that microscale cantilever structures are able to detect a wide range of chemicals, biomolecules or even single bacterial cells. In this approach, cantilever deflection replaces optical fluorescence detection thereby eliminating complex chemical tagging steps that are difficult to achieve with chip-based architectures. A key challenge to utilizing this new detection scheme is the incorporation of functionalized MEMS structures within complex microfluidic channel architectures. The ability to accomplish this integration is currently limited by the processing approaches used to seal lids on pre-etched microfluidic channels. This report describes Sandia's first construction of MEMS instrumented microfluidic chips, which were fabricated by combining our leading capabilities in MEMS processing with our low-temperature photolithographic method for fabricating microfluidic channels. We have explored in-situ cantilevers and other similar passive MEMS devices as a new approach to directly sense fluid transport, and have successfully monitored local flow rates and viscosities within microfluidic channels. Actuated MEMS structures have also been incorporated into microfluidic channels, and the electrical requirements for actuation in liquids have been quantified with an elegant theory. Electrostatic actuation in water has been accomplished, and a novel technique for monitoring local electrical conductivities has been invented.

  15. On-chip Extraction of Intracellular Molecules in White Blood Cells from Whole Blood.

    Science.gov (United States)

    Choi, Jongchan; Hyun, Ji-chul; Yang, Sung

    2015-10-14

    The extraction of virological markers in white blood cells (WBCs) from whole blood--without reagents, electricity, or instruments--is the most important first step for diagnostic testing of infectious diseases in resource-limited settings. Here we develop an integrated microfluidic chip that continuously separates WBCs from whole blood and mechanically ruptures them to extract intracellular proteins and nucleic acids for diagnostic purposes. The integrated chip is assembled with a device that separates WBCs by using differences in blood cell size and a mechanical cell lysis chip with ultra-sharp nanoblade arrays. We demonstrate the performance of the integrated device by quantitatively analyzing the levels of extracted intracellular proteins and genomic DNAs. Our results show that compared with a conventional method, the device yields 120% higher level of total protein amount and similar levels of gDNA (90.3%). To demonstrate its clinical application to human immunodeficiency virus (HIV) diagnostics, the developed chip was used to process blood samples containing HIV-infected cells. Based on PCR results, we demonstrate that the chip can extract HIV proviral DNAs from infected cells with a population as low as 10(2)/μl. These findings suggest that the developed device has potential application in point-of-care testing for infectious diseases in developing countries.

  16. Isolation of cancer cells by "in situ" microfluidic biofunctionalization protocols

    DEFF Research Database (Denmark)

    De Vitis, Stefania; Matarise, Giuseppina; Pardeo, Francesca

    2014-01-01

    The aim of this work is the development of a microfluidic immunosensor for the immobilization of cancer cells and their separation from healthy cells by using "in situ" microfluidic biofunctionalization protocols. These protocols allow to link antibodies on microfluidic device surfaces and can...... for the isolation of cancer cells in heterogeneous blood samples by exploiting the binding of specific antibody to an adhesion protein (EpCAM), overexpressed on the tumor cell membranes. The presented biofunctionalization protocols can be performed right before running the experiment: this allows to have a flexible...... be used to study the interaction between cell membrane and biomolecules. Moreover they allow to perform analysis with high processing speed, small quantity of reagents and samples, short reaction times and low production costs. In this work the developed protocols were used in microfluidic devices...

  17. Microfluidic bioreactors for culture of non-adherent cells

    DEFF Research Database (Denmark)

    Shah, Pranjul Jaykumar; Vedarethinam, Indumathi; Kwasny, Dorota

    2011-01-01

    Microfluidic bioreactors (μBR) are becoming increasingly popular for cell culture, sample preparation and analysis in case of routine genetic and clinical diagnostics. We present a novel μBR for non-adherent cells designed to mimic in vivo perfusion of cells based on diffusion of media through...

  18. Impact of the phlebotomy training based on CLSI/NCCLS H03-A6 - procedures for the collection of diagnostic blood specimens by venipuncture.

    Science.gov (United States)

    Lima-Oliveira, Gabriel; Lippi, Giuseppe; Salvagno, Gian Luca; Montagnana, Martina; Picheth, Geraldo; Guidi, Gian Cesare

    2012-01-01

    Introduction: The activities involving phlebotomy, a critical task for obtaining diagnostic blood samples, are poorly studied as regards the major sources of errors and the procedures related to laboratory quality control. The aim of this study was to verify the compliance with CLSI documents of clinical laboratories from South America and to assess whether teaching phlebotomists to follow the exact procedure for blood collection by venipuncture from CLSI/NCCLS H03-A6 - Procedures for the Collection of Diagnostic Blood Specimens by Venipuncture might improve the quality of the process. Materials and methods: A survey was sent by mail to 3674 laboratories from South America to verify the use of CLSI documents. Thirty skilled phlebotomists were trained with the CLSI H03-A6 document to perform venipuncture procedures for a period of 20 consecutive working days. The overall performances of the phlebotomists were further compared before and after the training program. Results: 2622 from 2781 laboratories that did answer our survey used CLSI documents to standardize their procedures and process. The phlebotomists’ training for 20 days before our evaluation completely eliminated non-conformity procedures for: i) incorrect friction of the forearm, during the cleaning of the venipuncture site to ease vein location; ii) incorrect sequence of vacuum tubes collection; and iii) inadequate mixing of the blood in primary vacuum tubes containing anticoagulants or clot activators. Unfortunately the CLSI H03-A6 document does not caution against both unsuitable tourniquet application time (i.e., for more than one minute) and inappropriate request to clench the fist repeatedly. These inadequate procedures were observed for all phlebotomists. Conclusion: We showed that strict observance of the CLSI H03-A6 document can remarkably improve quality, although the various steps for collecting diagnostic blood specimens are not a gold standard, since they may still permit errors. Tourniquet

  19. Liquid metal enabled microfluidics.

    Science.gov (United States)

    Khoshmanesh, Khashayar; Tang, Shi-Yang; Zhu, Jiu Yang; Schaefer, Samira; Mitchell, Arnan; Kalantar-Zadeh, Kourosh; Dickey, Michael D

    2017-03-14

    Several gallium-based liquid metal alloys are liquid at room temperature. As 'liquid', such alloys have a low viscosity and a high surface tension while as 'metal', they have high thermal and electrical conductivities, similar to mercury. However, unlike mercury, these liquid metal alloys have low toxicity and a negligible vapor pressure, rendering them much safer. In comparison to mercury, the distinguishing feature of these alloys is the rapid formation of a self-limiting atomically thin layer of gallium oxide over their surface when exposed to oxygen. This oxide layer changes many physical and chemical properties of gallium alloys, including their interfacial and rheological properties, which can be employed and modulated for various applications in microfluidics. Injecting liquid metal into microfluidic structures has been extensively used to pattern and encapsulate highly deformable and reconfigurable electronic devices including electrodes, sensors, antennas, and interconnects. Likewise, the unique features of liquid metals have been employed for fabricating miniaturized microfluidic components including pumps, valves, heaters, and electrodes. In this review, we discuss liquid metal enabled microfluidic components, and highlight their desirable attributes including simple fabrication, facile integration, stretchability, reconfigurability, and low power consumption, with promising applications for highly integrated microfluidic systems.

  20. Complex polarization-phase and spatial-frequency selections of laser images of blood-plasma films in diagnostics of changes in their polycrystalline structure

    Science.gov (United States)

    Ushenko, Yu. A.; Angelskii, P. O.; Dubolazov, A. V.; Karachevtsev, A. O.; Sidor, M. I.; Mintser, O. P.; Oleinichenko, B. P.; Bizer, L. I.

    2013-10-01

    We present a theoretical formalism of correlation phase analysis of laser images of human blood plasma with spatial-frequency selection of manifestations of mechanisms of linear and circular birefringence of albumin and globulin polycrystalline networks. Comparative results of the measurement of coordinate distributions of the correlation parameter—the modulus of the degree of local correlation of amplitudes—of laser images of blood plasma taken from patients of three groups—healthy patients (donors), rheumatoid-arthritis patients, and breast-cancer patients—are presented. We investigate values and ranges of change of statistical (the first to fourth statistical moments), correlation (excess of autocorrelation functions), and fractal (slopes of approximating curves and dispersion of extrema of logarithmic dependences of power spectra) parameters of coordinate distributions of the degree of local correlation of amplitudes. Objective criteria for diagnostics of occurrence and differentiation of inflammatory and oncological states are determined.

  1. Performing diagnostics, especially blood cultures, on-time for infectious patients reduces length of stay and costs

    NARCIS (Netherlands)

    Dik, JH; Lo Ten Foe, J. R.; Sinha, B; Nannan Panday, P; Hendrix, R; Postma, MJ; Friedrich, AW

    2015-01-01

    Objectives As an academic center, the University Medical Center Groningen in the Netherlands receives large numbers of patients with (complex) infectious problems. It is imperative that the correct diagnostics are performed on time for these patients in order to correctly diagnose them and treat the

  2. Microfluidics as a functional tool for cell mechanics.

    Science.gov (United States)

    Vanapalli, Siva A; Duits, Michel H G; Mugele, Frieder

    2009-01-05

    Living cells are a fascinating demonstration of nature's most intricate and well-coordinated micromechanical objects. They crawl, spread, contract, and relax-thus performing a multitude of complex mechanical functions. Alternatively, they also respond to physical and chemical cues that lead to remodeling of the cytoskeleton. To understand this intricate coupling between mechanical properties, mechanical function and force-induced biochemical signaling requires tools that are capable of both controlling and manipulating the cell microenvironment and measuring the resulting mechanical response. In this review, the power of microfluidics as a functional tool for research in cell mechanics is highlighted. In particular, current literature is discussed to show that microfluidics powered by soft lithographic techniques offers the following capabilities that are of significance for understanding the mechanical behavior of cells: (i) Microfluidics enables the creation of in vitro models of physiological environments in which cell mechanics can be probed. (ii) Microfluidics is an excellent means to deliver physical cues that affect cell mechanics, such as cell shape, fluid flow, substrate topography, and stiffness. (iii) Microfluidics can also expose cells to chemical cues, such as growth factors and drugs, which alter their mechanical behavior. Moreover, these chemical cues can be delivered either at the whole cell or subcellular level. (iv) Microfluidic devices offer the possibility of measuring the intrinsic mechanical properties of cells in a high throughput fashion. (v) Finally, microfluidic methods provide exquisite control over drop size, generation, and manipulation. As a result, droplets are being increasingly used to control the physicochemical environment of cells and as biomimetic analogs of living cells. These powerful attributes of microfluidics should further stimulate novel means of investigating the link between physicochemical cues and the biomechanical

  3. Array CGH on unstimulated blood does not detect all cases of Pallister-Killian syndrome: a skin biopsy should remain the diagnostic gold standard.

    Science.gov (United States)

    Hodge, Jennelle C; Hulshizer, Rachael L; Seger, Pam; St Antoine, Angelique; Bair, Jennifer; Kirmani, Salman

    2012-03-01

    A child whose features are consistent with Pallister-Killian syndrome (PKS) did not have detectable tetrasomy 12p due to an additional isochromosome 12p in an unstimulated blood specimen by interphase FISH or array CGH analysis. The diagnosis of PKS was made through these methods solely in a skin biopsy specimen. To determine the sensitivity of our array CGH platform to tetrasomy 12p mosaicism, dilutions of DNA from both the child's skin fibroblasts and a PKS cell line were analyzed. Tetrasomy 12p at 10% mosaicism was identifiable but 5% was below the limit of detection. This result suggests through extrapolation that the tetrasomy 12p is present in <10% of cells in our patient's blood, confirming the tissue-limited mosaicism of PKS. Multiple recent studies show that array CGH provides greater sensitivity than chromosome analysis to detect mosaic abnormalities including that of tetrasomy 12p in blood specimens. However, our case demonstrates that the biology of PKS precludes the exclusive use of array CGH on blood for diagnosis. A tissue sample should continue to be the diagnostic gold standard for PKS.

  4. Microfluidic Flame Barrier

    Science.gov (United States)

    Mungas, Gregory S. (Inventor); Fisher, David J. (Inventor); Mungas, Christopher (Inventor)

    2013-01-01

    Propellants flow through specialized mechanical hardware that is designed for effective and safe ignition and sustained combustion of the propellants. By integrating a micro-fluidic porous media element between a propellant feed source and the combustion chamber, an effective and reliable propellant injector head may be implemented that is capable of withstanding transient combustion and detonation waves that commonly occur during an ignition event. The micro-fluidic porous media element is of specified porosity or porosity gradient selected to be appropriate for a given propellant. Additionally the propellant injector head design integrates a spark ignition mechanism that withstands extremely hot running conditions without noticeable spark mechanism degradation.

  5. A microfluidic chip for ICPMS sample introduction.

    Science.gov (United States)

    Verboket, Pascal E; Borovinskaya, Olga; Meyer, Nicole; Günther, Detlef; Dittrich, Petra S

    2015-03-05

    This protocol discusses the fabrication and usage of a disposable low cost microfluidic chip as sample introduction system for inductively coupled plasma mass spectrometry (ICPMS). The chip produces monodisperse aqueous sample droplets in perfluorohexane (PFH). Size and frequency of the aqueous droplets can be varied in the range of 40 to 60 µm and from 90 to 7,000 Hz, respectively. The droplets are ejected from the chip with a second flow of PFH and remain intact during the ejection. A custom-built desolvation system removes the PFH and transports the droplets into the ICPMS. Here, very stable signals with a narrow intensity distribution can be measured, showing the monodispersity of the droplets. We show that the introduction system can be used to quantitatively determine iron in single bovine red blood cells. In the future, the capabilities of the introduction device can easily be extended by the integration of additional microfluidic modules.

  6. Analysis of Hemoglobin Glycation Using Microfluidic CE-MS: A Rapid, Mass Spectrometry Compatible Method for Assessing Diabetes Management.

    Science.gov (United States)

    Redman, Erin A; Ramos-Payan, Maria; Mellors, J Scott; Ramsey, J Michael

    2016-05-17

    Diabetes has become a significant health problem worldwide with the rate of diagnosis increasing rapidly in recent years. Measurement of glycated blood proteins, particularly glycated hemoglobin (HbA1c), is an important diagnostic tool used to detect and manage the condition in patients. Described here is a method using microfluidic capillary electrophoresis with mass spectrometry detection (CE-MS) to assess hemoglobin glycation in whole blood lysate. Using denaturing conditions, the hemoglobin (Hb) tetramer dissociates into the alpha and beta subunits (α- and β-Hb), which are then separated via CE directly coupled to MS detection. Nearly baseline resolution is achieved between α-Hb, β-Hb, and glycated β-Hb. A second glycated β-Hb isomer that is partially resolved from β-Hb is detected in extracted ion electropherograms for glycated β-Hb. Glycation on α-Hb is also detected in the α-Hb mass spectrum. Additional modifications to the β-Hb are detected, including acetylation and a +57 Da species that could be the addition of a glyoxal moiety. Patient blood samples were analyzed using the microfluidic CE-MS method and a clinically used immunoassay to measure HbA1c. The percentage of glycated α-Hb and β-Hb was calculated from the microfluidic CE-MS data using peak areas generated from extracted ion electropherograms. The values for glycated β-Hb were found to correlate well with the HbA1c levels derived in the clinic, giving a slope of 1.20 and an R(2) value of 0.99 on a correlation plot. Glycation of human serum albumin (HSA) can also be measured using this technique. It was observed that patients with elevated glycated Hb levels also had higher levels of HSA glycation. Interestingly, the sample with the highest HbA1c levels did not have the highest levels of glycated HSA. Because the lifetime of HSA is shorter than Hb, this could indicate a recent lapse in glycemic control for that patient. The ability to assess both Hb and HSA glycation has the potential

  7. Blood plasma separation in a long two-phase plug flowing through disposable tubing.

    Science.gov (United States)

    Sun, Meng; Khan, Zeina S; Vanapalli, Siva A

    2012-12-21

    We report a simple technique to separate plasma from blood in a flowing immiscible plug. We investigate the effect of various control parameters such as blood dilution, injection flow rate, observation time and fluid properties on plasma separation. We find that the technique works best for diluted blood samples at low plug velocities and long observation times. We postulate that the main mechanism responsible for efficient separation is the sedimentation of blood cells in the plug and their subsequent collection by the moving plug causing a significant accumulation of cells at the rear of the plug. We discuss the time scales determining the sedimentation, advection and collection of a blood cell in the immiscible plug and propose a phase diagram that is able to predict the operating space for effective plasma separation. We demonstrate that the technique allows for the extraction of more than 60% of the plasma by volume from 1 μL of diluted blood. We show the practical significance of this method by compartmentalizing the separated plasma into discrete microfluidic droplets and detecting cholesterol. This technique features low consumption of blood (nL-scale) and low shear rate (∼1 s(-1)). It is inexpensive, easy to use, and has the potential to be developed as an efficient point-of-care device for blood diagnostics in resource-poor environments. More advanced applications could also be envisioned by integrating our plasma separation method into existing microfluidic drop manipulation techniques.

  8. Comparison of venous and capillary differential leukocyte counts using a standard hematology analyzer and a novel microfluidic impedance cytometer.

    Science.gov (United States)

    Hollis, Veronica S; Holloway, Judith A; Harris, Scott; Spencer, Daniel; van Berkel, Cees; Morgan, Hywel

    2012-01-01

    Capillary blood sampling has been identified as a potentially suitable technique for use in diagnostic testing of the full blood count (FBC) at the point-of-care (POC), for which a recent need has been highlighted. In this study we assess the accuracy of capillary blood counts and evaluate the potential of a miniaturized cytometer developed for POC testing. Differential leukocyte counts in the normal clinical range from fingerprick (capillary) and venous blood samples were measured and compared using a standard hematology analyzer. The accuracy of our novel microfluidic impedance cytometer (MIC) was then tested by comparing same-site measurements to those obtained with the standard analyzer. The concordance between measurements of fingerprick and venous blood samples using the standard hematology analyzer was high, with no clinically relevant differences observed between the mean differential leukocyte counts. Concordance data between the MIC and the standard analyzer on same-site measurements presented significantly lower leukocyte counts determined by the MIC. This systematic undercount was consistent across the measured (normal) concentration range, suggesting that an internal correction factor could be applied. Differential leukocyte counts obtained from fingerprick samples accurately reflect those from venous blood, which confirms the potential of capillary blood sampling for POC testing of the FBC. Furthermore, the MIC device demonstrated here presents a realistic technology for the future development of FBC and related tests for use at the site of patient care.

  9. Microfluidic immunosensor for rapid and highly-sensitive salivary cortisol quantification.

    Science.gov (United States)

    Pinto, V; Sousa, P; Catarino, S O; Correia-Neves, M; Minas, G

    2017-04-15

    This paper presents a novel poly(dimethylsiloxane) (PDMS) microfluidic immunosensor that integrates a complementary metal-oxide-semiconductor (CMOS) optical detection system for a rapid and highly-sensitive quantification of salivary cortisol. The simple and non-invasive method of saliva sampling provides an interesting alternative to the blood, allowing a fast sampling at short intervals, relevant for many clinical diagnostic applications. The developed approach is based on the covalent immobilization of a coating antibody (Ab), a polyclonal anti-IgG, onto a treated PDMS surface. The coating Ab binds the capture Ab, an IgG specific for cortisol, allowing its correct orientation. Horseradish peroxidase (HRP)-labelled cortisol is added to compete with the cortisol in the sample, for the capture Ab binding sites. The HRP-labelled cortisol, bonded to the capture Ab, is measured through the HRP enzyme and the tetramethylbenzidine (TMB) substrate reaction. The cortisol quantification is performed by colorimetric detection of HRP-labelled cortisol, through optical absorption at 450nm, using a CMOS silicon photodiode as the photodetector. Under the developed optimized conditions presented here, e.g., microfluidic channels geometry, immobilization method and immunoassay conditions, the immunosensor shows a linear range of detection between 0.01-20ng/mL, a limit of detection (LOD) of 18pg/mL and an analysis time of 35min, featuring a great potential for point-of-care applications requiring continuous monitoring of the salivary cortisol levels during a circadian cycle.

  10. Chemistry in Microfluidic Channels

    Science.gov (United States)

    Chia, Matthew C.; Sweeney, Christina M.; Odom, Teri W.

    2011-01-01

    General chemistry introduces principles such as acid-base chemistry, mixing, and precipitation that are usually demonstrated in bulk solutions. In this laboratory experiment, we describe how chemical reactions can be performed in a microfluidic channel to show advanced concepts such as laminar fluid flow and controlled precipitation. Three sets of…

  11. Surfactants in microfluidics

    NARCIS (Netherlands)

    Michler, D.

    2015-01-01

    The rapid development of microfluidic techniques in the last two decades has revolutionized chemical and biological research. This technology has enabled scientists in a manifold of research fields to analyze and synthesize specimens with hither to unreached speed and precision. The number of applic

  12. Basic Microfluidics Theory

    DEFF Research Database (Denmark)

    Svendsen, Winnie Edith

    2015-01-01

    ,000 m−1, which is a huge difference and has a large impact on flow behavior. In this chapter the basic microfluidic theory will be presented, enabling the reader to gain a comprehensive understanding of how liquids behave at the microscale, enough to be able to engage in design of micro systems...

  13. Enzyme detection by microfluidics

    DEFF Research Database (Denmark)

    2013-01-01

    Microfluidic-implemented methods of detecting an enzyme, in particular a DNA-modifying enzyme, are provided, as well as methods for detecting a cell, or a microorganism expressing said enzyme. The enzyme is detected by providing a nucleic acid substrate, which is specifically targeted...... by that enzyme...

  14. DESIGN AND CONSTRUCTION OF A LAB-ON-A-PAPER FOR LOW-COST AND DISPOSABLE POINT-OF CARE DIAGNOSTICS

    Directory of Open Access Journals (Sweden)

    Afnidar Afnidar

    2017-01-01

      This paper presents a low-cost and disposable paper based microfluidic analysis system for point-of-care diagnostics. Detection is achieved by using a colorimetric or visual indicator. Immobilized specific reagent or enzymes designed for the parameter under consideration act as capture molecules on the surface of the detection zone. The sensor is integrated into a microfluidic system made of paper (cellulose. An additional component of the analysis system is a capillary unit which is used to introduce the analyte to the detection zone. For this purpose well- defined, millimeter-sized channel, comprising hydrophobic polymer bounded onto hydrophilic paper was created. Then the detection zone was coated with a sensitive reagent layer as a sensor region. The paper based microfluidics also called lab on paper, has been fabricated using screen printing technology as the basis for low-cost, disposable, portable and technically simple fabrication for mass production. Microfluidics in paper make it feasible to run single, dual or even multiple clinical analyses on one strip of paper while still using only small volumes of a single sample. The capability of lab on paper for detection of importance clinical analyte protein in urine, saliva and blood samples has been demonstrate successfully. Lab on paper as a diagnostic system is small, disposable, and easy to use and requires no external equipment, reagents, or power sources. This kind of diagnostic system is attractive for use in developing countries, in the field, or as a low-cost alternative to more-advanced technologies already used in clinical diagnostics.   Keywords: Lab-on-a-paper, Point-of-care, Visual detection, Clinical diagnostic, Disposable sensor

  15. Flexible packaging of solid-state integrated circuit chips with elastomeric microfluidics

    Science.gov (United States)

    Zhang, Bowei; Dong, Quan; Korman, Can E.; Li, Zhenyu; Zaghloul, Mona E.

    2013-01-01

    A flexible technology is proposed to integrate smart electronics and microfluidics all embedded in an elastomer package. The microfluidic channels are used to deliver both liquid samples and liquid metals to the integrated circuits (ICs). The liquid metals are used to realize electrical interconnects to the IC chip. This avoids the traditional IC packaging challenges, such as wire-bonding and flip-chip bonding, which are not compatible with current microfluidic technologies. As a demonstration we integrated a CMOS magnetic sensor chip and associate microfluidic channels on a polydimethylsiloxane (PDMS) substrate that allows precise delivery of small liquid samples to the sensor. Furthermore, the packaged system is fully functional under bending curvature radius of one centimetre and uniaxial strain of 15%. The flexible integration of solid-state ICs with microfluidics enables compact flexible electronic and lab-on-a-chip systems, which hold great potential for wearable health monitoring, point-of-care diagnostics and environmental sensing among many other applications.

  16. Thirty years of research on diagnostic and therapeutic thresholds for the self-measured blood pressure at home.

    NARCIS (Netherlands)

    Staessen, J.A.; Thijs, L.; Ohkubo, T.; Kikuya, M.; Richart, T.; Boggia, J.; Adiyaman, A.; Dechering, D.G.; Kuznetsova, T.; Thien, Th.; Leeuw, P de; Imai, Y.; O'brien, E.; Parati, G.

    2008-01-01

    OBJECTIVE: The goal of this review study is to summarize 30 years of research on cut-off limits for the self-measured blood pressure. METHODS: We reviewed two meta-analyses, several prospective outcome studies in populations and hypertensive patients, studies in pregnant women, three clinical trials

  17. 3D origami-based multifunction-integrated immunodevice: low-cost and multiplexed sandwich chemiluminescence immunoassay on microfluidic paper-based analytical device.

    Science.gov (United States)

    Ge, Lei; Wang, Shoumei; Song, Xianrang; Ge, Shenguang; Yu, Jinghua

    2012-09-07

    A novel 3D microfluidic paper-based immunodevice, integrated with blood plasma separation from whole blood samples, automation of rinse steps, and multiplexed CL detections, was developed for the first time based on the principle of origami (denoted as origami-based device). This 3D origami-based device, comprised of one test pad surrounded by four folding tabs, could be patterned and fabricated by wax-printing on paper in bulk. In this work, a sandwich-type chemiluminescence (CL) immunoassay was introduced into this 3D origami-based immunodevice, which could separate the operational procedures into several steps including (i) folding pads above/below and (ii) addition of reagent/buffer under a specific sequence. The CL behavior, blood plasma separation, washing protocol, and incubation time were investigated in this work. The developed 3D origami-based CL immunodevice, combined with a typical luminuol-H(2)O(2) CL system and catalyzed by Ag nanoparticles, showed excellent analytical performance for the simultaneous detection of four tumor markers. The whole blood samples were assayed and the results obtained were in agreement with the reference values from the parallel single-analyte test. This paper-based microfluidic origami CL detection system provides a new strategy for a low-cost, sensitive, simultaneous multiplex immunoassay and point-of-care diagnostics.

  18. Sample to answer visualization pipeline for low-cost point-of-care blood cell counting

    Science.gov (United States)

    Smith, Suzanne; Naidoo, Thegaran; Davies, Emlyn; Fourie, Louis; Nxumalo, Zandile; Swart, Hein; Marais, Philip; Land, Kevin; Roux, Pieter

    2015-03-01

    We present a visualization pipeline from sample to answer for point-of-care blood cell counting applications. Effective and low-cost point-of-care medical diagnostic tests provide developing countries and rural communities with accessible healthcare solutions [1], and can be particularly beneficial for blood cell count tests, which are often the starting point in the process of diagnosing a patient [2]. The initial focus of this work is on total white and red blood cell counts, using a microfluidic cartridge [3] for sample processing. Analysis of the processed samples has been implemented by means of two main optical visualization systems developed in-house: 1) a fluidic operation analysis system using high speed video data to determine volumes, mixing efficiency and flow rates, and 2) a microscopy analysis system to investigate homogeneity and concentration of blood cells. Fluidic parameters were derived from the optical flow [4] as well as color-based segmentation of the different fluids using a hue-saturation-value (HSV) color space. Cell count estimates were obtained using automated microscopy analysis and were compared to a widely accepted manual method for cell counting using a hemocytometer [5]. The results using the first iteration microfluidic device [3] showed that the most simple - and thus low-cost - approach for microfluidic component implementation was not adequate as compared to techniques based on manual cell counting principles. An improved microfluidic design has been developed to incorporate enhanced mixing and metering components, which together with this work provides the foundation on which to successfully implement automated, rapid and low-cost blood cell counting tests.

  19. [Concentration of lipids in ascitic fluid and the concentration gradient of albumin in blood and ascites: diagnostic significance].

    Science.gov (United States)

    Barbare, J C; Diab, G; Delavenne, J; Philippe, J M; Vorhauer, W; Latrive, J P; Capron, J P

    1989-11-01

    The aim of this study was to test the diagnostic value of ascitic fluid cholesterol and triglycerides concentrations and of serum-ascites albumin concentration gradient in the differentiation between cirrhotic and malignant ascites. These biological parameters were determined, on the one hand in 34 cirrhotic patients, 6 of them having an hepatocellular carcinoma and 6 others having a spontaneous bacterial peritonitis and, on the other hand, in 16 patients with malignant ascites, 13 of them having an abdominal extra-hepatic or pelvic cancer, and 3 others having an extra-abdominal cancer with multiple liver metastases. Ascitic carcinoembryonic antigen assay and ascitic fluid cytology were also done in the 50 patients. In differentiating the cirrhotic patients from those with malignancy, ascitic fluid cholesterol concentration (discriminating value less than 1.1 mmol/l) ascitic fluid triglycerides concentration (discriminating value 0.5 mmol/l) and serum-ascites albumin concentration gradient (discriminating value greater than 11 g/l) allowed a diagnostic efficiency of 0.92, 0.80 and 0.77, respectively. Ascitic fluid cytology showed presence of malignant cells in 3/6 patients with hepatocellular carcinoma associated with cirrhosis, in 9/16 patients having a malignant ascites, and was negative in other patients. Ascitic carcinoembryonic antigen assay was abnormal only in 3/16 patients with malignant ascites. These results suggest that measurement of ascitic fluid cholesterol concentration must be included in the initial evaluation of patients with ascites of unknown origin.

  20. Diagnostic imaging of musculoskeletal infection. Roentgenography; Gallium, indium-labeled white blood cell, gammaglobulin, bone scintigraphy; and MRI

    Energy Technology Data Exchange (ETDEWEB)

    Wegener, W.A.; Alavi, A. (Hospital of the University of Pennsylvania, Philadelphia (USA))

    1991-07-01

    A great deal of effort has been made to evaluate and define the role of various diagnostic imaging techniques in various clinical settings that complicate the diagnosis of osteomyelitis. Except possibly in neonates, bone scintigraphy remains generally recommended when there has been no previous osseous involvement. In other cases of chronic disease, previous fracture or trauma, prosthesis, and diabetic foot, In-WBC scintigraphy is generally accepted as an appropriate imaging technique. MRI will play an increasingly important role in diagnosing osteomyelitis and may prove to be an important adjunct in these cases. Research continues to improve our current diagnostic armamentarium. In-IgG appears to avoid practical deficiencies encountered with 67Ga and In-WBC; it remains to be seen what role this agent will play in routine clinical practice. All agents to date image inflammation, not infection, and most require delayed imaging sessions, usually at 24 hours. These shortcomings necessitate further research to develop new radiotracers that can provide useful images within several hours and that are specific for infection, perhaps ultimately delineating the particular microorganism involved.84 references.

  1. Magnetic permeability based diagnostic test for the determination of the canine C-reactive protein concentration in undiluted whole blood

    Energy Technology Data Exchange (ETDEWEB)

    Ibraimi, Filiz; Kriz, Kirstin [Department of Pure and Applied Biochemistry, Lund University, P.O. Box 124, SE-221 00 Lund (Sweden); LifeAssays AB, IDEON Science Park, SE-223 70 Lund (Sweden); Merin, Henrik [Malmoe Animal Hospital, P.O. Box 9090, SE-213 63 Malmoe (Sweden); Kriz, Dario [Department of Pure and Applied Biochemistry, Lund University, P.O. Box 124, SE-221 00 Lund (Sweden); LifeAssays AB, IDEON Science Park, SE-223 70 Lund (Sweden)], E-mail: dario.kriz@euris.org

    2009-05-15

    We describe an one-step 11-min magnetic permeability based two-site immunoassay for C-reactive protein (CRP) utilizing polyclonal anti-canine CRP antibody conjugated dextran iron oxide nanoparticles (79 nm) as superparamagnetic labels and polyclonal anti-canine CRP conjugated silica microparticles (15 to 40 {mu}m) as carriers. An inductance based magnetic permeability reader was used to detect the target analyte, CRP, in 10 {mu}L whole blood samples, by measuring the magnetic permeability increase of the silica microparticle sediment due to immuno complex superparamagnetic nanoparticles. Measurements on standards showed a linear response between 0 and 17.5 mg/L CRP. Measurements performed on 16 whole blood samples from mixed breeds showed good correlation with a commercially available ELISA assay.

  2. Magnetic permeability based diagnostic test for the determination of the canine C-reactive protein concentration in undiluted whole blood

    Science.gov (United States)

    Ibraimi, Filiz; Kriz, Kirstin; Merin, Henrik; Kriz, Dario

    2009-05-01

    We describe an one-step 11-min magnetic permeability based two-site immunoassay for C-reactive protein (CRP) utilizing polyclonal anti-canine CRP antibody conjugated dextran iron oxide nanoparticles (79 nm) as superparamagnetic labels and polyclonal anti-canine CRP conjugated silica microparticles (15 to 40 μm) as carriers. An inductance based magnetic permeability reader was used to detect the target analyte, CRP, in 10 μL whole blood samples, by measuring the magnetic permeability increase of the silica microparticle sediment due to immuno complex superparamagnetic nanoparticles. Measurements on standards showed a linear response between 0 and 17.5 mg/L CRP. Measurements performed on 16 whole blood samples from mixed breeds showed good correlation with a commercially available ELISA assay.

  3. A critical insight into the development pipeline of microfluidic immunoassay devices for the sensitive quantitation of protein biomarkers at the point of care.

    Science.gov (United States)

    Barbosa, Ana I; Reis, Nuno M

    2017-03-13

    The latest clinical procedures for the timely and cost-effective diagnosis of chronic and acute clinical conditions, such as cardiovascular diseases, cancer, chronic respiratory diseases, diabetes or sepsis (i.e. the biggest causes of death worldwide), involve the quantitation of specific protein biomarkers released into the blood stream or other physiological fluids (e.g. urine or saliva). The clinical thresholds are usually in the femtomolar to picolomar range, and consequently the measurement of these protein biomarkers heavily relies on highly sophisticated, bulky and automated equipment in centralised pathology laboratories. The first microfluidic devices capable of measuring protein biomarkers in miniaturised immunoassays were presented nearly two decades ago and promised to revolutionise point-of-care (POC) testing by offering unmatched sensitivity and automation in a compact POC format; however, the development and adoption of microfluidic protein biomarker tests has fallen behind expectations. This review presents a detailed critical overview into the pipeline of microfluidic devices developed in the period 2005-2016 capable of measuring protein biomarkers from the pM to fM range in formats compatible with POC testing, with a particular focus on the use of affordable microfluidic materials and compact low-cost signal interrogation. The integration of these two important features (essential unique selling points for the successful microfluidic diagnostic products) has been missed in previous review articles and explain the poor adoption of microfluidic technologies in this field. Most current miniaturised devices compromise either on the affordability, compactness and/or performance of the test, making current tests unsuitable for the POC measurement of protein biomarkers. Seven core technical areas, including (i) the selected strategy for antibody immobilisation, (ii) the surface area and surface-area-to-volume ratio, (iii) surface passivation, (iv) the

  4. Droplet microfluidics based microseparation systems.

    Science.gov (United States)

    Xiao, Zhiliang; Niu, Menglei; Zhang, Bo

    2012-06-01

    Lab on a chip (LOC) technology is a promising miniaturization approach. The feature that it significantly reduced sample consumption makes great sense in analytical and bioanalytical chemistry. Since the start of LOC technology, much attention has been focused on continuous flow microfluidic systems. At the turn of the century, droplet microfluidics, which was also termed segmented flow microfluidics, was introduced. Droplet microfluidics employs two immiscible phases to form discrete droplets, which are ideal vessels with confined volume, restricted dispersion, limited cross-contamination, and high surface area. Due to these unique features, droplet microfluidics proves to be a versatile tool in microscale sample handling. This article reviews the utility of droplet microfluidics in microanalytical systems with an emphasize on separation science, including sample encapsulation at ultra-small volume, compartmentalization of separation bands, isolation of droplet contents, and related detection techniques.

  5. Isolation of plasma from whole blood using planar microfilters for lab-on-a-chip applications.

    Science.gov (United States)

    Crowley, Timothy A; Pizziconi, Vincent

    2005-09-01

    Researchers are actively developing devices for the microanalysis of complex fluids, such as blood. These devices have the potential to revolutionize biological analysis in a manner parallel to the computer chip by providing very high throughput screening of complex samples and massively parallel bioanalytical capabilities. A necessary step performed in clinical chemistry is the isolation of plasma from whole blood, and effective sample preparation techniques are needed for the development of miniaturized clinical diagnostic devices. This study demonstrates the use of passive, operating entirely on capillary action, transverse-flow microfilter devices for the microfluidic isolation of plasma from whole blood. Using these planar microfilters, blood can be controllably fractionated with minimal cell lysis. A characterization of the device performance reveals that plasma filter flux is dependent upon the wall shear rate of blood in the filtration channel, and this result is consistent with macroscale blood filtration using microporous membranes. Also, an innovative microfluidic layout is demonstrated that extends device operation time via capillary action from seconds to minutes. Efficiency of these microfilters is approximately three times higher than the separation efficiencies predicted for microporous membranes under similar conditions. As such, the application of the microscale blood filtration designs used in this study may have broad implications in the design of lab-on-a-chip devices, as well as the field of separation science.

  6. Microfluidic Production of Multiple Emulsions

    Directory of Open Access Journals (Sweden)

    Goran T. Vladisavljević

    2017-03-01

    Full Text Available Microfluidic devices are promising tools for the production of monodispersed tuneable complex emulsions. This review highlights the advantages of microfluidics for the fabrication of emulsions and presents an overview of the microfluidic emulsification methods including two-step and single-step methods for the fabrication of high-order multiple emulsions (double, triple, quadruple and quintuple and emulsions with multiple and/or multi-distinct inner cores. The microfluidic methods for the formation of multiple emulsion drops with ultra-thin middle phase, multi-compartment jets, and Janus and ternary drops composed of two or three distinct surface regions are also presented. Different configurations of microfluidic drop makers are covered, such as co-flow, T-junctions and flow focusing (both planar and three-dimensional (3D. Furthermore, surface modifications of microfluidic channels and different modes of droplet generation are summarized. Non-confined microfluidic geometries used for buoyancy-driven drop generation and membrane integrated microfluidics are also discussed. The review includes parallelization and drop splitting strategies for scaling up microfluidic emulsification. The productivity of a single drop maker is typically <1 mL/h; thus, more than 1000 drop makers are needed to achieve commercially relevant droplet throughputs of >1 L/h, which requires combining drop makers into twodimensional (2D and 3D assemblies fed from a single set of inlet ports through a network of distribution and collection channels.

  7. An attempt to evaluate diagnostic and prognostic significance of blood endogenous ethanol in alcoholics and their relatives.

    Science.gov (United States)

    Ostrovsky, Y M; Pronko, P S; Shishkin, S N; Kolesnikov, V B; Volynets, S I

    1989-01-01

    Endogenous ethanol in the blood of human subjects was measured by gas chromatography. In healthy males, 12-13-year-old boys (sons of alcoholic and nonalcoholic fathers), and alcoholic inpatients (after cessation of all drugs), the endogenous ethanol levels ranged from 0 to 4.3 mg/l. The results showed no significant differences between the groups. At the period of alcohol withdrawal reactions the concentrations of endogenous ethanol were minimal in patients with delirium tremens and maximal in patients with mild alcohol withdrawal syndrome, the dynamics of this parameter being dependent on the severity of the alcohol withdrawal syndrome and the nature of the drugs prescribed.

  8. The Microfluidic Jukebox

    Science.gov (United States)

    Tan, Say Hwa; Maes, Florine; Semin, Benoît; Vrignon, Jérémy; Baret, Jean-Christophe

    2014-04-01

    Music is a form of art interweaving people of all walks of life. Through subtle changes in frequencies, a succession of musical notes forms a melody which is capable of mesmerizing the minds of people. With the advances in technology, we are now able to generate music electronically without relying solely on physical instruments. Here, we demonstrate a musical interpretation of droplet-based microfluidics as a form of novel electronic musical instruments. Using the interplay of electric field and hydrodynamics in microfluidic devices, well controlled frequency patterns corresponding to musical tracks are generated in real time. This high-speed modulation of droplet frequency (and therefore of droplet sizes) may also provide solutions that reconciles high-throughput droplet production and the control of individual droplet at production which is needed for many biochemical or material synthesis applications.

  9. Microfluidic colloid filtration

    Science.gov (United States)

    Linkhorst, John; Beckmann, Torsten; Go, Dennis; Kuehne, Alexander J. C.; Wessling, Matthias

    2016-03-01

    Filtration of natural and colloidal matter is an essential process in today’s water treatment processes. The colloidal matter is retained with the help of micro- and nanoporous synthetic membranes. Colloids are retained in a “cake layer” – often coined fouling layer. Membrane fouling is the most substantial problem in membrane filtration: colloidal and natural matter build-up leads to an increasing resistance and thus decreasing water transport rate through the membrane. Theoretical models exist to describe macroscopically the hydrodynamic resistance of such transport and rejection phenomena; however, visualization of the various phenomena occurring during colloid retention is extremely demanding. Here we present a microfluidics based methodology to follow filter cake build up as well as transport phenomena occuring inside of the fouling layer. The microfluidic colloidal filtration methodology enables the study of complex colloidal jamming, crystallization and melting processes as well as translocation at the single particle level.

  10. Microfluidic redox battery.

    Science.gov (United States)

    Lee, Jin Wook; Goulet, Marc-Antoni; Kjeang, Erik

    2013-07-01

    A miniaturized microfluidic battery is proposed, which is the first membraneless redox battery demonstrated to date. This unique concept capitalizes on dual-pass flow-through porous electrodes combined with stratified, co-laminar flow to generate electrical power on-chip. The fluidic design is symmetric to allow for both charging and discharging operations in forward, reverse, and recirculation modes. The proof-of-concept device fabricated using low-cost materials integrated in a microfluidic chip is shown to produce competitive power levels when operated on a vanadium redox electrolyte. A complete charge/discharge cycle is performed to demonstrate its operation as a rechargeable battery, which is an important step towards providing sustainable power to lab-on-a-chip and microelectronic applications.

  11. Microfluidic vascular channels in gels using commercial 3D printers

    Science.gov (United States)

    Selvaganapathy, P. Ravi; Attalla, Rana

    2016-03-01

    This paper details the development of a three dimensional (3D) printing system with a modified microfluidic printhead used for the generation of complex vascular tissue scaffolds. The print-head features an integrated coaxial nozzle that allows the fabrication of hollow, calcium-polymerized alginate tubes that can easily be patterned using 3Dbioprinting techniques. This microfluidic design allows the incorporation of a wide range of scaffold materials as well as biological constituents such as cells, growth factors, and ECM material. With this setup, gel constructs with embedded arrays of hollow channels can be created and used as a potential substitute for blood vessel networks.

  12. Microfluidic biosensor for cholera toxin detection in fecal samples.

    Science.gov (United States)

    Bunyakul, Natinan; Promptmas, Chamras; Baeumner, Antje J

    2015-01-01

    Sample preparation and processing steps are the most critical assay aspects that require our attention in the development of diagnostic devices for analytes present in complex matrices. In the best scenarios, diagnostic devices should use only simple sample processing. We have therefore investigated minimal preparation of stool samples and their effect on our sensitive microfluidic immunosensor for the detection of cholera toxin. This biosensor was previously developed and tested in buffer solutions only, using either fluorescence or electrochemical detection strategies. The microfluidic devices were made from polydimethylsiloxane using soft lithography and silicon templates. Cholera toxin subunit B (CTB)-specific antibodies immobilized onto superparamagnetic beads and ganglioside GM1-containing liposomes were used for CTB recognition in the detection system. Quantification of CTB was tested by spiking it in human stool samples. Here, optimal minimal sample processing steps, including filtration and centrifugation, were optimized using a microtiter plate assay owing to its high-throughput capabilities. Subsequently, it was transferred to the microfluidic systems, enhancing the diagnostic characteristic of the biosensor. It was found that the debris removal obtained through simple centrifugation resulted in an acceptable removal of matrix effects for the fluorescence format, reaching a limit of detection of only 9.0 ng/mL. However, the electron transfer in the electrochemical format was slightly negatively affected (limit of detection of 31.7 ng/mL). Subsequently, cross-reactivity using the heat-labile Escherichia coli toxin was investigated using the electrochemical microfluidic immunosensors and was determined to be negligible. With minimal sample preparation required, these microfluidic liposome-based systems have demonstrated excellent analytical performance in a complex matrix and will thus be applicable to other sample matrices.

  13. The Correlation-Base-Selection Algorithm for Diagnostic Schizophrenia Based on Blood-Based Gene Expression Signatures

    Science.gov (United States)

    Zhang, Hang; Xie, Ziyang; Yang, Yuwen; Zhao, Yizhen

    2017-01-01

    Microarray analysis of gene expression is often used to diagnose different types of disease. Many studies report remarkable achievements in nervous system disease. Clinical diagnosis of schizophrenia (SCZ) still depends on doctors' experience, which is unreliable and needs to be more objective and quantified. To solve this problem, we collected whole blood gene expression data from four studies, including 152 individuals with schizophrenia (SCZ) and 138 normal controls in different regions. The correlation-based feature selection (CFS, one of the machine learning methods) algorithm was applied in this study, and 103 significantly differentially expressed genes between patients and controls, called “feature genes,” were selected; then, a model for SCZ diagnosis was built. The samples were subdivided into 10 groups, and cross-validation showed that the model we constructed achieved nearly 100% classification accuracy. Mathematical evaluation of the datasets before and after data processing proved the effectiveness of our algorithm. Feature genes were enriched in Parkinson's disease, oxidative phosphorylation, and TGF-beta signaling pathways, which were previously reported to be associated with SCZ. These results suggest that the analysis of gene expression in whole blood by our model could be a useful tool for diagnosing SCZ. PMID:28280741

  14. Two-way FSI modelling of blood flow through CCA accounting on-line medical diagnostics in hypertension

    Science.gov (United States)

    Czechowicz, K.; Badur, J.; Narkiewicz, K.

    2014-08-01

    Flow parameters can induce pathological changes in the arteries. We propose a method to asses those parameters using a 3D computer model of the flow in the Common Carotid Artery. Input data was acquired using an automatic 2D ultrasound wall tracking system. This data has been used to generate a 3D geometry of the artery. The diameter and wall thickness have been assessed individually for every patient, but the artery has been taken as a 75mm straight tube. The Young's modulus for the arterial walls was calculated using the pulse pressure, diastolic (minimal) diameter and wall thickness (IMT). Blood flow was derived from the pressure waveform using a 2-parameter Windkessel model. The blood is assumed to be non-Newtonian. The computational models were generated and calculated using commercial code. The coupling method required the use of Arbitrary Lagrangian-Euler formulation to solve Navier-Stokes and Navier-Lame equations in a moving domain. The calculations showed that the distention of the walls in the model is not significantly different from the measurements. Results from the model have been used to locate additional risk factors, such as wall shear stress or circumferential stress, that may predict adverse hypertension complications.

  15. Droplet based microfluidics

    Science.gov (United States)

    Seemann, Ralf; Brinkmann, Martin; Pfohl, Thomas; Herminghaus, Stephan

    2012-01-01

    Droplet based microfluidics is a rapidly growing interdisciplinary field of research combining soft matter physics, biochemistry and microsystems engineering. Its applications range from fast analytical systems or the synthesis of advanced materials to protein crystallization and biological assays for living cells. Precise control of droplet volumes and reliable manipulation of individual droplets such as coalescence, mixing of their contents, and sorting in combination with fast analysis tools allow us to perform chemical reactions inside the droplets under defined conditions. In this paper, we will review available drop generation and manipulation techniques. The main focus of this review is not to be comprehensive and explain all techniques in great detail but to identify and shed light on similarities and underlying physical principles. Since geometry and wetting properties of the microfluidic channels are crucial factors for droplet generation, we also briefly describe typical device fabrication methods in droplet based microfluidics. Examples of applications and reaction schemes which rely on the discussed manipulation techniques are also presented, such as the fabrication of special materials and biophysical experiments.

  16. Droplet based microfluidics.

    Science.gov (United States)

    Seemann, Ralf; Brinkmann, Martin; Pfohl, Thomas; Herminghaus, Stephan

    2012-01-01

    Droplet based microfluidics is a rapidly growing interdisciplinary field of research combining soft matter physics, biochemistry and microsystems engineering. Its applications range from fast analytical systems or the synthesis of advanced materials to protein crystallization and biological assays for living cells. Precise control of droplet volumes and reliable manipulation of individual droplets such as coalescence, mixing of their contents, and sorting in combination with fast analysis tools allow us to perform chemical reactions inside the droplets under defined conditions. In this paper, we will review available drop generation and manipulation techniques. The main focus of this review is not to be comprehensive and explain all techniques in great detail but to identify and shed light on similarities and underlying physical principles. Since geometry and wetting properties of the microfluidic channels are crucial factors for droplet generation, we also briefly describe typical device fabrication methods in droplet based microfluidics. Examples of applications and reaction schemes which rely on the discussed manipulation techniques are also presented, such as the fabrication of special materials and biophysical experiments.

  17. Fabrication of gravity-driven microfluidic device

    Science.gov (United States)

    Yamada, H.; Yoshida, Y.; Terada, N.; Hagihara, S.; Komatsu, T.; Terasawa, A.

    2008-12-01

    We have studied the micro total analysis system as a blood test. A microfluidic device with a three-pronged microchannel and artificial capillary vessels was fabricated. The microchannel is to transport blood, focus blood cells, and line them up. The vessels are to observe red blood cell deformation. An excimer laser was used to form grooves and so on. Numbers of thermosetting resin film and fluororesin were piled up on a cover glass. A laser fabricated part of the channel at the each film every lamination, and then a three-dimensional structure microchannel was fabricated. The channel sizes have widths of 50-150 μm and depths of 45 μm. Through holes used as artificial capillary vessels are made in the fluororesin having a minimum diameter of 5 μm and a length of 100 μm. As blood and a physiological saline are injected into the microchannel, the device stands upward facing the channel, and blood cells go into the vessels by the force of gravity and sheath flow of the saline. By gravity various groove patterns were made changing the width and length for measurement of blood focusing. Moreover, the red blood cell deformation was observed in the vessels with a microscope.

  18. Over-Expression of Dopamine D2 Receptor and Inwardly Rectifying Potassium Channel Genes in Drug-Naive Schizophrenic Peripheral Blood Lymphocytes as Potential Diagnostic Markers

    Directory of Open Access Journals (Sweden)

    Ágnes Zvara

    2005-01-01

    Full Text Available Schizophrenia is one of the most common neuropsychiatric disorders affecting nearly 1% of the human population. Current diagnosis of schizophrenia is based on complex clinical symptoms. The use of easily detectable peripheral molecular markers could substantially help the diagnosis of psychiatric disorders. Recent studies showed that peripheral blood lymphocytes (PBL express subtypes of D1 and D2 subclasses of dopamine receptors. Recently, dopamine receptor D3 (DRD3 was found to be over-expressed in schizophrenic PBL and proposed to be a diagnostic and follow-up marker for schizophrenia. In this study we screened PBL of 13 drug-naive/drug-free schizophrenic patients to identify additional markers of schizophrenia. One of the benefits of our study is the use of blood samples of non-medicated, drug-naive patients. This excludes the possibility that changes detected in gene expression levels might be attributed to the medication rather than to the disorder itself. Among others, genes for dopamine receptor D2 (DRD2 and the inwardly rectifying potassium channel (Kir2.3 were found to be over-expressed in microarray analysis. Increased mRNA levels were confirmed by quantitative real-time PCR (QRT-PCR using the SybrGreen method and dual labeled TaqMan probes. The use of both molecular markers allows a more rapid and precise prediction of schizophrenia and might help find the optimal medication for schizophrenic patients.

  19. Over-expression of dopamine D2 receptor and inwardly rectifying potassium channel genes in drug-naive schizophrenic peripheral blood lymphocytes as potential diagnostic markers.

    Science.gov (United States)

    Zvara, Agnes; Szekeres, György; Janka, Zoltán; Kelemen, János Z; Cimmer, Csongor; Sántha, Miklós; Puskás, László G

    2005-01-01

    Schizophrenia is one of the most common neuropsychiatric disorders affecting nearly 1% of the human population. Current diagnosis of schizophrenia is based on complex clinical symptoms. The use of easily detectable peripheral molecular markers could substantially help the diagnosis of psychiatric disorders. Recent studies showed that peripheral blood lymphocytes (PBL) express subtypes of D1 and D2 subclasses of dopamine receptors. Recently, dopamine receptor D3 (DRD3) was found to be over-expressed in schizophrenic PBL and proposed to be a diagnostic and follow-up marker for schizophrenia. In this study we screened PBL of 13 drug-naive/drug-free schizophrenic patients to identify additional markers of schizophrenia. One of the benefits of our study is the use of blood samples of non-medicated, drug-naive patients. This excludes the possibility that changes detected in gene expression levels might be attributed to the medication rather than to the disorder itself. Among others, genes for dopamine receptor D2 (DRD2) and the inwardly rectifying potassium channel (Kir2.3) were found to be over-expressed in microarray analysis. Increased mRNA levels were confirmed by quantitative real-time PCR (QRT-PCR) using the SybrGreen method and dual labeled TaqMan probes. The use of both molecular markers allows a more rapid and precise prediction of schizophrenia and might help find the optimal medication for schizophrenic patients.

  20. Travel-related schistosomiasis, strongyloidiasis, filariasis, and toxocariasis: the risk of infection and the diagnostic relevance of blood eosinophilia

    Directory of Open Access Journals (Sweden)

    Sonder Gerard J

    2011-04-01

    Full Text Available Abstract Background This study prospectively assessed the occurrence of clinical and subclinical schistosomiasis, strongyloidiasis, filariasis, and toxocariasis, and the screening value of eosinophilia in adult short-term travelers to helminth-endemic countries. Methods Visitors of a pre-travel health advice centre donated blood samples for serology and blood cell count before and after travel. Samples were tested for eosinophilia, and for antibodies against schistosomiasis, strongyloidiasis, filariasis, and toxocariasis. Previous infection was defined as seropositivity in pre- and post-travel samples. Recent infection was defined as a seroconversion. Symptoms of parasitic disease were recorded in a structured diary. Results Previous infection was found in 112 of 1207 subjects: schistosomiasis in 2.7%, strongyloidiasis in 2.4%, filariasis in 3.4%, and toxocariasis in 1.8%. Recent schistosomiasis was found in 0.51% of susceptible subjects at risk, strongyloidiasis in 0.25%, filariasis in 0.09%, and toxocariasis in 0.08%. The incidence rate per 1000 person-months was 6.4, 3.2, 1.1, and 1.1, respectively. Recent infections were largely contracted in Asia. The positive predictive value of eosinophilia for diagnosis was 15% for previous infection and 0% for recent infection. None of the symptoms studied had any positive predictive value. Conclusion The chance of infection with schistosomiasis, strongyloidiasis, filariasis, and toxocariasis during one short-term journey to an endemic area is low. However, previous stay leads to a cumulative risk of infection. Testing for eosinophilia appeared to be of no value in routine screening of asymptomatic travelers for the four helminthic infections. Findings need to be replicated in larger prospective studies.

  1. Increasing of Blood-Brain Tumor Barrier Permeability through Transcellular and Paracellular Pathways by Microbubble-Enhanced Diagnostic Ultrasound in a C6 Glioma Model

    Science.gov (United States)

    Zhang, Jinlong; Liu, Heng; Du, Xuesong; Guo, Yu; Chen, Xiao; Wang, Shunan; Fang, Jingqin; Cao, Peng; Zhang, Bo; Liu, Zheng; Zhang, Weiguo

    2017-01-01

    Most of the anticancer agents cannot be efficiently delivered into the brain tumor because of the existence of blood-brain tumor barrier (BTB). The objective of this study was to explore the effect of microbubble-enhanced diagnostic ultrasound (MEUS) on the BTB permeability and the possible mechanism. Glioma-bearing rats were randomized into three groups as follows: the microbubble-enhanced continued diagnostic ultrasound (MECUS) group; the microbubble-enhanced intermittent diagnostic ultrasound (MEIUS) group and the control group. The gliomas were insonicated through the skull with a diagnostic ultrasound and injected with microbubbles through the tail veins. Evans Blue (EB) and dynamic contrast-enhanced-MRI were used to test changes in the BTB permeability. Confocal laser scanning microscopy was used to observe the deposition of the EB in the tumor tissues. The distribution and expression of junctional adhesion molecule-A (JAM-A) and calcium-activated potassium channels (KCa channels) were detected by a Western blot, qRT-PCR, and immunohistochemical staining. In the MEUS groups, the EB extravasation (11.0 ± 2.2 μg/g in MECUS group and 17.9 ± 2.3 μg/g in MEIUS group) exhibited a significant increase compared with the control group (5.3 ± 0.9 μg/g). The MEIUS group had more EB extravasation than the MECUS group. The Ktrans value of the dynamic contrast-enhanced-MRI in the MEUS groups was higher than that of the control group and correlated strongly with the EB extravasation in the tumor (R2 = 0.97). This showed that the Ktrans value might be a non-invasive method to evaluate the BTB permeability in rat glioma after microbubble-enhanced ultrasound treatment.Western blot, qRT-PCR and immunohistochemical staining revealed that MEUS increased the KCa channels expression and reduced JAM-A expression in glioma. This change was more obvious in the MEIUS group than in the MECUS group. The results demonstrated that MEUS effectively increased the BTB permeability in

  2. Magnetic microfluidic platform for biomedical applications using magnetic nanoparticles

    KAUST Repository

    Stipsitz, Martin

    2015-05-01

    Microfluidic platforms are well-suited for biomedical analysis and usually consist of a set of units which guarantee the manipulation, detection and recognition of bioanalyte in a reliable and flexible manner. Additionally, the use of magnetic fields for perfoming the aforementioned tasks has been steadily gainining interest. This is due to the fact that magnetic fields can be well tuned and applied either externally or from a directly integrated solution in the diagnostic system. In combination with these applied magnetic fields, magnetic nanoparticles are used. In this paper, we present some of our most recent results in research towards a) microfluidic diagnostics using MR sensors and magnetic particles and b) single cell analysis using magnetic particles. We have successfully manipulated magnetically labeled bacteria and measured their response with integrated GMR sensors and we have also managed to separate magnetically labeled jurkat cells for single cell analysis. © 2015 Trans Tech Publications, Switzerland.

  3. Path to Low Cost Microfluidics

    CERN Document Server

    Govyadinov, Alexander N; Kornilovitch, Pavel; Markel, David

    2016-01-01

    The paper describes a novel concept for a low cost microfluidic platform utilizing materials and processes used in low cost thermal inkjet printing. The concept re-purposes the jetting elements to create pumps, mixers, and valves all necessary components for the transport of fluids in a broad range of microfluidic applications.

  4. Development of a preliminary diagnostic measure for bovine leukosis in dairy cows using peripheral white blood cell and lymphocyte counts

    Science.gov (United States)

    NISHIIKE, Masao; HAOKA, Michiyo; DOI, Takashi; KOHDA, Tomoko; MUKAMOTO, Masafumi

    2016-01-01

    Analysis of the association between antibodies against bovine leukemia virus (BLV), BLV proviral load, and white blood cell (WBC) and lymphocyte counts was performed with 774 dairy cows. The average age, WBC counts and lymphoid cell counts tended to be higher in BLV antibody-positive cows than in antibody-negative cows. There was a similar trend in levels of proviral DNA. We analyzed age, WBC counts and lymphocyte counts by principal component analyses to create a distribution chart of the principle component scores. Using the chart, we categorized cows into four quadrants based on additional information, such as the presence of antibody and the levels of proviral DNA. Antibody-positive cows and cows with high BLV proviral load were found mostly in one quadrant of the chart, indicating that it is possible to predict the risk of infection without any knowledge on antibody status by using information, such as WBC counts as a biomarker. When only antibody-positive cows were included in the analysis, a characteristic distribution of different levels of proviral DNA was seen in the quadrants, suggesting that it is possible to estimate the extent of bovine leukosis infection by using this analysis. For this analysis and categorization of the cows into quadrants, we computed a mathematical formulation using discriminant analysis based on age and WBC and lymphocyte counts. This mathematical formulation for the hematological preliminary diagnosis of the disease is recommended as a screening tool to monitor bovine leukosis. PMID:27064146

  5. Microfluidic devices for label-free separation of cells through transient interaction with asymmetric receptor patterns

    Science.gov (United States)

    Bose, S.; Singh, R.; Hollatz, M. H.; Lee, C.-H.; Karp, J.; Karnik, R.

    2012-02-01

    Cell sorting serves an important role in clinical diagnosis and biological research. Most of the existing microscale sorting techniques are either non-specific to antigen type or rely on capturing cells making sample recovery difficult. We demonstrate a simple; yet effective technique for isolating cells in an antigen specific manner by using transient interactions of the cell surface antigens with asymmetric receptor patterned surface. Using microfluidic devices incorporating P-selectin patterns we demonstrate separation of HL60 cells from K562 cells. We achieved a sorting purity above 90% and efficiency greater than 85% with this system. We also present a mathematical model incorporating flow mediated and adhesion mediated transport of cells in the microchannel that can be used to predict the performance of these devices. Lastly, we demonstrate the clinical significance of the method by demonstrating single step separation of neutrophils from whole blood. When whole blood is introduced in the device, the granulocyte population gets separated exclusively yielding neutrophils of high purity (<10% RBC contamination). To our knowledge, this is the first ever demonstration of continuous label free sorting of neutrophils from whole blood. We believe this technology will be useful in developing point-of-care diagnostic devices and also for a host of cell sorting applications.

  6. Multiplexing slanted spiral microchannels for ultra-fast blood plasma separation.

    Science.gov (United States)

    Rafeie, Mehdi; Zhang, Jun; Asadnia, Mohsen; Li, Weihua; Warkiani, Majid Ebrahimi

    2016-08-07

    Blood and blood products are critical components of health care. Blood components perform distinct functions in the human body and thus the ability to efficiently fractionate blood into its individual components (i.e., plasma and cellular components) is of utmost importance for therapeutic and diagnostic purposes. Although conventional approaches like centrifugation and membrane filtration for blood processing have been successful in generating relatively pure fractions, they are largely limited by factors such as the required blood sample volume, component purity, clogging, processing time and operation efficiency. In this work, we developed a high-throughput inertial microfluidic system for cell focusing and blood plasma separation from small to large volume blood samples (1-100 mL). Initially, polystyrene beads and blood cells were used to investigate the inertial focusing performance of a single slanted spiral microchannel as a function of particle size, flow rate, and blood cell concentration. Afterwards, blood plasma separation was conducted using an optimised spiral microchannel with relatively large dimensions. It was found that the reject ratio of the slanted spiral channel is close to 100% for blood samples with haematocrit (HCT) values of 0.5% and 1% under an optimal flow rate of 1.5 mL min(-1). Finally, through a unique multiplexing approach, we built a high-throughput system consisting of 16 spiral channels connected together, which can process diluted samples with a total flow rate as high as 24 mL min(-1). The proposed multiplexed system can surmount the shortcomings of previously reported microfluidic systems for plasma separation and cell sorting in terms of throughput, yield and operation efficiency.

  7. Laboratory diagnosis of malaria by conventional peripheral blood smear examination with Quantitative Buffy Coat (QBC and Rapid Diagnostic Tests (RDT - A comparative study

    Directory of Open Access Journals (Sweden)

    Bhat Sandhya K

    2012-10-01

    Full Text Available Aim: Rapid diagnosis is prerequisite for effective treatment and reducing mortality and morbidity of malaria. Microscopy has been the Gold standard for malaria diagnosis for decades. Recently, many new rapid diagnostic tests like Quantitative Buffy Coat (QBC examination and rapid antigen detection methods are being widely used. We made an attempt to compare peripheral smear, QBC and rapid antigen detection methods for the diagnosis of malaria. Materials and Methods: A total number of 500 samples were collected from patients presenting with classical symptoms of malaria. Thick and thin blood smears were prepared and stained with Leishman’s stain. QBC, Histidine Rich Protein-II antigen test and plasmodium Lactate Dehydrogenase tests were done using commercially available kits. Results: Taking thick smear as gold standard, thin smear had sensitivity, specificity, positive and negative predictive values of 90.9%, 100%, 100% and 98.6% respectively. QBC showed sensitivity, specificity, positive and negative predictive values of 95.45%, 100%, 100% and 99.31% respectively. HRP-II antigen detection showed sensitivity, specificity, positive and negative predictive values of 56.06%, 100%, 100% and 94.20%. pLDH showed sensitivity, specificity, PPV and NPV of 95.45%, 100%, 100% and 99.40% respectively. Conclusion: In our study, QBC had highest sensitivity followed by pLDH assay. Leishman’s stained thick smear is cost effective but requires technical expertise to interpret the results, so if facilities are available, QBC can be used for routine diagnosis. In places where facilities are not available rapid diagnostic test devices can be used, especially in endemic areas.

  8. Microfluidic device for continuous single cells analysis via Raman spectroscopy enhanced by integrated plasmonic nanodimers

    KAUST Repository

    Perozziello, Gerardo

    2015-12-11

    In this work a Raman flow cytometer is presented. It consists of a microfluidic device that takes advantages of the basic principles of Raman spectroscopy and flow cytometry. The microfluidic device integrates calibrated microfluidic channels- where the cells can flow one-by-one -, allowing single cell Raman analysis. The microfluidic channel integrates plasmonic nanodimers in a fluidic trapping region. In this way it is possible to perform Enhanced Raman Spectroscopy on single cell. These allow a label-free analysis, providing information about the biochemical content of membrane and cytoplasm of the each cell. Experiments are performed on red blood cells (RBCs), peripheral blood lymphocytes (PBLs) and myelogenous leukemia tumor cells (K562). © 2015 Optical Society of America.

  9. Microfluidic Cell Culture Device

    Science.gov (United States)

    Takayama, Shuichi (Inventor); Cabrera, Lourdes Marcella (Inventor); Heo, Yun Seok (Inventor); Smith, Gary Daniel (Inventor)

    2014-01-01

    Microfluidic devices for cell culturing and methods for using the same are disclosed. One device includes a substrate and membrane. The substrate includes a reservoir in fluid communication with a passage. A bio-compatible fluid may be added to the reservoir and passage. The reservoir is configured to receive and retain at least a portion of a cell mass. The membrane acts as a barrier to evaporation of the bio-compatible fluid from the passage. A cover fluid may be added to cover the bio-compatible fluid to prevent evaporation of the bio-compatible fluid.

  10. Microfluidic Scintillation Detectors

    CERN Multimedia

    Microfluidic scintillation detectors are devices of recent introduction for the detection of high energy particles, developed within the EP-DT group at CERN. Most of the interest for such technology comes from the use of liquid scintillators, which entails the possibility of changing the active material in the detector, leading to an increased radiation resistance. This feature, together with the high spatial resolution and low thickness deriving from the microfabrication techniques used to manufacture such devices, is desirable not only in instrumentation for high energy physics experiments but also in medical detectors such as beam monitors for hadron therapy.

  11. Fourier-transform infrared spectroscopy coupled with a classification machine for the analysis of blood plasma or serum: a novel diagnostic approach for ovarian cancer.

    Science.gov (United States)

    Gajjar, Ketan; Trevisan, Júlio; Owens, Gemma; Keating, Patrick J; Wood, Nicholas J; Stringfellow, Helen F; Martin-Hirsch, Pierre L; Martin, Francis L

    2013-07-21

    Currently available screening tests do not deliver the required sensitivity and specificity for accurate diagnosis of ovarian or endometrial cancer. Infrared (IR) spectroscopy of blood plasma or serum is a rapid, versatile, and relatively non-invasive approach which could characterize biomolecular alterations due to cancer and has potential to be utilized as a screening or diagnostic tool. In the past, no such approach has been investigated for its applicability in screening and/or diagnosis of gynaecological cancers. We set out to determine whether attenuated total reflection Fourier-transform IR (ATR-FTIR) spectroscopy coupled with a proposed classification machine could be applied to IR spectra obtained from plasma and serum for accurate class prediction (cancer vs. normal). Plasma and serum samples were obtained from ovarian cancer cases (n = 30), endometrial cancer cases (n = 30) and non-cancer controls (n = 30), and subjected to ATR-FTIR spectroscopy. Four derived datasets were processed to estimate the real-world diagnosis of ovarian and endometrial cancer. Classification results for ovarian cancer were remarkable (up to 96.7%), whereas endometrial cancer was classified with a relatively high accuracy (up to 81.7%). The results from different combinations of feature extraction and classification methods, and also classifier ensembles, were compared. No single classification system performed best for all different datasets. This demonstrates the need for a framework that can accommodate a diverse set of analytical methods in order to be adaptable to different datasets. This pilot study suggests that ATR-FTIR spectroscopy of blood is a robust tool for accurate diagnosis, and carries the potential to be utilized as a screening test for ovarian cancer in primary care settings. The proposed classification machine is a powerful tool which could be applied to classify the vibrational spectroscopy data of different biological systems (e.g., tissue, urine, saliva

  12. Multiplexed electrochemical protein detection and translation to personalized cancer diagnostics.

    Science.gov (United States)

    Rusling, James F

    2013-06-04

    Measuring diagnostic panels of multiple proteins promises a new, personalized approach to early detection and therapy of diseases like cancer. Levels of biomarker proteins in patient serum can provide a continually updated record of disease status. Research in electrochemical detection of proteins has produced exquisitely sensitive approaches. Most utilize ELISA-like sandwich immunoassays incorporating various aspects of nanotechnology. Several of these ultrasensitive methodologies have been extended to microfluidic multiplexed protein detection, but engineered solutions are needed to measure more proteins in a single device from a small patient sample such as a drop of blood or tissue lysate. To achieve clinical or point-of-care (POC) use, simplicity and low cost are essential. In multiplexed microfluidic immunoassays, required reagent additions and washing steps pose a significant problem calling for creative engineering. A grand challenge is to develop a general cancer screening device to accurately measure 50-100 proteins in a simple, cost-effective fashion. This will require creative solutions to simplified reagent addition and multiplexing.

  13. Microfluidic fuel cells and batteries

    CERN Document Server

    Kjeang, Erik

    2014-01-01

    Microfluidic fuel cells and batteries represent a special type of electrochemical power generators that can be miniaturized and integrated in a microfluidic chip. Summarizing the initial ten years of research and development in this emerging field, this SpringerBrief is the first book dedicated to microfluidic fuel cell and battery technology for electrochemical energy conversion and storage. Written at a critical juncture, where strategically applied research is urgently required to seize impending technology opportunities for commercial, analytical, and educational utility, the intention is

  14. Polymer-Based Microfluidic Devices for Pharmacy, Biology and Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Kerstin Ramser

    2012-07-01

    Full Text Available This paper reviews microfluidic technologies with emphasis on applications in the fields of pharmacy, biology, and tissue engineering. Design and fabrication of microfluidic systems are discussed with respect to specific biological concerns, such as biocompatibility and cell viability. Recent applications and developments on genetic analysis, cell culture, cell manipulation, biosensors, pathogen detection systems, diagnostic devices, high-throughput screening and biomaterial synthesis for tissue engineering are presented. The pros and cons of materials like polydimethylsiloxane (PDMS, polymethylmethacrylate (PMMA, polystyrene (PS, polycarbonate (PC, cyclic olefin copolymer (COC, glass, and silicon are discussed in terms of biocompatibility and fabrication aspects. Microfluidic devices are widely used in life sciences. Here, commercialization and research trends of microfluidics as new, easy to use, and cost-effective measurement tools at the cell/tissue level are critically reviewed.

  15. Microfluidic very large-scale integration for biochips: Technology, testing and fault-tolerant design

    DEFF Research Database (Denmark)

    Araci, Ismail Emre; Pop, Paul; Chakrabarty, Krishnendu

    2015-01-01

    in the deployment of microfluidic biochips is their low reliability and lack of test techniques to screen defective devices before they are used for biochemical analysis. Defective chips lead to repetition of experiments, which is undesirable due to high reagent cost and limited availability of samples. This paper......Microfluidic biochips are replacing the conventional biochemical analyzers by integrating all the necessary functions for biochemical analysis using microfluidics. Biochips are used in many application areas, such as, in vitro diagnostics, drug discovery, biotech and ecology. The focus...... of this paper is on continuous-flow biochips, where the basic building block is a microvalve. By combining these microvalves, more complex units such as mixers, switches, multiplexers can be built, hence the name of the technology, “microfluidic Very Large-Scale Integration” (mVLSI). A roadblock...

  16. Antifungal Susceptibility Patterns, In Vitro Production of Virulence Factors, and Evaluation of Diagnostic Modalities for the Speciation of Pathogenic Candida from Blood Stream Infections and Vulvovaginal Candidiasis

    Directory of Open Access Journals (Sweden)

    Chaitanya Tellapragada

    2014-01-01

    Full Text Available Candida spp. have emerged as successful pathogens in both invasive and mucosal infections. Varied virulence factors and growing resistance to antifungal agents have contributed to their pathogenicity. We studied diagnostic accuracy of HiCrome Candida Differential Agar and Vitek 2 Compact system for identification of Candida spp. in comparison with species-specific PCR on 110 clinical isolates of Candida from blood stream infections (54, 49% and vulvovaginal candidiasis (56, 51%. C. albicans (61% was the leading pathogen in VVC, while C. tropicalis (46% was prominent among BSIs. HiCrome Agar and Vitek 2 Compact had good measures of agreement (κ 0.826 and 0.895, respectively, in comparison with PCR. We also tested these isolates for in vitro production of proteinase, esterase, phospholipases, and biofilms. Proteinase production was more among invasive isolates (P=0.017, while phospholipase production was more among noninvasive isolates (P=0.001. There was an overall increase in the production of virulence factors among non-albicans Candida. Identification of clinical isolates of Candida up to species level either by chromogenic agar or by Vitek 2 Compact system should be routinely done to choose appropriate therapy.

  17. Microfluidic structures for LOC devices designed by laser lithography

    Science.gov (United States)

    Figurova, M.; Pudis, D.; Gaso, P.

    2016-12-01

    Nowadays, lab on a chip (LOC) applications are very popular in the field of biomedicine. LOC device works with biological materials and enables to arrange conventional laboratory operations on a small chip. Philosophy of LOC applications stands on quick and precise diagnostics process and technology, which uses cheap materials with possibility of rapid prototyping. LOC, as a time saving application, works with small volume of samples and reagents and enables better control over the sample. We present fabrication method of functional LOC chip for different biomedical microfluidic applications based on direct laser writing (DLW) lithography. We present fabrication of few types of microfluidic and micro-optic structures with different capabilities created by DLW system. The combination of DLW lithography in photoresist layer deposited on glass substrate and polydimethylsiloxane (PDMS) replica molding process were used for patterning of designed microstructures. Prepared microfluidic and micro-optic structures were observed by confocal microscope and microfluidic flow observations were investigated by conventional optical microscope and CCD camera.

  18. Diagnostic examination performance by using microvascular leakage, cerebral blood volume, and blood flow derived from 3-T dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging in the differentiation of glioblastoma multiforme and brain metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Server, Andres; Nakstad, Per H. [Oslo University Hospital-Ullevaal, Section of Neuroradiology, Department of Radiology and Nuclear Medicine, Oslo (Norway); University of Oslo, Oslo (Norway); Orheim, Tone E.D. [Oslo University Hospital, Interventional Centre, Oslo (Norway); Graff, Bjoern A. [Oslo University Hospital-Ullevaal, Department of Radiology and Nuclear Medicine, Oslo (Norway); Josefsen, Roger [Oslo University Hospital-Ullevaal, Department of Neurosurgery, Oslo (Norway); Kumar, Theresa [Oslo University Hospital-Ullevaal, Department of Pathology, Oslo (Norway)

    2011-05-15

    Conventional magnetic resonance (MR) imaging has limited capacity to differentiate between glioblastoma multiforme (GBM) and metastasis. The purposes of this study were: (1) to compare microvascular leakage (MVL), cerebral blood volume (CBV), and blood flow (CBF) in the distinction of metastasis from GBM using dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging (DSC-MRI), and (2) to estimate the diagnostic accuracy of perfusion and permeability MR imaging. A prospective study of 61 patients (40 GBMs and 21 metastases) was performed at 3 T using DSC-MRI. Normalized rCBV and rCBF from tumoral (rCBVt, rCBFt), peri-enhancing region (rCBVe, rCBFe), and by dividing the value in the tumor by the value in the peri-enhancing region (rCBVt/e, rCBFt/e), as well as MVL were calculated. Hemodynamic and histopathologic variables were analyzed statistically and Spearman/Pearson correlations. Receiver operating characteristic curve analysis was performed for each of the variables. The rCBVe, rCBFe, and MVL were significantly greater in GBMs compared with those of metastases. The optimal cutoff value for differentiating GBM from metastasis was 0.80 which implies a sensitivity of 95%, a specificity of 92%, a positive predictive value of 86%, and a negative predictive value of 97% for rCBVe ratio. We found a modest correlation between rCBVt and rCBFt ratios. MVL measurements in GBMs are significantly higher than those in metastases. Statistically, both rCBVe, rCBVt/e and rCBFe, rCBFt/e were useful in differentiating between GBMs and metastases, supporting the hypothesis that perfusion MR imaging can detect infiltration of tumor cells in the peri-enhancing region. (orig.)

  19. Measurements of diagnostic examination performance and correlation analysis using microvascular leakage, cerebral blood volume, and blood flow derived from 3T dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging in glial tumor grading

    Energy Technology Data Exchange (ETDEWEB)

    Server, Andres; Nakstad, Per H. [Oslo University Hospital-Ullevaal, Section of Neuroradiology, Department of Radiology and Nuclear Medicine, Oslo (Norway); University of Oslo, Oslo (Norway); Graff, Bjoern A. [Oslo University Hospital-Ullevaal, Department of Radiology and Nuclear Medicine, Oslo (Norway); Orheim, Tone E.D.; Gadmar, Oeystein B. [Oslo University Hospital, Interventional Centre, Oslo (Norway); Schellhorn, Till [Oslo University Hospital-Ullevaal, Section of Neuroradiology, Department of Radiology and Nuclear Medicine, Oslo (Norway); Josefsen, Roger [Oslo University Hospital-Ullevaal, Department of Neurosurgery, Oslo (Norway)

    2011-06-15

    To assess the diagnostic accuracy of microvascular leakage (MVL), cerebral blood volume (CBV) and blood flow (CBF) values derived from dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging (DSC-MR imaging) for grading of cerebral glial tumors, and to estimate the correlation between vascular permeability/perfusion parameters and tumor grades. A prospective study of 79 patients with cerebral glial tumors underwent DSC-MR imaging. Normalized relative CBV (rCBV) and relative CBF (rCBF) from tumoral (rCBVt and rCBFt), peri-enhancing region (rCBVe and rCBFe), and the value in the tumor divided by the value in the peri-enhancing region (rCBVt/e and rCBFt/e), as well as MVL, expressed as the leakage coefficient K{sub 2} were calculated. Hemodynamic variables and tumor grades were analyzed statistically and with Pearson correlations. Receiver operating characteristic (ROC) curve analyses were also performed for each of the variables. The differences in rCBVt and the maximum MVL (MVL{sub max}) values were statistically significant among all tumor grades. Correlation analysis using Pearson was as follows: rCBVt and tumor grade, r = 0.774; rCBFt and tumor grade, r = 0.417; MVL{sub max} and tumor grade, r = 0.559; MVL{sub max} and rCBVt, r = 0.440; MVL{sub max} and rCBFt, r = 0.192; and rCBVt and rCBFt, r = 0.605. According to ROC analyses for distinguishing tumor grade, rCBVt showed the largest areas under ROC curve (AUC), except for grade III from IV. Both rCBVt and MVL{sub max} showed good discriminative power in distinguishing all tumor grades. rCBVt correlated strongly with tumor grade; the correlation between MVL{sub max} and tumor grade was moderate. (orig.)

  20. Microfluidic Multichannel Flow Cytometer Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed innovation is a "Microfluidic Multichannel Flow Cytometer." Several novel concepts are integrated to produce the final design, which is compatible with...

  1. Microfluidics - Sorting particles with light

    DEFF Research Database (Denmark)

    Glückstad, J.

    2004-01-01

    Microfluidic systems have great potential to perform complex chemical and biological processing and analysis on a single disposable chip. That goal is now a step closer with the demonstration of an efficient all-optical particle sorter.......Microfluidic systems have great potential to perform complex chemical and biological processing and analysis on a single disposable chip. That goal is now a step closer with the demonstration of an efficient all-optical particle sorter....

  2. Microfluidic Mechanics and Applications: a Review

    Directory of Open Access Journals (Sweden)

    Sandeep Arya

    2014-01-01

    Full Text Available Microfluidics involves the transportation, splitting and mixing of minute fluids to perform several chemical and biological reactions including drug screening, heating, cooling or dissolution of reagents. Efforts have been made to develop different microfluidic devices, droplets and valves that can stop and resume flow of liquids inside a microchannel. This paper provides the review related to the theory and mechanics of microfluidic devices and fluid flow. Different materials and techniques for fabricating microfluidic devices are discussed. Subsequently, the microfluidic components that are responsible for successful micrfluidic device formation are presented. Finally, recent applications related to the microfluidics are highlighted.

  3. Simulation of magnetic active polymers for versatile microfluidic devices

    CERN Document Server

    Gusenbauer, Markus; Fischbacher, Johann; Reichel, Franz; Exl, Lukas; Bance, Simon; Kataeva, Nadezhda; Binder, Claudia; Brückl, Hubert; Schrefl, Thomas

    2013-01-01

    We propose to use a compound of magnetic nanoparticles (20-100 nm) embedded in a flexible polymer (Polydimethylsiloxane PDMS) to filter circulating tumor cells (CTCs). The analysis of CTCs is an emerging tool for cancer biology research and clinical cancer management including the detection, diagnosis and monitoring of cancer. The combination of experiments and simulations lead to a versatile microfluidic lab-on-chip device. Simulations are essential to understand the influence of the embedded nanoparticles in the elastic PDMS when applying a magnetic gradient field. It combines finite element calculations of the polymer, magnetic simulations of the embedded nanoparticles and the fluid dynamic calculations of blood plasma and blood cells. With the use of magnetic active polymers a wide range of tunable microfluidic structures can be created. The method can help to increase the yield of needed isolated CTCs.

  4. Spiral microfluidic nanoparticle separators

    Science.gov (United States)

    Bhagat, Ali Asgar S.; Kuntaegowdanahalli, Sathyakumar S.; Dionysiou, Dionysios D.; Papautsky, Ian

    2008-02-01

    Nanoparticles have potential applications in many areas such as consumer products, health care, electronics, energy and other industries. As the use of nanoparticles in manufacturing increases, we anticipate a growing need to detect and measure particles of nanometer scale dimensions in fluids to control emissions of possible toxic nanoparticles. At present most particle separation techniques are based on membrane assisted filtering schemes. Unfortunately their efficiency is limited by the membrane pore size, making them inefficient for separating a wide range of sizes. In this paper, we propose a passive spiral microfluidic geometry for momentum-based particle separations. The proposed design is versatile and is capable of separating particulate mixtures over a wide dynamic range and we expect it will enable a variety of environmental, medical, or manufacturing applications that involve rapid separation of nanoparticles in real-world samples with a wide range of particle components.

  5. Parallel imaging microfluidic cytometer.

    Science.gov (United States)

    Ehrlich, Daniel J; McKenna, Brian K; Evans, James G; Belkina, Anna C; Denis, Gerald V; Sherr, David H; Cheung, Man Ching

    2011-01-01

    By adding an additional degree of freedom from multichannel flow, the parallel microfluidic cytometer (PMC) combines some of the best features of fluorescence-activated flow cytometry (FCM) and microscope-based high-content screening (HCS). The PMC (i) lends itself to fast processing of large numbers of samples, (ii) adds a 1D imaging capability for intracellular localization assays (HCS), (iii) has a high rare-cell sensitivity, and (iv) has an unusual capability for time-synchronized sampling. An inability to practically handle large sample numbers has restricted applications of conventional flow cytometers and microscopes in combinatorial cell assays, network biology, and drug discovery. The PMC promises to relieve a bottleneck in these previously constrained applications. The PMC may also be a powerful tool for finding rare primary cells in the clinic. The multichannel architecture of current PMC prototypes allows 384 unique samples for a cell-based screen to be read out in ∼6-10 min, about 30 times the speed of most current FCM systems. In 1D intracellular imaging, the PMC can obtain protein localization using HCS marker strategies at many times for the sample throughput of charge-coupled device (CCD)-based microscopes or CCD-based single-channel flow cytometers. The PMC also permits the signal integration time to be varied over a larger range than is practical in conventional flow cytometers. The signal-to-noise advantages are useful, for example, in counting rare positive cells in the most difficult early stages of genome-wide screening. We review the status of parallel microfluidic cytometry and discuss some of the directions the new technology may take.

  6. Microfluidic Plastic Devices for Single-use Applications in High-Throughput Screening and DNA-Analysis

    OpenAIRE

    Gerlach, Andreas; Knebel, Günther; Guber, A. E.; Heckele, M.; Herrmann, D; Muslija, A.; Schaller, T.

    2001-01-01

    Microfluidic devices fabricated by mass production offer an immense potential of applications such as high-throughput drug screening, clinical diagnostics and gene analysis [1]. The low unit production costs of plastic substrates make it possible to produce single-use devices, eliminating the need for cleaning and reuse [2]. Fabrication of microfluidic devices can be applied by microtechnical fabrication processes in combination with plastic molding techniques [3]. Basically, replication...

  7. Plasma treatments of wool fiber surface for microfluidic applications

    Energy Technology Data Exchange (ETDEWEB)

    Jeon, So-Hyoun; Hwang, Ki-Hwan; Lee, Jin Su [Department of Chemistry, Sungkyunkwan University, 440-746 Suwon (Korea, Republic of); Boo, Jin-Hyo, E-mail: jhboo@skku.edu [Department of Chemistry, Sungkyunkwan University, 440-746 Suwon (Korea, Republic of); Yun, Sang H., E-mail: shy@kth.se [Institute of Basic Science, Sungkyunkwan University, 440-746 Suwon (Korea, Republic of)

    2015-09-15

    Highlights: • We used atmospheric plasma for tuning the wettability of wool fibers. • The wicking rates of the wool fibers increased with increasing treatment time. • The increasing of wettability results in removement of fatty acid on the wool surface. - Abstract: Recent progress in health diagnostics has led to the development of simple and inexpensive systems. Thread-based microfluidic devices allow for portable and inexpensive field-based technologies enabling medical diagnostics, environmental monitoring, and food safety analysis. However, controlling the flow rate of wool thread, which is a very important part of thread-based microfluidic devices, is quite difficult. For this reason, we focused on thread-based microfluidics in the study. We developed a method of changing the wettability of hydrophobic thread, including wool thread. Thus, using natural wool thread as a channel, we demonstrate herein that the manipulation of the liquid flow, such as micro selecting and micro mixing, can be achieved by applying plasma treatment to wool thread. In addition to enabling the flow control of the treated wool channels consisting of all natural substances, this procedure will also be beneficial for biological sensing devices. We found that wools treated with various gases have different flow rates. We used an atmospheric plasma with O{sub 2}, N{sub 2} and Ar gases.

  8. Pumpless microfluidic platform for drug testing on human skin equivalents

    OpenAIRE

    Abaci, Hasan Erbil; Gledhill, Karl; Guo, Zongyou; Christiano, Angela M.; Shuler, Michael L.

    2015-01-01

    Advances in bio-mimetic in vitro human skin models increase the efficiency of drug screening studies. In this study, we designed and developed a microfluidic platform that allows for long-term maintenance of full thickness human skin equivalents (HSE) which are comprised of both the epidermal and dermal compartments. The design is based on the physiologically relevant blood residence times in human skin tissue and allows for the establishment of an air-epidermal interface which is crucial for...

  9. Isolation of cancer cells by "in situ" microfluidic biofunctionalization protocols

    KAUST Repository

    De Vitis, Stefania

    2014-07-01

    The aim of this work is the development of a microfluidic immunosensor for the immobilization of cancer cells and their separation from healthy cells by using "in situ" microfluidic biofunctionalization protocols. These protocols allow to link antibodies on microfluidic device surfaces and can be used to study the interaction between cell membrane and biomolecules. Moreover they allow to perform analysis with high processing speed, small quantity of reagents and samples, short reaction times and low production costs. In this work the developed protocols were used in microfluidic devices for the isolation of cancer cells in heterogeneous blood samples by exploiting the binding of specific antibody to an adhesion protein (EpCAM), overexpressed on the tumor cell membranes. The presented biofunctionalization protocols can be performed right before running the experiment: this allows to have a flexible platform where biomolecules of interest can be linked on the device surface according to the user\\'s needs. © 2014 Elsevier B.V. All rights reserved.

  10. Next-generation confirmatory disease diagnostics

    Science.gov (United States)

    Lin, Robert; Gerver, Rachel; Karns, Kelly; Apori, Akwasi A.; Denisin, Aleksandra K.; Herr, Amy E.

    2014-06-01

    Microfluidic tools are advancing capabilities in screening diagnostics for use in near-patient settings. Here, we review three case studies to illustrate the flexibility and analytical power offered by microanalytical tools. We first overview a near-patient tool for detection of protein markers found in cerebrospinal fluid (CSF), as a means to identify the presence of cerebrospinal fluid in nasal mucous - an indication that CSF is leaking into the nasal cavity. Microfluidic design allowed integration of several up-stream preparatory steps and rapid, specific completion of the human CSF protein assay. Second, we overview a tear fluid based assay for lactoferrin, a protein produced in the lacrimal gland, then secreted into tear fluid. Tear Lf is a putative biomarker for primary SS. A critical contribution of this and related work being measurement of Lf, even in light of well-known and significant matrix interactions and losses during the tear fluid collection and preparation. Lastly, we review a microfluidic barcode platform that enables rapid measurement of multiple infectious disease biomarkers in human sera. The assay presents a new approach to multiplexed biomarker detection, yet in a simple straight microchannel - thus providing a streamlined, simplified microanalytical platform, as is relevant to robust operation in diagnostic settings. We view microfluidic design and analytical chemistry as the basis for emerging, sophisticated assays that will advance not just screening diagnostic technology, but confirmatory assays, sample preparation and handling, and thus introduction and utilization of new biomarkers and assay formats.

  11. Shrink-film microfluidic education modules: Complete devices within minutes.

    Science.gov (United States)

    Nguyen, Diep; McLane, Jolie; Lew, Valerie; Pegan, Jonathan; Khine, Michelle

    2011-06-01

    As advances in microfluidics continue to make contributions to diagnostics and life sciences, broader awareness of this expanding field becomes necessary. By leveraging low-cost microfabrication techniques that require no capital equipment or infrastructure, simple, accessible, and effective educational modules can be made available for a broad range of educational needs from middle school demonstrations to college laboratory classes. These modules demonstrate key microfluidic concepts such as diffusion and separation as well as "laboratory on-chip" applications including chemical reactions and biological assays. These modules are intended to provide an interdisciplinary hands-on experience, including chip design, fabrication of functional devices, and experiments at the microscale. Consequently, students will be able to conceptualize physics at small scales, gain experience in computer-aided design and microfabrication, and perform experiments-all in the context of addressing real-world challenges by making their own lab-on-chip devices.

  12. Microfluidics: applications for analytical purposes in chemistry and biochemistry.

    Science.gov (United States)

    Ohno, Ken-ichi; Tachikawa, Kaoru; Manz, Andreas

    2008-11-01

    In this review, we present recent advancements and novel developments in fluidic systems for applied analytical purposes in chemistry, biochemistry, and life science in general that employ and reflect the full benefits of microfluidics. A staggering rise in publications related to integrated, all-in-one microfluidic chips capable of separation, reaction, and detection have been observed, all of which realise the principal of micro total analysis systems or lab-on-a-chip. These integrated chips actively adopt the scaling law concepts, utilising the highly developed fabrication techniques. Their aim is to multi-functionalise and fully automate devices believed to assist the future advancements of point-of-care, clinical, and medical diagnostics.

  13. Dried reagents for multiplex genotyping by tag-array minisequencing to be used in microfluidic devices

    DEFF Research Database (Denmark)

    Ahlford, Annika; Kjeldsen, Bastian; Reimers, Jakob;

    2010-01-01

    was carried out with freeze-dried reagents stored in reaction chambers fabricated by micromilling in a cyclic olefin copolymer substrate. The results reported in this study are a key step towards the development of an integrated microfluidic device for point-of-care DNA-based diagnostics....

  14. Microfluidic approach of Sickled Cell Anemia

    Science.gov (United States)

    Abkarian, Manouk; Loiseau, Etienne; Massiera, Gladys

    2012-11-01

    Sickle Cell Anemia is a disorder of the microcirculation caused by a genetic point mutation that produces an altered hemoglobin protein called HbS. HbS self-assembles reversibly into long rope like fibers inside the red blood cells. The resulting distorded sickled red blood cells are believed to block the smallest capillaries of the tissues producing anemia. Despite the large amount of work that provided a thorough understanding of HbS polymerization in bulk as well as in intact red blood cells at rest, no consequent cellular scale approaches of the study of polymerization and its link to the capillary obstruction have been proposed in microflow, although the problem of obstruction is in essence a circulatory problem. Here, we use microfluidic channels, designed to mimic physiological conditions (flow velocity, oxygen concentration, hematocrit...) of the microcirculation to carry out a biomimetic study at the cellular scale of sickled cell vaso-occlusion. We show that flow geometry, oxygen concentration, white blood cells and free hemoglobin S are essential in the formation of original cell aggregates which could play a role in the vaso-occlusion events.

  15. Electrorheological fluid-actuated microfluidic pump

    Science.gov (United States)

    Liu, Liyu; Chen, Xiaoqing; Niu, Xize; Wen, Weijia; Sheng, Ping

    2006-08-01

    The authors report the design and implementation of an electrorheological (ER) fluid-actuated microfluidic pump, with programmable digital control. Our microfluidic pump has a multilayered structure fabricated on polydimethylsiloxane by soft-lithographic technique. The ER microfluidic pump exhibits good performance at high pumping frequencies and uniform liquid flow characteristics. It can be easily integrated with other microfluidic components. The programmable control also gives the device flexibility in its operations.

  16. Colloidal core-seeded semiconductor nanorods as fluorescent labels for in-vitro diagnostics (Conference Presentation)

    Science.gov (United States)

    Chan, YinThai

    2016-03-01

    Colloidal semiconductor nanocrystals are ideal fluorophores for clinical diagnostics, therapeutics, and highly sensitive biochip applications due to their high photostability, size-tunable color of emission and flexible surface chemistry. The relatively recent development of core-seeded semiconductor nanorods showed that the presence of a rod-like shell can confer even more advantageous physicochemical properties than their spherical counterparts, such as large multi-photon absorption cross-sections and facet-specific chemistry that can be exploited to deposit secondary nanoparticles. It may be envisaged that these highly fluorescent nanorods can be integrated with large scale integrated (LSI) microfluidic systems that allow miniaturization and integration of multiple biochemical processes in a single device at the nanoliter scale, resulting in a highly sensitive and automated detection platform. In this talk, I will describe a LSI microfluidic device that integrates RNA extraction, reverse transcription to cDNA, amplification and target pull-down to detect histidine decarboxylase (HDC) gene directly from human white blood cells samples. When anisotropic colloidal semiconductor nanorods (NRs) were used as the fluorescent readout, the detection limit was found to be 0.4 ng of total RNA, which was much lower than that obtained using spherical quantum dots (QDs) or organic dyes. This was attributed to the large action cross-section of NRs and their high probability of target capture in a pull-down detection scheme. The combination of large scale integrated microfluidics with highly fluorescent semiconductor NRs may find widespread utility in point-of-care devices and multi-target diagnostics.

  17. Multi-Dimensional Nanostructures for Microfluidic Screening of Biomarkers: From Molecular Separation to Cancer Cell Detection.

    Science.gov (United States)

    Ng, Elaine; Chen, Kaina; Hang, Annie; Syed, Abeer; Zhang, John X J

    2016-04-01

    Rapid screening of biomarkers, with high specificity and accuracy, is critical for many point-of-care diagnostics. Microfluidics, the use of microscale channels to manipulate small liquid samples and carry reactions in parallel, offers tremendous opportunities to address fundamental questions in biology and provide a fast growing set of clinical tools for medicine. Emerging multi-dimensional nanostructures, when coupled with microfluidics, enable effective and efficient screening with high specificity and sensitivity, both of which are important aspects of biological detection systems. In this review, we provide an overview of current research and technologies that utilize nanostructures to facilitate biological separation in microfluidic channels. Various important physical parameters and theoretical equations that characterize and govern flow in nanostructure-integrated microfluidic channels will be introduced and discussed. The application of multi-dimensional nanostructures, including nanoparticles, nanopillars, and nanoporous layers, integrated with microfluidic channels in molecular and cellular separation will also be reviewed. Finally, we will close with insights on the future of nanostructure-integrated microfluidic platforms and their role in biological and biomedical applications.

  18. Vacuum-driven power-free microfluidics utilizing the gas solubility or permeability of polydimethylsiloxane (PDMS).

    Science.gov (United States)

    Xu, Linfeng; Lee, Hun; Jetta, Deekshitha; Oh, Kwang W

    2015-10-21

    Suitable pumping methods for flow control remain a major technical hurdle in the path of biomedical microfluidic systems for point-of-care (POC) diagnostics. A vacuum-driven power-free micropumping method provides a promising solution to such a challenge. In this review, we focus on vacuum-driven power-free microfluidics based on the gas solubility or permeability of polydimethylsiloxane (PDMS); degassed PDMS can restore air inside itself due to its high gas solubility or gas permeable nature. PDMS allows the transfer of air into a vacuum through it due to its high gas permeability. Therefore, it is possible to store or transfer air into or through the gas soluble or permeable PDMS in order to withdraw liquids into the embedded dead-end microfluidic channels. This article provides a comprehensive look at the physics of the gas solubility and permeability of PDMS, a systematic review of different types of vacuum-driven power-free microfluidics, and guidelines for designing solubility-based or permeability-based PDMS devices, alongside existing applications. Advanced topics and the outlook in using micropumping that utilizes the gas solubility or permeability of PDMS will be also discussed. We strongly recommend that microfluidics and lab-on-chip (LOC) communities harness vacuum energy to develop smart vacuum-driven microfluidic systems.

  19. Imaging label-free biosensor with microfluidic system

    Science.gov (United States)

    Jahns, S.; Glorius, P.; Hansen, M.; Nazirizadeh, Y.; Gerken, M.

    2015-06-01

    We present a microfluidic system suitable for parallel label-free detection of several biomarkers utilizing a compact imaging measurement system. The microfluidic system contains a filter unit to separate the plasma from human blood and a functionalized, photonic crystal slab sensor chip. The nanostructure of the photonic crystal slab sensor chip is fabricated by nanoimprint lithography of a period grating surface into a photoresist and subsequent deposition of a TiO2 layer. Photonic crystal slabs are slab waveguides supporting quasi-guided modes coupling to far-field radiation, which are sensitive to refractive index changes due to biomarker binding on the functionalized surface. In our imaging read-out system the resulting resonance shift of the quasi-guided mode in the transmission spectrum is converted into an intensity change detectable with a simple camera. By continuously taking photographs of the sensor surface local intensity changes are observed revealing the binding kinetics of the biomarker to its specific target. Data from two distinct measurement fields are used for evaluation. For testing the sensor chip, 1 μM biotin as well as 1 μM recombinant human CD40 ligand were immobilized in spotsvia amin coupling to the sensor surface. Each binding experiment was performed with 250 nM streptavidin and 90 nM CD40 ligand antibody dissolved in phosphate buffered saline. In the next test series, a functionalized sensor chip was bonded onto a 15 mm x 15 mm opening of the 75 mm x 25 mm x 2 mm microfluidic system. We demonstrate the functionality of the microfluidic system for filtering human blood such that only blood plasma was transported to the sensor chip. The results of first binding experiments in buffer with this test chip will be presented.

  20. Vibration Induced Microfluidic Atomization

    Science.gov (United States)

    Yeo, Leslie; Qi, Aisha; Friend, James

    2008-11-01

    We demonstrate rapid generation of micron aerosol droplets in a microfluidic device in which a fluid drop is exposed to surface vibration as it sits atop a piezoelectric substrate. Little, however, is understood about the processes by which these droplets form due to the complex hydrodynamic processes that occur across widely varying length and time scales. Through experiments, scaling theory and numerical modelling, we elucidate the interfacial destabilization mechanisms that lead to droplet formation. Droplets form due to the axisymmetric break-up of cylindrical liquid jets ejected as a consequence of interfacial destabilization. Their 10 μm size correlates with the jet radius and the instability wavelength, both determined from a viscous-capillary dominant force balance and confirmed through a numerical solution. With the exception of drops that spread into thin films with thicknesses on the order of the boundary layer dimension, the free surface is always observed to vibrate at the capillary-viscous resonance frequency despite the surface vibration frequency being several orders larger. This is contrary to common assumptions used in deriving subharmonic models resulting in a Mathieu equation, which has commonly led to spurious predictions in the droplet size.

  1. A microfluidic microprocessor: controlling biomimetic containers and cells using hybrid integrated circuit/microfluidic chips.

    Science.gov (United States)

    Issadore, David; Franke, Thomas; Brown, Keith A; Westervelt, Robert M

    2010-11-01

    We present an integrated platform for performing biological and chemical experiments on a chip based on standard CMOS technology. We have developed a hybrid integrated circuit (IC)/microfluidic chip that can simultaneously control thousands of living cells and pL volumes of fluid, enabling a wide variety of chemical and biological tasks. Taking inspiration from cellular biology, phospholipid bilayer vesicles are used as robust picolitre containers for reagents on the chip. The hybrid chip can be programmed to trap, move, and porate individual living cells and vesicles and fuse and deform vesicles using electric fields. The IC spatially patterns electric fields in a microfluidic chamber using 128 × 256 (32,768) 11 × 11 μm(2) metal pixels, each of which can be individually driven with a radio frequency (RF) voltage. The chip's basic functions can be combined in series to perform complex biological and chemical tasks and can be performed in parallel on the chip's many pixels for high-throughput operations. The hybrid chip operates in two distinct modes, defined by the frequency of the RF voltage applied to the pixels: Voltages at MHz frequencies are used to trap, move, and deform objects using dielectrophoresis and voltages at frequencies below 1 kHz are used for electroporation and electrofusion. This work represents an important step towards miniaturizing the complex chemical and biological experiments used for diagnostics and research onto automated and inexpensive chips.

  2. Hydrogel-coated microfluidic channels for cardiomyocyte culture

    Science.gov (United States)

    Annabi, Nasim; Selimović, Šeila; Cox, Juan Pablo Acevedo; Ribas, João; Bakooshli, Mohsen Afshar; Heintze, Déborah; Weiss, Anthony S.; Cropek, Donald; Khademhosseini, Ali

    2013-01-01

    The research areas of tissue engineering and drug development have displayed increased interest in organ-on-a-chip studies, in which physiologically or pathologically relevant tissues can be engineered to test pharmaceutical candidates. Microfluidic technologies enable the control of the cellular microenvironment for these applications through the topography, size, and elastic properties of the microscale cell culture environment, while delivering nutrients and chemical cues to the cells through continuous media perfusion. Traditional materials used in the fabrication of microfluidic devices, such as poly(dimethylsiloxane) (PDMS), offer high fidelity and high feature resolution, but do not facilitate cell attachment. To overcome this challenge, we have developed a method for coating microfluidic channels inside a closed PDMS device with a cell-compatible hydrogel layer. We have synthesized photocrosslinkable gelatin and tropoelastin-based hydrogel solutions that were used to coat the surfaces under continuous flow inside 50 μm wide, straight microfluidic channels to generate a hydrogel layer on the channel walls. Our observation of primary cardiomyocytes seeded on these hydrogel layers showed preferred attachment as well as higher spontaneous beating rates on tropoelastin coatings compared to gelatin. In addition, cellular attachment, alignment and beating were stronger on 5 % (w/v) hydrogel-coated devices than on 10 % (w/v) gel-coated channels. Our results demonstrate that cardiomyocytes respond favorably to the elastic, soft tropoelastin culture substrates, indicating that tropoelastin-based hydrogels may be a suitable coating choice for some organ-on-a-chip applications. We anticipate that the proposed hydrogel coating method and tropoelastin as a cell culture substrate may be useful for the generation of elastic tissues, e.g. blood vessels, using microfluidic approaches. PMID:23728018

  3. Microfluidic Technologies for Synthetic Biology

    Directory of Open Access Journals (Sweden)

    Sung Kuk Lee

    2011-06-01

    Full Text Available Microfluidic technologies have shown powerful abilities for reducing cost, time, and labor, and at the same time, for increasing accuracy, throughput, and performance in the analysis of biological and biochemical samples compared with the conventional, macroscale instruments. Synthetic biology is an emerging field of biology and has drawn much attraction due to its potential to create novel, functional biological parts and systems for special purposes. Since it is believed that the development of synthetic biology can be accelerated through the use of microfluidic technology, in this review work we focus our discussion on the latest microfluidic technologies that can provide unprecedented means in synthetic biology for dynamic profiling of gene expression/regulation with high resolution, highly sensitive on-chip and off-chip detection of metabolites, and whole-cell analysis.

  4. Magnetic separation in microfluidic systems

    DEFF Research Database (Denmark)

    Smistrup, Kristian

    2007-01-01

    This Ph.D. thesis presents theory, modeling, design, fabrication, experiments and results for microfluidic magnetic separators. A model for magnetic bead movement in a microfluidic channel is presented, and the limits of the model are discussed. The effective magnetic field gradient is defined...... for fabrication of silicon based systems. This fabrication scheme is explained, and it is shown how, it is applied with variations for several designs of magnetic separators. An experimental setup for magnetic separation experiments has been developed. It has been coupled with an image analysis program....... It is shown conceptually how such a system can be applied for parallel biochemical processing in a microfluidic system. ’Passive’ magnetic separators are presented, where on-chip soft magnetic elements are magnetized by an external magnetic field and create strong magnetic fields and gradients inside...

  5. Analysis system for characterisation of simple, low-cost microfluidic components

    Science.gov (United States)

    Smith, Suzanne; Naidoo, Thegaran; Nxumalo, Zandile; Land, Kevin; Davies, Emlyn; Fourie, Louis; Marais, Philip; Roux, Pieter

    2014-06-01

    There is an inherent trade-off between cost and operational integrity of microfluidic components, especially when intended for use in point-of-care devices. We present an analysis system developed to characterise microfluidic components for performing blood cell counting, enabling the balance between function and cost to be established quantitatively. Microfluidic components for sample and reagent introduction, mixing and dispensing of fluids were investigated. A simple inlet port plugging mechanism is used to introduce and dispense a sample of blood, while a reagent is released into the microfluidic system through compression and bursting of a blister pack. Mixing and dispensing of the sample and reagent are facilitated via air actuation. For these microfluidic components to be implemented successfully, a number of aspects need to be characterised for development of an integrated point-of-care device design. The functional components were measured using a microfluidic component analysis system established in-house. Experiments were carried out to determine: 1. the force and speed requirements for sample inlet port plugging and blister pack compression and release using two linear actuators and load cells for plugging the inlet port, compressing the blister pack, and subsequently measuring the resulting forces exerted, 2. the accuracy and repeatability of total volumes of sample and reagent dispensed, and 3. the degree of mixing and dispensing uniformity of the sample and reagent for cell counting analysis. A programmable syringe pump was used for air actuation to facilitate mixing and dispensing of the sample and reagent. Two high speed cameras formed part of the analysis system and allowed for visualisation of the fluidic operations within the microfluidic device. Additional quantitative measures such as microscopy were also used to assess mixing and dilution accuracy, as well as uniformity of fluid dispensing - all of which are important requirements towards the

  6. Microfluidic 3D Helix Mixers

    Directory of Open Access Journals (Sweden)

    Georgette B. Salieb-Beugelaar

    2016-10-01

    Full Text Available Polymeric microfluidic systems are well suited for miniaturized devices with complex functionality, and rapid prototyping methods for 3D microfluidic structures are increasingly used. Mixing at the microscale and performing chemical reactions at the microscale are important applications of such systems and we therefore explored feasibility, mixing characteristics and the ability to control a chemical reaction in helical 3D channels produced by the emerging thread template method. Mixing at the microscale is challenging because channel size reduction for improving solute diffusion comes at the price of a reduced Reynolds number that induces a strictly laminar flow regime and abolishes turbulence that would be desired for improved mixing. Microfluidic 3D helix mixers were rapidly prototyped in polydimethylsiloxane (PDMS using low-surface energy polymeric threads, twisted to form 2-channel and 3-channel helices. Structure and flow characteristics were assessed experimentally by microscopy, hydraulic measurements and chromogenic reaction, and were modeled by computational fluid dynamics. We found that helical 3D microfluidic systems produced by thread templating allow rapid prototyping, can be used for mixing and for controlled chemical reaction with two or three reaction partners at the microscale. Compared to the conventional T-shaped microfluidic system used as a control device, enhanced mixing and faster chemical reaction was found to occur due to the combination of diffusive mixing in small channels and flow folding due to the 3D helix shape. Thus, microfluidic 3D helix mixers can be rapidly prototyped using the thread template method and are an attractive and competitive method for fluid mixing and chemical reactions at the microscale.

  7. Fluid control in microfluidic devices using a fluid conveyance extension and an absorbent microfluidic flow modulator.

    Science.gov (United States)

    Yuen, Po Ki

    2013-05-07

    This article presents a simple method for controlling fluid in microfluidic devices without the need for valves or pumps. A fluid conveyance extension is fluidly coupled to the enclosed outlet chamber of a microfluidic device. After a fluid is introduced into the microfluidic device and saturates the fluid conveyance extension, a fluid flow in the microfluidic device is generated by contacting an absorbent microfluidic flow modulator with the fluid conveyance extension to absorb the fluid from the fluid conveyance extension through capillary action. Since the fluid in the microfluidic device is fluidly coupled with the fluid conveyance extension and the fluid conveyance extension is fluidly coupled with the absorbent microfluidic flow modulator, the absorption rate of the absorbent microfluidic flow modulator, which is the rate at which the absorbent microfluidic flow modulator absorbs fluid, matches the fluid flow rate in the microfluidic device. Thus, the fluid flow rate in the microfluidic device is set by the absorption rate of the absorbent microfluidic flow modulator. Sheath flow and fluid switching applications are demonstrated using this simple fluid control method without the need for valves or pumps. Also, the ability to control the fluid flow rate in the microfluidic device is demonstrated using absorbent microfluidic flow modulators with various absorbent characteristics and dimensions.

  8. High efficiency microfluidic beta detector for pharmacokinetic studies in small animals

    Energy Technology Data Exchange (ETDEWEB)

    Convert, Laurence, E-mail: Laurence.Convert@USherbrooke.ca [Nanofabrication and Nanocharacterization Research Center (CRN2), Department of Electrical and Computer Engineering, Faculty of Engineering, Universite de Sherbrooke, 2500 Blvd Universite, Sherbrooke, Quebec, J1K 2R1 (Canada); Girard-Baril, Frederique, E-mail: Frederique.Girard.Baril@USherbrooke.ca [Nanofabrication and Nanocharacterization Research Center (CRN2), Department of Electrical and Computer Engineering, Faculty of Engineering, Universite de Sherbrooke, 2500 Blvd Universite, Sherbrooke, Quebec, J1K 2R1 (Canada); Renaudin, Alan, E-mail: Alan.Renaudin@USherbrooke.ca [Nanofabrication and Nanocharacterization Research Center (CRN2), Department of Electrical and Computer Engineering, Faculty of Engineering, Universite de Sherbrooke, 2500 Blvd Universite, Sherbrooke, Quebec, J1K 2R1 (Canada); Grondin, Etienne, E-mail: E.Grondin@USherbrooke.ca [Nanofabrication and Nanocharacterization Research Center (CRN2), Department of Electrical and Computer Engineering, Faculty of Engineering, Universite de Sherbrooke, 2500 Blvd Universite, Sherbrooke, Quebec, J1K 2R1 (Canada); Jaouad, Abdelatif, E-mail: Abdelatif.Jaouad@USherbrooke.ca [Nanofabrication and Nanocharacterization Research Center (CRN2), Department of Electrical and Computer Engineering, Faculty of Engineering, Universite de Sherbrooke, 2500 Blvd Universite, Sherbrooke, Quebec, J1K 2R1 (Canada); Aimez, Vincent, E-mail: Vincent.Aimez@USherbrooke.ca [Nanofabrication and Nanocharacterization Research Center (CRN2), Department of Electrical and Computer Engineering, Faculty of Engineering, Universite de Sherbrooke, 2500 Blvd Universite, Sherbrooke, Quebec, J1K 2R1 (Canada); and others

    2011-10-01

    New radiotracers are continuously being developed to improve diagnostic efficiency using Single Photon Emission Computed Tomography (SPECT) or Positron Emission Tomography (PET). The characterization of their pharmacokinetics requires blood radioactivity monitoring over time during the scan and is very challenging in small animals because of the low volume of blood available. In this work, a prototype microfluidic blood counter made of a microchannel atop a silicon substrate containing PIN photodiodes is proposed to improve beta detection efficiency in a small volume by eliminating unnecessary interfaces between fluid and detector. A flat rectangular-shaped epoxy channel, 36 {mu}mx1.26 mm cross section and 31.5 mm in length, was microfabricated over a die containing an array of 2x2 mm{sup 2} PIN photodiodes, leaving only a few micrometers of epoxy floor layer between the fluid and the photodiode sensitive surface. This geometry leads to a quasi 2D source, optimizing geometrical detection efficiency that was estimated at 41% using solid angle calculation. CV-IV measurements were made at each fabrication step to confirm that the microchannel components had no significant effects on the diodes' electrical characteristics. The chip was wire-bonded to a PCB and connected to charge sensitive preamplifier and amplifier modules for pulse shaping. Energy spectra recorded for different isotopes showed continuous beta distribution for PET isotopes and monoenergetic conversion electron peaks for {sup 99m}Tc. Absolute sensitivity was determined for the most popular PET and SPECT radioisotopes and ranged from 26% to 33% for PET tracers ({sup 18}F, {sup 13}N, {sup 11}C, {sup 68}Ga) and more than 2% for {sup 99m}Tc. Input functions were successfully simulated with {sup 18}F, confirming the setup's suitability for pharmacokinetic modeling of PET and SPECT radiotracers in animal experiments. By using standard materials and procedures, the fabrication process is well suited

  9. Microfluidic device for drug delivery

    Science.gov (United States)

    Beebe, David J. (Inventor); MacDonald, Michael J. (Inventor); Eddington, David T. (Inventor); Mensing, Glennys A. (Inventor)

    2010-01-01

    A microfluidic device is provided for delivering a drug to an individual. The microfluidic device includes a body that defines a reservoir for receiving the drug therein. A valve interconnects the reservoir to an output needle that is insertable into the skin of an individual. A pressure source urges the drug from the reservoir toward the needle. The valve is movable between a closed position preventing the flow of the drug from the reservoir to the output needle and an open position allowing for the flow of the drug from the reservoir to the output needle in response to a predetermined condition in the physiological fluids of the individual.

  10. Microfluidic devices for droplet injection

    Science.gov (United States)

    Aubrecht, Donald; Akartuna, Ilke; Weitz, David

    2012-02-01

    As picoliter-scale reaction vessels, microfluidic water-in-oil emulsions have found application for high-throughput, large-sample number analyses. Often, the biological or chemical system under investigation needs to be encapsulated into droplets to prevent cross contamination prior to the introduction of reaction reagents. Previous techniques of picoinjection or droplet synchronization and merging enable the addition of reagents to individual droplets, but present limitations on what can be added to each droplet. We present microfluidic devices that couple the strengths of picoinjection and droplet merging, allowing us to selectively add precise volume to our droplet reactions.

  11. Integrated microfluidic systems for DNA analysis.

    Science.gov (United States)

    Njoroge, Samuel K; Chen, Hui-Wen; Witek, Małgorzata A; Soper, Steven A

    2011-01-01

    The potential utility of genome-related research in terms of evolving basic discoveries in biology has generated widespread use of DNA diagnostics and DNA forensics and driven the accelerated development of fully integrated microfluidic systems for genome processing. To produce a microsystem with favorable performance characteristics for genetic-based analyses, several key operational elements must be strategically chosen, including device substrate material, temperature control, fluidic control, and reaction product readout. As a matter of definition, a microdevice is a chip that performs a single processing step, for example microchip electrophoresis. Several microdevices can be integrated to a single wafer, or combined on a control board as separate devices to form a microsystem. A microsystem is defined as a chip composed of at least two microdevices. Among the many documented analytical microdevices, those focused on the ability to perform the polymerase chain reaction (PCR) have been reported extensively due to the importance of this processing step in most genetic-based assays. Other microdevices that have been detailed in the literature include those for solid-phase extractions, microchip electrophoresis, and devices composed of DNA microarrays used for interrogating DNA primary structure. Great progress has also been made in the areas of chip fabrication, bonding and sealing to enclose fluidic networks, evaluation of different chip substrate materials, surface chemistries, and the architecture of reaction conduits for basic processing steps such as mixing. Other important elements that have been developed to realize functional systems include miniaturized readout formats comprising optical or electrochemical transduction and interconnect technologies. These discoveries have led to the development of fully autonomous and functional integrated systems for genome processing that can supply "sample in/answer out" capabilities. In this chapter, we focus on

  12. A personification heuristic Genetic Algorithm for Digital Microfluidics-based Biochips Placement

    Directory of Open Access Journals (Sweden)

    Jingsong Yang

    2013-06-01

    Full Text Available A personification heuristic Genetic Algorithm is established for the placement of digital microfluidics-based biochips, in which, the personification heuristic algorithm is used to control the packing process, while the genetic algorithm is designed to be used in multi-objective placement results optimizing. As an example, the process of microfluidic module physical placement in multiplexed in-vitro diagnostics on human physiological fluids is simulated. The experiment results show that personification heuristic genetic algorithm can achieve better results in multi-objective optimization, compare to the parallel recombinative simulated annealing algorithm.

  13. MICROFLUIDIC MODULES FOR ISOLATION OF RECOMBINANT CYTOKINE FROM BACTERIAL LYSATES

    Energy Technology Data Exchange (ETDEWEB)

    Retterer, Scott T [ORNL; Doktycz, Mitchel John [ORNL

    2014-01-01

    The portability and personalization of health-care diagnostics and treatments benefits from advancements and applications of micro and nanotechnology. Modularization and miniaturization of standardized biochemical processes and tests facilitates the advancement and customization of analyte detection and diagnosis on-chip. The goal of our work here is to develop modular platforms for on-chip biochemical processing of synthesized biologics for a range of on-demand applications. Our report focuses on the initial development, characterization and application of microfluidic size exclusion/gel filtration and ion exchange protein concentration modules for cytokine isolation from spiked cell extracts.

  14. Latex micro-balloon pumping in centrifugal microfluidic platforms.

    Science.gov (United States)

    Aeinehvand, Mohammad Mahdi; Ibrahim, Fatimah; Harun, Sulaiman Wadi; Al-Faqheri, Wisam; Thio, Tzer Hwai Gilbert; Kazemzadeh, Amin; Madou, Marc

    2014-03-01

    Centrifugal microfluidic platforms have emerged as point-of-care diagnostic tools. However, the unidirectional nature of the centrifugal force limits the available space for multi-step processes on a single microfluidic disc. To overcome this limitation, a passive pneumatic pumping method actuated at high rotational speeds has been previously proposed to pump liquid against the centrifugal force. In this paper, a novel micro-balloon pumping method that relies on elastic energy stored in a latex membrane is introduced. It operates at low rotational speeds and pumps a larger volume of liquid towards the centre of the disc. Two different micro-balloon pumping mechanisms have been designed to study the pump performance at a range of rotational frequencies from 0 to 1500 rpm. The behaviour of the micro-balloon pump on the centrifugal microfluidic platforms has been theoretically analysed and compared with the experimental data. The experimental data show that the developed pumping method dramatically decreases the required rotational speed to pump liquid compared to the previously developed pneumatic pumping methods. It also shows that within a range of rotational speed, a desirable volume of liquid can be stored and pumped by adjusting the size of the micro-balloon.

  15. Challenges and Opportunities of Centrifugal Microfluidics for Extreme Point-of-Care Testing

    Directory of Open Access Journals (Sweden)

    Issac J. Michael

    2016-02-01

    Full Text Available The advantages offered by centrifugal microfluidic systems have encouraged its rapid adaptation in the fields of in vitro diagnostics, clinical chemistry, immunoassays, and nucleic acid tests. Centrifugal microfluidic devices are currently used in both clinical and point-of-care settings. Recent studies have shown that this new diagnostic platform could be potentially used in extreme point-of-care settings like remote villages in the Indian subcontinent and in Africa. Several technological inventions have decentralized diagnostics in developing countries; however, very few microfluidic technologies have been successful in meeting the demand. By identifying the finest difference between the point-of-care testing and extreme point-of-care infrastructure, this review captures the evolving diagnostic needs of developing countries paired with infrastructural challenges with technological hurdles to healthcare delivery in extreme point-of-care settings. In particular, the requirements for making centrifugal diagnostic devices viable in developing countries are discussed based on a detailed analysis of the demands in different clinical settings including the distinctive needs of extreme point-of-care settings.

  16. The impact of new trends in POCTs for companion diagnostics, non-invasive testing and molecular diagnostics.

    Science.gov (United States)

    Huckle, David

    2015-06-01

    Point-of-care diagnostics have been slowly developing over several decades and have taken on a new importance in current healthcare delivery for both diagnostics and development of new drugs. Molecular diagnostics have become a key driver of technology change and opened up new areas in companion diagnostics for use alongside pharmaceuticals and in new clinical approaches such as non-invasive testing. Future areas involving smartphone and other information technology advances, together with new developments in molecular biology, microfluidics and surface chemistry are adding to advances in the market. The focus for point-of-care tests with molecular diagnostic technologies is focused on advancing effective applications.

  17. Mixing in a Microfluid Device

    DEFF Research Database (Denmark)

    Hjorth, Poul G.; Deryabin, Mikhail

    Mixing of fluids in microchannels cannot rely on turbulence since the flow takes place at extremly low Reynolds numbers. Various active and passive devices have been developed to induce mixing in microfluid flow devices. We describe here a model of an active mixer where a transverse periodic flow...

  18. Microfluidic fabrication of plasmonic microcapsules

    NARCIS (Netherlands)

    Wang, J.; Jin, M.L.; Eijkel, J.C.T.; Berg, van den A.; Zhou, G.F.; Shui, L.L.

    2016-01-01

    This paper presents the plasmonic microcapsules with well-ordered nanoparticles embedded in polymer network fabricated by using a microfluidic device. The well-ordered nanoparticle arrays on the microcapsule form high-density uniform “hot-spots” with a deposited metal film, on which the localized su

  19. Microfluidic technology for PET radiochemistry

    Energy Technology Data Exchange (ETDEWEB)

    Gillies, J.M. [Cancer Research-UK/University of Manchester Radiochemical Targeting and Imaging Group, Paterson Institute for Cancer Research, Manchester, M20 4BX (United Kingdom)]. E-mail: jgillies@picr.man.ac.uk; Prenant, C. [Cancer Research-UK/University of Manchester Radiochemical Targeting and Imaging Group, Paterson Institute for Cancer Research, Manchester, M20 4BX (United Kingdom); School of Chemical Engineering and Analytical Sciences, University of Manchester, P.O. Box 88, Manchester, M60 1QD (United Kingdom); Chimon, G.N. [Cancer Research-UK/University of Manchester Radiochemical Targeting and Imaging Group, Paterson Institute for Cancer Research, Manchester, M20 4BX (United Kingdom); School of Chemical Engineering and Analytical Sciences, University of Manchester, P.O. Box 88, Manchester, M60 1QD (United Kingdom); Smethurst, G.J. [Cancer Research-UK/University of Manchester Radiochemical Targeting and Imaging Group, Paterson Institute for Cancer Research, Manchester, M20 4BX (United Kingdom); Dekker, B.A. [Cancer Research-UK/University of Manchester Radiochemical Targeting and Imaging Group, Paterson Institute for Cancer Research, Manchester, M20 4BX (United Kingdom); Zweit, J. [Cancer Research-UK/University of Manchester Radiochemical Targeting and Imaging Group, Paterson Institute for Cancer Research, Manchester, M20 4BX (United Kingdom); School of Chemical Engineering and Analytical Sciences, University of Manchester, P.O. Box 88, Manchester, M60 1QD (United Kingdom)

    2006-03-15

    This paper describes the first application of a microfabricated reaction system to positron emission tomography (PET) radiochemistry. We have applied microfluidic technology to synthesise PET radiopharmaceuticals using {sup 18}F and {sup 124}I as labels for fluorodeoxyglucose (FDG) and Annexin-V, respectively. These reactions involved established methods of nucleophilic substitution on a mannose triflate precursor and direct iodination of the protein using iodogen as an oxidant. This has demonstrated a proof of principle of using microfluidic technology to radiochemical reactions involving low and high molecular weight compounds. Using microfluidic reactions, [{sup 18}F]FDG was synthesised with a 50% incorporation of the available F-18 radioactivity in a very short time of 4 s. The radiolabelling efficiency of {sup 124}I Annexin-V was 40% after 1 min reaction time. Chromatographic analysis showed that such reaction yields are comparable to conventional methods, but in a much shorter time. The yields can be further improved with more optimisation of the microfluidic device itself and its fluid mixing profiles. This demonstrates the potential for this technology to have an impact on rapid and simpler radiopharmaceutical synthesis using short and medium half-life radionuclides.

  20. Topology optimization of microfluidic mixers

    DEFF Research Database (Denmark)

    Andreasen, Casper Schousboe; Gersborg, Allan Roulund; Sigmund, Ole

    2009-01-01

    This paper demonstrates the application of the topology optimization method as a general and systematic approach for microfluidic mixer design. The mixing process is modeled as convection dominated transport in low Reynolds number incompressible flow. The mixer performance is maximized by altering...

  1. Microfluidic free-flow zone electrophoresis and isotachophoresis using carbon black nano-composite PDMS sidewall membranes.

    Science.gov (United States)

    Fu, Xiaotong; Mavrogiannis, Nicholas; Ibo, Markela; Crivellari, Francesca; Gagnon, Zachary R

    2017-01-01

    We present a new type of free-flow electrophoresis (FFE) device for performing on-chip microfluidic isotachophoresis and zone electrophoresis. FFE is performed using metal gallium electrodes, which are isolated from a main microfluidic flow channel using thin micron-scale polydimethylsiloxane/carbon black (PDMS/CB) composite membranes integrated directly into the sidewalls of the microfluidic channel. The thin membrane allows for field penetration and effective electrophoresis, but serves to prevent bubble generation at the electrodes from electrolysis. We experimentally demonstrate the ability to use this platform to perform on-chip free-flow electrophoretic separation and isotachophoretic concentration. Due to the small size and simple fabrication procedure, this PDMS/CB platform could be used as a part of an on-chip upstream sample preparation toolkit for portable microfluidic diagnostic applications.

  2. Spintronic microfluidic platform for biomedical and environmental applications

    Science.gov (United States)

    Cardoso, F. A.; Martins, V. C.; Fonseca, L. P.; Germano, J.; Sousa, L. A.; Piedade, M. S.; Freitas, P. P.

    2010-09-01

    Faster, more sensitive and easy to operate biosensing devices still are a need at important areas such as biomedical diagnostics, food control and environmental monitoring. Recently, spintronic-devices have emerged as a promising alternative to the existent technologies [1-3]. A number of advantages, namely high sensitivity, easy integration, miniaturization, scalability, robustness and low cost make these devices potentially capable of responding to the existent technological need. In parallel, the field of microfluidics has shown great advances [4]. Microfluidic systems allow the analysis of small sample volumes (from micro- down to pico-liters), often by automate sample processing with the ability to integrate several steps into a single device (analyte amplification, concentration, separation and/or labeling), all in a reduced assay time (minutes to hours) and affordable cost. The merging of these two technologies, magnetoresistive biochips and microfluidics, will enable the development of highly competitive devices. This work reports the integration of a magnetoresistive biochip with a microfluidic system inside a portable and autonomous electronic platform aiming for a fully integrated device. A microfluidic structure fabricated in polydimethylsiloxane with dimensions of W: 0.5mm, H: 0.1mm, L: 10mm, associated to a mechanical system to align and seal the channel by pressure is presented (Fig. 1) [5]. The goal is to perform sample loading and transportation over the chip and simultaneously control the stringency and uniformity of the wash-out process. The biochip output is acquired by an electronic microsystem incorporating the circuitry to control, address and read-out the 30 spin-valve sensors sequentially (Fig. 1) [2]. This platform is being applied to the detection of water-borne microbial pathogens (e.g. Salmonella and Escherichia coli) and genetic diseases diagnosis (e.g. cystic fibrosis) through DNA hybridization assays. Open chamber measurements were

  3. Optimization of a microfluidic electrophoretic immunoassay using a Peltier cooler.

    Science.gov (United States)

    Mukhitov, Nikita; Yi, Lian; Schrell, Adrian M; Roper, Michael G

    2014-11-07

    Successful analysis of electrophoretic affinity assays depends strongly on the preservation of the affinity complex during separations. Elevated separation temperatures due to Joule heating promotes complex dissociation leading to a reduction in sensitivity. Affinity assays performed in glass microfluidic devices may be especially prone to this problem due to poor heat dissipation due to the low thermal conductivity of glass and the large amount of bulk material surrounding separation channels. To address this limitation, a method to cool a glass microfluidic chip for performing an affinity assay for insulin was achieved by a Peltier cooler localized over the separation channel. The Peltier cooler allowed for rapid stabilization of temperatures, with 21°C the lowest temperature that was possible to use without producing detrimental thermal gradients throughout the device. The introduction of cooling improved the preservation of the affinity complex, with even passive cooling of the separation channel improving the amount of complex observed by 2-fold. Additionally, the capability to thermostabilize the separation channel allowed for utilization of higher separation voltages than what was possible without temperature control. Kinetic CE analysis was utilized as a diagnostic of the affinity assay and indicated that optimal conditions were at the highest separation voltage, 6 kV, and the lowest separation temperature, 21°C, leading to 3.4% dissociation of the complex peak during the separation. These optimum conditions were used to generate a calibration curve and produced 1 nM limits of detection, representing a 10-fold improvement over non-thermostated conditions. This methodology of cooling glass microfluidic devices for performing robust and high sensitivity affinity assays on microfluidic systems should be amenable in a number of applications.

  4. Probing cell mechanical properties with microfluidic devices

    Science.gov (United States)

    Rowat, Amy

    2012-02-01

    Exploiting flow on the micron-scale is emerging as a method to probe cell mechanical properties with 10-1000x advances in throughput over existing technologies. The mechanical properties of cells and the cell nucleus are implicated in a wide range of biological contexts: for example, the ability of white blood cells to deform is central to immune response; and malignant cells show decreased stiffness compared to benign cells. We recently developed a microfluidic device to probe cell and nucleus mechanical properties: cells are forced to deform through a narrow constrictions in response to an applied pressure; flowing cells through a series of constrictions enables us to probe the ability of hundreds of cells to deform and relax during flow. By tuning the constriction width so it is narrower than the width of the cell nucleus, we can specifically probe the effects of nuclear physical properties on whole cell deformability. We show that the nucleus is the rate-limiting step in cell passage: inducing a change in its shape to a multilobed structure results in cells that transit more quickly; increased levels of lamin A, a nuclear protein that is key for nuclear shape and mechanical stability, impairs the passage of cells through constrictions. We are currently developing a new class of microfluidic devices to simultaneously probe the deformability of hundreds of cell samples in parallel. Using the same soft lithography techniques, membranes are fabricated to have well-defined pore distribution, width, length, and tortuosity. We design the membranes to interface with a multiwell plate, enabling simultaneous measurement of hundreds of different samples. Given the wide spectrum of diseases where altered cell and nucleus mechanical properties are implicated, such a platform has great potential, for example, to screen cells based on their mechanical phenotype against a library of drugs.

  5. Flow Manipulation in Thread-Based Microfluidics by Tuning the Wettability of Wool.

    Science.gov (United States)

    Jeon, So-Hyoun; Hwang, Ki-Hwan; Jung, Won Suk; Seo, Hyeon-Jin; Nam, Sung Woo; Boo, Jin-Hyo; Yun, Sang H

    2015-02-01

    Recent progress in thread-based microfluidic devices has provided portable and inexpensive field-based technologies enabling medical diagnostics, environmental monitoring, and food safety analysis. However, capillary-driven liquid flow in a single thread, a crucial aspect of thread-based microfluidics, is difficult to control. Among potential materials, hydrophobic wool thread is an appropriate candidate for liquid flow control in thread-based microfluidics because its wettability can be readily tuned by the introduction of a natural color pigment, thereby manipulating flow. Thus, utilizing natural wool thread as a channel, we demonstrate here that liquid flow manipulations, such as microselecting and micromixing, can be achieved by coating the complex Al(III) (Alum) brazilein onto wool thread. In addition to enabling flow control, the coated wool channels consisting entirely of naturally occurring substances will be beneficial for biological sensing devices.

  6. Vacuum/compression valving (VCV) using parrafin-wax on a centrifugal microfluidic CD platform.

    Science.gov (United States)

    Al-Faqheri, Wisam; Ibrahim, Fatimah; Thio, Tzer Hwai Gilbert; Moebius, Jacob; Joseph, Karunan; Arof, Hamzah; Madou, Marc

    2013-01-01

    This paper introduces novel vacuum/compression valves (VCVs) utilizing paraffin wax. A VCV is implemented by sealing the venting channel/hole with wax plugs (for normally-closed valve), or to be sealed by wax (for normally-open valve), and is activated by localized heating on the CD surface. We demonstrate that the VCV provides the advantages of avoiding unnecessary heating of the sample/reagents in the diagnostic process, allowing for vacuum sealing of the CD, and clear separation of the paraffin wax from the sample/reagents in the microfluidic process. As a proof of concept, the microfluidic processes of liquid flow switching and liquid metering is demonstrated with the VCV. Results show that the VCV lowers the required spinning frequency to perform the microfluidic processes with high accuracy and ease of control.

  7. Distribution of certain drug products by registered blood establishments and comprehensive hemophilia diagnostic treatment centers that qualify as health care entities; Prescription Drug Marketing Act of 1987; Prescription Drug Amendments of 1992; policies, requirements and administrative procedures. Final rule.

    Science.gov (United States)

    2008-10-09

    The Food and Drug Administration (FDA) is amending its regulations to allow certain registered blood establishments and comprehensive hemophilia diagnostic treatment centers that are also health care entities to distribute certain drug products. The final rule amends limited provisions of the regulations implementing the Prescription Drug Marketing Act of 1987 (PDMA), as modified by the Prescription Drug Amendments of 1992 (PDA). These regulations, among other things, restrict the sale, purchase, or trade of, or the offer to sell, purchase, or trade, prescription drugs purchased by hospitals and other health care entities.

  8. Performance and scaling effects in a multilayer microfluidic extracorporeal lung oxygenation device.

    Science.gov (United States)

    Kniazeva, Tatiana; Epshteyn, Alla A; Hsiao, James C; Kim, Ernest S; Kolachalama, Vijaya B; Charest, Joseph L; Borenstein, Jeffrey T

    2012-05-07

    Microfluidic fabrication technologies are emerging as viable platforms for extracorporeal lung assist devices and oxygenators for cardiac surgical support and critical care medicine, based in part on their ability to more closely mimic the architecture of the human vasculature than existing technologies. In comparison with current hollow fiber oxygenator technologies, microfluidic systems have more physiologically-representative blood flow paths, smaller cross section blood conduits and thinner gas transfer membranes. These features can enable smaller device sizes and a reduced blood volume in the oxygenator, enhanced gas transfer efficiencies, and may also reduce the tendency for clotting in the system. Several critical issues need to be addressed in order to advance this technology from its current state and implement it in an organ-scale device for clinical use. Here we report on the design, fabrication and characterization of multilayer microfluidic oxygenators, investigating scaling effects associated with fluid mechanical resistance, oxygen transfer efficiencies, and other parameters in multilayer devices. Important parameters such as the fluidic resistance of interconnects are shown to become more predominant as devices are scaled towards many layers, while other effects such as membrane distensibility become less significant. The present study also probes the relationship between blood channel depth and membrane thickness on oxygen transfer, as well as the rate of oxygen transfer on the number of layers in the device. These results contribute to our understanding of the complexity involved in designing three-dimensional microfluidic oxygenators for clinical applications.

  9. What is happening? The evolving role of the blood bank in the management of the bleeding patient: The impact of TEG as an early diagnostic predictor for bleeding.

    Science.gov (United States)

    Espinosa, Aurora; Seghatchian, Jerard

    2014-12-01

    Despite recent advances in the understanding and treatment of coagulopathy, the management of the bleeding patient remains as a major challenge. Traditionally, the main task of the blood bank has been to guarantee the supply of high quality blood and blood components/products to the hospital. Decisions regarding the use of blood components have always been the clinicians' responsibility, with little active involvement of the transfusion service. In the last years, many hospitals have implemented the use of "acute transfusion packages" for massively bleeding patients and point-of-care (POC) instruments such as TEG and RoTEM for monitoring coagulation status in this patient group. This, in addition to the implementation of patient blood management programs in the hospitals, has led to an increasing involvement of transfusion medicine specialists in transfusion decision making, especially regarding strategies for monitoring and treatment of the massively bleeding patient. This new trend may contribute to a more optimal management and monitoring of the bleeding patient, as POC testing may be used as an early predictor for blood usage. The blood bank should optimise the use of POC testing to provide accurate information in a cost-effective way.

  10. Microfluidics-Based Biosensors: A Microfluidic Paper-Based Origami Nanobiosensor for Label-Free, Ultrasensitive Immunoassays (Adv. Healthcare Mater. 11/2016).

    Science.gov (United States)

    Li, Xiao; Liu, Xinyu

    2016-06-01

    The first microfluidic paper-based origami nano-biosensor featuring zinc oxide nanowires and an electrochemical impedance spectroscopy biosensing mechanism, for label-free, ultrasensitive immunoassays is reported by X. Li and X. Liu on page 1326. The sensor consists of cellulose paper, a carbon ink electrode, and zinc oxide nanowires directly grown on the top. Possible parallelization of assays and high storage stability render the sensor promising for clinical diagnostics applications.

  11. Plastic-Based Structurally Programmable Microfluidic Biochips for Clinical Diagnostics

    Science.gov (United States)

    2005-05-01

    327-330. 85 Appendix B: List of Theses from the Project Chein -Chong Hong, (Committee Chair: Chong H. Ahn), “On-chip passive fluidic...array,” M.S. Thesis, University of Cincinnati, 2003. 86 Chein -Chong Hong, (Committee Chair: Chong H. Ahn), “On-chip passive fluidic micromixer and

  12. Rapid, low-cost and instrument-free CD4+ cell counting for HIV diagnostics in resource-poor settings.

    Science.gov (United States)

    Glynn, Macdara T; Kinahan, David J; Ducrée, Jens

    2014-08-07

    We present a novel, user-friendly and widely autonomous point-of-care diagnostic to enable HIV monitoring in resource-poor regions where the current pandemic is most prevalent. To specifically isolate magnetically tagged CD4+ cells directly from patient blood, the low-cost and disposable microfluidic chip operates by dual-force CD4+ cell magnetophoresis; whereby the interplay of flow and magnetic fields governs the trajectory of target cells depending on whether the cell binds to a magnetic microbead. Instrument-free pumping is implemented by a finger-actuated elastic membrane; tagged beads are laterally deflected by a small and re-useable permanent magnet. The single-depth and monolithic microfluidic structure can easily be fabricated in a single casting step. After their magnetophoretic isolation from whole blood, estimation of CD4+ cell concentrations is then measured by bright-field inspection of the capture chamber. In addition, an optional fluorescence measurement can be used for confirmation of the bright-field result if required. On-chip CD4+ estimation produces a linear response over the full range of medically relevant CD4+ cell concentrations. Our technology combines high-efficiency capture (93.0 ± 3.3%) and cell enumeration.

  13. A microfluidic D-subminiature connector.

    Science.gov (United States)

    Scott, Adina; Au, Anthony K; Vinckenbosch, Elise; Folch, Albert

    2013-06-07

    Standardized, affordable, user-friendly world-to-chip interfaces represent one of the major barriers to the adoption of microfluidics. We present a connector system for plug-and-play interfacing of microfluidic devices to multiple input and output lines. The male connectors are based on existing standardized housings from electronics that are inexpensive and widely available. The female connectors are fabricated using familiar replica molding techniques that can easily be adopted by microfluidic developers.

  14. Microfluidics for optics and quantitative cell biology

    OpenAIRE

    Campbell, James Kyle

    2008-01-01

    Microfluidics is a quickly expanding field with numerous applications. The advent of rapid-prototyping and soft- lithography allow for easy and inexpensive fabrication of microfluidic devices. Fluid manipulation on the microscale allows for new functionalities of devices and components not available on the macroscale. Fluid flows on the microscale are laminar with chemical mixing defined strictly by diffusion allowing us to design microfluidic devices with precise control of fluid flow and ch...

  15. Dynamics of Microvalve Operations in Integrated Microfluidics

    OpenAIRE

    Alan T. H. Lau; Hon Ming Yip; Kathy C. C. Ng; Xin Cui; Lam, Raymond H. W.

    2014-01-01

    Pneumatic microvalves are widely used key components for automating liquid manipulation and flow control in microfluidics for more than one decade. Due to their robust operations and the ease of fabrication, tremendous microfluidic systems have been developed with the multiple microvalves for higher throughput and extended functionalities. Therefore, operation performance of the microvalves in the integrated microfluidic devices is crucial to the related applications, in fields such as micro-...

  16. Microsphere integrated microfluidic disk: synergy of two techniques for rapid and ultrasensitive dengue detection

    Science.gov (United States)

    Hosseini, Samira; Aeinehvand, Mohammad M.; Uddin, Shah M.; Benzina, Abderazak; Rothan, Hussin A.; Yusof, Rohana; Koole, Leo H.; Madou, Marc J.; Djordjevic, Ivan; Ibrahim, Fatimah

    2015-11-01

    The application of microfluidic devices in diagnostic systems is well-established in contemporary research. Large specific surface area of microspheres, on the other hand, has secured an important position for their use in bioanalytical assays. Herein, we report a combination of microspheres and microfluidic disk in a unique hybrid platform for highly sensitive and selective detection of dengue virus. Surface engineered polymethacrylate microspheres with carefully designed functional groups facilitate biorecognition in a multitude manner. In order to maximize the utility of the microspheres’ specific surface area in biomolecular interaction, the microfluidic disk was equipped with a micromixing system. The mixing mechanism (microballoon mixing) enhances the number of molecular encounters between spheres and target analyte by accessing the entire sample volume more effectively, which subsequently results in signal amplification. Significant reduction of incubation time along with considerable lower detection limits were the prime motivations for the integration of microspheres inside the microfluidic disk. Lengthy incubations of routine analytical assays were reduced from 2 hours to 5 minutes while developed system successfully detected a few units of dengue virus. Obtained results make this hybrid microsphere-microfluidic approach to dengue detection a promising avenue for early detection of this fatal illness.

  17. Microsphere integrated microfluidic disk: synergy of two techniques for rapid and ultrasensitive dengue detection.

    Science.gov (United States)

    Hosseini, Samira; Aeinehvand, Mohammad M; Uddin, Shah M; Benzina, Abderazak; Rothan, Hussin A; Yusof, Rohana; Koole, Leo H; Madou, Marc J; Djordjevic, Ivan; Ibrahim, Fatimah

    2015-11-09

    The application of microfluidic devices in diagnostic systems is well-established in contemporary research. Large specific surface area of microspheres, on the other hand, has secured an important position for their use in bioanalytical assays. Herein, we report a combination of microspheres and microfluidic disk in a unique hybrid platform for highly sensitive and selective detection of dengue virus. Surface engineered polymethacrylate microspheres with carefully designed functional groups facilitate biorecognition in a multitude manner. In order to maximize the utility of the microspheres' specific surface area in biomolecular interaction, the microfluidic disk was equipped with a micromixing system. The mixing mechanism (microballoon mixing) enhances the number of molecular encounters between spheres and target analyte by accessing the entire sample volume more effectively, which subsequently results in signal amplification. Significant reduction of incubation time along with considerable lower detection limits were the prime motivations for the integration of microspheres inside the microfluidic disk. Lengthy incubations of routine analytical assays were reduced from 2 hours to 5 minutes while developed system successfully detected a few units of dengue virus. Obtained results make this hybrid microsphere-microfluidic approach to dengue detection a promising avenue for early detection of this fatal illness.

  18. Integrated lenses in polystyrene microfluidic devices

    KAUST Repository

    Fan, Yiqiang

    2013-04-01

    This paper reports a new method for integrating microlenses into microfluidic devices for improved observation. Two demonstration microfluidic devices were provided which were fabricated using this new technique. The integrated microlenses were fabricated using a free-surface thermo-compression molding method on a polystyrene (PS) sheet which was then bonded on top of microfluidic channels as a cover plate, with the convex microlenses providing a magnified image of the channel for the easier observation of the flow in the microchannels. This approach for fabricating the integrated microlens in microfluidic devices is rapid, low cost and without the requirement of cleanroom facilities. © 2013 IEEE.

  19. Advances in microfluidics for environmental analysis.

    Science.gov (United States)

    Jokerst, Jana C; Emory, Jason M; Henry, Charles S

    2012-01-07

    During the past few years, a growing number of groups have recognized the utility of microfluidic devices for environmental analysis. Microfluidic devices offer a number of advantages and in many respects are ideally suited to environmental analyses. Challenges faced in environmental monitoring, including the ability to handle complex and highly variable sample matrices, lead to continued growth and research. Additionally, the need to operate for days to months in the field requires further development of robust, integrated microfluidic systems. This review examines recently published literature on the applications of microfluidic systems for environmental analysis and provides insight in the future direction of the field.

  20. Validation of cytogenetic risk groups according to International Prognostic Scoring Systems by peripheral blood CD34+FISH: results from a German diagnostic study in comparison with an international control group

    Science.gov (United States)

    Braulke, Friederike; Platzbecker, Uwe; Müller-Thomas, Catharina; Götze, Katharina; Germing, Ulrich; Brümmendorf, Tim H.; Nolte, Florian; Hofmann, Wolf-Karsten; Giagounidis, Aristoteles A. N.; Lübbert, Michael; Greenberg, Peter L.; Bennett, John M.; Solé, Francesc; Mallo, Mar; Slovak, Marilyn L.; Ohyashiki, Kazuma; Le Beau, Michelle M.; Tüchler, Heinz; Pfeilstöcker, Michael; Nösslinger, Thomas; Hildebrandt, Barbara; Shirneshan, Katayoon; Aul, Carlo; Stauder, Reinhard; Sperr, Wolfgang R.; Valent, Peter; Fonatsch, Christa; Trümper, Lorenz; Haase, Detlef; Schanz, Julie

    2015-01-01

    International Prognostic Scoring Systems are used to determine the individual risk profile of myelodysplastic syndrome patients. For the assessment of International Prognostic Scoring Systems, an adequate chromosome banding analysis of the bone marrow is essential. Cytogenetic information is not available for a substantial number of patients (5%–20%) with dry marrow or an insufficient number of metaphase cells. For these patients, a valid risk classification is impossible. In the study presented here, the International Prognostic Scoring Systems were validated based on fluorescence in situ hybridization analyses using extended probe panels applied to cluster of differentiation 34 positive (CD34+) peripheral blood cells of 328 MDS patients of our prospective multicenter German diagnostic study and compared to chromosome banding results of 2902 previously published patients with myelodysplastic syndromes. For cytogenetic risk classification by fluorescence in situ hybridization analyses of CD34+ peripheral blood cells, the groups differed significantly for overall and leukemia-free survival by uni- and multivariate analyses without discrepancies between treated and untreated patients. Including cytogenetic data of fluorescence in situ hybridization analyses of peripheral CD34+ blood cells (instead of bone marrow banding analysis) into the complete International Prognostic Scoring System assessment, the prognostic risk groups separated significantly for overall and leukemia-free survival. Our data show that a reliable stratification to the risk groups of the International Prognostic Scoring Systems is possible from peripheral blood in patients with missing chromosome banding analysis by using a comprehensive probe panel (clinicaltrials.gov identifier:01355913). PMID:25344522

  1. The microfluidic Kelvin water dropper

    CERN Document Server

    Marin, Alvaro G; García-Sánchez, Pablo; Shui, Lingling; Xie, Yanbo; Fontelos, Marco A; Eijkel, Jan C T; Berg, Albert van den; Lohse, Detlef

    2013-01-01

    The so-called "Kelvin water dropper" is a simple experiment demonstrating the spontaneous appearance of induced free charge in droplets emitted through a tube. As Lord Kelvin explained, water droplets spontaneously acquire a net charge during detachment from a faucet due to the presence of electrical fields in their surrounding created by any metallic object. In his experiment, two streams of droplets are allowed to drip from separated nozzles into separated buckets, which are at the same time interconnected through the dripping needles. In this paper we build a microfluidic water dropper and demonstrate that the droplets get charged and break-up due to electrohydrodynamic instabilities. A comparison with recent simulations shows the dependence of the acquired charge in the droplets on different parameters of the system. The phenomenon opens a door to cheap and accessible transformation of pneumatic pressure into electrical energy and to an enhanced control in microfluidic and biophysical manipulation of caps...

  2. High-throughput microfluidic line scan imaging for cytological characterization

    Science.gov (United States)

    Hutcheson, Joshua A.; Powless, Amy J.; Majid, Aneeka A.; Claycomb, Adair; Fritsch, Ingrid; Balachandran, Kartik; Muldoon, Timothy J.

    2015-03-01

    Imaging cells in a microfluidic chamber with an area scan camera is difficult due to motion blur and data loss during frame readout causing discontinuity of data acquisition as cells move at relatively high speeds through the chamber. We have developed a method to continuously acquire high-resolution images of cells in motion through a microfluidics chamber using a high-speed line scan camera. The sensor acquires images in a line-by-line fashion in order to continuously image moving objects without motion blur. The optical setup comprises an epi-illuminated microscope with a 40X oil immersion, 1.4 NA objective and a 150 mm tube lens focused on a microfluidic channel. Samples containing suspended cells fluorescently stained with 0.01% (w/v) proflavine in saline are introduced into the microfluidics chamber via a syringe pump; illumination is provided by a blue LED (455 nm). Images were taken of samples at the focal plane using an ELiiXA+ 8k/4k monochrome line-scan camera at a line rate of up to 40 kHz. The system's line rate and fluid velocity are tightly controlled to reduce image distortion and are validated using fluorescent microspheres. Image acquisition was controlled via MATLAB's Image Acquisition toolbox. Data sets comprise discrete images of every detectable cell which may be subsequently mined for morphological statistics and definable features by a custom texture analysis algorithm. This high-throughput screening method, comparable to cell counting by flow cytometry, provided efficient examination including counting, classification, and differentiation of saliva, blood, and cultured human cancer cells.

  3. Direct molecular detection of pathogens in blood as specific rule-in diagnostic biomarker in patients with presumed sepsis: our experience on a heterogeneous cohort of patients with signs of infective systemic inflammatory response syndrome.

    Science.gov (United States)

    Avolio, Manuela; Diamante, Paola; Modolo, Maria Luisa; De Rosa, Rita; Stano, Paola; Camporese, Alessandro

    2014-08-01

    The practical value of blood cultures in the diagnosis of sepsis is impaired by a delay in the turnaround time to result and by the fact that blood culture positive can be found for only about 30% of these patients. Conventional laboratory signs of sepsis and acute phase protein biomarkers are sensitive and easy to use, but often also very nonspecific. Molecular diagnostic reflects currently the most promising avenue to decrease time to result and to influence decision making for antibiotic therapy in the septic host. In this study, we wish to highlight the impact of the LightCycler SeptiFast, a multipathogen probe-based real-time polymerase chain reaction, in the rapid etiological diagnosis of sepsis in patients with clinical and laboratory signs of bloodstream infections. We have evaluated prospectively 830 adult patients with suspected bloodstream infection and at least two criteria of systemic inflammatory response syndrome. In more than 50% of critically ill patients strongly suspected of having sepsis, we arrived to an etiological diagnosis only by the molecular method in a median time of 15 h, with specificity and predictive positive values of 96% and 94%, respectively. We highlight the role of DNAemia as time-critical, high-specificity, etiological, non-culture-based rule-in diagnostic biomarker in patients with presumed sepsis.

  4. Acoustically-driven microfluidic systems

    Energy Technology Data Exchange (ETDEWEB)

    Wang, A W; Benett, W J; Tarte, L R

    2000-06-23

    We have demonstrated a non-contact method of concentrating and mixing particles in a plastic microfluidic chamber employing acoustic radiation pressure. A flaw cell package has also been designed that integrates liquid sample interconnects, electrical contacts and a removable sample chamber. Experiments were performed on 1, 3, 6, and 10 {micro}m polystyrene beads. Increased antibody binding to a solid-phase substrate was observed in the presence of acoustic mixing due to improve mass transport.

  5. Microfluidic fabrication of plasmonic microcapsules

    OpenAIRE

    Wang, J.; Jin, M. L.; Eijkel, J.C.T.; Berg, van den, A.E.; Zhou, G.F.; Shui, L.L.

    2016-01-01

    This paper presents the plasmonic microcapsules with well-ordered nanoparticles embedded in polymer network fabricated by using a microfluidic device. The well-ordered nanoparticle arrays on the microcapsule form high-density uniform “hot-spots” with a deposited metal film, on which the localized surface plasmon resonance effect is obtained. These plasmonic microcapsules can be engineered and modified by nanoparticle size and the metal film thickness. Repeatable Surfaced-Enhanced Raman Scatte...

  6. Optical detection in microfluidic systems

    DEFF Research Database (Denmark)

    Mogensen, Klaus Bo; Kutter, Jörg Peter

    2009-01-01

    Optical detection schemes continue to be favoured for measurements in microfluidic systems. A selection of the latest progress mainly within the last two years is critically reviewed. Emphasis is on integrated solutions, such as planar waveguides, coupling schemes to the outside world, evanescent...... to ease commercialisation of the devices. This work will hopefully result in more commercial products that benefit from integrated optics, because the impact on commercial devices so far has been modest....

  7. A Microfluidic Platform to design crosslinked Hyaluronic Acid Nanoparticles (cHANPs) for enhanced MRI

    Science.gov (United States)

    Russo, Maria; Bevilacqua, Paolo; Netti, Paolo Antonio; Torino, Enza

    2016-11-01

    Recent advancements in imaging diagnostics have focused on the use of nanostructures that entrap Magnetic Resonance Imaging (MRI) Contrast Agents (CAs), without the need to chemically modify the clinically approved compounds. Nevertheless, the exploitation of microfluidic platforms for their controlled and continuous production is still missing. Here, a microfluidic platform is used to synthesize crosslinked Hyaluronic Acid NanoParticles (cHANPs) in which a clinically relevant MRI-CAs, gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA), is entrapped. This microfluidic process facilitates a high degree of control over particle synthesis, enabling the production of monodisperse particles as small as 35 nm. Furthermore, the interference of Gd-DTPA during polymer precipitation is overcome by finely tuning process parameters and leveraging the use of hydrophilic-lipophilic balance (HLB) of surfactants and pH conditions. For both production strategies proposed to design Gd-loaded cHANPs, a boosting of the relaxation rate T1 is observed since a T1 of 1562 is achieved with a 10 μM of Gd-loaded cHANPs while a similar value is reached with 100 μM of the relevant clinical Gd-DTPA in solution. The advanced microfluidic platform to synthesize intravascularly-injectable and completely biocompatible hydrogel nanoparticles entrapping clinically approved CAs enables the implementation of straightforward and scalable strategies in diagnostics and therapy applications.

  8. Same-day prenatal diagnosis of common chromosomal aneuploidies using microfluidics-fluorescence in situ hybridization.

    Science.gov (United States)

    Ho, Sherry S Y; Chua, Cuiwen; Gole, Leena; Biswas, Arijit; Koay, Evelyn; Choolani, Mahesh

    2012-04-01

    Rapid molecular prenatal diagnostic methods, such as fluorescence in situ hybridization (FISH), quantitative fluorescence-PCR, and multiplex ligation-dependent probe amplification, can detect common fetal aneuploidies within 24 to 48 h. However, specific diagnosis or aneuploidy exclusion should be ideally available within the same day as fetal sampling to alleviate parental anxiety. Microfluidic technologies integrate different steps into a microchip, saving time and costs. We have developed a cost-effective, same-day prenatal diagnostic FISH assay using microfluidics. Amniotic fluids (1-4 mL from 40 pregnant women at 15-22 weeks of gestation) were fixed with Carnoy's before loading into the microchannels of a microfluidic FISH-integrated nanostructured device. The glass slides were coated with nanostructured titanium dioxide to facilitate cell adhesion. Pretreatment and hybridization were performed within the microchannels. Fifty nuclei were counted by two independent analysts, and all results were validated with their respective karyotypes. Of the 40 samples, we found three cases of fetal aneuploidies (trisomies 13, 18, and 21), whereas the remaining 37 cases were normal. Results were concordant with their karyotypes and ready to be released within 3 h of sample receipt. Microfluidic FISH, using 20-fold less than the recommended amount of probe, is a cost-effective method to diagnose common fetal aneuploidies within the same day of fetal sampling.

  9. Whole-Teflon microfluidic chips.

    Science.gov (United States)

    Ren, Kangning; Dai, Wen; Zhou, Jianhua; Su, Jing; Wu, Hongkai

    2011-05-17

    Although microfluidics has shown exciting potential, its broad applications are significantly limited by drawbacks of the materials used to make them. In this work, we present a convenient strategy for fabricating whole-Teflon microfluidic chips with integrated valves that show outstanding inertness to various chemicals and extreme resistance against all solvents. Compared with other microfluidic materials [e.g., poly(dimethylsiloxane) (PDMS)] the whole-Teflon chip has a few more advantages, such as no absorption of small molecules, little adsorption of biomolecules onto channel walls, and no leaching of residue molecules from the material bulk into the solution in the channel. Various biological cells have been cultured in the whole-Teflon channel. Adherent cells can attach to the channel bottom, spread, and proliferate well in the channels (with similar proliferation rate to the cells in PDMS channels with the same dimensions). The moderately good gas permeability of the Teflon materials makes it suitable to culture cells inside the microchannels for a long time.

  10. Particle sorting using a porous membrane in a microfluidic device.

    Science.gov (United States)

    Wei, Huibin; Chueh, Bor-han; Wu, Huiling; Hall, Eric W; Li, Cheuk-wing; Schirhagl, Romana; Lin, Jin-Ming; Zare, Richard N

    2011-01-21

    Porous membranes have been fabricated based on the development of the perforated membrane mold [Y. Luo and R. N. Zare, Lab Chip, 2008, 8, 1688-1694] to create a single filter that contains multiple pore sizes ranging from 6.4 to 16.6 µm inside a monolithic three-dimensional poly(dimethylsiloxane) microfluidic structure. By overlapping two filters we are able to achieve smaller pore size openings (2.5 to 3.3 µm). This filter operates without any detectable irreversible clogging, which is achieved using a cross-flow placed in front of each filtration section. The utility of a particle-sorting device that contains this filter is demonstrated by separating polystyrene beads of different diameters with an efficiency greater than 99.9%. Additionally, we demonstrate the effectiveness of this particle-sorting device by separating whole blood samples into white blood cells and red blood cells with platelets.

  11. Blood Types

    Science.gov (United States)

    ... maternity. Learn About Blood Blood Facts and Statistics Blood Components Whole Blood and Red Blood Cells Platelets Plasma ... About Blood Blood Facts and Statistics Blood Types Blood Components What Happens to Donated Blood Blood and Diversity ...

  12. Real-time polymerase chain reaction with melting analysis of positive blood culture specimens in bloodstream infections: diagnostic value and turnaround time.

    Science.gov (United States)

    Angeletti, Silvia; Gherardi, Giovanni; De Florio, Lucia; Avola, Alessandra; Crea, Francesca; Riva, Elisabetta; Vitali, Massimiliano Andrea; Galluzzo, Sara; Dicuonzo, Giordano

    2013-01-01

    A Real-time polymerase chain reaction (PCR) with melting analysis was devised to target bacterial and fungal genes together with the most prevalent antimicrobial resistance genes in 250 positive blood culture broths. This method allowed the blood culture cultivated pathogens to be classified into clinically relevant groups such as Enterobacteriaceae, oxidase-positive bacilli, oxidase-positive coccobacilli, S. aureus and yeast. Enterococci and streptococci could be distinguished from CoNS only by the Gram stain. Gram-positive bacilli were discriminated from Gram-positive cocci by Gram stain. Furthermore, the most important antimicrobial resistant genes such as mecA, vanA, bla TEM , bla SHV and bla CTX-M could be identified. All results were obtained with a turnaround time of three hours from the moment of blood culture positivity compared to 24-72 hours for phenotypic methods. In conclusion, the proposed approach can allow the clinician to implement proper early management of sepsis patients.

  13. Evaluation of an automated rapid diagnostic assay for detection of Gram-negative bacteria and their drug-resistance genes in positive blood cultures.

    Science.gov (United States)

    Tojo, Masayoshi; Fujita, Takahiro; Ainoda, Yusuke; Nagamatsu, Maki; Hayakawa, Kayoko; Mezaki, Kazuhisa; Sakurai, Aki; Masui, Yoshinori; Yazaki, Hirohisa; Takahashi, Hiroshi; Miyoshi-Akiyama, Tohru; Totsuka, Kyoichi; Kirikae, Teruo; Ohmagari, Norio

    2014-01-01

    We evaluated the performance of the Verigene Gram-Negative Blood Culture Nucleic Acid Test (BC-GN; Nanosphere, Northbrook, IL, USA), an automated multiplex assay for rapid identification of positive blood cultures caused by 9 Gram-negative bacteria (GNB) and for detection of 9 genes associated with β-lactam resistance. The BC-GN assay can be performed directly from positive blood cultures with 5 minutes of hands-on and 2 hours of run time per sample. A total of 397 GNB positive blood cultures were analyzed using the BC-GN assay. Of the 397 samples, 295 were simulated samples prepared by inoculating GNB into blood culture bottles, and the remaining were clinical samples from 102 patients with positive blood cultures. Aliquots of the positive blood cultures were tested by the BC-GN assay. The results of bacterial identification between the BC-GN assay and standard laboratory methods were as follows: Acinetobacter spp. (39 isolates for the BC-GN assay/39 for the standard methods), Citrobacter spp. (7/7), Escherichia coli (87/87), Klebsiella oxytoca (13/13), and Proteus spp. (11/11); Enterobacter spp. (29/30); Klebsiella pneumoniae (62/72); Pseudomonas aeruginosa (124/125); and Serratia marcescens (18/21); respectively. From the 102 clinical samples, 104 bacterial species were identified with the BC-GN assay, whereas 110 were identified with the standard methods. The BC-GN assay also detected all β-lactam resistance genes tested (233 genes), including 54 bla(CTX-M), 119 bla(IMP), 8 bla(KPC), 16 bla(NDM), 24 bla(OXA-23), 1 bla(OXA-24/40), 1 bla(OXA-48), 4 bla(OXA-58), and 6 blaVIM. The data shows that the BC-GN assay provides rapid detection of GNB and β-lactam resistance genes in positive blood cultures and has the potential to contributing to optimal patient management by earlier detection of major antimicrobial resistance genes.

  14. Microfluidic devices, systems, and methods for quantifying particles using centrifugal force

    Science.gov (United States)

    Schaff, Ulrich Y.; Sommer, Gregory J.; Singh, Anup K.

    2015-11-17

    Embodiments of the present invention are directed toward microfluidic systems, apparatus, and methods for measuring a quantity of cells in a fluid. Examples include a differential white blood cell measurement using a centrifugal microfluidic system. A method may include introducing a fluid sample containing a quantity of cells into a microfluidic channel defined in part by a substrate. The quantity of cells may be transported toward a detection region defined in part by the substrate, wherein the detection region contains a density media, and wherein the density media has a density lower than a density of the cells and higher than a density of the fluid sample. The substrate may be spun such that at least a portion of the quantity of cells are transported through the density media. Signals may be detected from label moieties affixed to the cells.

  15. Materials for microfluidic chip fabrication.

    Science.gov (United States)

    Ren, Kangning; Zhou, Jianhua; Wu, Hongkai

    2013-11-19

    Through manipulating fluids using microfabricated channel and chamber structures, microfluidics is a powerful tool to realize high sensitive, high speed, high throughput, and low cost analysis. In addition, the method can establish a well-controlled microenivroment for manipulating fluids and particles. It also has rapid growing implementations in both sophisticated chemical/biological analysis and low-cost point-of-care assays. Some unique phenomena emerge at the micrometer scale. For example, reactions are completed in a shorter amount of time as the travel distances of mass and heat are relatively small; the flows are usually laminar; and the capillary effect becomes dominant owing to large surface-to-volume ratios. In the meantime, the surface properties of the device material are greatly amplified, which can lead to either unique functions or problems that we would not encounter at the macroscale. Also, each material inherently corresponds with specific microfabrication strategies and certain native properties of the device. Therefore, the material for making the device plays a dominating role in microfluidic technologies. In this Account, we address the evolution of materials used for fabricating microfluidic chips, and discuss the application-oriented pros and cons of different materials. This Account generally follows the order of the materials introduced to microfluidics. Glass and silicon, the first generation microfluidic device materials, are perfect for capillary electrophoresis and solvent-involved applications but expensive for microfabriaction. Elastomers enable low-cost rapid prototyping and high density integration of valves on chip, allowing complicated and parallel fluid manipulation and in-channel cell culture. Plastics, as competitive alternatives to elastomers, are also rapid and inexpensive to microfabricate. Their broad variety provides flexible choices for different needs. For example, some thermosets support in-situ fabrication of

  16. Optical diagnostics of osteoblast cells and osteogenic drug screening

    Science.gov (United States)

    Kolanti, Elayaraja; Veerla, Sarath C.; Khajuria, Deepak K.; Roy Mahapatra, D.

    2016-02-01

    Microfluidic device based diagnostics involving optical fibre path, in situ imaging and spectroscopy are gaining importance due to recent advances in diagnostics instrumentation and methods, besides other factors such as low amount of reagent required for analysis, short investigation times, and potential possibilities to replace animal model based study in near future. It is possible to grow and monitor tissues in vitro in microfluidic lab-on-chip. It may become a transformative way of studying how cells interact with drugs, pathogens and biomaterials in physiologically relevant microenvironments. To a large extent, progress in developing clinically viable solutions has been constrained because of (i) contradiction between in vitro and in vivo results and (ii) animal model based and clinical studies which is very expensive. Our study here aims to evaluate the usefulness of microfluidic device based 3D tissue growth and monitoring approach to better emulate physiologically and clinically relevant microenvironments in comparison to conventional in vitro 2D culture. Moreover, the microfluidic methodology permits precise high-throughput investigations through real-time imaging while using very small amounts of reagents and cells. In the present study, we report on the details of an osteoblast cell based 3D microfluidic platform which we employ for osteogenic drug screening. The drug formulation is functionalized with fluorescence and other biomarkers for imaging and spectroscopy, respectively. Optical fibre coupled paths are used to obtain insight regarding the role of stress/flow pressure fluctuation and nanoparticle-drug concentration on the osteoblast growth and osteogenic properties of bone.

  17. Droplet-based Biosensing for Lab-on-a-Chip, Open Microfluidics Platforms

    Directory of Open Access Journals (Sweden)

    Piyush Dak

    2016-04-01

    Full Text Available Low cost, portable sensors can transform health care by bringing easily available diagnostic devices to low and middle income population, particularly in developing countries. Sample preparation, analyte handling and labeling are primary cost concerns for traditional lab-based diagnostic systems. Lab-on-a-chip (LoC platforms based on droplet-based microfluidics promise to integrate and automate these complex and expensive laboratory procedures onto a single chip; the cost will be further reduced if label-free biosensors could be integrated onto the LoC platforms. Here, we review some recent developments of label-free, droplet-based biosensors, compatible with “open” digital microfluidic systems. These low-cost droplet-based biosensors overcome some of the fundamental limitations of the classical sensors, enabling timely diagnosis. We identify the key challenges that must be addressed to make these sensors commercially viable and summarize a number of promising research directions.

  18. Droplet-based Biosensing for Lab-on-a-Chip, Open Microfluidics Platforms.

    Science.gov (United States)

    Dak, Piyush; Ebrahimi, Aida; Swaminathan, Vikhram; Duarte-Guevara, Carlos; Bashir, Rashid; Alam, Muhammad A

    2016-04-14

    Low cost, portable sensors can transform health care by bringing easily available diagnostic devices to low and middle income population, particularly in developing countries. Sample preparation, analyte handling and labeling are primary cost concerns for traditional lab-based diagnostic systems. Lab-on-a-chip (LoC) platforms based on droplet-based microfluidics promise to integrate and automate these complex and expensive laboratory procedures onto a single chip; the cost will be further reduced if label-free biosensors could be integrated onto the LoC platforms. Here, we review some recent developments of label-free, droplet-based biosensors, compatible with "open" digital microfluidic systems. These low-cost droplet-based biosensors overcome some of the fundamental limitations of the classical sensors, enabling timely diagnosis. We identify the key challenges that must be addressed to make these sensors commercially viable and summarize a number of promising research directions.

  19. Integrating Electronics and Microfluidics on Paper.

    Science.gov (United States)

    Hamedi, Mahiar M; Ainla, Alar; Güder, Firat; Christodouleas, Dionysios C; Fernández-Abedul, M Teresa; Whitesides, George M

    2016-07-01

    Paper microfluidics and printed electronics have developed independently, and are incompatible in many aspects. Monolithic integration of microfluidics and electronics on paper is demonstrated. This integration makes it possible to print 2D and 3D fluidic, electrofluidic, and electrical components on paper, and to fabricate devices using them.

  20. A microfluidic method to study demulsification kinetics

    NARCIS (Netherlands)

    Krebs, T.; Schroën, C.G.P.H.; Boom, R.M.

    2012-01-01

    We present the results of experiments studying droplet coalescence in a dense layer of emulsion droplets using microfluidic circuits. The microfluidic structure allows direct observation of collisions and coalescence events between oil droplets dispersed in water. The coalescence rate of a flowing h

  1. Principles, Techniques, and Applications of Tissue Microfluidics

    Science.gov (United States)

    Wade, Lawrence A.; Kartalov, Emil P.; Shibata, Darryl; Taylor, Clive

    2011-01-01

    The principle of tissue microfluidics and its resultant techniques has been applied to cell analysis. Building microfluidics to suit a particular tissue sample would allow the rapid, reliable, inexpensive, highly parallelized, selective extraction of chosen regions of tissue for purposes of further biochemical analysis. Furthermore, the applicability of the techniques ranges beyond the described pathology application. For example, they would also allow the posing and successful answering of new sets of questions in many areas of fundamental research. The proposed integration of microfluidic techniques and tissue slice samples is called "tissue microfluidics" because it molds the microfluidic architectures in accordance with each particular structure of each specific tissue sample. Thus, microfluidics can be built around the tissues, following the tissue structure, or alternatively, the microfluidics can be adapted to the specific geometry of particular tissues. By contrast, the traditional approach is that microfluidic devices are structured in accordance with engineering considerations, while the biological components in applied devices are forced to comply with these engineering presets.

  2. Cell Culture Microfluidic Biochips: Experimental Throughput Maximization

    DEFF Research Database (Denmark)

    Minhass, Wajid Hassan; Pop, Paul; Madsen, Jan

    2011-01-01

    Microfluidic biochips offer a promising alternative to a conventional biochemical laboratory, integrating all necessary functionalities on-chip in order to perform biochemical applications. Researchers have started to propose computer-aided design tools for the synthesis of such biochips. Our focus...... metaheuristic for experimental design generation for the cell culture microfluidic biochips, and we have evaluated our approach using multiple experimental setups....

  3. Reduced-gravity environment hardware demonstrations of a prototype miniaturized flow cytometer and companion microfluidic mixing technology.

    Science.gov (United States)

    Phipps, William S; Yin, Zhizhong; Bae, Candice; Sharpe, Julia Z; Bishara, Andrew M; Nelson, Emily S; Weaver, Aaron S; Brown, Daniel; McKay, Terri L; Griffin, DeVon; Chan, Eugene Y

    2014-11-13

    Until recently, astronaut blood samples were collected in-flight, transported to earth on the Space Shuttle, and analyzed in terrestrial laboratories. If humans are to travel beyond low Earth orbit, a transition towards space-ready, point-of-care (POC) testing is required. Such testing needs to be comprehensive, easy to perform in a reduced-gravity environment, and unaffected by the stresses of launch and spaceflight. Countless POC devices have been developed to mimic laboratory scale counterparts, but most have narrow applications and few have demonstrable use in an in-flight, reduced-gravity environment. In fact, demonstrations of biomedical diagnostics in reduced gravity are limited altogether, making component choice and certain logistical challenges difficult to approach when seeking to test new technology. To help fill the void, we are presenting a modular method for the construction and operation of a prototype blood diagnostic device and its associated parabolic flight test rig that meet the standards for flight-testing onboard a parabolic flight, reduced-gravity aircraft. The method first focuses on rig assembly for in-flight, reduced-gravity testing of a flow cytometer and a companion microfluidic mixing chip. Components are adaptable to other designs and some custom components, such as a microvolume sample loader and the micromixer may be of particular interest. The method then shifts focus to flight preparation, by offering guidelines and suggestions to prepare for a successful flight test with regard to user training, development of a standard operating procedure (SOP), and other issues. Finally, in-flight experimental procedures specific to our demonstrations are described.

  4. Manipulation of microfluidic droplets by electrorheological fluid

    KAUST Repository

    Zhang, Menying

    2009-09-01

    Microfluidics, especially droplet microfluidics, attracts more and more researchers from diverse fields, because it requires fewer materials and less time, produces less waste and has the potential of highly integrated and computer-controlled reaction processes for chemistry and biology. Electrorheological fluid, especially giant electrorheological fluid (GERF), which is considered as a kind of smart material, has been applied to the microfluidic systems to achieve active and precise control of fluid by electrical signal. In this review article, we will introduce recent results of microfluidic droplet manipulation, GERF and some pertinent achievements by introducing GERF into microfluidic system: digital generation, manipulation of "smart droplets" and droplet manipulation by GERF. Once it is combined with real-time detection, integrated chip with multiple functions can be realized. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA.

  5. Microfluidics: a new cosset for neurobiology.

    Science.gov (United States)

    Wang, Jinyi; Ren, Li; Li, Li; Liu, Wenming; Zhou, Jing; Yu, Wenhao; Tong, Denwen; Chen, Shulin

    2009-03-07

    Recently, microfluidic systems have shown great potential in the study of molecular and cellular biology. With its excellent properties, such as miniaturization, integration and automation, to name just a few, microfluidics creates new opportunities for the spatial and temporal control of cell growth and environmental stimuli in vitro. In the field of neuroscience, microfluidic devices offer precise control of the microenvironment surrounding individual cells, and the delivery of biochemical or physical cues to neural networks or single neurons. The intent of this review is to outline recent advances in microfluidic-based applications in neurobiology, with emphasis on neuron culture, neuron manipulation, neural stem cell differentiation, neuropharmacology, neuroelectrophysiology, and neuron biosensors. It also aims to stimulate development of microfluidic-based applications in neurobiology by involving scientists from various disciplines, especially neurobiology and microtechnology.

  6. Microfluidic desalination techniques and their potential applications.

    Science.gov (United States)

    Roelofs, S H; van den Berg, A; Odijk, M

    2015-09-07

    In this review we discuss recent developments in the emerging research field of miniaturized desalination. Traditionally desalination is performed to convert salt water into potable water and research is focused on improving performance of large-scale desalination plants. Microfluidic desalination offers several new opportunities in comparison to macro-scale desalination, such as providing a platform to increase fundamental knowledge of ion transport on the nano- and microfluidic scale and new microfluidic sample preparation methods. This approach has also lead to the development of new desalination techniques, based on micro/nanofluidic ion-transport phenomena, which are potential candidates for up-scaling to (portable) drinking water devices. This review assesses microfluidic desalination techniques on their applications and is meant to contribute to further implementation of microfluidic desalination techniques in the lab-on-chip community.

  7. Manipulation of microfluidic droplets by electrorheological fluid.

    Science.gov (United States)

    Zhang, Menying; Gong, Xiuqing; Wen, Weijia

    2009-09-01

    Microfluidics, especially droplet microfluidics, attracts more and more researchers from diverse fields, because it requires fewer materials and less time, produces less waste and has the potential of highly integrated and computer-controlled reaction processes for chemistry and biology. Electrorheological fluid, especially giant electrorheological fluid (GERF), which is considered as a kind of smart material, has been applied to the microfluidic systems to achieve active and precise control of fluid by electrical signal. In this review article, we will introduce recent results of microfluidic droplet manipulation, GERF and some pertinent achievements by introducing GERF into microfluidic system: digital generation, manipulation of "smart droplets" and droplet manipulation by GERF. Once it is combined with real-time detection, integrated chip with multiple functions can be realized.

  8. Electrorheological fluid and its applications in microfluidics.

    Science.gov (United States)

    Wang, Limu; Gong, Xiuqing; Wen, Weijia

    2011-01-01

    Microfluidics is a low-cost technique for fast-diagnosis and microsynthesis. Within a decade it might become the foundation of point-of-care and lab-on-a-chip applications. With microfluidic chips, high-throughput sample screening and information processing are made possible. The picoliter droplet runs in microfluidic chips are ideal miniaturized vessels for microdetection and microsynthesis. Meanwhile, individual manipulation of microdroplets remains a challenge: the shortcomings in automatic, reliable, and scalable methods for logic control prevent further integration of microfluidic applications. The giant electrorheological fluid (GERF), which is a kind of "smart" colloid, has tunable viscosity under the influence of external electric field. Therefore, GERF is introduced as the active controlling medium, with real-time response in on-chip fluid control. This review article introduces the working principles and fabrication methods of different types of electrorheological fluid, and extensively describes the strategies of GERF-assisted microfluidic controlling schemes.

  9. Inversion of hematocrit partition at microfluidic bifurcations.

    Science.gov (United States)

    Shen, Zaiyi; Coupier, Gwennou; Kaoui, Badr; Polack, Benoît; Harting, Jens; Misbah, Chaouqi; Podgorski, Thomas

    2016-05-01

    Partitioning of red blood cells (RBCs) at the level of bifurcations in the microcirculatory system affects many physiological functions yet it remains poorly understood. We address this problem by using T-shaped microfluidic bifurcations as a model. Our computer simulations and in vitro experiments reveal that the hematocrit (ϕ0) partition depends strongly on RBC deformability, as long as ϕ0<20% (within the normal range in microcirculation), and can even lead to complete deprivation of RBCs in a child branch. Furthermore, we discover a deviation from the Zweifach-Fung effect which states that the child branch with lower flow rate recruits less RBCs than the higher flow rate child branch. At small enough ϕ0, we get the inverse scenario, and the hematocrit in the lower flow rate child branch is even higher than in the parent vessel. We explain this result by an intricate up-stream RBC organization and we highlight the extreme dependence of RBC transport on geometrical and cell mechanical properties. These parameters can lead to unexpected behaviors with consequences on the microcirculatory function and oxygen delivery in healthy and pathological conditions.

  10. Inversion of hematocrit partition at microfluidic bifurcations

    CERN Document Server

    Shen, Zaiyi; Kaoui, Badr; Polack, Benoît; Harting, Jens; Misbah, Chaouqi; Podgorski, Thomas

    2016-01-01

    Partitioning of red blood cells (RBCs) at the level of bifurcations in the microcirculatory system affects many physiological functions yet it remains poorly understood. We address this problem by using T-shaped microfluidic bifurcations as a model. Our computer simulations and in vitro experiments reveal that the hematocrit ($\\phi_0$) partition depends strongly on RBC deformability, as long as $\\phi_0 <20$% (within the normal range in microcirculation), and can even lead to complete deprivation of RBCs in a child branch. Furthermore, we discover a deviation from the Zweifach-Fung effect which states that the child branch with lower flow rate recruits less RBCs than the higher flow rate child branch. At small enough $\\phi_0$, we get the inverse scenario, and the hematocrit in the lower flow rate child branch is even higher than in the parent vessel. We explain this result by an intricate up-stream RBC organization and we highlight the extreme dependence of RBC transport on geometrical and cell mechanical p...

  11. Multiplexed microfluidic quantification of proteins in serum

    Science.gov (United States)

    Rajan, Nitin; Rajauria, Sukumar; Cleland, Andrew

    2015-03-01

    Rapid and low cost immunoassays targeting proteins in blood or other bodily fluids are highly sought after for point-of-care devices and early screening of patients. Immunoturbidimetric assays utilize latex particles functionalized with antibodies, with particle aggregation in the presence of the analyte detected by a change in absorbance. Using a high throughput micro-fluidic particle analyzer based solely on electrical signals (resistive pulse sensing), we are able to accurately quantify the degree of aggregation by analyzing the changes in the particle size distribution. Thus we study the aggregation of streptavidin (SAv) coated beads in the presence of biotinylated bovine serum albumin as a proof-of-principle assay and extract the binding capacity of the SAv beads from the dose-response curve. We also use our aggregation measurement platform to characterize a commercial C-reactive protein (CRP) immunoturbidimetric assay (hsCRP, Diazyme Inc.). We obtain a linear calibration curve as well as a better limit of detection of CRP than that obtained by absorbance measurements. By using different bead sizes functionalized with different antibodies, multiplexed analyte detection is also possible. We demonstrate this by combining the commercial anti-CRP functionalized beads (0.4 microns) with biotin coated beads (1.0 microns), and carry out the simultaneous detection of SAv and CRP in a single sample.

  12. Diagnostic hematology of reptiles.

    Science.gov (United States)

    Stacy, Nicole I; Alleman, A Rick; Sayler, Katherine A

    2011-03-01

    The hematologic evaluation of reptiles is an indispensable diagnostic tool in exotic veterinary practice. The diversity of reptile species, their characteristic physiologic features, and effects of intrinsic and extrinsic factors present unique challenges for accurate interpretation of the hemogram. Combining the clinical presentation with hematologic findings provides valuable information in the diagnosis and monitoring of disease and helps guide the clinician toward therapy and further diagnostic testing. This article outlines the normal and pathologic morphology of blood cells of reptile species. The specific comparative aspects of reptiles are emphasized, and structural and functional abnormalities in the reptilian hemogram are described.

  13. Over-Expression of Dopamine D2 Receptor and Inwardly Rectifying Potassium Channel Genes in Drug-Naive Schizophrenic Peripheral Blood Lymphocytes as Potential Diagnostic Markers

    OpenAIRE

    Ágnes Zvara; György Szekeres; Zoltán Janka; Kelemen, János Z.; Csongor Cimmer; Miklós Sántha; Puskás, László G.

    2005-01-01

    Schizophrenia is one of the most common neuropsychiatric disorders affecting nearly 1% of the human population. Current diagnosis of schizophrenia is based on complex clinical symptoms. The use of easily detectable peripheral molecular markers could substantially help the diagnosis of psychiatric disorders. Recent studies showed that peripheral blood lymphocytes (PBL) express subtypes of D1 and D2 subclasses of dopamine receptors. Recently, dopamine receptor D3 (DRD3) was found to be over-exp...

  14. A microfluidic platform with a flow-balanced fluidic network for osteoarthritis diagnosis

    Science.gov (United States)

    Kim, Kangil; Park, Yoo Min; Yoon, Hyun C.; Yang, Sang Sik

    2013-05-01

    Osteoarthritis (OA) is one of the most common human diseases, and the occurrence of OA is likely to increase with the increase of population ages. The diagnosis of OA is based on patientrelevant measures, structural measures, and measurement of biomarkers that are released through joint metabolism. Traditionally, radiography or magnetic resonance imaging (MRI) is used to diagnose OA and predict its course. However, diagnostic imaging in OA provides only indirect information on pathology and treatment response. A sensing of OA based on the detection of biomarkers insignificantly improves the accuracy and sensitivity of diagnosis and reduces the cost compared with that of radiography or MRI. In our former study, we proposed microfluidic platform to detect biomarker of OA. But the platform can detect only one biomarker because it has one microfluidic channel. In this report, we proposes microfluidic platform that can detect several biomarkers. The proposed platform has three layers. The bottom layer has gold patterns on a Si substrate for optical sensing. The middle layer and top layer were fabricated by polydimethysiloxane (PDMS) using soft-lithography. The middle layer has four channels connecting top layer to bottom layer. The top layer consists of one sample injection inlet, and four antibody injection inlets. To this end, we designed a flow-balanced microfluidic network using analogy between electric and hydraulic systems. Also, the designed microfluidic network was confirmed by finite element model (FEM) analysis using COMSOL FEMLAB. To verify the efficiency of fabricated platform, the optical sensing test was performed to detect biomarker of OA using fluorescence microscope. We used cartilage oligomeric matrix protein (COMP) as biomarker because it reflects specific changes in joint tissues. The platform successfully detected various concentration of COMP (0, 100, 500, 1000 ng/ml) at each chamber. The effectiveness of the microfluidic platform was verified

  15. Kinetic ELISA in Microfluidic Channels

    Directory of Open Access Journals (Sweden)

    Debashis Dutta

    2011-06-01

    Full Text Available In this article, we describe the kinetic ELISA of Blue Tongue and Epizootic Hemorrhagic Disease viral antibodies in microfluidic channels by monitoring the rate of generation of the enzyme reaction product under static conditions. It has been shown that this format of the immunoassay allows very reliable quantitation of the target species using inexpensive glass microchips and a standard epifluorescence microscope system coupled to a CCD camera. For the viral antibodies assayed here, the limit of detection (LOD for the analyte concentration in our microchips was established to be 3–5 times lower than that obtained on commercial microwell plates using a fiftieth of the sample volume and less than a third of the incubation time. Our analyses further show that when compared to the end-point ELISA format, the kinetic mode of this assay yields an improvement in the LOD by over an order of magnitude in microfluidic devices. This benefit is primarily realized as the observed variation in the background fluorescence (signal at the start of the enzyme reaction period was significantly larger than that in the rate of signal generation upon repeating these assays in different microchannels/microchips. Because the kinetic ELISA results depend only on the latter quantity, the noise level in them was substantially lower compared to that in its end-point counterpart in which the absolute fluorescence measurements are of greater significance. While a similar benefit was also recorded through implementation of kinetic ELISAs on the microwell platform, the improvement in LOD registered in that system was not as significant as was observed in the case of microfluidic assays.

  16. Optical biosensor system with integrated microfluidic sample preparation and TIRF based detection

    Science.gov (United States)

    Gilli, Eduard; Scheicher, Sylvia R.; Suppan, Michael; Pichler, Heinz; Rumpler, Markus; Satzinger, Valentin; Palfinger, Christian; Reil, Frank; Hajnsek, Martin; Köstler, Stefan

    2013-05-01

    There is a steadily growing demand for miniaturized bioanalytical devices allowing for on-site or point-of-care detection of biomolecules or pathogens in applications like diagnostics, food testing, or environmental monitoring. These, so called labs-on-a-chip or micro-total analysis systems (μ-TAS) should ideally enable convenient sample-in - result-out type operation. Therefore, the entire process from sample preparation, metering, reagent incubation, etc. to detection should be performed on a single disposable device (on-chip). In the early days such devices were mainly fabricated using glass or silicon substrates and adapting established fabrication technologies from the electronics and semiconductor industry. More recently, the development focuses on the use of thermoplastic polymers as they allow for low-cost high volume fabrication of disposables. One of the most promising materials for the development of plastic based lab-on-achip systems are cyclic olefin polymers and copolymers (COP/COC) due to their excellent optical properties (high transparency and low autofluorescence) and ease of processing. We present a bioanalytical system for whole blood samples comprising a disposable plastic chip based on TIRF (total internal reflection fluorescence) optical detection. The chips were fabricated by compression moulding of COP and microfluidic channels were structured by hot embossing. These microfluidic structures integrate several sample pretreatment steps. These are the separation of erythrocytes, metering of sample volume using passive valves, and reagent incubation for competitive bioassays. The surface of the following optical detection zone is functionalized with specific capture probes in an array format. The plastic chips comprise dedicated structures for simple and effective coupling of excitation light from low-cost laser diodes. This enables TIRF excitation of fluorescently labeled probes selectively bound to detection spots at the microchannel surface

  17. Microfluidics and the life sciences.

    Science.gov (United States)

    Becker, Holger; Gärtner, Claudia

    2012-01-01

    The field of microfluidics, often also referred to as "Lab-on-a-Chip" has made significant progress in the last 15 years and is an essential tool in the development of new products and protocols in the life sciences. This article provides a broad overview on the developments on the academic as well as the commercial side. Fabrication technologies for polymer-based devices are presented and a strategy for the development of complex integrated devices is discussed, together with an example on the use of these devices in pathogen detection.

  18. Automated microfluidic DNA/RNA extraction with both disposable and reusable components

    Science.gov (United States)

    Kim, Jungkyu; Johnson, Michael; Hill, Parker; Sonkul, Rahul S.; Kim, Jongwon; Gale, Bruce K.

    2012-01-01

    An automated microfluidic nucleic extraction system was fabricated with a multilayer polydimethylsiloxane (PDMS) structure that consists of sample wells, microvalves, a micropump and a disposable microfluidic silica cartridge. Both the microvalves and micropump structures were fabricated in a single layer and are operated pneumatically using a 100 µm PDMS membrane. To fabricate the disposable microfluidic silica cartridge, two-cavity structures were made in a PDMS replica to fit the stacked silica membranes. A handheld controller for the microvalves and pumps was developed to enable system automation. With purified ribonucleic acid (RNA), whole blood and E. coli samples, the automated microfluidic nucleic acid extraction system was validated with a guanidine-based solid phase extraction procedure. An extraction efficiency of ~90% for deoxyribonucleic acid (DNA) and ~54% for RNA was obtained in 12 min from whole blood and E. coli samples, respectively. In addition, the same quantity and quality of extracted DNA was confirmed by polymerase chain reaction (PCR) amplification. The PCR also presented the appropriate amplification and melting profiles. Automated, programmable fluid control and physical separation of the reusable components and the disposable components significantly decrease the assay time and manufacturing cost and increase the flexibility and compatibility of the system with downstream components.

  19. Haemocompatibility of iron oxide nanoparticles synthesized for theranostic applications: a high-sensitivity microfluidic tool

    Science.gov (United States)

    Rodrigues, Raquel O.; Bañobre-López, Manuel; Gallo, Juan; Tavares, Pedro B.; Silva, Adrián M. T.; Lima, Rui; Gomes, Helder T.

    2016-07-01

    The poor heating efficiency of the most reported magnetic nanoparticles (MNPs), allied to the lack of comprehensive biocompatibility and haemodynamic studies, hampers the spread of multifunctional nanoparticles as the next generation of therapeutic bio-agents in medicine. The present work reports the synthesis and characterization, with special focus on biological/toxicological compatibility, of superparamagnetic nanoparticles with diameter around 18 nm, suitable for theranostic applications (i.e. simultaneous diagnosis and therapy of cancer). Envisioning more insights into the complex nanoparticle-red blood cells (RBCs) membrane interaction, the deformability of the human RBCs in contact with magnetic nanoparticles (MNPs) was assessed for the first time with a microfluidic extensional approach, and used as an indicator of haematological disorders in comparison with a conventional haematological test, i.e. the haemolysis analysis. Microfluidic results highlight the potential of this microfluidic tool over traditional haemolysis analysis, by detecting small increments in the rigidity of the blood cells, when traditional haemotoxicology analysis showed no significant alteration (haemolysis rates lower than 2 %). The detected rigidity has been predicted to be due to the wrapping of small MNPs by the bilayer membrane of the RBCs, which is directly related to MNPs size, shape and composition. The proposed microfluidic tool adds a new dimension into the field of nanomedicine, allowing to be applied as a high-sensitivity technique capable of bringing a better understanding of the biological impact of nanoparticles developed for clinical applications.

  20. Development of a rapid diagnostic method for identification of Staphylococcus aureus and antimicrobial resistance in positive blood culture bottles using a PCR-DNA-chromatography method.

    Science.gov (United States)

    Ohshiro, Takeya; Miyagi, Chihiro; Tamaki, Yoshikazu; Mizuno, Takuya; Ezaki, Takayuki

    2016-06-01

    Blood culturing and the rapid reporting of results are essential for infectious disease clinics to obtain bacterial information that can affect patient prognosis. When gram-positive coccoid cells are observed in blood culture bottles, it is important to determine whether the strain is Staphylococcus aureus and whether the strain has resistance genes, such as mecA and blaZ, for proper antibiotic selection. Previous work led to the development of a PCR method that is useful for rapid identification of bacterial species and antimicrobial susceptibility. However, that method has not yet been adopted in community hospitals due to the high cost and methodological complexity. We report here the development of a quick PCR and DNA-chromatography test, based on single-tag hybridization chromatography, that permits detection of S. aureus and the mecA and blaZ genes; results can be obtained within 1 h for positive blood culture bottles. We evaluated this method using 42 clinical isolates. Detection of S. aureus and the resistance genes by the PCR-DNA-chromatography method was compared with that obtained via the conventional identification method and actual antimicrobial susceptibility testing. Our method had a sensitivity of 97.0% and a specificity of 100% for the identification of the bacterial species. For the detection of the mecA gene of S. aureus, the sensitivity was 100% and the specificity was 95.2%. For the detection of the blaZ gene of S. aureus, the sensitivity was 100% and the specificity was 88.9%. The speed and simplicity of this PCR-DNA-chromatography method suggest that our method will facilitate rapid diagnoses.

  1. Simplified prototyping of perfusable polystyrene microfluidics

    Science.gov (United States)

    Tran, Reginald; Ahn, Byungwook; R. Myers, David; Qiu, Yongzhi; Sakurai, Yumiko; Moot, Robert; Mihevc, Emma; Trent Spencer, H.; Doering, Christopher; A. Lam, Wilbur

    2014-01-01

    Cell culture in microfluidic systems has primarily been conducted in devices comprised of polydimethylsiloxane (PDMS) or other elastomers. As polystyrene (PS) is the most characterized and commonly used substrate material for cell culture, microfluidic cell culture would ideally be conducted in PS-based microsystems that also enable tight control of perfusion and hydrodynamic conditions, which are especially important for culture of vascular cell types. Here, we report a simple method to prototype perfusable PS microfluidics for endothelial cell culture under flow that can be fabricated using standard lithography and wet laboratory equipment to enable stable perfusion at shear stresses up to 300 dyn/cm2 and pumping pressures up to 26 kPa for at least 100 h. This technique can also be extended to fabricate perfusable hybrid PS-PDMS microfluidics of which one application is for increased efficiency of viral transduction in non-adherent suspension cells by leveraging the high surface area to volume ratio of microfluidics and adhesion molecules that are optimized for PS substrates. These biologically compatible microfluidic devices can be made more accessible to biological-based laboratories through the outsourcing of lithography to various available microfluidic foundries. PMID:25379106

  2. Contactless diagnostics of biophysical parameters of skin and blood on the basis of approximating functions for radiation fluxes scattered by skin

    Energy Technology Data Exchange (ETDEWEB)

    Lisenko, S A; Kugeiko, M M [Belarusian State University, Minsk (Belarus)

    2014-03-28

    Approximating expressions are derived to calculate spectral and spatial characteristics of diffuse reflection of light from a two-layer medium mimicking human skin. The effectiveness of the use of these expressions in the optical diagnosis of skin biophysical parameters (tissue scattering parameters, concentration of melanin in the epidermis, concentration of total haemoglobin and bilirubin in the tissues of the dermis) and content of haemoglobin derivatives in blood (oxy-, deoxy-, met-, carboxy- and sulfhaemoglobin) is analysed numerically. The methods are proposed to determine in realtime these parameters without contact of the measuring instrument with the patient's body. (biophotonics)

  3. Contactless diagnostics of biophysical parameters of skin and blood on the basis of approximating functions for radiation fluxes scattered by skin

    Science.gov (United States)

    Lisenko, S. A.; Kugeiko, M. M.

    2014-03-01

    Approximating expressions are derived to calculate spectral and spatial characteristics of diffuse reflection of light from a two-layer medium mimicking human skin. The effectiveness of the use of these expressions in the optical diagnosis of skin biophysical parameters (tissue scattering parameters, concentration of melanin in the epidermis, concentration of total haemoglobin and bilirubin in the tissues of the dermis) and content of haemoglobin derivatives in blood (oxy-, deoxy-, met-, carboxy- and sulfhaemoglobin) is analysed numerically. The methods are proposed to determine in realtime these parameters without contact of the measuring instrument with the patient's body.

  4. Enzymatic Reactions in Microfluidic Devices

    Science.gov (United States)

    Ristenpart, W. D.; Wan, J.; Stone, H. A.

    2008-11-01

    We establish simple scaling laws for enzymatic reactions in microfluidic devices, and we demonstrate that kinetic parameters obtained conventionally using multiple stop-flow experiments may instead be extracted from a single microfluidic experiment. Introduction of an enzyme and substrate species in different arms of a Y-shaped channel allows the two species to diffuse across the parallel streamlines and to begin reacting. Measurements of the product concentration versus distance down the channel provide information about the kinetics of the reaction. In the limit where the enzyme is much larger (and thus less diffusive) than the substrate, we show that near the entrance the total amount of product (P) formed varies as a power law in the distance x down the channel. For reactions that follow standard Michaelis-Menten kinetics, the power law takes the form P˜(Vmax/Km) x^5/2, where Vmax and Km are the maximum reaction rate and Michaelis constant respectively. If a large excess of substrate is used, then Km is identified by measuring Vmax far downstream where the different species are completely mixed by diffusion. Numerical simulations and experiments using the bioluminescent reaction between luciferase and ATP as a model system are both shown to accord with the model. We discuss the implications for significant savings in the amount of time and enzyme required for determination of kinetic parameters.

  5. The microfluidic Kelvin water dropper.

    Science.gov (United States)

    Marín, Álvaro G; van Hoeve, Wim; García-Sánchez, Pablo; Shui, Lingling; Xie, Yanbo; Fontelos, Marco A; Eijkel, Jan C T; van den Berg, Albert; Lohse, Detlef

    2013-12-07

    The so-called "Kelvin water dropper" is a simple experiment demonstrating the spontaneous appearance of induced free charge in droplets emitted through a tube. As Lord Kelvin explained, water droplets spontaneously acquire a net charge during detachment from a faucet due to the presence of electrical fields in their surroundings created by any metallic object. In his experiment, two streams of droplets are allowed to drip from separate nozzles into separate buckets, which are, at the same time, interconnected through the dripping needles. In this paper, we build a microfluidic water dropper and demonstrate that the droplets get charged and break up due to electrohydrodynamic instabilities. A comparison with recent simulations shows the dependence of the acquired charge in the droplets on different parameters of the system. The phenomenon opens a door to cheap and accessible transformation of pneumatic pressure into electrical energy and to an enhanced control in microfluidic and biophysical manipulation of capsules, cells and droplets via self-induced charging of the elements.

  6. The analysis of diagnostic markers of genetic disorders in human blood and urine using tandem mass spectrometry with liquid secondary ion mass spectrometry

    Science.gov (United States)

    Millington, David S.; Kodo, Naoki; Terada, Naoto; Roe, Diane; Chace, Donald H.

    1991-12-01

    A method has been developed for the rapid diagnosis of metabolic diseases based on the analysis of characteristic metabolites in body fluids by fast atom bombardment or liquid secondary ion tandem mass spectrometry (FAB-MS--MS or LSIMS--MS). Acylcarnitine profiles were obtained from 100 [mu]l urine. 200 [mu]l plasma or 25 [mu]l whole blood spotted onto filter paper by simple solvent extraction, esterification and analysis using a precursor ion scan function on a triple quadrupole mass spectrometer. Specificity and sensitivity were improved by adding a small percentage of sodium octyl sulfate to the liquid matrix, which forms ion pairs with acylcarnitine esters. Acylglycines in urine were specifically detected as a group using a different precursor ion scan function. By forming methyl esters, metabolic profiles of both acylcarnitines and acylglycines were achieved in the same sample loading by application of alternating scan functions. Quantitative analysis of selected metabolites was achieved by use of stable isotope-labeled internal standards. Amino acid profiles were obtained from 100 [mu]l plasma and 25 [mu]l whole blood spots using butyl esters and a neutral loss scan function. The quantitative analysis of phenylalanine and tyrosine was achieved in these samples using stable isotope dilution. This capability will facilitate the diagnosis of phenylketonuria and other amino acidemias. These new methods have the requirements of speed, accuracy and capability for automation necessary for large-scale neonatal screening of inborn errors of matabolism.

  7. Analogy among microfluidics, micromechanics, and microelectronics.

    Science.gov (United States)

    Li, Sheng-Shian; Cheng, Chao-Min

    2013-10-07

    We wish to illuminate the analogous link between microfluidic-based devices, and the already established pairing of micromechanics and microelectronics to create a triangular/three-way scientific relationship as a means of interlinking familial disciplines and accomplishing two primary goals: (1) to facilitate the modeling of multidisciplinary domains; and, (2) to enable us to co-simulate the entire system within a compact circuit simulator (e.g., Cadence or SPICE). A microfluidic channel-like structure embedded in a micro-electro-mechanical resonator via our proposed CMOS-MEMS technology is used to illustrate the connections among microfluidics, micromechanics, and microelectronics.

  8. Wireless induction heating in a microfluidic device for cell lysis.

    Science.gov (United States)

    Baek, Seung-ki; Min, Junghong; Park, Jung-Hwan

    2010-04-07

    A wireless induction heating system in a microfluidic device was devised for cell lysis to extract DNA and RNA from Escherichia coli. The thermal responses of nickel, iron and copper heating units were studied by applying an alternating magnetic field as a function of geometry of unit, strength of magnetic field, and kind of metal. Heating units were prepared by cutting metal film using a fiber laser, and the units were integrated into a microchannel system using a soft lithographic process. Variation and distribution of temperature on the surface of the heating units was observed using a thermographic camera and temperature labels. The amount of protein released from E. coli by thermal lysis was determined by protein concentration measurement. Hemoglobin released from red blood cells was observed using colorimetric intensity measurement. Extracted DNA was quantified by real-time polymerase chain reaction, and the profile was compared with that of a positive control of ultrasonically disrupted E. coli. The stability of RNA extracted by induction heating was quantified by the measurement of 23S/16S rRNA ratio and comparison with that by normal RNA extraction kit as a gold standard. A solid-shaped nickel structure was selected as the induction heating element in the microfluidic device because of the relatively small influence of geometries and faster thermal response.The amount of protein extracted from E. coli and hemoglobin released from red blood cells by induction heating of the nickel unit in the microfluidic device was proportional to the strength of the applied magnetic field. The lysis of E. coli by induction heating was as effective as lysis of DNA by the ultrasonication method because the threshold cycle values of the sample were compatible with those of the positive control as measured by ultrasonication. Thermal lysis of E. coli by induction heating represents a reasonable alternative to a commercial RNA extraction method as shown by the comparative

  9. High-viscosity fluid threads in weakly diffusive microfluidic systems

    Science.gov (United States)

    Cubaud, T.; Mason, T. G.

    2009-07-01

    We provide an overview of the flow dynamics of highly viscous miscible liquids in microfluidic geometries. We focus on the lubricated transport of high-viscosity fluids interacting with less viscous fluids, and we review methods for producing and manipulating single and multiple core-annular flows, i.e. viscous threads, in compact and plane microgeometries. In diverging slit microchannels, a thread's buckling instabilities can be employed for generating ordered and disordered miscible microstructures, as well as for partially blending low- and high-viscosity materials. The shear-induced destabilization of a thread that flows off-center in a square microchannel is examined as a means for continuously producing miscible dispersions. We show original compound threads and viscous dendrites that are generated using three fluids, each of which has a large viscosity contrast with the others. Thread motions in zones of microchannel extensions are examined in both miscible and immiscible environments. We demonstrate that high-viscosity fluid threads in weakly diffusive microfluidic systems correspond to the viscous primary flow and can be used as a starting point for studying and understanding the destabilizing effects of interfacial tension as well as diffusion. Characteristic of lubricated transport, threads facilitate the transport of very viscous materials in small fluidic passages, while mitigating dissipation. Threads are also potentially promising for soft material synthesis and diagnostics with independent control of the thread specific surface and residence time in micro-flow reactors.

  10. Performance of rapid diagnostic test, blood-film microscopy and PCR for the diagnosis of malaria infection among febrile children from Korogwe District, Tanzania

    DEFF Research Database (Denmark)

    Mahende, Coline; Ngasala, Billy; Lusingu, John

    2016-01-01

    were enrolled into the study. Malaria-positive samples were 85/867 (9.8 %, 95 % CI, 7.9-12.0 %) by RDT, 72/867 (8.3 %, 95 % CI, 6.5-10.1 %) by microscopy and 79/677 (11.7 %, 95 % CI, 9.3-14.3 %) by PCR. The performance of malaria RDT compared with microscopy results had sensitivity and positive...... predictive value (PPV) of 88.9 % (95 % CI, 79.3-95.1 %) and 75.3 % (95 % CI, 64.8-84.0 %), respectively. Confirmation of P. falciparum infection with PCR analysis provided lower sensitivity and PPV of 88.6 % (95 % CI, 79.5-94.7 %) and 84.3 % (95 % CI, 74.7-91.4 %) for RDT compared to microscopy. Conclusion...... of transmission. The study evaluated the diagnostic performance of malaria RDT, light microscopy and polymerase chain reaction (PCR) in detecting malaria infections among febrile children at outpatient clinic in Korogwe District, northeastern Tanzania. Methods: The study enrolled children aged 2-59 months...

  11. High sensitivity automated multiplexed immunoassays using photonic crystal enhanced fluorescence microfluidic system.

    Science.gov (United States)

    Tan, Yafang; Tang, Tiantian; Xu, Haisheng; Zhu, Chenqi; Cunningham, Brian T

    2015-11-15

    We demonstrate a platform that integrates photonic crystal enhanced fluorescence (PCEF) detection of a surface-based microspot fluorescent assay with a microfluidic cartridge to achieve simultaneous goals of high analytic sensitivity (single digit pg/mL), high selectivity, low sample volume, and assay automation. The PC surface, designed to provide optical resonances for the excitation wavelength and emission wavelength of Cyanines 5 (Cy5), was used to amplify the fluorescence signal intensity measured from a multiplexed biomarker microarray. The assay system is comprised of a plastic microfluidic cartridge for holding the PC and an assay automation system that provides a leak-free fluid interface during introduction of a sequence of fluids under computer control. Through the use of the assay automation system and the PC embedded within the microfluidic cartridge, we demonstrate pg/mL-level limits of detection by performing representative biomarker assays for interleukin 3 (IL3) and Tumor Necrosis Factor (TNF-α). The results are consistent with limits of detection achieved without the use of the microfluidic device with the exception that coefficients of variability from spot-to-spot are substantially lower than those obtained by performing assays with manual manipulation of assay liquids. The system's capabilities are compatible with the goal of diagnostic instruments for point-of-care settings.

  12. Microvalve Enabled Digital Microfluidic Systems for High Performance Biochemical and Genetic Analysis.

    Science.gov (United States)

    Jensen, Erik C; Zeng, Yong; Kim, Jungkyu; Mathies, Richard A

    2010-12-01

    Microfluidic devices offer unparalleled capability for digital microfluidic automation of sample processing and complex assay protocols in medical diagnostic and research applications. In our own work, monolithic membrane valves have enabled the creation of two platforms that precisely manipulate discrete, nanoliter-scale volumes of sample. The digital microfluidic Automaton uses two-dimensional microvalve arrays to combinatorially process nanoliter-scale sample volumes. This programmable system enables rapid integration of diverse assay protocols using a universal processing architecture. Microfabricated emulsion generator array (MEGA) devices integrate actively controlled 3-microvalve pumps to enable on-demand generation of uniform droplets for statistical encapsulation of microbeads and cells. A MEGA device containing 96 channels confers the capability of generating up to 3.4 × 10(6) nanoliter-volume droplets per hour for ultrahigh-throughput detection of rare mutations in a vast background of normal genotypes. These novel digital microfluidic platforms offer significant enhancements in throughput, sensitivity, and programmability for automated sample processing and analysis.

  13. A microfluidic DNA computing processor for gene expression analysis and gene drug synthesis.

    Science.gov (United States)

    Zhang, Yu; Yu, Hao; Qin, Jianhua; Lin, Bingcheng

    2009-11-06

    Boolean logic performs a logical operation on one or more logic input and produces a single logic output. Here, we describe a microfluidic DNA computing processor performing Boolean logic operations for gene expression analysis and gene drug synthesis. Multiple cancer-related genes were used as input molecules. Their expression levels were identified by interacting with the computing related DNA strands, which were designed according to the sequences of cancer-related genes and the suicide gene. When all the expressions of the cancer-related genes fit in with the diagnostic criteria, positive diagnosis would be confirmed and then a complete suicide gene (gene drug) could be synthesized as an output molecule. Microfluidic chip was employed as an effective platform to realize the computing process by integrating multistep biochemical reactions involving hybridization, displacement, denaturalization, and ligation. By combining the specific design of the computing related molecules and the integrated functions of the microfluidics, the microfluidic DNA computing processor is able to analyze the multiple gene expressions simultaneously and realize the corresponding gene drug synthesis with simplicity and fast speed, which demonstrates the potential of this platform for DNA computing in biomedical applications.

  14. Microfluidics Integrated Biosensors: A Leading Technology towards Lab-on-a-Chip and Sensing Applications

    Directory of Open Access Journals (Sweden)

    George Luka

    2015-12-01

    Full Text Available A biosensor can be defined as a compact analytical device or unit incorporating a biological or biologically derived sensitive recognition element immobilized on a physicochemical transducer to measure one or more analytes. Microfluidic systems, on the other hand, provide throughput processing, enhance transport for controlling the flow conditions, increase the mixing rate of different reagents, reduce sample and reagents volume (down to nanoliter, increase sensitivity of detection, and utilize the same platform for both sample preparation and detection. In view of these advantages, the integration of microfluidic and biosensor technologies provides the ability to merge chemical and biological components into a single platform and offers new opportunities for future biosensing applications including portability, disposability, real-time detection, unprecedented accuracies, and simultaneous analysis of different analytes in a single device. This review aims at representing advances and achievements in the field of microfluidic-based biosensing. The review also presents examples extracted from the literature to demonstrate the advantages of merging microfluidic and biosensing technologies and illustrate the versatility that such integration promises in the future biosensing for emerging areas of biological engineering, biomedical studies, point-of-care diagnostics, environmental monitoring, and precision agriculture.

  15. Fabrication of dielectrophoretic microfluidic chips using a facile screen-printing technique for microparticle trapping

    Science.gov (United States)

    Wee, Wei Hong; Li, Zedong; Hu, Jie; Adib Kadri, Nahrizul; Xu, Feng; Li, Fei; Pingguan-Murphy, Belinda

    2015-10-01

    Trapping of microparticles finds wide applications in numerous fields. Microfluidic chips based on a dielectrophoresis (DEP) technique hold several advantages for trapping microparticles, such as fast result processing, a small amount of sample required, high spatial resolution, and high accuracy of target selection. There is an unmet need to develop DEP microfluidic chips on different substrates for different applications in a low cost, facile, and rapid way. This study develops a new facile method based on a screen-printing technique for fabrication of electrodes of DEP chips on three types of substrates (i.e. polymethyl-methacrylate (PMMA), poly(ethylene terephthalate) and A4 paper). The fabricated PMMA-based DEP microfluidic chip was selected as an example and successfully used to trap and align polystyrene microparticles in a suspension and cardiac fibroblasts in a cell culture solution. The developed electrode fabrication method is compatible with different kinds of DEP substrates, which could expand the future application field of DEP microfluidic chips, including new forms of point-of care diagnostics and trapping circulating tumor cells.

  16. Enzyme kinetic measurements using a droplet-based microfluidic system with a concentration gradient.

    Science.gov (United States)

    Bui, Minh-Phuong Ngoc; Li, Cheng Ai; Han, Kwi Nam; Choo, Jaebum; Lee, Eun Kyu; Seong, Gi Hun

    2011-03-01

    In this paper, we propose a microfluidic device that is capable of generating a concentration gradient followed by parallel droplet formation within channels with a simple T-junction geometry. Linear concentration gradient profiles can be obtained based on fluid diffusion under laminar flow. Optimized conditions for generating a linear concentration gradient and parallel droplet formation were investigated using fluorescent dye. The concentration gradient profile under diffusive mixing was dominated by the flow rate at sample inlets, while parallel droplet formation was affected by the channel geometry at both the inlet and outlet. The microfluidic device was experimentally characterized using optimal layout and operating conditions selected through a design process. Furthermore, in situ enzyme kinetic measurements of the β-galactosidase-catalyzed hydrolysis of resorufin-β-d-galactopyranoside were performed to demonstrate the application potential of our simple, time-effective, and low sample volume microfluidic device. We expect that, in addition to enzyme kinetics, drug screening and clinical diagnostic tests can be rapidly and accurately performed using this droplet-based microfluidic system.

  17. Microfluidics Integrated Biosensors: A Leading Technology towards Lab-on-a-Chip and Sensing Applications.

    Science.gov (United States)

    Luka, George; Ahmadi, Ali; Najjaran, Homayoun; Alocilja, Evangelyn; DeRosa, Maria; Wolthers, Kirsten; Malki, Ahmed; Aziz, Hassan; Althani, Asmaa; Hoorfar, Mina

    2015-12-01

    A biosensor can be defined as a compact analytical device or unit incorporating a biological or biologically derived sensitive recognition element immobilized on a physicochemical transducer to measure one or more analytes. Microfluidic systems, on the other hand, provide throughput processing, enhance transport for controlling the flow conditions, increase the mixing rate of different reagents, reduce sample and reagents volume (down to nanoliter), increase sensitivity of detection, and utilize the same platform for both sample preparation and detection. In view of these advantages, the integration of microfluidic and biosensor technologies provides the ability to merge chemical and biological components into a single platform and offers new opportunities for future biosensing applications including portability, disposability, real-time detection, unprecedented accuracies, and simultaneous analysis of different analytes in a single device. This review aims at representing advances and achievements in the field of microfluidic-based biosensing. The review also presents examples extracted from the literature to demonstrate the advantages of merging microfluidic and biosensing technologies and illustrate the versatility that such integration promises in the future biosensing for emerging areas of biological engineering, biomedical studies, point-of-care diagnostics, environmental monitoring, and precision agriculture.

  18. Microfluidics Integrated Biosensors: A Leading Technology towards Lab-on-a-Chip and Sensing Applications

    Science.gov (United States)

    Luka, George; Ahmadi, Ali; Najjaran, Homayoun; Alocilja, Evangelyn; DeRosa, Maria; Wolthers, Kirsten; Malki, Ahmed; Aziz, Hassan; Althani, Asmaa; Hoorfar, Mina

    2015-01-01

    A biosensor can be defined as a compact analytical device or unit incorporating a biological or biologically derived sensitive recognition element immobilized on a physicochemical transducer to measure one or more analytes. Microfluidic systems, on the other hand, provide throughput processing, enhance transport for controlling the flow conditions, increase the mixing rate of different reagents, reduce sample and reagents volume (down to nanoliter), increase sensitivity of detection, and utilize the same platform for both sample preparation and detection. In view of these advantages, the integration of microfluidic and biosensor technologies provides the ability to merge chemical and biological components into a single platform and offers new opportunities for future biosensing applications including portability, disposability, real-time detection, unprecedented accuracies, and simultaneous analysis of different analytes in a single device. This review aims at representing advances and achievements in the field of microfluidic-based biosensing. The review also presents examples extracted from the literature to demonstrate the advantages of merging microfluidic and biosensing technologies and illustrate the versatility that such integration promises in the future biosensing for emerging areas of biological engineering, biomedical studies, point-of-care diagnostics, environmental monitoring, and precision agriculture. PMID:26633409

  19. Using Nano-mechanics and Surface Acoustic Wave (SAW) for Disease Monitoring and Diagnostics at a Cellular Level in Red Blood Cells

    Science.gov (United States)

    Sivanantha, Ninnuja; Ma, Charles; Collins, David J.; Sesen, Muhsincan; Brenker, Jason; Coppel, Ross L.; Neild, Adrian; Alan, Tuncay

    A popular approach to monitoring diseases and their diagnosis is through biological, pathological or immunological characterization. However, at a cellular level progression of certain diseases manifests itself through mechanical effects as well. Here, we present a method which exploits localised flow; surface acoustic wave (SAW) induced acoustic streaming in a 9 μL droplet to characterize the adhesive properties of red blood cells (healthy, gluteraldehyde treated and malaria infected) in approximately 50 seconds. Our results show a 79% difference in cell mobilization between healthy malaria infected RBCs (and a 39% difference between healthy and treated ones), indicating that the method can serve as a platform for rapid clinical diagnosis; where separation of two or more different cell populations in a mixed solution is desirable. It can also act as a key biomarker for monitoring some diseases offering quantitative measures of disease progression and response to therapy.

  20. Microfluidic Tools for Protein Crystallography

    Science.gov (United States)

    Abdallah, Bahige G.

    X-ray crystallography is the most widely used method to determine the structure of proteins, providing an understanding of their functions in all aspects of life to advance applications in fields such as drug development and renewable energy. New techniques, namely serial femtosecond crystallography (SFX), have unlocked the ability to unravel the structures of complex proteins with vital biological functions. A key step and major bottleneck of structure determination is protein crystallization, which is very arduous due to the complexity of proteins and their natural environments. Furthermore, crystal characteristics govern data quality, thus need to be optimized to attain the most accurate reconstruction of the protein structure. Crystal size is one such characteristic in which narrowed distributions with a small modal size can significantly reduce the amount of protein needed for SFX. A novel microfluidic sorting platform was developed to isolate viable ~200 nm -- ~600 nm photosystem I (PSI) membrane protein crystals from ~200 nm -- ~20 ?m crystal samples using dielectrophoresis, as confirmed by fluorescence microscopy, second-order nonlinear imaging of chiral crystals (SONICC), and dynamic light scattering. The platform was scaled-up to rapidly provide 100s of microliters of sorted crystals necessary for SFX, in which similar crystal size distributions were attained. Transmission electron microscopy was used to view the PSI crystal lattice, which remained well-ordered postsorting, and SFX diffraction data was obtained, confirming a high-quality, viable crystal sample. Simulations indicated sorted samples provided accurate, complete SFX datasets with 3500-fold less protein than unsorted samples. Microfluidic devices were also developed for versatile, rapid protein crystallization screening using nanovolumes of sample. Concentration gradients of protein and precipitant were generated to crystallize PSI, phycocyanin, and lysozyme using modified counterdiffusion

  1. Microfluidic Analytical Separator for Proteomics Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed innovation is a microfluidic device designed to effect a 2-dimensional resolution of a mixture of proteins based on isoelectric point (pI) and molecular...

  2. Microfluidic Analytical Separator for Proteomics Project

    Data.gov (United States)

    National Aeronautics and Space Administration — SHOT proposes an innovative microfluidic device designed to effect a 2-dimensional resolution of a mixture of proteins based on isoelectric point (pI) and molecular...

  3. Multiplex single particle analysis in microfluidics.

    Science.gov (United States)

    Dannhauser, D; Romeo, G; Causa, F; De Santo, I; Netti, P A

    2014-10-21

    A straightforward way to measure separated micrometric sized particles in microfluidic flow is reported. The light scattering profile (LSP) of each single particle is fully characterized by using a CMOS-camera based small angle light scattering (SALS) apparatus, ranging from 2° up to 30°. To ensure controlled particle passage through the incident laser, a viscoelastic 3D alignment effect by viscoelastic induced particle migration has been implemented in a simple and cost-effective microfluidic device. Different polystyrene particle sizes are measured in microfluidic flows and the obtained scattering signatures are matched with the Lorenz-Mie based scattering theory. The results confirm the possibility of using this apparatus for real multiplex particle analyses in microfluidic particle flows.

  4. An integratable microfluidic cartridge for forensic swab samples lysis.

    Science.gov (United States)

    Yang, Jianing; Brooks, Carla; Estes, Matthew D; Hurth, Cedric M; Zenhausern, Frederic

    2014-01-01

    Fully automated rapid forensic DNA analysis requires integrating several multistep processes onto a single microfluidic platform, including substrate lysis, extraction of DNA from the released lysate solution, multiplexed PCR amplification of STR loci, separation of PCR products by capillary electrophoresis, and analysis for allelic peak calling. Over the past several years, most of the rapid DNA analysis systems developed started with the reference swab sample lysate and involved an off-chip lysis of collected substrates. As a result of advancement in technology and chemistry, addition of a microfluidic module for swab sample lysis has been achieved in a few of the rapid DNA analysis systems. However, recent reports on integrated rapid DNA analysis systems with swab-in and answer-out capability lack any quantitative and qualitative characterization of the swab-in sample lysis module, which is important for downstream forensic sample processing. Maximal collection and subsequent recovery of the biological material from the crime scene is one of the first and critical steps in forensic DNA technology. Herein we present the design, fabrication and characterization of an integratable swab lysis cartridge module and the test results obtained from different types of commonly used forensic swab samples, including buccal, saliva, and blood swab samples, demonstrating the compatibility with different downstream DNA extraction chemistries. This swab lysis cartridge module is easy to operate, compatible with both forensic and microfluidic requirements, and ready to be integrated with our existing automated rapid forensic DNA analysis system. Following the characterization of the swab lysis module, an integrated run from buccal swab sample-in to the microchip CE electropherogram-out was demonstrated on the integrated prototype instrument. Therefore, in this study, we demonstrate that this swab lysis cartridge module is: (1) functionally, comparable with routine benchtop lysis

  5. In vitro microfluidic model of sickle cell disease

    Science.gov (United States)

    Wood, D. K.; Higgins, J. M.; Mahadevan, L.; Bhatia, S. N.

    2010-03-01

    The pathophysiology of sickle cell disease is complicated by the multiscale processes that link the molecular genotype to the organismal phenotype: hemoglobin polymerization occurring in milliseconds, microscopic cellular sickling in a few seconds or less, and macroscopic vessel occlusion over a time scale of minutes. The rheology of sickle blood, which captures many of these processes, can be studied in vitro using physical tools and insights. We present a minimal microfluidic device in which blood flow dynamics can be directly manipulated by modulating physical factors such as oxygen concentration, capillary size, and fluid shear. We have used this system to map out the phase space of blood flow with respect to a combination of geometric, physical, chemical, and biological parameters. We show that morphological changes in erythrocytes due to sickle hemoglobin polymerization and melting are alone sufficient to change blood rheology. We characterize whole blood from many patients in this device and correlate in vitro performance to clinical outcomes, suggesting the potential utility of such a device for patient monitoring. Our experimental study integrates the dynamics of many of the processes associated with vasoocclusion and provides a potential tool for optimizing and individualizing treatment, and identifying new therapies.

  6. Study of individual erythrocyte deformability susceptibility to INFeD and ethanol using a microfluidic chip

    Science.gov (United States)

    Liu, Lihong; Huang, Sha; Xu, Xiaoying; Han, Jongyoon

    2016-01-01

    Human red blood cells (RBCs) deformability in vitro was assessed during iron dextran (INFeD) loading and/or ethanol co-administration using microfluidic deformability screening. The results showed donor-specific variations in dose dependent deformability shift were revealed below 500 μg/mL iron dextran. Two out of nine blood samples exhibited significant cell stiffening at 500 μg/mL iron dextran loading concentration (p < 0.05, Tukey test). More interestingly, co-administration of moderate amount of ethanol was identified to have significant protective effects on RBC deformability. We also noted that ethanol can reverse the deformability of impaired RBCs. Meanwhile obvious donor dependent response to ethanol administration on RBC deformability was noted using our biomimetic microfluidic chip. PMID:26964754

  7. A microfluidic two-pump system inspired by liquid feeding in mosquitoes

    Science.gov (United States)

    Marino, Andrew; Goad, Angela; Stremler, Mark; Socha, John; Jung, Sunghwan

    Mosquitoes feed on nectar and blood using a two-pump system in the head-a smaller cibarial pump in line with a larger a pharyngeal pump, with a valve in between. To suck, mosquitoes transport the liquid (which may be a multi-component viscous fluid, blood) through a long micro-channel, the proboscis. In the engineering realm, microfluidic devices in biomedical applications, such as lab-on-a-chip technology, necessitate implementing a robust pump design to handle clogging and increase flow control compared to a single-pump system. In this talk, we introduce a microfluidic pump design inspired by the mosquito's two-pump system. The pumping performance (flow rate) in presence of impurities (air bubbles, soft clogs) is quantified as a function of phase difference and volume expansion of the pumps, and the elasticity of the valve.

  8. Sampling by Fluidics and Microfluidics

    Directory of Open Access Journals (Sweden)

    V. Tesař

    2002-01-01

    Full Text Available Selecting one from several available fluid samples is a procedure often performed especially in chemical engineering. It is usually done by an array of valves sequentially opened and closed. Not generally known is an advantageous alternative: fluidic sampling units without moving parts. In the absence of complete pipe closure, cross-contamination between samples cannot be ruled out. This is eliminated by arranging for small protective flows that clear the cavities and remove any contaminated fluid. Although this complicates the overall circuit layout, fluidic sampling units with these "guard" flows were successfully built and tested. Recent interest in microchemistry leads to additional problems due very low operating Reynolds numbers. This necessitated the design of microfluidic sampling units based on new operating principles.

  9. Surface Sensitive Microfluidic Optomechanical Sensors

    CERN Document Server

    Kim, Kyu Hyun

    2014-01-01

    The microfluidic optomechanical resonator (uFOMR) based on a thin-walled glass capillary supports high Q-factor (>1000) mechanical modes in the presence of liquids. In this Letter, the sensitivity of the uFOMR to the surface change is studied by layer-by-layer removal of SiO2 molecules from the uFOMR inner surface using various concentrations of hydrofluoric acid solutions. A frequency downshift is observed with a sensitivity of 1.2 Hz/(pg/mm2), which translates to a surface density detection limit of 83 pg/mm2. This work opens a door to using the optomechanical mode for detection and characterization of molecules present near the resonator surface.

  10. Microfluidic Sample Preparation for Immunoassays

    Energy Technology Data Exchange (ETDEWEB)

    Visuri, S; Benett, W; Bettencourt, K; Chang, J; Fisher, K; Hamilton, J; Krulevitch, P; Park, C; Stockton, C; Tarte, L; Wang, A; Wilson, T

    2001-08-09

    Researchers at Lawrence Livermore National Laboratory are developing means to collect and identify fluid-based biological pathogens in the forms of proteins, viruses, and bacteria. to support detection instruments, they are developing a flexible fluidic sample preparation unit. The overall goal of this Microfluidic Module is to input a fluid sample, containing background particulates and potentially target compounds, and deliver a processed sample for detection. They are developing techniques for sample purification, mixing, and filtration that would be useful to many applications including immunologic and nucleic acid assays. Many of these fluidic functions are accomplished with acoustic radiation pressure or dielectrophoresis. They are integrating these technologies into packaged systems with pumps and valves to control fluid flow through the fluidic circuit.

  11. Microfluidic Devices in Advanced Caenorhabditis elegans Research

    Directory of Open Access Journals (Sweden)

    Muniesh Muthaiyan Shanmugam

    2016-08-01

    Full Text Available The study of model organisms is very important in view of their potential for application to human therapeutic uses. One such model organism is the nematode worm, Caenorhabditis elegans. As a nematode, C. elegans have ~65% similarity with human disease genes and, therefore, studies on C. elegans can be translated to human, as well as, C. elegans can be used in the study of different types of parasitic worms that infect other living organisms. In the past decade, many efforts have been undertaken to establish interdisciplinary research collaborations between biologists, physicists and engineers in order to develop microfluidic devices to study the biology of C. elegans. Microfluidic devices with the power to manipulate and detect bio-samples, regents or biomolecules in micro-scale environments can well fulfill the requirement to handle worms under proper laboratory conditions, thereby significantly increasing research productivity and knowledge. The recent development of different kinds of microfluidic devices with ultra-high throughput platforms has enabled researchers to carry out worm population studies. Microfluidic devices primarily comprises of chambers, channels and valves, wherein worms can be cultured, immobilized, imaged, etc. Microfluidic devices have been adapted to study various worm behaviors, including that deepen our understanding of neuromuscular connectivity and functions. This review will provide a clear account of the vital involvement of microfluidic devices in worm biology.

  12. Dynamics of Microvalve Operations in Integrated Microfluidics

    Directory of Open Access Journals (Sweden)

    Alan T. H. Lau

    2014-02-01

    Full Text Available Pneumatic microvalves are widely used key components for automating liquid manipulation and flow control in microfluidics for more than one decade. Due to their robust operations and the ease of fabrication, tremendous microfluidic systems have been developed with the multiple microvalves for higher throughput and extended functionalities. Therefore, operation performance of the microvalves in the integrated microfluidic devices is crucial to the related applications, in fields such as micro-flows, cell analyses, drug discovery, and physical/chemical detections. It has been reported that operation performance of the microvalves are highly sensitive to the device configuration and pressurization scheme. This implies the further development of integrated microfluidics with a larger number of the valves may suffer the problems of undetermined microvalve behaviors during operations, which can become an unavoidable hurdle in the device design and optimization processes. Herein, we characterize responses of the individual microvalves for different operation configurations, e.g., membrane thicknesses and driving pressures. We investigate also the effects in microfluidics integrated with the more valves, through experiments, modeling and simulations. We show that dynamics of the microvalves is indeed influenced by the configurations, levels of design complexity and positions in the devices. Overall, taken dynamics of the microvalve responses into considerations, this work provides insights and guidelines for better designs of integrated microfluidics for the future applications requiring higher throughput and improved operation performance.

  13. Microfluidic microwell and microcapillary biochips

    Science.gov (United States)

    Minot, Michael J.; Stowe, David W.; Detarando, Michael A.; Krans, Joseph A.; Kass, Jason L.

    2006-02-01

    Utilizing nanotechnology, proprietary chemistry, and microfluidics, innovative firms are developing biochips and instrument systems that enable high-speed automated biomedical sequencing. Incom Inc. presents development results on five novel biochip technologies based on FiberOptic MicroSlide and microcapillary technology. FiberOptic MicroSlides are fiber optic interrogated (FOI) biochips made up of millions of fused optical fibers, and are uniquely suited as a platform for microarray applications. FiberOptic MicroSlides (henceforth referred to as "MicroSlides" or "slides" in this paper) act as a 'zero thickness substrate' transmitting optical signals from top to bottom without spreading, so that fluorescent or luminescent activity on the surface or within a well can be directly coupled to a CCD device without additional optics. In contrast to bulk optics, the slides are compact and have excellent light-gathering power. They are an alternative to conventional microscope slides for applications involving moderate-resolution bottom viewing (inverted microscopy). The surface of the MicroSlides can be etched or patterned with a permanent polymer to form microwell arrays, or microfluidic structures suitable for genomic and proteomic analysis, cell migration studies and other applications. Low-cost microcapillary array plates have also been developed. These plates act as microscopic test tubes, which enable picoliter reactions to be detected, counted and analyzed. Progress in developing large area (300 mm X 300 mm) arrays with up to 100 million capillaries, and diameter / length aspect ratios up to 10,000: 1 is presented. Results demonstrate negligible optical cross talk between capillaries, resulting in improved signal-to-noise ratios while minimizing false hits.

  14. Migration distance-based platelet function analysis in a microfluidic system

    OpenAIRE

    Song, Suk-Heung; Lim, Chae-Seung; Shin, Sehyun

    2013-01-01

    Aggregation and adhesion of platelets to the vascular wall are shear-dependent processes that play critical roles in hemostasis and thrombosis at vascular injury sites. In this study, we designed a simple and rapid assay of platelet aggregation and adhesion in a microfluidic system. A shearing mechanism using a rotating stirrer provided adjustable shear rate and shearing time and induced platelet activation. When sheared blood was driven through the microchannel under vacuum pressure, shear-a...

  15. Real-time measurement of thrombin generation using continuous droplet microfluidics

    OpenAIRE

    Yu, Jiaqing; Tao, Ding; Ng, Ee Xing; Drum, Chester L.; Liu, Ai Qun; Chen, Chia-Hung

    2014-01-01

    Thrombin, which has the leading role in the blood coagulation cascade, is an important biomarker in hemostasis and cardiovascular disease (CVD) development. In this study, a measurement system capable of continuously monitoring individual thrombin generation using droplet microfluidic technology is manipulated. The thrombin generation assay based on fluogenic substrate is performed within the droplets and the thrombin generation curve of plasma sample activated by tissue factor is measured in...

  16. [Anti-alpha-gliadin antibodies. Sensitivity, specificity and correlation with blood xylose test in the 3 diagnostic stages of celiac disease in children].

    Science.gov (United States)

    Ventura, A; Florean, P; Trevisan, M; Not, T; Perticarari, S; Quadrifoglio, F; Torre, G; Cauci, S

    1987-01-01

    The specificity and sensibility of IgA and IgG alfagliadin antibody test (AaGA) for screening, diagnosis and follow-up of childhood coeliac disease has been evaluated. We have compared AaGA test to D-xylose blood test and at last we have examined the false positive and negative results given by the test. Two groups of subjects were considered: 1) 90 children with untreated coeliac disease (21 newly diagnosed (I stage), 50 in gluten withdrawal (II stage), 19 in challenge (III stage); 2) 255 disease controls including: 157 healthy controls; 31 children with gastroenterological disorders other than coeliac disease; 31 children with food allergy and atopic dermatitis; 36 children with "constitutional" short stature (without GH deficiency and with normal intestinal mucosa). The sensibility of AaGA test in the first stage of coeliac disease has been of 95.2% for the IgG class antibody and 90.4% for the IgA class; on the other hand the showed a specificity of 83.6% for IgG class antibody and 96.9% for IgA class. In only two newly diagnosed coeliac children we have found false negative results: in the first case the patient was IgA-deficient, in the second the age was above 3 years. AaGA IgA resulted positive only in the 12.9% of the group of gastroenterological and atopic controls; particularly most cases were affected by multiple food allergies and two patients by chronic autoimmune disease of small intestine.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Droplet Microfluidics Platform for Highly Sensitive and Quantitative Detection of Malaria-Causing Plasmodium Parasites Based on Enzyme Activity Measurement

    DEFF Research Database (Denmark)

    Juul, Sissel; Nielsen, Christine Juul Fælled; Labouriau, Rodrigo

    2012-01-01

    detectable at the single-molecule level. Combined with a droplet microfluidics lab-on-a-chip platform, this design allowed for sensitive, specific, and quantitative detection of all human-malaria-causing Plasmodium species in single drops of unprocessed blood with a detection limit of less than one parasite...... detection of even a few parasites is becoming increasingly important for the continued combat against the disease. We believe that the presented droplet microfluidics platform, which has a high potential for adaptation to point-of-care setups suitable for low-resource settings, may contribute significantly...

  18. Standard and high-throughput microfluidic disposables based on laminar fluid diffusion interfaces

    Science.gov (United States)

    Weigl, Bernhard H.; Morris, Chris; Kesler, Natasa; Battrell, Fred; Bardell, Ron L.

    2002-06-01

    Laminar Fluid Diffusion Interfaces are generated when tow or more streams flow in parallel in a microfluidic structure. This technology can be used for diffusion-based separation and detection applications, for example: DNA desalting, the extraction of small proteins from whole-blood samples, and the detection of various constituents in while blood. Additional applications are the establishment of stable concentration gradients, and the exposure of chemical constituents or biological particles to these concentration gradients, enabling the uniform and controlled exposure of cells to lysing agents, allowing the differentiation of cells by their sensitivity to specific agents in an on-chip cytometer coupled directly to the lysing structure. We have developed integrated systems using machine-controlled disposable cartridges and passive self-contained disposable cards including particle separators, flow cytometers, valves, detection channels, mixers, and diluters that are used in a hematology analyzer, stand-alone blood plasma separators, and a variety of chemical and biological assays. Microfluidic arrays compatible with common well-plate formats have been designed for high-throughout toxicology screening applications. All these devices were manufactured using Micronics' unique rapid-prototyping process yielding low-cost plastic disposable microfluidic chips.

  19. ESTUDIO DIAGNÓSTICO DEL CLIMA LABORAL EN LA EMPRESA DE SUEROS Y PRODUCTOS HEMODERIVADOS / DIAGNOSTIC STUDY OF ORGANIZATIONAL ENVIRONMENT IN THE ENTERPRISE OF SERA AND BLOOD PRODUCTS

    Directory of Open Access Journals (Sweden)

    Yoanys Paule-Hernández

    2011-03-01

    Full Text Available

    El objetivo del presente trabajo es determinar las variables que inciden negativamente sobre la percepción que tienen las personas acerca de la calidad del trabajo que realizan y la actitud que asumen al respecto, en la Empresa de Sueros y Hemoderivados. Se evalúa el estado del clima socio-psicológico mediante el cuestionario OLARIS, con escala de 78 ítems, dividida en cinco variables y 19 subvariables; y el cuestionario autodiagnóstico sobre estilos de dirección, realizado a los jefes directos por áreas, que permite determinar su orientación como: analizador, controlador, apoyador, promocionador. Para ello se utilizó una muestra de 73 trabajadores, pertenecientes a todas las áreas de la planta, especificándose un 99,5% de confianza. En el trabajo se estableció la existencia de un estado del clima favorable, aunque también se reflejan las insatisfacciones con el propio desempeño del trabajo y del Centro, así como la percepción de un inadecuado funcionamiento de la organización, que entorpecen un mejor estado del mismo.

    Abstract

    The aim of this paper is to identify the variables that have a negative impact in people´s perception about the quality of their work and the attitude they assume in this regard at the enterprise of sera and blood products. To assess the state of socio-psychological environment it is applied the questionnaire OLARIS which has a scale of 78 items divided into five variables and 19 sub-variables, and the questionnaire of self-management style to direct supervisors from different areas in order to evaluate the management styles, such as: analyzer, supervisor, supporter, promotioner. It was selected a sample with 73 workers from all areas at the plant, with a 99.5% of confidence. As a result of this work it is shown that the state of socio-psychological environment is conducive to performance, however, also it reflected a number of dissatisfactions with the proper

  20. System-level network simulation for robust centrifugal-microfluidic lab-on-a-chip systems.

    Science.gov (United States)

    Schwarz, I; Zehnle, S; Hutzenlaub, T; Zengerle, R; Paust, N

    2016-05-10

    Centrifugal microfluidics shows a clear trend towards a higher degree of integration and parallelization. This trend leads to an increase in the number and density of integrated microfluidic unit operations. The fact that all unit operations are processed by the same common spin protocol turns higher integration into higher complexity. To allow for efficient development anyhow, we introduce advanced lumped models for network simulations in centrifugal microfluidics. These models consider the interplay of centrifugal and Euler pressures, viscous dissipation, capillary pressures and pneumatic pressures. The simulations are fast and simple to set up and allow for the precise prediction of flow rates as well as switching and valving events. During development, channel and chamber geometry variations due to manufacturing tolerances can be taken into account as well as pipetting errors, variations of contact angles, compliant chamber walls and temperature variations in the processing device. As an example of considering these parameters during development, we demonstrate simulation based robustness analysis for pneumatic siphon valving in centrifugal microfluidics. Subsequently, the influence of liquid properties on pumping and valving is studied for four liquids relevant for biochemical analysis, namely, water (large surface tension), blood plasma (large contact angle hysteresis), ethanol/water (highly wetting) and glycerine/water (highly viscous). In a second example, we derive a spin protocol to attain a constant flow rate under varying pressure conditions. Both examples show excellent agreement with experimental validations.

  1. Blood sugar test - blood

    Science.gov (United States)

    ... blood glucose level ( hypoglycemia ) may be due to: Hypopituitarism (a pituitary gland disorder) Underactive thyroid gland or ... tonic-clonic seizure Glucagon blood test Glucagonoma Hyperthyroidism Hypopituitarism Hypothyroidism Insulinoma Low blood sugar Multiple endocrine neoplasia ( ...

  2. Rapid microfluidic thermal cycler for nucleic acid amplification

    Energy Technology Data Exchange (ETDEWEB)

    Beer, Neil Reginald; Vafai, Kambiz

    2015-10-27

    A system for thermal cycling a material to be thermal cycled including a microfluidic heat exchanger; a porous medium in the microfluidic heat exchanger; a microfluidic thermal cycling chamber containing the material to be thermal cycled, the microfluidic thermal cycling chamber operatively connected to the microfluidic heat exchanger; a working fluid at first temperature; a first system for transmitting the working fluid at first temperature to the microfluidic heat exchanger; a working fluid at a second temperature, a second system for transmitting the working fluid at second temperature to the microfluidic heat exchanger; a pump for flowing the working fluid at the first temperature from the first system to the microfluidic heat exchanger and through the porous medium; and flowing the working fluid at the second temperature from the second system to the heat exchanger and through the porous medium.

  3. Microfluidic Surface Plasmon Resonance Sensors: From Principles to Point-of-Care Applications.

    Science.gov (United States)

    Wang, Da-Shin; Fan, Shih-Kang

    2016-07-27

    Surface plasmon resonance (SPR) is a label-free, highly-sensitive, and real-time sensing technique. Conventional SPR sensors, which involve a planar thin gold film, have been widely exploited in biosensing; various miniaturized formats have been devised for portability purposes. Another type of SPR sensor which utilizes localized SPR (LSPR), is based on metal nanostructures with surface plasmon modes at the structural interface. The resonance condition is sensitive to the refractive index change of the local medium. The principles of these two types of SPR sensors are reviewed and their integration with microfluidic platforms is described. Further applications of microfluidic SPR sensors to point-of-care (POC) diagnostics are discussed.

  4. Microfluidic Organ/Body-on-a-Chip Devices at the Convergence of Biology and Microengineering

    Directory of Open Access Journals (Sweden)

    Ana Rubina Perestrelo

    2015-12-01

    Full Text Available Recent advances in biomedical technologies are mostly related to the convergence of biology with microengineering. For instance, microfluidic devices are now commonly found in most research centers, clinics and hospitals, contributing to more accurate studies and therapies as powerful tools for drug delivery, monitoring of specific analytes, and medical diagnostics. Most remarkably, integration of cellularized constructs within microengineered platforms has enabled the recapitulation of the physiological and pathological conditions of complex tissues and organs. The so-called “organ-on-a-chip” technology, which represents a new avenue in the field of advanced in vitro models, with the potential to revolutionize current approaches to drug screening and toxicology studies. This review aims to highlight recent advances of microfluidic-based devices towards a body-on-a-chip concept, exploring their technology and broad applications in the biomedical field.

  5. Microfluidics: an enabling technology for the life sciences

    OpenAIRE

    Zengerle, Roland; Koltay, P.; Ducrée, Jens

    2004-01-01

    During the last year we have investigated existing and future markets, products and technologies for microfluidics in the life sciences. Within this paper we present some of the findings and discuss a major trend identified within this project: the development of microfluidic platforms for flexible design of application specific integrated microfluidic systems. We discuss two platforms in detail which are currently under development in our lab: microfluidics on a rotating CD ("Lab-CD") as wel...

  6. Astrovirus Diagnostics

    Science.gov (United States)

    Pérot, Philippe; Lecuit, Marc; Eloit, Marc

    2017-01-01

    Various methods exist to detect an astrovirus infection. Current methods include electron microscopy (EM), cell culture, immunoassays, polymerase chain reaction (PCR) and various other molecular approaches that can be applied in the context of diagnostic or in surveillance studies. With the advent of metagenomics, novel human astrovirus (HAstV) strains have been found in immunocompromised individuals in association with central nervous system (CNS) infections. This work reviews the past and current methods for astrovirus detection and their uses in both research laboratories and for medical diagnostic purposes. PMID:28085120

  7. Bead-based microfluidic immunoassay for diagnosis of Johne's disease

    Energy Technology Data Exchange (ETDEWEB)

    Wadhwa, Ashutosh [University of Tennessee, Center for Wildlife Health, Department of Forestry; Foote, Robert [ORNL; Shaw, Robert W [ORNL; Eda, Shigetoshi [ORNL

    2012-01-01

    Microfluidics technology offers a platform for development of point-of-care diagnostic devices for various infectious diseases. In this study, we examined whether serodiagnosis of Johne s disease (JD) can be conducted in a bead-based microfluidic assay system. Magnetic micro-beads were coated with antigens of the causative agent of JD, Mycobacterium avium subsp. paratuberculosis. The antigen-coated beads were incubated with serum samples of JD-positive or negative serum samples and then with a fluorescently-labeled secondary antibody (SAB). To confirm binding of serum antibodies to the antigen, the beads were subjected to flow cytometric analysis. Different conditions (dilutions of serum and SAB, types of SAB, and types of magnetic beads) were optimized for a great degree of differentiation between the JD-negative and JD-positive samples. Using the optimized conditions, we tested a well-classified set of 155 serum samples from JD negative and JD-positive cattle by using the bead-based flow cytometric assay. Of 105 JD-positive samples, 63 samples (60%) showed higher antibody binding levels than a cut-off value determined by using antibody binding levels of JD-negative samples. In contrast, only 43-49 JD-positive samples showed higher antibody binding levels than the cut-off value when the samples were tested by commercially-available immunoassays. Microfluidic assays were performed by magnetically immobilizing a number of beads within a microchannel of a glass microchip and detecting antibody on the collected beads by laser-induced fluorescence. Antigen-coated magnetic beads treated with bovine serum sample and fluorescently-labeled SAB were loaded into a microchannel to measure the fluorescence (reflecting level of antibody binding) on the beads in the microfluidic system. When the results of five bovine serum samples obtained with the system were compared to those obtained with the flow cytometer, a high level of correlation (linear regression, r2 = 0.994) was

  8. Optical manipulation with two beam traps in microfluidic polymer systems

    DEFF Research Database (Denmark)

    Khoury Arvelo, Maria; Matteucci, Marco; Sørensen, Kristian Tølbøl;

    2015-01-01

    An optical trapping system with two opposing laser beams, also known as the optical stretcher, are naturally constructed inside a microfluidic lab-on-chip system. We present and compare two approaches to combine a simple microfluidic system with either waveguides directly written...... in the microfluidic chip or with optical fibers mounted in the chip....

  9. Mechanically activated artificial cell by using microfluidics.

    Science.gov (United States)

    Ho, Kenneth K Y; Lee, Lap Man; Liu, Allen P

    2016-01-01

    All living organisms sense mechanical forces. Engineering mechanosensitive artificial cell through bottom-up in vitro reconstitution offers a way to understand how mixtures of macromolecules assemble and organize into a complex system that responds to forces. We use stable double emulsion droplets (aqueous/oil/aqueous) to prototype mechanosensitive artificial cells. In order to demonstrate mechanosensation in artificial cells, we develop a novel microfluidic device that is capable of trapping double emulsions into designated chambers, followed by compression and aspiration in a parallel manner. The microfluidic device is fabricated using multilayer soft lithography technology, and consists of a control layer and a deformable flow channel. Deflections of the PDMS membrane above the main microfluidic flow channels and trapping chamber array are independently regulated pneumatically by two sets of integrated microfluidic valves. We successfully compress and aspirate the double emulsions, which result in transient increase and permanent decrease in oil thickness, respectively. Finally, we demonstrate the influx of calcium ions as a response of our mechanically activated artificial cell through thinning of oil. The development of a microfluidic device to mechanically activate artificial cells creates new opportunities in force-activated synthetic biology.

  10. Mechanically activated artificial cell by using microfluidics

    Science.gov (United States)

    Ho, Kenneth K. Y.; Lee, Lap Man; Liu, Allen P.

    2016-01-01

    All living organisms sense mechanical forces. Engineering mechanosensitive artificial cell through bottom-up in vitro reconstitution offers a way to understand how mixtures of macromolecules assemble and organize into a complex system that responds to forces. We use stable double emulsion droplets (aqueous/oil/aqueous) to prototype mechanosensitive artificial cells. In order to demonstrate mechanosensation in artificial cells, we develop a novel microfluidic device that is capable of trapping double emulsions into designated chambers, followed by compression and aspiration in a parallel manner. The microfluidic device is fabricated using multilayer soft lithography technology, and consists of a control layer and a deformable flow channel. Deflections of the PDMS membrane above the main microfluidic flow channels and trapping chamber array are independently regulated pneumatically by two sets of integrated microfluidic valves. We successfully compress and aspirate the double emulsions, which result in transient increase and permanent decrease in oil thickness, respectively. Finally, we demonstrate the influx of calcium ions as a response of our mechanically activated artificial cell through thinning of oil. The development of a microfluidic device to mechanically activate artificial cells creates new opportunities in force-activated synthetic biology. PMID:27610921

  11. Valve Concepts for Microfluidic Cell Handling

    Directory of Open Access Journals (Sweden)

    M. Grabowski

    2010-01-01

    Full Text Available In this paper we present various pneumatically actuated microfluidic valves to enable user-defined fluid management within a microfluidic chip. To identify a feasible valve design, certain valve concepts are simulated in ANSYS to investigate the pressure dependent opening and closing characteristics of each design. The results are verified in a series of tests. Both the microfluidic layer and the pneumatic layer are realized by means of soft-lithographic techniques. In this way, a network of channels is fabricated in photoresist as a molding master. By casting these masters with PDMS (polydimethylsiloxane we get polymeric replicas containing the channel network. After a plasma-enhanced bonding process, the two layers are irreversibly bonded to each other. The bonding is tight for pressures up to 2 bar. The valves are integrated into a microfluidic cell handling system that is designed to manipulate cells in the presence of a liquid reagent (e.g. PEG – polyethylene glycol, for cell fusion. For this purpose a user-defined fluid management system is developed. The first test series with human cell lines show that the microfluidic chip is suitable for accumulating cells within a reaction chamber, where they can be flushed by a liquid medium.

  12. Mechanically activated artificial cell by using microfluidics

    Science.gov (United States)

    Ho, Kenneth K. Y.; Lee, Lap Man; Liu, Allen P.

    2016-09-01

    All living organisms sense mechanical forces. Engineering mechanosensitive artificial cell through bottom-up in vitro reconstitution offers a way to understand how mixtures of macromolecules assemble and organize into a complex system that responds to forces. We use stable double emulsion droplets (aqueous/oil/aqueous) to prototype mechanosensitive artificial cells. In order to demonstrate mechanosensation in artificial cells, we develop a novel microfluidic device that is capable of trapping double emulsions into designated chambers, followed by compression and aspiration in a parallel manner. The microfluidic device is fabricated using multilayer soft lithography technology, and consists of a control layer and a deformable flow channel. Deflections of the PDMS membrane above the main microfluidic flow channels and trapping chamber array are independently regulated pneumatically by two sets of integrated microfluidic valves. We successfully compress and aspirate the double emulsions, which result in transient increase and permanent decrease in oil thickness, respectively. Finally, we demonstrate the influx of calcium ions as a response of our mechanically activated artificial cell through thinning of oil. The development of a microfluidic device to mechanically activate artificial cells creates new opportunities in force-activated synthetic biology.

  13. Microfluidic CODES: a scalable multiplexed electronic sensor for orthogonal detection of particles in microfluidic channels.

    Science.gov (United States)

    Liu, Ruxiu; Wang, Ningquan; Kamili, Farhan; Sarioglu, A Fatih

    2016-04-21

    Numerous biophysical and biochemical assays rely on spatial manipulation of particles/cells as they are processed on lab-on-a-chip devices. Analysis of spatially distributed particles on these devices typically requires microscopy negating the cost and size advantages of microfluidic assays. In this paper, we introduce a scalable electronic sensor technology, called microfluidic CODES, that utilizes resistive pulse sensing to orthogonally detect particles in multiple microfluidic channels from a single electrical output. Combining the techniques from telecommunications and microfluidics, we route three coplanar electrodes on a glass substrate to create multiple Coulter counters producing distinct orthogonal digital codes when they detect particles. We specifically design a digital code set using the mathematical principles of Code Division Multiple Access (CDMA) telecommunication networks and can decode signals from different microfluidic channels with >90% accuracy through computation even if these signals overlap. As a proof of principle, we use this technology to detect human ovarian cancer cells in four different microfluidic channels fabricated using soft lithography. Microfluidic CODES offers a simple, all-electronic interface that is well suited to create integrated, low-cost lab-on-a-chip devices for cell- or particle-based assays in resource-limited settings.

  14. Rapid wasted-free microfluidic fabrication based on ink-jet approach for microfluidic sensing applications

    Science.gov (United States)

    Jarujareet, Ungkarn; Amarit, Rattasart; Sumriddetchkajorn, Sarun

    2016-11-01

    Realizing that current microfluidic chip fabrication techniques are time consuming and labor intensive as well as always have material leftover after chip fabrication, this research work proposes an innovative approach for rapid microfluidic chip production. The key idea relies on a combination of a widely-used inkjet printing method and a heat-based polymer curing technique with an electronic-mechanical control, thus eliminating the need of masking and molds compared to typical microfluidic fabrication processes. In addition, as the appropriate amount of polymer is utilized during printing, there is much less amount of material wasted. Our inkjet-based microfluidic printer can print out the desired microfluidic chip pattern directly onto a heated glass surface, where the printed polymer is suddenly cured. Our proof-of-concept demonstration for widely-used single-flow channel, Y-junction, and T-junction microfluidic chips shows that the whole microfluidic chip fabrication process requires only 3 steps with a fabrication time of 6 minutes.

  15. An integrated microfluidic system for measurement of glycated hemoglobin levels by using an aptamer-antibody assay on magnetic beads.

    Science.gov (United States)

    Chang, Ko-Wei; Li, Jinglun; Yang, Ching-Hsuan; Shiesh, Shu-Chu; Lee, Gwo-Bin

    2015-06-15

    Blood glycated hemoglobin (HbA1c), reflecting the average blood glucose level in the proceeding 2-3 months, is recommended for screening/diagnosing and patient management of diabetes. However, accurate measurement of the HbA1c level at the point of care is hampered by costly, large-scale instruments (such as high-performance liquid chromatography) or reagent instability of classical immunologic methods, which involve antibody-based immunoturbidimetry. In this work, an integrated microfluidic system using aptamer-based testing to measure HbA1c in blood samples is therefore presented. This measuring system used nucleic-acid aptamers that exhibited high sensitivity and high specificity for hemoglobin and HbA1c to perform a stable and robust testing. The compact microfluidic system consumed less samples and reagents and significantly shortened the detection time. Combining the advantages of microfluidics and aptamers, this integrated microsystem presents a promising tool for accurate and point-of-case HbA1c detection. To demonstrate its clinical utility, whole blood samples with clinically-relevant concentrations of HbA1c and Hb were automatically measured on the integrated microfluidic system. Experimental data showed that the developed aptamer-based microfluidic system is capable of detecting HbA1c and Hb with a good linear response. The entire process was completed within 25 min. The aptamer-antibody on-chip sandwich immunoassay may be further refined to allow diabetes screening and diagnosis at lower cost and earlier phase to minimize the risk of diabetic complications.

  16. Surfactant adsorption kinetics in microfluidics

    Science.gov (United States)

    Riechers, Birte; Maes, Florine; Akoury, Elias; Semin, Benoît; Gruner, Philipp; Baret, Jean-Christophe

    2016-10-01

    Emulsions are metastable dispersions. Their lifetimes are directly related to the dynamics of surfactants. We design a microfluidic method to measure the kinetics of adsorption of surfactants to the droplet interface, a key process involved in foaming, emulsification, and droplet coarsening. The method is based on the pH decay in the droplet as a direct measurement of the adsorption of a carboxylic acid surfactant to the interface. From the kinetic measurement of the bulk equilibration of the pH, we fully determine the adsorption process of the surfactant. The small droplet size and the convection during the droplet flow ensure that the transport of surfactant through the bulk is not limiting the kinetics of adsorption. To validate our measurements, we show that the adsorption process determines the timescale required to stabilize droplets against coalescence, and we show that the interface should be covered at more than 90% to prevent coalescence. We therefore quantitatively link the process of adsorption/desorption, the stabilization of emulsions, and the kinetics of solute partitioning—here through ion exchange—unraveling the timescales governing these processes. Our method can be further generalized to other surfactants, including nonionic surfactants, by making use of fluorophore-surfactant interactions.

  17. Microfluidic mixing using contactless dielectrophoresis.

    Science.gov (United States)

    Salmanzadeh, Alireza; Shafiee, Hadi; Davalos, Rafael V; Stremler, Mark A

    2011-09-01

    The first experimental evidence of mixing enhancement in a microfluidic system using contactless dielectrophoresis (cDEP) is presented in this work. Pressure-driven flow of deionized water containing 0.5 μm beads was mixed in various chamber geometries by imposing a dielectrophoresis (DEP) force on the beads. In cDEP the electrodes are not in direct contact with the fluid sample but are instead capacitively coupled to the mixing chamber through thin dielectric barriers, which eliminates many of the problems encountered with standard DEP. Four system designs with rectangular and circular mixing chambers were fabricated in PDMS. Mixing tests were conducted for flow rates from 0.005 to 1 mL/h subject to an alternating current signal range of 0-300 V at 100-600 kHz. When the time scales of the bulk fluid motion and the DEP motion were commensurate, rapid mixing was observed. The rectangular mixing chambers were found to be more efficient than the circular chambers. This approach shows potential for mixing low diffusivity biological samples, which is a very challenging problem in laminar flows at small scales.

  18. Microfluidic serpentine antennas with designed mechanical tunability.

    Science.gov (United States)

    Huang, YongAn; Wang, Yezhou; Xiao, Lin; Liu, Huimin; Dong, Wentao; Yin, Zhouping

    2014-11-07

    This paper describes the design and characterization of microfluidic serpentine antennas with reversible stretchability and designed mechanical frequency modulation (FM). The microfluidic antennas are designed based on the Poisson's ratio of the elastomer in which the liquid alloy antenna is embedded, to controllably decrease, stabilize or increase its resonance frequency when being stretched. Finite element modelling was used in combination with experimental verification to investigate the effects of substrate dimensions and antenna aspect ratios on the FM sensitivity to uniaxial stretching. It could be designed within the range of -1.2 to 0.6 GHz per 100% stretch. When the aspect ratio of the serpentine antenna is between 1.0 and 1.5, the resonance frequency is stable under stretching, bending, and twisting. The presented microfluidic serpentine antenna design could be utilized in the field of wireless mobile communication for the design of wearable electronics, with a stable resonance frequency under dynamic applied strain up to 50%.

  19. A self-triggered picoinjector in microfluidics

    Science.gov (United States)

    Yang, Yiming; Liu, Songsheng; Jia, Chunping; Mao, Hongju; Jin, Qinghui; Zhao, Jianlong; Zhou, Hongbo

    2016-12-01

    Droplet-based microfluidics has recently emerged as a potential platform for studies of single-cell, directed evolution, and genetic sequencing. In droplet-based microfluidics, adding reagents into drops is one of the most important functions. In this paper, we develop a new self-triggered picoinjector to add controlled volumes of reagent into droplets at kilohertz rates. In the picoinjector, the reagent injecting is triggered by the coming droplet itself, without needing a droplet detection module. Meanwhile, the dosing volume can be precisely controlled. These features make the system more practical and reliable. We expect the new picoinjector will find important applications of droplet-based microfluidics in automated biological assay, directed evolution, enzyme assay, and so on.

  20. 3D-printed microfluidic automation.

    Science.gov (United States)

    Au, Anthony K; Bhattacharjee, Nirveek; Horowitz, Lisa F; Chang, Tim C; Folch, Albert

    2015-04-21

    Microfluidic automation - the automated routing, dispensing, mixing, and/or separation of fluids through microchannels - generally remains a slowly-spreading technology because device fabrication requires sophisticated facilities and the technology's use demands expert operators. Integrating microfluidic automation in devices has involved specialized multi-layering and bonding approaches. Stereolithography is an assembly-free, 3D-printing technique that is emerging as an efficient alternative for rapid prototyping of biomedical devices. Here we describe fluidic valves and pumps that can be stereolithographically printed in optically-clear, biocompatible plastic and integrated within microfluidic devices at low cost. User-friendly fluid automation devices can be printed and used by non-engineers as replacement for costly robotic pipettors or tedious manual pipetting. Engineers can manipulate the designs as digital modules into new devices of expanded functionality. Printing these devices only requires the digital file and electronic access to a printer.

  1. Bridging Flows: Microfluidic End‐User Solutions

    DEFF Research Database (Denmark)

    Sabourin, David

    . A second practical challenge users face stems from the peripheral equipment, e.g. pumps, required to drive microfluidic devices. This equipment is often costly and bulky and results in limitations and restrictions on microfluidic device operation, such as the number of channels or devices which can...... be actuated or microscopic observation. To address the above issues interconnection and pumping solutions were developed. Methods for creating multiple, aligned, parallel and planar interconnections well suited to microscopy are described. Both reusable, non‐integrated, and permanent, integrated...... interconnection solutions are presented. The construction of twelve and eight channel miniaturized, mechanically actuated peristaltic pumps is also described. The small footprint of the pumps allows their placement adjacent to microfluidic devices and on microscope stages. The reusable, non...

  2. Electroporation of cells in microfluidic droplets.

    Science.gov (United States)

    Zhan, Yihong; Wang, Jun; Bao, Ning; Lu, Chang

    2009-03-01

    Droplet-based microfluidics has raised a lot of interest recently due to its wide applications to screening biological/chemical assays with high throughput. Despite the advances on droplet-based assays involving cells, gene delivery methods that are compatible with the droplet platform have been lacking. In this report, we demonstrate a simple microfluidic device that encapsulates cells into aqueous droplets and then electroporates the encapsulated cells. The electroporation occurs when the cell-containing droplets (in oil) flow through a pair of microelectrodes with a constant voltage established in between. We investigate the parameters and characteristics of the electroporation. We demonstrate delivering enhanced green fluorescent protein (EGFP) plasmid into Chinese hamster ovary (CHO) cells. We envision the application of this technique to high-throughput functional genomics studies based on droplet microfluidics.

  3. 3D-Printed Microfluidic Automation

    Science.gov (United States)

    Au, Anthony K.; Bhattacharjee, Nirveek; Horowitz, Lisa F.; Chang, Tim C.; Folch, Albert

    2015-01-01

    Microfluidic automation – the automated routing, dispensing, mixing, and/or separation of fluids through microchannels – generally remains a slowly-spreading technology because device fabrication requires sophisticated facilities and the technology’s use demands expert operators. Integrating microfluidic automation in devices has involved specialized multi-layering and bonding approaches. Stereolithography is an assembly-free, 3D-printing technique that is emerging as an efficient alternative for rapid prototyping of biomedical devices. Here we describe fluidic valves and pumps that can be stereolithographically printed in optically-clear, biocompatible plastic and integrated within microfluidic devices at low cost. User-friendly fluid automation devices can be printed and used by non-engineers as replacement for costly robotic pipettors or tedious manual pipetting. Engineers can manipulate the designs as digital modules into new devices of expanded functionality. Printing these devices only requires the digital file and electronic access to a printer. PMID:25738695

  4. Thermophoresis of DNA determined by microfluidic fluorescence.

    Science.gov (United States)

    Duhr, S; Arduini, S; Braun, D

    2004-11-01

    We describe a microfluidic all-optical technique to measure the thermophoresis of molecules. Within micrometer-thick chambers, we heat aqueous solutions with a micrometer-sized focus of infrared light. The temperature increase of about 1 K is monitored with temperature-sensitive fluorescent dyes. We test the approach in measuring the thermophoresis of DNA. We image the concentration of DNA in a second fluorescence-color channel. DNA is depleted away from the heated spot. The profile of depletion is fitted by the thermophoretic theory to reveal the Soret coefficient. We evaluate the method with numerical 3D calculations of temperature profiles, drift, convection and thermophoretic depletion using finite element methods. The approach opens new ways to monitor thermophoresis at the single molecule level, near boundaries and in complex mixtures. The flexible microfluidic setting is a good step towards microfluidic applications of thermophoresis in biotechnology.

  5. Microfluidics for research and applications in oncology.

    Science.gov (United States)

    Chaudhuri, Parthiv Kant; Ebrahimi Warkiani, Majid; Jing, Tengyang; Kenry; Lim, Chwee Teck

    2016-01-21

    Cancer is currently one of the top non-communicable human diseases, and continual research and developmental efforts are being made to better understand and manage this disease. More recently, with the improved understanding in cancer biology as well as the advancements made in microtechnology and rapid prototyping, microfluidics is increasingly being explored and even validated for use in the detection, diagnosis and treatment of cancer. With inherent advantages such as small sample volume, high sensitivity and fast processing time, microfluidics is well-positioned to serve as a promising platform for applications in oncology. In this review, we look at the recent advances in the use of microfluidics, from basic research such as understanding cancer cell phenotypes as well as metastatic behaviors to applications such as the detection, diagnosis, prognosis and drug screening. We then conclude with a future outlook on this promising technology.

  6. Microfluidic Pumps Containing Teflon [Trademark] AF Diaphragms

    Science.gov (United States)

    Willis, Peter; White, Victor; Grunthaner, Frank; Ikeda, Mike; Mathies, Richard A.

    2009-01-01

    Microfluidic pumps and valves based on pneumatically actuated diaphragms made of Teflon AF polymers are being developed for incorporation into laboratory-on-a-chip devices that must perform well over temperature ranges wider than those of prior diaphragm-based microfluidic pumps and valves. Other potential applications include implanted biomedical microfluidic devices, wherein the biocompatability of Teflon AF polymers would be highly advantageous. These pumps and valves have been demonstrated to function stably after cycling through temperatures from -125 to 120 C. These pumps and valves are intended to be successors to similar prior pumps and valves containing diaphragms made of polydimethylsiloxane (PDMS) [commonly known as silicone rubber]. The PDMS-containing valves ae designed to function stably only within the temperature range from 5 to 80 C. Undesirably, PDMS membranes are somwehat porous and retain water. PDMS is especially unsuitable for use at temperatures below 0 C because the formation of ice crystals increases porosity and introduces microshear.

  7. Temperature Sensing in Modular Microfluidic Architectures

    Directory of Open Access Journals (Sweden)

    Krisna C. Bhargava

    2016-01-01

    Full Text Available A discrete microfluidic element with integrated thermal sensor was fabricated and demonstrated as an effective probe for process monitoring and prototyping. Elements were constructed using stereolithography and market-available glass-bodied thermistors within the modular, standardized framework of previous discrete microfluidic elements demonstrated in the literature. Flow rate-dependent response due to sensor self-heating and microchannel heating and cooling was characterized and shown to be linear in typical laboratory conditions. An acid-base neutralization reaction was performed in a continuous flow setting to demonstrate applicability in process management: the ratio of solution flow rates was varied to locate the equivalence point in a titration, closely matching expected results. This element potentially enables complex, three-dimensional microfluidic architectures with real-time temperature feedback and flow rate sensing, without application specificity or restriction to planar channel routing formats.

  8. A microfluidic toolbox approach to CBRNE sensing

    Science.gov (United States)

    Gärtner, Claudia; Klemm, Richard; Hlawatsch, Nadine; Becker, Holger

    2012-06-01

    Microfluidics has proven to be a very effective technology for the identification of biological and chemical analytes in a CBRNE scenario. As it will be shown in the following, the required steps of those analytical processes are manifold making the development of an integrated microfluidic device a complicated project with a high level of technological risk, because all necessary analytical processes have to be implemented into a single device. The implementation is initiated by a dissection of the biochemical workflow into mandatory bio-analytical steps and the resulting protocol for each of those steps is translated into an appropriate design of a chip-based unit. In this report, examples for such chipbased functional modules are given. In addition, examples for a merging of positively tested modules into an integrated chip are shown and, finally, representatives for a smooth interaction between outer world, microfluidic chip, and chip driving instrument are presented.

  9. Burn injury reduces neutrophil directional migration speed in microfluidic devices.

    Directory of Open Access Journals (Sweden)

    Kathryn L Butler

    Full Text Available Thermal injury triggers a fulminant inflammatory cascade that heralds shock, end-organ failure, and ultimately sepsis and death. Emerging evidence points to a critical role for the innate immune system, and several studies had documented concurrent impairment in neutrophil chemotaxis with these post-burn inflammatory changes. While a few studies suggest that a link between neutrophil motility and patient mortality might exist, so far, cumbersome assays have prohibited exploration of the prognostic and diagnostic significance of chemotaxis after burn injury. To address this need, we developed a microfluidic device that is simple to operate and allows for precise and robust measurements of chemotaxis speed and persistence characteristics at single-cell resolution. Using this assay, we established a reference set of migration speed values for neutrophils from healthy subjects. Comparisons with samples from burn patients revealed impaired directional migration speed starting as early as 24 hours after burn injury, reaching a minimum at 72-120 hours, correlated to the size of the burn injury and potentially serving as an early indicator for concurrent infections. Further characterization of neutrophil chemotaxis using this new assay may have important diagnostic implications not only for burn patients but also for patients afflicted by other diseases that compromise neutrophil functions.

  10. Operation placement for application-specific digital microfluidic biochips

    DEFF Research Database (Denmark)

    Alistar, Mirela; Pop, Paul; Madsen, Jan

    2013-01-01

    , but as discrete droplets on an array of electrodes. Microfluidic operations, such as transport, mixing, split, are performed on this array by routing the corresponding droplets on a series of electrodes. Researchers have proposed several approaches for the synthesis of digital microfluidic biochips. All previous......Microfluidic-based biochips are replacing the conventional biochemical analyzers, and are able to integrate onchip all the necessary functions for biochemical analysis using microfluidics. The digital microfluidic biochips are based on the manipulation of liquids not as a continuous flow...

  11. Microfluidic Multichannel Flow Cytometer Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Techshot, Inc. proposes continued research and development of an on-orbit cell counter culminating in a deliverable hand-held blood cell counter in the form of a...

  12. Microfluidic platforms for plant cells studies.

    Science.gov (United States)

    Sanati Nezhad, A

    2014-09-07

    Conventional methods of plant cell analysis rely on growing plant cells in soil pots or agarose plates, followed by screening the plant phenotypes in traditional greenhouses and growth chambers. These methods are usually costly, need a large number of experiments, suffer from low spatial resolution and disorderly growth behavior of plant cells, with lack of ability to locally and accurately manipulate the plant cells. Microfluidic platforms take advantage of miniaturization for handling small volume of liquids and providing a closed environment, with the purpose of in vitro single cell analysis and characterizing cell response to external cues. These platforms have shown their ability for high-throughput cellular analysis with increased accuracy of experiments, reduced cost and experimental times, versatility in design, ability for large-scale and combinatorial screening, and integration with other miniaturized sensors. Despite extensive research on animal cells within microfluidic environments for high-throughput sorting, manipulation and phenotyping studies, the application of microfluidics for plant cells studies has not been accomplished yet. Novel devices such as RootChip, RootArray, TipChip, and PlantChip developed for plant cells analysis, with high spatial resolution on a micrometer scale mimicking the internal microenvironment of plant cells, offering preliminary results on the capability of microfluidics to conquer the constraints of conventional methods. These devices have been used to study different aspects of plant cell biology such as gene expression, cell biomechanics, cellular mechanism of growth, cell division, and cells fusion. This review emphasizes the advantages of current microfluidic systems for plant science studies, and discusses future prospects of microfluidic platforms for characterizing plant cells response to diverse external cues.

  13. Microfluidic chip-capillary electrophoresis devices

    CERN Document Server

    Fung, Ying Sing; Du, Fuying; Guo, Wenpeng; Ma, Tongmei; Nie, Zhou; Sun, Hui; Wu, Ruige; Zhao, Wenfeng

    2015-01-01

    Capillary electrophoresis (CE) and microfluidic chip (MC) devices are relatively mature technologies, but this book demonstrates how they can be integrated into a single, revolutionary device that can provide on-site analysis of samples when laboratory services are unavailable. By introducing the combination of CE and MC technology, Microfluidic Chip-Capillary Electrophoresis Devices broadens the scope of chemical analysis, particularly in the biomedical, food, and environmental sciences.The book gives an overview of the development of MC and CE technology as well as technology that now allows

  14. Integrated Microfluidic Sensor System with Magnetostrictive Resonators

    KAUST Repository

    Liang, Cai

    2011-12-08

    The present embodiments describe a method that integrates a magnetostrictive sensor with driving and detecting elements into a microfluidic chip to detect a chemical, biochemical or biomedical species. These embodiments may also measure the properties of a fluid such as viscosity, pH values. The whole system can be referred to lab-on-a-chip (LOC) or micro-total-analysis-systems (.mu.TAS). In particular, this present embodiments include three units, including a microfluidics unit, a magnetostrictive sensor, and driving/detecting elements. An analyzer may also be provided to analyze an electrical signal associated with a feature of a target specimen.

  15. Microfluidic fuel cells for energy generation.

    Science.gov (United States)

    Safdar, M; Jänis, J; Sánchez, S

    2016-08-07

    Sustainable energy generation is of recent interest due to a growing energy demand across the globe and increasing environmental issues caused by conventional non-renewable means of power generation. In the context of microsystems, portable electronics and lab-on-a-chip based (bio)chemical sensors would essentially require fully integrated, reliable means of power generation. Microfluidic-based fuel cells can offer unique advantages compared to conventional fuel cells such as high surface area-to-volume ratio, ease of integration, cost effectiveness and portability. Here, we summarize recent developments which utilize the potential of microfluidic devices for energy generation.

  16. Micro-Fluidic Device for Drug Delivery

    Science.gov (United States)

    Beebe, David J. (Inventor); MacDonald, Michael J. (Inventor); Eddington, David T. (Inventor); Mensing, Glennys A. (Inventor)

    2014-01-01

    A microfluidic device is provided for delivering a drug to an individual. The microfluidic device includes a body that defines a reservoir for receiving the drug therein. A valve interconnects the reservoir to an output needle that is insertable into the skin of an individual. A pressure source urges the drug from the reservoir toward the needle. The valve is movable between a closed position preventing the flow of the drug from the reservoir to the output needle and an open position allowing for the flow of the drug from the reservoir to the output needle in response to a predetermined condition in the physiological fluids of the individual.

  17. Diffusion dynamics in microfluidic dye lasers

    DEFF Research Database (Denmark)

    Gersborg-Hansen, Morten; Balslev, Søren; Mortensen, Niels Asger

    2007-01-01

    We have investigated the bleaching dynamics that occur in opto-fluidic dye lasers, where the liquid laser dye in a channel is locally bleached due to optical pumping. Our studies suggest that for micro-fluidic devices, the dye bleaching may be compensated through diffusion of dye molecules alone....... By relying on diffusion rather than convection to generate the necessary dye replenishment, our observation potentially allows for a significant simplification of opto-fluidic dye laser device layouts, omitting the need for cumbersome and costly external fluidic handling or on-chip micro-fluidic pumping...

  18. Microfluidic Assessment of Frying Oil Degradation

    Science.gov (United States)

    Liu, Mei; Xie, Shaorong; Ge, Ji; Xu, Zhensong; Wu, Zhizheng; Ru, Changhai; Luo, Jun; Sun, Yu

    2016-06-01

    Monitoring the quality of frying oil is important for the health of consumers. This paper reports a microfluidic technique for rapidly quantifying the degradation of frying oil. The microfluidic device generates monodispersed water-in-oil droplets and exploits viscosity and interfacial tension changes of frying oil samples over their frying/degradation process. The measured parameters were correlated to the total polar material percentage that is widely used in the food industry. The results reveal that the steady-state length of droplets can be used for unambiguously assessing frying oil quality degradation.

  19. Physics and applications of microfluidics in biology.

    Science.gov (United States)

    Beebe, David J; Mensing, Glennys A; Walker, Glenn M

    2002-01-01

    Fluid flow at the microscale exhibits unique phenomena that can be leveraged to fabricate devices and components capable of performing functions useful for biological studies. The physics of importance to microfluidics are reviewed. Common methods of fabricating microfluidic devices and systems are described. Components, including valves, mixers, and pumps, capable of controlling fluid flow by utilizing the physics of the microscale are presented. Techniques for sensing flow characteristics are described and examples of devices and systems that perform bioanalysis are presented. The focus of this review is microscale phenomena and the use of the physics of the scale to create devices and systems that provide functionality useful to the life sciences.

  20. Detection methods for centrifugal microfluidic platforms

    DEFF Research Database (Denmark)

    Burger, Robert; Amato, Letizia; Boisen, Anja

    2016-01-01

    Centrifugal microfluidics has attracted much interest from academia as well as industry, since it potentially offers solutions for affordable, user-friendly and portable biosensing. A wide range of so-called fluidic unit operations, e.g. mixing, metering, liquid routing, and particle separation......, have been developed and allow automation and integration of complex assay protocols in lab-on-a-disc systems. Besides liquid handling, the detection strategy for reading out the assay is crucial for developing a fully integrated system. In this review, we focus on biosensors and readout methods...... for the centrifugal microfluidics platform and cover optical as well as mechanical and electrical detection principles....

  1. 3D tracking and phase-contrast imaging by twin-beams digital holographic microscope in microfluidics

    Science.gov (United States)

    Miccio, L.; Memmolo, P.; Finizio, A.; Paturzo, M.; Merola, F.; Grilli, S.; Ferraro, P.

    2012-06-01

    A compact twin-beam interferometer that can be adopted as a flexible diagnostic tool in microfluidic platforms is presented. The devise has two functionalities, as explained in the follow, and can be easily integrated in microfluidic chip. The configuration allows 3D tracking of micro-particles and, at same time, furnishes Quantitative Phase-Contrast maps of tracked micro-objects by interference microscopy. Experimental demonstration of its effectiveness and compatibility with biological field is given on for in vitro cells in microfluidic environment. Nowadays, several microfluidic configuration exist and many of them are commercially available, their development is due to the possibility for manipulating droplets, handling micro and nano-objects, visualize and quantify processes occurring in small volumes and, clearly, for direct applications on lab-on-a chip devices. In microfluidic research field, optical/photonics approaches are the more suitable ones because they have various advantages as to be non-contact, full-field, non-invasive and can be packaged thanks to the development of integrable optics. Moreover, phase contrast approaches, adapted to a lab-on-a-chip configurations, give the possibility to get quantitative information with remarkable lateral and vertical resolution directly in situ without the need to dye and/or kill cells. Furthermore, numerical techniques for tracking of micro-objects needs to be developed for measuring velocity fields, trajectories patterns, motility of cancer cell and so on. Here, we present a compact holographic microscope that can ensure, by the same configuration and simultaneously, accurate 3D tracking and quantitative phase-contrast analysis. The system, simple and solid, is based on twin laser beams coming from a single laser source. Through a easy conceptual design, we show how these two different functionalities can be accomplished by the same optical setup. The working principle, the optical setup and the mathematical

  2. Migration distance-based platelet function analysis in a microfluidic system.

    Science.gov (United States)

    Song, Suk-Heung; Lim, Chae-Seung; Shin, Sehyun

    2013-01-01

    Aggregation and adhesion of platelets to the vascular wall are shear-dependent processes that play critical roles in hemostasis and thrombosis at vascular injury sites. In this study, we designed a simple and rapid assay of platelet aggregation and adhesion in a microfluidic system. A shearing mechanism using a rotating stirrer provided adjustable shear rate and shearing time and induced platelet activation. When sheared blood was driven through the microchannel under vacuum pressure, shear-activated platelets adhered to a collagen-coated surface, causing blood flow to significantly slow and eventually stop. To measure platelet adhesion and aggregation, the migration distance (MD) of blood through the microchannel was monitored. As the microstirrer speed increased, MD initially decreased exponentially but then increased beyond a critical rpm. For platelet-excluded blood samples, there were no changes in MD with increasing stirrer speed. These findings imply that the stirrer provided sufficiently high shear to activate platelets and that blood MD is a potentially valuable index for measuring the shear-dependence of platelet activation. Our microfluidic system is quick and simple, while providing a precise assay to measure the effects of shear on platelet aggregation and adhesion.

  3. Recent developments in microfluidics-based chemotaxis studies.

    Science.gov (United States)

    Wu, Jiandong; Wu, Xun; Lin, Francis

    2013-07-07

    Microfluidic devices can better control cellular microenvironments compared to conventional cell migration assays. Over the past few years, microfluidics-based chemotaxis studies showed a rapid growth. New strategies were developed to explore cell migration in manipulated chemical gradients. In addition to expanding the use of microfluidic devices for a broader range of cell types, microfluidic devices were used to study cell migration and chemotaxis in complex environments. Furthermore, high-throughput microfluidic chemotaxis devices and integrated microfluidic chemotaxis systems were developed for medical and commercial applications. In this article, we review recent developments in microfluidics-based chemotaxis studies and discuss the new trends in this field observed over the past few years.

  4. Microfluidics and Raman microscopy: current applications and future challenges.

    Science.gov (United States)

    Chrimes, Adam F; Khoshmanesh, Khashayar; Stoddart, Paul R; Mitchell, Arnan; Kalantar-Zadeh, Kourosh

    2013-07-07

    Raman microscopy systems are becoming increasingly widespread and accessible for characterising chemical species. Microfluidic systems are also progressively finding their way into real world applications. Therefore, it is anticipated that the integration of Raman systems with microfluidics will become increasingly attractive and practical. This review aims to provide an overview of Raman microscopy-microfluidics integrated systems for researchers who are actively interested in utilising these tools. The fundamental principles and application strengths of Raman microscopy are discussed in the context of microfluidics. Various configurations of microfluidics that incorporate Raman microscopy methods are presented, with applications highlighted. Data analysis methods are discussed, with a focus on assisting the interpretation of Raman-microfluidics data from complex samples. Finally, possible future directions of Raman-microfluidic systems are presented.

  5. Diagnostic Criteria

    Directory of Open Access Journals (Sweden)

    Narender P. Van Orshoven

    2010-01-01

    Full Text Available The aims of this study were to find out whether Postprandial hypotension (PPH occurs more frequently in patients admitted to a geriatric ward than in healthy elderly individuals, what the optimal interval between blood pressure measurements is in order to diagnose PPH and how often it is associated with symptoms.The result of this study indicates that PPH is present in a high number of frail elderly, but also in a few healthy older persons. Measuring blood pressure at least every 10 minutes for 60 minutes after breakfast will adequately diagnose PPH, defined as >20 mmHg systolic fall, in most patients. However with definition of PPH as >30 mmHg systolic fall, measuring blood pressure every 10 minutes will miss PPH in one of three patients. With the latter definition of PPH the presence of postprandial complaints is not associated with the existence of PPH.

  6. Blood flow and microgravity

    Science.gov (United States)

    Bureau, Lionel; Coupier, Gwennou; Dubois, Frank; Duperray, Alain; Farutin, Alexander; Minetti, Christophe; Misbah, Chaouqi; Podgorski, Thomas; Tsvirkun, Daria; Vysokikh, Mikhail

    2017-01-01

    The absence of gravity during space flight can alter cardio-vascular functions partially due to reduced physical activity. This affects the overall hemodynamics, and in particular the level of shear stresses to which blood vessels are submitted. Long-term exposure to space environment is thus susceptible to induce vascular remodeling through a mechanotransduction cascade that couples vessel shape and function with the mechanical cues exerted by the circulating cells on the vessel walls. Central to such processes, the glycocalyx - i.e. the micron-thick layer of biomacromolecules that lines the lumen of blood vessels and is directly exposed to blood flow - is a major actor in the regulation of biochemical and mechanical interactions. We discuss in this article several experiments performed under microgravity, such as the determination of lift force and collective motion in blood flow, and some preliminary results obtained in artificial microfluidic circuits functionalized with endothelium that offer interesting perspectives for the study of the interactions between blood and endothelium in healthy condition as well as by mimicking the degradation of glycocalyx caused by long space missions. A direct comparison between experiments and simulations is discussed. xml:lang="fr"

  7. High Purity DNA Extraction with a SPE Microfluidic Chip Using KI as the Binding Salt

    Institute of Scientific and Technical Information of China (English)

    Xing CHEN; Da Fu CUI; Chang Chun LIU

    2006-01-01

    Based on solid phase extraction method, a novel silicon-PDMS-glass microchip for high purity DNA extraction has been developed by using KI as the binding salt. The microfluidic chip fabricated by MEMS technology was composed of a silicon substrate with a coiled channel and a compounded PDMS-glass cover. With this microfluidic chip, the wall of the coiled channel was used as solid phase matrix for binding DNA and DNA was extracted by the fluxion of the binding buffer, washing buffer and elution buffer. KI as a substitute for guanidine, was used successfully as binding salt for purification DNA, obtaining higher purity of genomic DNA and about 13.9 ng DNA from 1 μL rat whole blood in 35 minutes.

  8. Integrated Amplification Microarrays for Infectious Disease Diagnostics

    Directory of Open Access Journals (Sweden)

    Darrell P. Chandler

    2012-11-01

    Full Text Available This overview describes microarray-based tests that combine solution-phase amplification chemistry and microarray hybridization within a single microfluidic chamber. The integrated biochemical approach improves microarray workflow for diagnostic applications by reducing the number of steps and minimizing the potential for sample or amplicon cross-contamination. Examples described herein illustrate a basic, integrated approach for DNA and RNA genomes, and a simple consumable architecture for incorporating wash steps while retaining an entirely closed system. It is anticipated that integrated microarray biochemistry will provide an opportunity to significantly reduce the complexity and cost of microarray consumables, equipment, and workflow, which in turn will enable a broader spectrum of users to exploit the intrinsic multiplexing power of microarrays for infectious disease diagnostics.

  9. Saliva Preservative for Diagnostic Purposes

    Science.gov (United States)

    Pierson, Duane L.; Mehta, Satish K.

    2012-01-01

    Saliva is an important body fluid for diagnostic purposes. Glycoproteins, glucose, steroids, DNA, and other molecules of diagnostic value are found in saliva. It is easier to collect as compared to blood or urine. Unfortunately, saliva also contains large numbers of bacteria that can release enzymes, which can degrade proteins and nucleic acids. These degradative enzymes destroy or reduce saliva s diagnostic value. This innovation describes the formulation of a chemical preservative that prevents microbial growth and inactivates the degradative enzymes. This extends the time that saliva can be stored or transported without losing its diagnostic value. Multiple samples of saliva can be collected if needed without causing discomfort to the subject and it does not require any special facilities to handle after it is collected.

  10. Solar thermal polymerase chain reaction for smartphone-assisted molecular diagnostics

    OpenAIRE

    Li Jiang; Matthew Mancuso; Zhengda Lu; Gunkut Akar; Ethel Cesarman; David Erickson

    2014-01-01

    Nucleic acid-based diagnostic techniques such as polymerase chain reaction (PCR) are used extensively in medical diagnostics due to their high sensitivity, specificity and quantification capability. In settings with limited infrastructure and unreliable electricity, however, access to such devices is often limited due to the highly specialized and energy-intensive nature of the thermal cycling process required for nucleic acid amplification. Here we integrate solar heating with microfluidics ...

  11. 外周血中钙调蛋白对阿尔茨海默病的诊断价值%Diagnostic value of calmodulin in peripheral blood for Alzheimer disease

    Institute of Scientific and Technical Information of China (English)

    高丽丽; 唐咏春; 毛德军; 邢岩

    2016-01-01

    目的 检测阿尔茨海默病(AD)患者外周血单个核细胞和血浆中钙调蛋白(CaM)的表达水平,评价其作为AD生物标志物的诊断价值. 方法 将2013年2月~2015年1月于青岛大学医学院附属海慈医院就诊和体检的对象共116例纳入本研究,包括AD患者40例、轻度认知障碍(MCI)患者20例、帕金森病(PD)患者20例、额颞叶痴呆(FTD)患者10例、路易体痴呆(DLB)患者10例、进行性核上性麻痹(PSP)患者6例、认知正常的健康体检者(对照组)10名.取外周血分离单个核细胞和血浆,采用Western blot和酶联免疫吸附测定(ELISA)检测CaM在外周血单个核细胞和血浆中的表达水平,并通过绘制ROC曲线判断其诊断能力. 结果 AD患者外周血单个核细胞和血浆中CaM的表达水平显著高于对照组,差异有统计学意义(P< 0.05),且CaM的表达水平不随AD的进展变化. 以对照组和PSP、DLB、FTD、PD患者中CaM的表达作为标准绘制ROC曲线,曲线下面积分别为0.958、0.946、0.846、0.958和0.896. 结论 CaM在AD患者外周血单个核细胞和血浆中高表达, 是一种潜在的AD生物标志物.%Objective To test the expression levels of calmodulin (CaM) in the mononuclear cells and plasma of peripheral blood of patients with Alzheimer disease (AD), and to evaluate its diagnostic value as the biomarker of AD. Methods Total 116 objects treated and examined in the Affiliated Hiser Hospital of Qingdao University Medical College from February 2013 to January 2015 were enrolled into the research, including 40 cases with AD, 20 cases with mild cognitive impairment (MCI), 20 cases with Parkinson disease (PD), 10 cases with frontotemporal dementia (FTD), 10 cases with dementia with Lewy bodies (DLB), 6 cases with progressive supranuclear palsy (PSP) and 10 healthy cases with normal cognition (control group). The peripheral blood was obtained to separate the mononuclear cells and plasma. Western blot and enzyme-linked immuno

  12. [Novel methods for dementia diagnostics].

    Science.gov (United States)

    Wiltfang, J

    2015-04-01

    Novel diagnostic methods, such as cerebrospinal fluid-based neurochemical dementia diagnostics (CSF-NDD) and [18F] amyloid positron emission tomography (PET) are meanwhile recommended for specific indications by international guidelines for the improved early and differential diagnostics of multigenic (sporadic) Alzheimer's dementia (AD). In the case of CSF-NDD the German neuropsychiatric guidelines have already been validated on the S3 level of evidence (http://www.DGPPN.de) and the additional consideration of [18F] amyloid-PET in the current update of the guidelines is to be expected. By means of CSF-NDD and/or [18F] amyloid-PET a predictive diagnosis of incipient (preclinical) AD is also possible for patients at high risk for AD who are in prodromal stages, such as mild cognitive impairment (MCI). As accompanying (secondary) preventive therapy of AD cannot be offered a predictive molecular dementia diagnostics is not recommended by the German neuropsychiatric dementia guidelines (http://www.DGPPN.de). However, novel diagnostic approaches, which offer molecular positive diagnostics of AD have already gained high relevance in therapy research as they allow promising preventive treatment avenues to be validated directly in the clinical trial. Moreover, future blood-based dementia diagnostics by means of multiplex assays is becoming increasingly more feasible; however, so far corresponding proteomic or epigenetic assays could not be consistently validated in independent studies.

  13. [BMW diagnostic criteria for IBS].

    Science.gov (United States)

    Matsueda, Kei

    2006-08-01

    Rome I diagnostic criteria for IBS was published in 1992 and it became a global diagnostic criteria. However, the criteria was not practical and somewhat complicated. Moreover, its symptomatic duration was too long (defined as more than 3 months) to be introduced in clinical practice. Therefore, Japanese member of BMW(Bowel Motility Workshop) tried to develop a new diagnostic criteria for IBS and it was established in 1995 by way of the Delphi method. The criteria was named as BMW diagnostic criteria and it was shown below: BMW diagnostic criteria for IBS (1995) At least one month or more of repetitive symptoms of the following 1) and 2) and no evidence of organic disease that likely to explain the symptoms. 1) Existence of abdominal pain, abdominal discomfort or abdominal distension 2) Existence of abnormal bowel movement (diarrhea, constipation) Abnormal bowel movement includes at least one of the below; (1) Abnormal stool frequency (2) Abnormal stool form (lumpy/hard or loose/wartery stool) Moreover, the following test should be performed as a rule to exclude organic diseases. (1) Urinalysis, fecal occult blood testing, CBC, chemistry (2) Barium enema or colonofiberscopic examination The other diagnostic criteria for IBS was also reviewed and their characteristics were compared with BMW diagnostic criteria.

  14. Highly Flexible Graphene Oxide Nanosuspension Liquid-Based Microfluidic Tactile Sensor.

    Science.gov (United States)

    Kenry; Yeo, Joo Chuan; Yu, Jiahao; Shang, Menglin; Loh, Kian Ping; Lim, Chwee Teck

    2016-03-23

    A novel graphene oxide (GO) nanosuspension liquid-based microfluidic tactile sensor is developed. It comprises a UV ozone-bonded Ecoflex-polydimethylsiloxane microfluidic assembly filled with GO nanosuspension, which serves as the working fluid of the tactile sensor. This device is highly flexible and able to withstand numerous modes of deformation as well as distinguish various user-applied mechanical forces it is subjected to, including pressing, stretching, and bending. This tactile sensor is also highly deformable and wearable, and capable of recognizing and differentiating distinct hand muscle-induced motions, such as finger flexing and fist clenching. Moreover, subtle differences in the handgrip strength derived from the first clenching gesture can be identified based on the electrical response of our device. This work highlights the potential application of the GO nanosuspension liquid-based flexible microfluidic tactile sensing platform as a wearable diagnostic and prognostic device for real-time health monitoring. Also importantly, this work can further facilitate the exploration and potential realization of a functional liquid-state device technology with superior mechanical flexibility and conformability.

  15. Slanted channel microfluidic chip for 3D fluorescence imaging of cells in flow.

    Science.gov (United States)

    Jagannadh, Veerendra Kalyan; Mackenzie, Mark D; Pal, Parama; Kar, Ajoy K; Gorthi, Sai Siva

    2016-09-19

    Three-dimensional cellular imaging techniques have become indispensable tools in biological research and medical diagnostics. Conventional 3D imaging approaches employ focal stack collection to image different planes of the cell. In this work, we present the design and fabrication of a slanted channel microfluidic chip for 3D fluorescence imaging of cells in flow. The approach employs slanted microfluidic channels fabricated in glass using ultrafast laser inscription. The slanted nature of the microfluidic channels ensures that samples come into and go out of focus, as they pass through the microscope imaging field of view. This novel approach enables the collection of focal stacks in a straight-forward and automated manner, even with off-the-shelf microscopes that are not equipped with any motorized translation/rotation sample stages. The presented approach not only simplifies conventional focal stack collection, but also enhances the capabilities of a regular widefield fluorescence microscope to match the features of a sophisticated confocal microscope. We demonstrate the retrieval of sectioned slices of microspheres and cells, with the use of computational algorithms to enhance the signal-to-noise ratio (SNR) in the collected raw images. The retrieved sectioned images have been used to visualize fluorescent microspheres and bovine sperm cell nucleus in 3D while using a regular widefield fluorescence microscope. We have been able to achieve sectioning of approximately 200 slices per cell, which corresponds to a spatial translation of ∼ 15 nm per slice along the optical axis of the microscope.

  16. Dynamics of magnetic modulation of ferrofluid droplets for digital microfluidic applications

    Science.gov (United States)

    Sen, Uddalok; Chatterjee, Souvick; Sen, Swarnendu; Tiwari, Manish K.; Mukhopadhyay, Achintya; Ganguly, Ranjan

    2017-01-01

    Active control of droplet generation in a microfluidic platform attracts interest for development of digital microfluidic devices ranging from biosensors to micro-reactors to point-of-care diagnostic devices. The present paper characterizes, through an unsteady three-dimensional Volume of Fluid (VOF) simulation, the active control of ferrofluid droplet generation in a microfluidic T-junction in presence of a non-uniform magnetic field created by an external magnetic dipole. Two distinctly different positions of the dipole were considered - one upstream of the junction and one downstream. While keeping the ferrofluid flow rate fixed, a parametric variation of the continuous phase capillary number, dipole strength, and dipole position was carried out. Differences in the flow behaviour in terms of dripping or jetting and the droplet characteristics in terms of droplet formation time period and droplet size were studied. The existence of a threshold dipole strength, below which the magnetic force was not able to influence the flow behaviour, was identified. It was also observed that, for dipoles placed upstream of the junction, droplet formation was suppressed at some higher dipole strengths, and this value was found to increase with increasing capillary number. Droplet time period was also found to increase with increasing dipole strength, along with droplet size, i.e. an increase in droplet volume.

  17. Microfluidic distillation chip for methanol concentration detection.

    Science.gov (United States)

    Wang, Yao-Nan; Liu, Chan-Chiung; Yang, Ruey-Jen; Ju, Wei-Jhong; Fu, Lung-Ming

    2016-03-17

    An integrated microfluidic distillation system is proposed for separating a mixed ethanol-methanol-water solution into its constituent components. The microfluidic chip is fabricated using a CO2 laser system and comprises a serpentine channel, a boiling zone, a heating zone, and a cooled collection chamber filled with de-ionized (DI) water. In the proposed device, the ethanol-methanol-water solution is injected into the microfluidic chip and driven through the serpentine channel and into the collection chamber by means of a nitrogen carrier gas. Following the distillation process, the ethanol-methanol vapor flows into the collection chamber and condenses into the DI water. The resulting solution is removed from the collection tank and reacted with a mixed indicator. Finally, the methanol concentration is inversely derived from the absorbance measurements obtained using a spectrophotometer. The experimental results show the proposed microfluidic system achieves an average methanol distillation efficiency of 97%. The practicality of the proposed device is demonstrated by detecting the methanol concentrations of two commercial fruit wines. It is shown that the measured concentration values deviate by no more than 3% from those obtained using a conventional bench top system.

  18. High content screening in microfluidic devices

    Science.gov (United States)

    Cheong, Raymond; Paliwal, Saurabh; Levchenko, Andre

    2011-01-01

    Importance of the field Miniaturization is key to advancing the state-of-the-art in high content screening (HCS), in order to enable dramatic cost savings through reduced usage of expensive biochemical reagents and to enable large-scale screening on primary cells. Microfluidic technology offers the potential to enable HCS to be performed with an unprecedented degree of miniaturization. Areas covered in this review This perspective highlights a real-world example from the authors’ work of HCS assays implemented in a highly miniaturized microfluidic format. Advantages of this technology are discussed, including cost savings, high throughput screening on primary cells, improved accuracy, the ability to study complex time-varying stimuli, and ease of automation, integration, and scaling. What the reader will gain The reader will understand the capabilities of a new microfluidics-based platform for HCS, and the advantages it provides over conventional plate-based HCS. Take home message Microfluidics technology will drive significant advancements and broader usage and applicability of HCS in drug discovery. PMID:21852997

  19. Design of microfluidic bioreactors using topology optimization

    DEFF Research Database (Denmark)

    Okkels, Fridolin; Bruus, Henrik

    2007-01-01

    We address the design of optimal reactors for supporting biological cultures using the method of topology optimization. For some years this method have been used to design various optimal microfluidic devices.1-4 We apply this method to distribute optimally biologic cultures within a flow of nutr...

  20. A microfluidic based optical particle detection method

    Science.gov (United States)

    Dou, James; Chen, Lu; Nayyar, Rakesh; Aitchison, Stewart

    2012-03-01

    An optical particle detection and analysis method is presented. This method combines the capillary microfluidics, integrated optics and novel image acquisition and analysis algorithms to form the basis of a portable or handheld cytometer instrument. Experimental results provided shows the testing results are closely matched with conventional flow cytometer data.

  1. Microfluidic desalination techniques and their potential applications

    NARCIS (Netherlands)

    Roelofs, S.H.; Berg, van den A.; Odijk, M.

    2015-01-01

    In this review we discuss recent developments in the emerging research field of miniaturized desalination. Traditionally desalination is performed to convert salt water into potable water and research is focused on improving performance of large-scale desalination plants. Microfluidic desalination o

  2. Microfluidic enzymatic biosensing systems: A review.

    Science.gov (United States)

    Mross, Stefan; Pierrat, Sebastien; Zimmermann, Tom; Kraft, Michael

    2015-08-15

    Microfluidic biosensing systems with enzyme-based detection have been extensively studied in the last years owing to features such as high specificity, a broad range of analytes and a high degree of automation. This review gives an overview of the most important factors associated with these systems. In the first part, frequently used immobilization protocols such as physisorption and covalent bonding and detection techniques such as amperometry and fluorescence measurements are discussed with respect to effort, lifetime and measurement range. The Michaelis-Menten model describing the kinetics of enzymatic reactions, the role of redox mediators and the limitations of the linear measurement range of enzymatic sensors are introduced. Several possibilities of extending the linear measurement range in microfluidic systems such as diffusion-limiting membranes and the flow injection setup are presented. Regarding the integration of enzymes into microfluidic systems during the fabrication process, the constraints imposed by the biomolecules due to the limited usage of high temperatures and solvents are addressed. In the second part, the most common forms of enzyme integration into microfluidic systems, i.e. in channels and on electrodes, on microparticles, on paper and thread and as injected enzyme solutions, are reviewed, focusing on fabrication, applications and performance.

  3. Microfluidics for Antibiotic Susceptibility and Toxicity Testing

    Directory of Open Access Journals (Sweden)

    Jing Dai

    2016-10-01

    Full Text Available The recent emergence of antimicrobial resistance has become a major concern for worldwide policy makers as very few new antibiotics have been developed in the last twenty-five years. To prevent the death of millions of people worldwide, there is an urgent need for a cheap, fast and accurate set of tools and techniques that can help to discover and develop new antimicrobial drugs. In the past decade, microfluidic platforms have emerged as potential systems for conducting pharmacological studies. Recent studies have demonstrated that microfluidic platforms can perform rapid antibiotic susceptibility tests to evaluate antimicrobial drugs’ efficacy. In addition, the development of cell-on-a-chip and organ-on-a-chip platforms have enabled the early drug testing, providing more accurate insights into conventional cell cultures on the drug pharmacokinetics and toxicity, at the early and cheaper stage of drug development, i.e., prior to animal and human testing. In this review, we focus on the recent developments of microfluidic platforms for rapid antibiotics susceptibility testing, investigating bacterial persistence and non-growing but metabolically active (NGMA bacteria, evaluating antibiotic effectiveness on biofilms and combinatorial effect of antibiotics, as well as microfluidic platforms that can be used for in vitro antibiotic toxicity testing.

  4. Wax-bonding 3D microfluidic chips

    KAUST Repository

    Gong, Xiuqing

    2013-10-10

    We report a simple, low-cost and detachable microfluidic chip incorporating easily accessible paper, glass slides or other polymer films as the chip materials along with adhesive wax as the recycling bonding material. We use a laser to cut through the paper or film to form patterns and then sandwich the paper and film between glass sheets or polymer membranes . The hot-melt adhesive wax can realize bridge bonding between various materials, for example, paper, polymethylmethacrylate (PMMA) film, glass sheets, or metal plate. The bonding process is reversible and the wax is reusable through a melting and cooling process. With this process, a three-dimensional (3D) microfluidic chip is achievable by vacuating and venting the chip in a hot-water bath. To study the biocompatibility and applicability of the wax-based microfluidic chip, we tested the PCR compatibility with the chip materials first. Then we applied the wax-paper based microfluidic chip to HeLa cell electroporation (EP ). Subsequently, a prototype of a 5-layer 3D chip was fabricated by multilayer wax bonding. To check the sealing ability and the durability of the chip, green fluorescence protein (GFP) recombinant Escherichia coli (E. coli) bacteria were cultured, with which the chemotaxis of E. coli was studied in order to determine the influence of antibiotic ciprofloxacin concentration on the E. coli migration.

  5. Microfluidic manipulation with artificial/bioinspired cilia

    NARCIS (Netherlands)

    den Toonder, Jaap M. J.; Onck, Patrick R.

    2013-01-01

    A recent development, inspired by nature, is the use of 'artificial cilia' to create pumping and/or mixing in microfluidic devices. Cilia are small hairs that can be found in biology and are used for (fluid) actuation and sensing. Microscopic actuators resembling cilia, actuated to move under the in

  6. Reaction and separation opportunities with microfluidic devices

    NARCIS (Netherlands)

    Kolfschoten, R.C.

    2011-01-01

    Microfluidic devices make precisely controlled processing of substances possible on a microliter level. The advantage is that, due to the small sizes, the driving forces for mass and heat transfer are high. The surface to volume ratios are also high, which can benefit many surface oriented processes

  7. Inventions Utilizing Microfluidics and Colloidal Particles

    Science.gov (United States)

    Marr, David W.; Gong, Tieying; Oakey, John; Terray, Alexander V.; Wu, David T.

    2009-01-01

    Several related inventions pertain to families of devices that utilize microfluidics and/or colloidal particles to obtain useful physical effects. The families of devices can be summarized as follows: (1) Microfluidic pumps and/or valves wherein colloidal-size particles driven by electrical, magnetic, or optical fields serve as the principal moving parts that propel and/or direct the affected flows. (2) Devices that are similar to the aforementioned pumps and/or valves except that they are used to manipulate light instead of fluids. The colloidal particles in these devices are substantially constrained to move in a plane and are driven to spatially order them into arrays that function, variously, as waveguides, filters, or switches for optical signals. (3) Devices wherein the ultra-laminar nature of microfluidic flows is exploited to effect separation, sorting, or filtering of colloidal particles or biological cells in suspension. (4) Devices wherein a combination of confinement and applied electrical and/or optical fields forces the colloidal particles to become arranged into three-dimensional crystal lattices. Control of the colloidal crystalline structures could be exploited to control diffraction of light. (5) Microfluidic devices, incorporating fluid waveguides, wherein switching of flows among different paths would be accompanied by switching of optical signals.

  8. Discrete elements for 3D microfluidics.

    Science.gov (United States)

    Bhargava, Krisna C; Thompson, Bryant; Malmstadt, Noah

    2014-10-21

    Microfluidic systems are rapidly becoming commonplace tools for high-precision materials synthesis, biochemical sample preparation, and biophysical analysis. Typically, microfluidic systems are constructed in monolithic form by means of microfabrication and, increasingly, by additive techniques. These methods restrict the design and assembly of truly complex systems by placing unnecessary emphasis on complete functional integration of operational elements in a planar environment. Here, we present a solution based on discrete elements that liberates designers to build large-scale microfluidic systems in three dimensions that are modular, diverse, and predictable by simple network analysis techniques. We develop a sample library of standardized components and connectors manufactured using stereolithography. We predict and validate the flow characteristics of these individual components to design and construct a tunable concentration gradient generator with a scalable number of parallel outputs. We show that these systems are rapidly reconfigurable by constructing three variations of a device for generating monodisperse microdroplets in two distinct size regimes and in a high-throughput mode by simple replacement of emulsifier subcircuits. Finally, we demonstrate the capability for active process monitoring by constructing an optical sensing element for detecting water droplets in a fluorocarbon stream and quantifying their size and frequency. By moving away from large-scale integration toward standardized discrete elements, we demonstrate the potential to reduce the practice of designing and assembling complex 3D microfluidic circuits to a methodology comparable to that found in the electronics industry.

  9. Planar microcoil-based microfluidic NMR probes.

    NARCIS (Netherlands)

    Massin, C.; Vincent, F.; Homsy, A.; Ehrmann, K.; Boero, G.; Besse, P-A; Daridon, A.; Verpoorte, E.; de Rooij, N.F.; Popovic, R.S.

    2003-01-01

    Microfabricated small-volume NMR probes consisting of electroplated planar microcoils integrated on a glass substrate with etched microfluidic channels are fabricated and tested. 1H NMR spectra are acquired at 300 MHz with three different probes having observed sample volumes of respectively 30, 120

  10. Integrated multifunctional microfluidics for automated proteome analyses.

    Science.gov (United States)

    Osiri, John K; Shadpour, Hamed; Witek, Małgorzata A; Soper, Steven A

    2011-01-01

    Proteomics is a challenging field for realizing totally integrated microfluidic systems for complete proteome processing due to several considerations, including the sheer number of different protein types that exist within most proteomes, the large dynamic range associated with these various protein types, and the diverse chemical nature of the proteins comprising a typical proteome. For example, the human proteome is estimated to have >10(6) different components with a dynamic range of >10(10). The typical processing pipeline for proteomics involves the following steps: (1) selection and/or extraction of the particular proteins to be analyzed; (2) multidimensional separation; (3) proteolytic digestion of the protein sample; and (4) mass spectral identification of either intact proteins (top-down proteomics) or peptide fragments generated from proteolytic digestions (bottom-up proteomics). Although a number of intriguing microfluidic devices have been designed, fabricated and evaluated for carrying out the individual processing steps listed above, work toward building fully integrated microfluidic systems for protein analysis has yet to be realized. In this chapter, information will be provided on the nature of proteomic analysis in terms of the challenges associated with the sample type and the microfluidic devices that have been tested to carry out individual processing steps. These include devices such as those for multidimensional electrophoretic separations, solid-phase enzymatic digestions, and solid-phase extractions, all of which have used microfluidics as the functional platform for their implementation. This will be followed by an in-depth review of microfluidic systems, which are defined as units possessing two or more devices assembled into autonomous systems for proteome processing. In addition, information will be provided on the challenges involved in integrating processing steps into a functional system and the approaches adopted for device

  11. Mixing in polymeric microfluidic devices.

    Energy Technology Data Exchange (ETDEWEB)

    Schunk, Peter Randall; Sun, Amy Cha-Tien; Davis, Robert H. (University of Colorado at Boulder, Boulder, CO); Brotherton, Christopher M. (University of Colorado at Boulder, Boulder, CO)

    2006-04-01

    This SAND report describes progress made during a Sandia National Laboratories sponsored graduate fellowship. The fellowship was funded through an LDRD proposal. The goal of this project is development and characterization of mixing strategies for polymeric microfluidic devices. The mixing strategies under investigation include electroosmotic flow focusing, hydrodynamic focusing, physical constrictions and porous polymer monoliths. For electroosmotic flow focusing, simulations were performed to determine the effect of electroosmotic flow in a microchannel with heterogeneous surface potential. The heterogeneous surface potential caused recirculations to form within the microchannel. These recirculations could then be used to restrict two mixing streams and reduce the characteristic diffusion length. Maximum mixing occurred when the ratio of the mixing region surface potential to the average channel surface potential was made large in magnitude and negative in sign, and when the ratio of the characteristic convection time to the characteristic diffusion time was minimized. Based on these results, experiments were performed to evaluate the manipulation of surface potential using living-radical photopolymerization. The material chosen to manipulate typically exhibits a negative surface potential. Using living-radical surface grafting, a positive surface potential was produced using 2-(Dimethylamino)ethyl methacrylate and a neutral surface was produced using a poly(ethylene glycol) surface graft. Simulations investigating hydrodynamic focusing were also performed. For this technique, mixing is enhanced by using a tertiary fluid stream to constrict the two mixing streams and reduce the characteristic diffusion length. Maximum mixing occurred when the ratio of the tertiary flow stream flow-rate to the mixing streams flow-rate was maximized. Also, like the electroosmotic focusing mixer, mixing was also maximized when the ratio of the characteristic convection time to the

  12. Thyroid diagnostics

    Energy Technology Data Exchange (ETDEWEB)

    Scriba, P.C.; Boerner, W.; Emrich, S.; Gutekunst, R.; Herrmann, J.; Horn, K.; Klett, M.; Krueskemper, H.L.; Pfannenstiel, P.; Pickardt, C.R.

    1985-03-01

    None of the in-vitro and in-vivo methods listed permits on unambiguous diagnosis when applied alone, owing to the fact that similar or even identical findings are obtained for various individual parameters in different thyroid diseases. Further, especially the in-vitro tests are also subject to extrathyroidal effects which may mask the typical findings. The limited and varying specificity and sensitivity of the tests applied, as well as the falsification of results caused by the patients' idiosyncracies and the methodology, make it necessary to interpret and evaluate the in-vivo and in-vitro findings only if the clinical situation (anamnesis and physical examination) is known. For maximum diagnostic quality of the tests, the initial probability of the assumed type of thyroid disease must be increased (formulation of the clinical problem). The concepts of exclusion diagnosis and identification must be distinguished as well as the diagnosis of functional disturbances on the one hand and of thyroid diseases on the other. Both of this requires a qualified, specific and detailed anamnesis and examination procedure, and the clinical examination remains the obligatory basis of clinical diagnostics. In case of inexplicable discrepancies between the clinical manifestations and the findings obtained with specific methods, or between the findings obtained with a specific method, the patient should be referred to an expert institution, or the expert institution should be consulted.

  13. A hybrid poly(dimethylsiloxane) microsystem for on-chip whole blood filtration optimized for steroid screening.

    Science.gov (United States)

    Thorslund, Sara; Klett, Oliver; Nikolajeff, Fredrik; Markides, Karin; Bergquist, Jonas

    2006-03-01

    Miniaturized biochemical devices in glass, silicon and polymer materials are starting to find their way from the academic laboratories to real-life applications. However, most attention has been given to miniaturize the downstream functions of various microfluidic systems, leaving the sample introduction and preparation steps to more conventional, bulkier solutions. For point-of-care diagnostics in particular, it becomes crucial to be able to handle complex human samples in a miniaturized format.In this work, we report on a microsystem for on-chip sample preparation that is able to remove blood cells from whole blood. The hybrid system consists of a commercially available membrane filter incorporated into a poly(dimethylsiloxane) (PDMS) casted device. Membrane materials were evaluated on the bases of low nonspecific adsorption of free and protein-bound testosterone as analyte substance. The hybrid system including a hydrophilic polypropylene filter successfully removed blood cells from diluted human whole blood. Surface oxidation was sufficient to make the plasma filtrate flow through the membrane filter and the channel system by capillary force alone and thus no external pumping source was needed.

  14. Microfluidic approach for fast labeling optimization and dose-on-demand implementation

    Energy Technology Data Exchange (ETDEWEB)

    Pascali, Giancarlo, E-mail: pascali@ifc.cnr.i [Radiopharmacy Department, Institute of Clinical Physiology, Via Moruzzi 1, 56124 Pisa (Italy); Mazzone, Grazia [Radiopharmacy Department, Institute of Clinical Physiology, Via Moruzzi 1, 56124 Pisa (Italy); IUSS, Piazza Ghislieri, 27100 Pavia (Italy); Saccomanni, Giuseppe; Manera, Clementina [Dipartimento di Scienze Farmaceutiche, Universita di Pisa, Via Bonanno 6, 56126 Pisa (Italy); Salvadori, Piero A. [Radiopharmacy Department, Institute of Clinical Physiology, Via Moruzzi 1, 56124 Pisa (Italy)

    2010-07-15

    Introduction: The diffusion of PET as a pivotal molecular imaging modality has emphasized the need for new positron-emitting radiotracers to be used in diagnostic applications and research. Microfluidic represents an innovative approach, owing to its potential to increase radiochemical productivity in terms of yields, time reduction, precursor consumption and flexible experimental planning. Methods: We focused on fluorine-18 labeling and used a microfluidic platform to perform sequential reactions, by using the same batch of {sup 18}F-labeling solution on one or more substrates, during the same experimental session. A solid-phase extraction (SPE) workup procedure was also implemented in the system to provide a repeatable purification step. Results: We were able to quickly optimize the conditions for labeling of ethyl and propyl ditosylate and of a new cannabinoid type 2 (CB2) receptor agonist, CB41. In all substrates, we obtained good incorporation yields (60% to 85%) in short (<90 s) reaction times. Single dosages of the CB2 ligand were sequentially prepared, upon request, in satisfactory quantities and purity for small animal PET scanning. Conclusion: This work demonstrates the usefulness of a microfluidic-based system for a rapid optimization of temperature, flow rate of reactants and their relative ratio in the labeling of different precursors by using the same {sup 18}F-fluoride batch. This approach was used to obtain in sequence several injectable doses of a novel CB2 ligand, thus providing the proof of principle that microfluidic systems permit a dose-on-demand production of new radiotracers.

  15. Interconnection blocks: a method for providing reusable, rapid, multiple, aligned and planar microfluidic interconnections

    DEFF Research Database (Denmark)

    Sabourin, David; Snakenborg, Detlef; Dufva, Hans Martin

    2009-01-01

    In this paper a method is presented for creating 'interconnection blocks' that are re-usable and provide multiple, aligned and planar microfluidic interconnections. Interconnection blocks made from polydimethylsiloxane allow rapid testing of microfluidic chips and unobstructed microfluidic...

  16. Rotorcraft Diagnostics

    Science.gov (United States)

    Haste, Deepak; Azam, Mohammad; Ghoshal, Sudipto; Monte, James

    2012-01-01

    Health management (HM) in any engineering systems requires adequate understanding about the system s functioning; a sufficient amount of monitored data; the capability to extract, analyze, and collate information; and the capability to combine understanding and information for HM-related estimation and decision-making. Rotorcraft systems are, in general, highly complex. Obtaining adequate understanding about functioning of such systems is quite difficult, because of the proprietary (restricted access) nature of their designs and dynamic models. Development of an EIM (exact inverse map) solution for rotorcraft requires a process that can overcome the abovementioned difficulties and maximally utilize monitored information for HM facilitation via employing advanced analytic techniques. The goal was to develop a versatile HM solution for rotorcraft for facilitation of the Condition Based Maintenance Plus (CBM+) capabilities. The effort was geared towards developing analytic and reasoning techniques, and proving the ability to embed the required capabilities on a rotorcraft platform, paving the way for implementing the solution on an aircraft-level system for consolidation and reporting. The solution for rotorcraft can he used offboard or embedded directly onto a rotorcraft system. The envisioned solution utilizes available monitored and archived data for real-time fault detection and identification, failure precursor identification, and offline fault detection and diagnostics, health condition forecasting, optimal guided troubleshooting, and maintenance decision support. A variant of the onboard version is a self-contained hardware and software (HW+SW) package that can be embedded on rotorcraft systems. The HM solution comprises components that gather/ingest data and information, perform information/feature extraction, analyze information in conjunction with the dependency/diagnostic model of the target system, facilitate optimal guided troubleshooting, and offer

  17. Integrated microfluidic platforms for investigating neuronal networks

    Science.gov (United States)

    Kim, Hyung Joon

    This dissertation describes the development and application of integrated microfluidics-based assay platforms to study neuronal activities in the nervous system in-vitro. The assay platforms were fabricated using soft lithography and micro/nano fabrication including microfluidics, surface patterning, and nanomaterial synthesis. The use of integrated microfluidics-based assay platform allows culturing and manipulating many types of neuronal tissues in precisely controlled microenvironment. Furthermore, they provide organized multi-cellular in-vitro model, long-term monitoring with live cell imaging, and compatibility with molecular biology techniques and electrophysiology experiment. In this dissertation, the integrated microfluidics-based assay platforms are developed for investigation of neuronal activities such as local protein synthesis, impairment of axonal transport by chemical/physical variants, growth cone path finding under chemical/physical cues, and synaptic transmission in neuronal circuit. Chapter 1 describes the motivation, objectives, and scope for developing in-vitro platform to study various neuronal activities. Chapter 2 introduces microfluidic culture platform for biochemical assay with large-scale neuronal tissues that are utilized as model system in neuroscience research. Chapter 3 focuses on the investigation of impaired axonal transport by beta-Amyloid and oxidative stress. The platform allows to control neuronal processes and to quantify mitochondrial movement in various regions of axons away from applied drugs. Chapter 4 demonstrates the development of microfluidics-based growth cone turning assay to elucidate the mechanism underlying axon guidance under soluble factors and shear flow. Using this platform, the behaviors of growth cone of mammalian neurons are verified under the gradient of inhibitory molecules and also shear flow in well-controlled manner. In Chapter 5, I combine in-vitro multicellular model with microfabricated MEA

  18. Digital microfluidic processing of mammalian embryos for vitrification.

    Directory of Open Access Journals (Sweden)

    Derek G Pyne

    Full Text Available Cryopreservation is a key technology in biology and clinical practice. This paper presents a digital microfluidic device that automates sample preparation for mammalian embryo vitrification. Individual micro droplets manipulated on the microfluidic device were used as micro-vessels to transport a single mouse embryo through a complete vitrification procedure. Advantages of this approach, compared to manual operation and channel-based microfluidic vitrification, include automated operation, cryoprotectant concentration gradient generation, and feasibility of loading and retrieval of embryos.

  19. Temporal Expression of Peripheral Blood Leukocyte Biomarkers in a Macaca fascicularis Infection Model of Tuberculosis; Comparison with Human Datasets and Analysis with Parametric/Non-parametric Tools for Improved Diagnostic Biomarker Identification.

    Directory of Open Access Journals (Sweden)

    Sajid Javed

    Full Text Available A temporal study of gene expression in peripheral blood leukocytes (PBLs from a Mycobacterium tuberculosis primary, pulmonary challenge model Macaca fascicularis has been conducted. PBL samples were taken prior to challenge and at one, two, four and six weeks post-challenge and labelled, purified RNAs hybridised to Operon Human Genome AROS V4.0 slides. Data analyses revealed a large number of differentially regulated gene entities, which exhibited temporal profiles of expression across the time course study. Further data refinements identified groups of key markers showing group-specific expression patterns, with a substantial reprogramming event evident at the four to six week interval. Selected statistically-significant gene entities from this study and other immune and apoptotic markers were validated using qPCR, which confirmed many of the results obtained using microarray hybridisation. These showed evidence of a step-change in gene expression from an 'early' FOS-associated response, to a 'late' predominantly type I interferon-driven response, with coincident reduction of expression of other markers. Loss of T-cell-associate marker expression was observed in responsive animals, with concordant elevation of markers which may be associated with a myeloid suppressor cell phenotype e.g. CD163. The animals in the study were of different lineages and these Chinese and Mauritian cynomolgous macaque lines showed clear evidence of differing susceptibilities to Tuberculosis challenge. We determined a number of key differences in response profiles between the groups, particularly in expression of T-cell and apoptotic makers, amongst others. These have provided interesting insights into innate susceptibility related to different host `phenotypes. Using a combination of parametric and non-parametric artificial neural network analyses we have identified key genes and regulatory pathways which may be important in early and adaptive responses to TB. Using

  20. Combining Electro-Osmotic Flow and FTA® Paper for DNA Analysis on Microfluidic Devices

    Directory of Open Access Journals (Sweden)

    Ryan Wimbles

    2016-07-01

    Full Text Available FTA® paper can be used to protect a variety of biological samples prior to analysis, facilitating ease-of-transport to laboratories or long-term archive storage. The use of FTA® paper as a solid phase eradicates the need to elute the nucleic acids from the matrix prior to DNA amplification, enabling both DNA purification and polymerase chain reaction (PCR-based DNA amplification to be performed in a single chamber on the microfluidic device. A disc of FTA® paper, containing a biological sample, was placed within the microfluidic device on top of wax-encapsulated DNA amplification reagents. The disc containing the biological sample was then cleaned up using Tris-EDTA (TE buffer, which was passed over the disc, via electro-osmotic flow, in order to remove any potential inhibitors of downstream processes. DNA amplification was successfully performed (from buccal cells, whole blood and semen using a Peltier thermal cycling system, whereupon the stored PCR reagents were released during the initial denaturing step due to the wax barrier melting between the FTA® disc and PCR reagents. Such a system offers advantages in terms of a simple sample introduction interface and the ability to process archived samples in an integrated microfluidic environment with minimal risk of contamination.