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Sample records for methacrylate microfluidic chips

  1. Materials for microfluidic chip fabrication.

    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

  2. Microfluidic desalination : capacitive deionization on chip for microfluidic sample preparation

    Roelofs, Susan Helena

    2015-01-01

    The main aim of the work described in this thesis is to implement the desalination technique capacitive deionization (CDI) on a microfluidic chip to improve the reproducibility in the analysis of biological samples for drug development. Secondly, microfluidic CDI allows for the in situ study of ion

  3. Optical bio-sensors in microfluidic chips

    Pollnau, Markus; Dongre, C.; Pham Van So, P.V.S.; Bernhardi, Edward; Worhoff, Kerstin; de Ridder, R.M.; Hoekstra, Hugo

    2012-01-01

    Direct femtosecond laser writing is used to integrate optical waveguides that intersect the microfluidic channels in a commercial optofluidic chip. With laser excitation, fluorescently labeled DNA molecules of different sizes are separated by capillary electrophoresis with high operating speed and

  4. Wax-bonding 3D microfluidic chips

    Gong, Xiuqing; Yi, Xin; Xiao, Kang; Li, Shunbo; Kodzius, Rimantas; Qin, Jianhua; Wen, Weijia

    2013-01-01

    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. Wax-bonding 3D microfluidic chips

    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.

  6. Research Progress of Microfluidic Chips Preparation and its Optical Element

    Feng WANG

    2014-03-01

    Full Text Available Microfluidic technology is the emerging technologies in researching fluid channel and related applications in the micro and nano-scale space. Microfluidic chip is a new miniaturized rapid analysis platform by microfluidic technology, it has many characteristics such as liquid flow control, minimal reagent consumption, rapid analysis, which is widely used in physics, chemistry, biology, and engineering science and other fields, it has strong interdisciplinary. This paper mainly discusses research progress of materials used for microfluidic chips and the devices based on microfluidic technology, including microfluidic chip, microfluidic optical devices, microfluidic laser preparation, microfluidic chip applications, focusing on the quasi-molecular laser processing technology and femtosecond laser processing technology in the microfluidic devices preparation, and make development prospects for it.

  7. Microfluidic chip-capillary electrophoresis devices

    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 for the fabrication of MC-CE devices. It describes the operating principles that make integration possible and illustrates some achievements already made by the application of MC-CE devices in hospitals, clinics, food safety, and environmental research. The authors envision further applications for private and public use once the proof-of-concept stage has been passed and obstacles to increased commercialization are ad...

  8. Material Biocompatibility for PCR Microfluidic Chips

    Kodzius, Rimantas; Chang, Donald Choy; Gong, Xiuqing; Wen, Weijia; Wu, Jinbo; Xiao, Kang; Yi, Xin

    2010-01-01

    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.

  9. Material Biocompatibility for PCR Microfluidic Chips

    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. Fabrication of dielectrophoretic microfluidic chips using a facile screen-printing technique for microparticle trapping

    Wee, Wei Hong; Kadri, Nahrizul Adib; Pingguan-Murphy, Belinda; Li, Zedong; Hu, Jie; Xu, Feng; Li, Fei

    2015-01-01

    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. (paper)

  11. Reagent-loaded plastic microfluidic chips for detecting homocysteine

    Suk, Ji Won; Jang, Jae-Young; Cho, Jun-Hyeong

    2008-01-01

    This report describes the preliminary study on plastic microfluidic chips with pre-loaded reagents for detecting homocysteine (Hcy). All reagents needed in an Hcy immunoassay were included in a microfluidic chip to remove tedious assay steps. A simple and cost-effective bonding method was developed to realize reagent-loaded microfluidic chips. This technique uses an intermediate layer between two plastic substrates by selectively patterning polydimethylsiloxane (PDMS) on the embossed surface of microchannels and fixing the substrates under pressure. Using this bonding method, the competitive immunoassay for SAH, a converted form of Hcy, was performed without any damage to reagents in chips, and the results showed that the fluorescent signal from antibody antigen binding decreased as the SAH concentration increased. Based on the SAH immunoassay, whole immunoassay steps for Hcy detection were carried out in plastic microfluidic chips with all necessary reagents. These experiments demonstrated the feasibility of the Hcy immunoassay in microfluidic devices

  12. Fabrication of 3D Microfluidic Devices by Thermal Bonding of Thin Poly(methyl methacrylate) Films

    Perez, Paul

    2012-07-01

    The use of thin-film techniques for the fabrication of microfluidic devices has gained attention over the last decade, particularly for three-dimensional channel structures. The reasons for this include effective use of chip volume, mechanical flexibility, dead volume reduction, enhanced design capabilities, integration of passive elements, and scalability. Several fabrication techniques have been adapted for use on thin films: laser ablation and hot embossing are popular for channel fabrication, and lamination is widely used for channel enclosure. However, none of the previous studies have been able to achieve a strong bond that is reliable under moderate positive pressures. The present work aims to develop a thin-film process that provides design versatility, speed, channel profile homogeneity, and the reliability that others fail to achieve. The three building blocks of the proposed baseline were fifty-micron poly(methyl methacrylate) thin films as substrates, channel patterning by laser ablation, and device assembly by thermal-fusion bonding. Channel fabrication was characterized and tuned to produce the desired dimensions and surface roughness. Thermal bonding was performed using an adapted mechanical testing device and optimized to produce the maximum bonding strength without significant channel deformation. Bonding multilayered devices, incorporating conduction lines, and integrating various types of membranes as passive elements demonstrated the versatility of the process. Finally, this baseline was used to fabricate a droplet generator and a DNA detection chip based on micro-bead agglomeration. It was found that a combination of low laser power and scanning speed produced channel surfaces with better uniformity than those obtained with higher values. In addition, the implemented bonding technique provided the process with the most reliable bond strength reported, so far, for thin-film microfluidics. Overall, the present work proved to be versatile

  13. One-step fabrication of microfluidic chips with in-plane, adhesive-free interconnections

    Sabourin, D; Dufva, M; Jensen, T; Kutter, J; Snakenborg, D

    2010-01-01

    A simple method for creating interconnections to a common microfluidic device material, poly(methyl methacrylate) (PMMA), is presented. A press-fit interconnection is created between oversized, deformable tubing and complementary, undersized semi-circular ports fabricated into PMMA bonding surfaces by direct micromilling. Upon UV-assisted bonding the tubing is trapped in the ports of the PMMA chip and forms an integrated, in-plane and adhesive-free interconnection. The interconnections support the average pressure of 6.1 bar and can be made with small dead volumes. A comparison is made to a similar interconnection approach which uses tubing to act as a gasket between a needle and port on the microfluidic chip. (technical note)

  14. Disposable world-to-chip interface for digital microfluidics

    Van Dam, R. Michael; Shah, Gaurav; Keng, Pei-Yuin

    2017-05-16

    The present disclosure sets forth incorporating microfluidic chips interfaces for use with digital microfluidic processes. Methods and devices according to the present disclosure utilize compact, integrated platforms that interface with a chip upstream and downstream of the reaction, as well as between intermediate reaction steps if needed. In some embodiments these interfaces are automated, including automation of a multiple reagent process. Various reagent delivery systems and methods are also disclosed.

  15. A microfluidic chip for electrochemical conversions in drug metabolism studies

    Odijk, Mathieu; Baumann, A.; Lohmann, W.; van den Brink, Floris Teunis Gerardus; Olthuis, Wouter; Karst, U.; van den Berg, Albert

    2009-01-01

    We have designed a microfluidic microreactor chip for electrochemical conversion of analytes, containing a palladium reference electrode and platinum working and counter electrodes. The counter electrode is placed in a separate side-channel on chip to prevent unwanted side-products appearing in the

  16. Microfluidic "Pouch" Chips for Immunoassays and Nucleic Acid Amplification Tests.

    Mauk, Michael G; Liu, Changchun; Qiu, Xianbo; Chen, Dafeng; Song, Jinzhao; Bau, Haim H

    2017-01-01

    Microfluidic cassettes ("chips") for processing and analysis of clinical specimens and other sample types facilitate point-of-care (POC) immunoassays and nucleic acid based amplification tests. These single-use test chips can be self-contained and made amenable to autonomous operation-reducing or eliminating supporting instrumentation-by incorporating laminated, pliable "pouch" and membrane structures for fluid storage, pumping, mixing, and flow control. Materials and methods for integrating flexible pouch compartments and diaphragm valves into hard plastic (e.g., acrylic and polycarbonate) microfluidic "chips" for reagent storage, fluid actuation, and flow control are described. We review several versions of these pouch chips for immunoassay and nucleic acid amplification tests, and describe related fabrication techniques. These protocols thus offer a "toolbox" of methods for storage, pumping, and flow control functions in microfluidic devices.

  17. Directed evolution of enzymes using microfluidic chips

    Pilát, Zdeněk.; Ježek, Jan; Šmatlo, Filip; Kaůka, Jan; Zemánek, Pavel

    2016-12-01

    Enzymes are highly versatile and ubiquitous biological catalysts. They can greatly accelerate large variety of reactions, while ensuring appropriate catalytic activity and high selectivity. These properties make enzymes attractive biocatalysts for a wide range of industrial and biomedical applications. Over the last two decades, directed evolution of enzymes has transformed the field of protein engineering. We have devised microfluidic systems for directed evolution of haloalkane dehalogenases in emulsion droplets. In such a device, individual bacterial cells producing mutated variants of the same enzyme are encapsulated in microdroplets and supplied with a substrate. The conversion of a substrate by the enzyme produced by a single bacterium changes the pH in the droplet which is signalized by pH dependent fluorescence probe. The droplets with the highest enzymatic activity can be separated directly on the chip by dielectrophoresis and the resultant cell lineage can be used for enzyme production or for further rounds of directed evolution. This platform is applicable for fast screening of large libraries in directed evolution experiments requiring mutagenesis at multiple sites of a protein structure.

  18. Various on-chip sensors with microfluidics for biological applications.

    Lee, Hun; Xu, Linfeng; Koh, Domin; Nyayapathi, Nikhila; Oh, Kwang W

    2014-09-12

    In this paper, we review recent advances in on-chip sensors integrated with microfluidics for biological applications. Since the 1990s, much research has concentrated on developing a sensing system using optical phenomena such as surface plasmon resonance (SPR) and surface-enhanced Raman scattering (SERS) to improve the sensitivity of the device. The sensing performance can be significantly enhanced with the use of microfluidic chips to provide effective liquid manipulation and greater flexibility. We describe an optical image sensor with a simpler platform for better performance over a larger field of view (FOV) and greater depth of field (DOF). As a new trend, we review consumer electronics such as smart phones, tablets, Google glasses, etc. which are being incorporated in point-of-care (POC) testing systems. In addition, we discuss in detail the current optical sensing system integrated with a microfluidic chip.

  19. Various On-Chip Sensors with Microfluidics for Biological Applications

    Hun Lee

    2014-09-01

    Full Text Available In this paper, we review recent advances in on-chip sensors integrated with microfluidics for biological applications. Since the 1990s, much research has concentrated on developing a sensing system using optical phenomena such as surface plasmon resonance (SPR and surface-enhanced Raman scattering (SERS to improve the sensitivity of the device. The sensing performance can be significantly enhanced with the use of microfluidic chips to provide effective liquid manipulation and greater flexibility. We describe an optical image sensor with a simpler platform for better performance over a larger field of view (FOV and greater depth of field (DOF. As a new trend, we review consumer electronics such as smart phones, tablets, Google glasses, etc. which are being incorporated in point-of-care (POC testing systems. In addition, we discuss in detail the current optical sensing system integrated with a microfluidic chip.

  20. Detection and classification of ebola on microfluidic chips

    Lin, Xue; Jin, Xiangyu; Fan, Yunqian; Huang, Qin; Kou, Yue; Zu, Guo; Huang, Shiguang; Liu, Xiaosheng; Huang, Guoliang

    2016-10-01

    Point-of-care testing (POCT) for an infectious diseases is the prerequisite to control of the disease and limitation of its spread. A microfluidic chip for detection and classification of four strains of Ebola virus was developed and evaluated. This assay was based on reverse transcription loop-mediated isothermal amplification (RT-LAMP) and specific primers for Ebola Zaire virus, Ebola Sudan virus, Ebola Tai Forest virus and Ebola Bundibugyo virus were designed. The sensitivity of the microfluidic chip was under 103 copies per milliliter, as determined by ten repeated tests. This assay is unique in its ability to enable diagnosis of the Ebola infections and simultaneous typing of Ebola virus on a single chip. It offers short reaction time, ease of use and high specificity. These features should enable POCT in remote area during outbreaks of Ebola virus.

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

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

    2010-11-07

    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. Simple photolithographic rapid prototyping of microfluidic chips

    Kunstmann-Olsen, Casper; Hoyland, James; Rubahn, Horst-Günter

    2012-01-01

    Vi præsenterer en simpel metode til at producere støbeforme til støbning af PDMS mikrofluide chips vha. fotolitografi, med 35mm fotonegativer som masker. Vi demonstrer metodens muligheder og begrænsninger. Vi har optimeret processen til at fremstille planare lab-on-a-chip strukturer med meget høj...

  3. Selection of Easily Accessible PCR- and Bio-Compatible Materials for Microfluidic Chips

    Xiao, Kang

    2013-10-30

    Conventional fabrication of microfluidic chip is a complicated and time, effort and material consuming process. Consequently, due to high expenses, it has poor applicability for performing mass biological analysis by microfluidics. In this study, we repor

  4. Selection of Easily Accessible PCR- and Bio-Compatible Materials for Microfluidic Chips

    Xiao, Kang; Kodzius, Rimantas; Wu, Jinbo

    2013-01-01

    Conventional fabrication of microfluidic chip is a complicated and time, effort and material consuming process. Consequently, due to high expenses, it has poor applicability for performing mass biological analysis by microfluidics. In this study, we

  5. Microfluidic-chip platform for cell sorting

    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.

  6. High Voltage Dielectrophoretic and Magnetophoretic Hybrid Integrated Circuit / Microfluidic Chip

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

    2010-01-01

    A hybrid integrated circuit (IC) / microfluidic chip is presented that independently and simultaneously traps and moves microscopic objects suspended in fluid using both electric and magnetic fields. This hybrid chip controls the location of dielectric objects, such as living cells and drops of fluid, on a 60 × 61 array of pixels that are 30 × 38 μm2 in size, each of which can be individually addressed with a 50 V peak-to-peak, DC to 10 MHz radio frequency voltage. These high voltage pixels produce electric fields above the chip’s surface with a magnitude , resulting in strong dielectrophoresis (DEP) forces . Underneath the array of DEP pixels there is a magnetic matrix that consists of two perpendicular sets of 60 metal wires running across the chip. Each wire can be sourced with 120 mA to trap and move magnetically susceptible objects using magnetophoresis (MP). The DEP pixel array and magnetic matrix can be used simultaneously to apply forces to microscopic objects, such as living cells or lipid vesicles, that are tagged with magnetic nanoparticles. The capabilities of the hybrid IC / microfluidic chip demonstrated in this paper provide important building blocks for a platform for biological and chemical applications. PMID:20625468

  7. Microfluidics and Lab-on-a-Chip Devices

    Castillo, Jaime

    2015-01-01

    The rapid advances in microfabrication and nanofabrication in combination with the synthesis and discovery of new materials have propelled the drive to develop new technological devices such as smartphones, personal and tablet computers. These devices have changed the way humankind interacts......TAS technologies need to join forces with those behind the new communication devices which provide sources of power, detection and data transmission complementing the features that lab-on-a-chip and microTAS platforms can offer. An increasing number of microfluidic-based devices, developed both in small start...

  8. Microfluidics on liquid handling stations (μF-on-LHS): an industry compatible chip interface between microfluidics and automated liquid handling stations.

    Waldbaur, Ansgar; Kittelmann, Jörg; Radtke, Carsten P; Hubbuch, Jürgen; Rapp, Bastian E

    2013-06-21

    We describe a generic microfluidic interface design that allows the connection of microfluidic chips to established industrial liquid handling stations (LHS). A molding tool has been designed that allows fabrication of low-cost disposable polydimethylsiloxane (PDMS) chips with interfaces that provide convenient and reversible connection of the microfluidic chip to industrial LHS. The concept allows complete freedom of design for the microfluidic chip itself. In this setup all peripheral fluidic components (such as valves and pumps) usually required for microfluidic experiments are provided by the LHS. Experiments (including readout) can be carried out fully automated using the hardware and software provided by LHS manufacturer. Our approach uses a chip interface that is compatible with widely used and industrially established LHS which is a significant advancement towards near-industrial experimental design in microfluidics and will greatly facilitate the acceptance and translation of microfluidics technology in industry.

  9. Microfluidics without channels: highly-flexible synthesis on a digital-microfluidic chip for production of diverse PET tracers

    Van Dam, Robert Michael [Univ. of California, Los Angeles, CA (United States)

    2010-09-01

    Positron emission tomography (PET) imaging is used for fundamental studies of living biological organisms and microbial ecosystems in applications ranging from biofuel production to environmental remediation to the study, diagnosis, and treatment monitoring of human disease. Routine access to PET imaging, to monitor biochemical reactions in living organisms in real time, could accelerate a broad range of research programs of interest to DOE. Using PET requires access to short-lived radioactive-labeled compounds that specifically probe the desired living processes. The overall aims of this project were to develop a miniature liquid-handling technology platform (called “microfluidics”) that increases the availability of diverse PET probes by reducing the cost and complexity of their production. Based on preliminary experiments showing that microfluidic chips can synthesis such compounds, we aimed to advance this technology to improve its robustness, increase its flexibility for a broad range of probes, and increase its user-friendliness. Through the research activities of this project, numerous advances were made; Tools were developed to enable the visualization of radioactive materials within microfluidic chips; Fundamental advances were made in the microfluidic chip architecture and fabrication process to increase its robustness and reliability; The microfluidic chip technology was shown to produce useful quantities of an example PET probes, and methods to further increase the output were successfully pursued; A “universal” chip was developed that could produce multiple types of PET probes, enabling the possibility of “on demand” synthesis of different probes; and Operation of the chip was automated to ensure minimal radiation exposure to the operator Based on the demonstrations of promising technical feasibility and performance, the microfluidic chip technology is currently being commercialized. It is anticipated that costs of microfluidic chips can be

  10. Microfluidic Organ-on-a-Chip Models of Human IntestineSummary

    Amir Bein

    Full Text Available Microfluidic organ-on-a-chip models of human intestine have been developed and used to study intestinal physiology and pathophysiology. In this article, we review this field and describe how microfluidic Intestine Chips offer new capabilities not possible with conventional culture systems or organoid cultures, including the ability to analyze contributions of individual cellular, chemical, and physical control parameters one-at-a-time; to coculture human intestinal cells with commensal microbiome for extended times; and to create human-relevant disease models. We also discuss potential future applications of human Intestine Chips, including how they might be used for drug development and personalized medicine. Keywords: Organs-on-Chips, Gut-on-a-Chip, Intestine-on-a-Chip, Microfluidic

  11. Mapping three-dimensional temperature in microfluidic chip.

    Wu, Jinbo

    2013-11-25

    Three-dimensional (3D) temperature mapping method with high spatial resolution and acquisition rate is of vital importance in evaluating thermal processes in micro-environment. We have synthesized a new temperature-sensitive functional material (Rhodamine B functionalized Polydimethylsiloxane). By performing optical sectioning of this material, we established an advanced method for visualizing the micro-scale 3D thermal distribution inside microfluidic chip with down to 10 ms temporal resolution and 2 ~ 6 °C temperature resolution depending the capture parameters. This method is successfully applied to monitor the local temperature variation throughout micro-droplet heat transfer process and further reveal exothermic nanoliter droplet reactions to be unique and milder than bench-top experiment.

  12. Stereolithographic hydrogel printing of 3D microfluidic cell culture chips

    Zhang, Rujing

    that support the required freedom in design, detail and chemistry for fabricating truly 3D constructs have remained limited. Here, we report a stereolithographic high-resolution 3D printing technique utilizing poly(ethylene glycol) diacrylate (PEGDA, MW 700) to manufacture diffusion-open and mechanically...... and material flexibility by embedding a highly compliant cell-laden gelatin hydrogel within the confines of a 3D printed resilient PEGDA hydrogel chip of intermediate compliance. Overall, our proposed strategy represents an automated, cost-effective and high resolution technique to manufacture complex 3D...... epoxy component as structural supports interfacing the external world as well as compliant PEGDA component as microfluidic channels have been manufactured and perfused. Although still in the preliminary stage, this dual-material printing approach shows the potential for constructing complex 3D...

  13. Electrochemical detection on electrowetting-on-dielectric digital microfluidic chip.

    Karuwan, Chanpen; Sukthang, Kreeta; Wisitsoraat, Anurat; Phokharatkul, Ditsayut; Patthanasettakul, Viyapol; Wechsatol, Wishsanuruk; Tuantranont, Adisorn

    2011-06-15

    In this work, the use of three-electrode electrochemical sensing system with an electrowetting-on-dielectric (EWOD) digital microfluidic device is reported for quantitative analysis of iodide. T-junction EWOD mixer device was designed using arrays of 50-μm spaced square electrodes for mixing buffer reagent and analyte droplets. For fabrication of EWOD chips, 5-μm thick silver EWOD electrodes were formed on a glass substrate by means of sputtering and lift-off process. PDMS and Teflon thin films were then coated on the electrodes by spin coating to yield hydrophobic surface. An external three-electrode system consisting of Au working, Ag reference and Pt auxiliary wires were installed over EWOD electrodes at the end of T-junction mixer. In experiment, a few-microliter droplets of Tris buffer and iodide solutions were moved toward the mixing junction and transported toward electrochemical electrodes by EWOD process. A short processing time within seconds was achieved at EWOD applied voltage of 300V. The analyte droplets mixed with different concentrations were successfully analyzed by cyclic voltametry. Therefore, the combination of EWOD digital microfluidic and electrochemical sensing system has successfully been demonstrated for rapid chemical analysis with minimal reagent consumption. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Patterned Fibers Embedded Microfluidic Chips Based on PLA and PDMS for Ag Nanoparticle Safety Testing

    Yaowen Liu

    2016-11-01

    Full Text Available A new method to integrate poly-dl-lactide (PLA patterned electrospun fibers with a polydimethylsiloxane (PDMS microfluidic chip was successfully developed via lithography. Hepatocyte behavior under static and dynamic conditions was investigated. Immunohistochemical analyses indicated good hepatocyte survival under the dynamic culture system with effective hepatocyte spheroid formation in the patterned microfluidic chip vs. static culture conditions and tissue culture plate (TCP. In particular, hepatocytes seeded in this microfluidic chip under a flow rate of 10 μL/min could re-establish hepatocyte polarity to support biliary excretion and were able to maintain high levels of albumin and urea secretion over 15 days. Furthermore, the optimized system could produce sensitive and consistent responses to nano-Ag-induced hepatotoxicity during culture. Thus, this microfluidic chip device provides a new means of fabricating complex liver tissue-engineered scaffolds, and may be of considerable utility in the toxicity screening of nanoparticles.

  15. Direct current insulator based dielectrophoresis (DC-iDEP) microfluidic chip for blood plasma separation

    Mohammadi, Mahdi

    2015-01-01

    Lab-on-a-Chip (LOC) integrated microfluidics has been a powerful tool for new developments in analytical chemistry. These microfluidic systems enable the miniaturization, integration and automation of complex biochemical assays through the reduction of reagent use and enabling portability.Cell and particle separation in microfluidic systems has recently gained significant attention in many sample preparations for clinical procedures. Direct-current insulator-based dielectrophoresis (DC-iDEP) ...

  16. Standardized and modular microfluidic platform for fast lab on chip system development

    Dekker, Stefan; van den Berg, Albert; Odijk, Mathieu; Lee, Abraham; DeVoe, Don

    2017-01-01

    This paper reports a modular microfluidic system with standardized parts, enabling rapid prototyping of lab on chip systems. Herewith contributing to the technology transfer from academy to industry. The use of standardized parts also makes it possible to design a microfluidic systems in a top down

  17. Making the invisible visible: a microfluidic chip using a low refractive index polymer.

    Hanada, Yasutaka; Ogawa, Tatsuya; Koike, Kazuhiko; Sugioka, Koji

    2016-07-07

    Microfluidic frameworks known as micro-total-analysis-systems or lab-on-a-chip have become versatile tools in cell biology research, since functional biochips are able to streamline dynamic observations of various cells. Glass or polymers are generally used as the substrate due to their high transparency, chemical stability and cost-effectiveness. However, these materials are not well suited for the microscopic observation of cell migration at the fluid boundary due to the refractive index mismatch between the medium and the biochip material. For this reason, we have developed a new method of fabricating three-dimensional (3D) microfluidic chips made of the low refractive index fluoric polymer CYTOP. This novel fabrication procedure involves the use of a femtosecond laser for direct writing, followed by wet etching with a dilute fluorinated solvent and annealing, to create high-quality 3D microfluidic chips inside a polymer substrate. A microfluidic chip made in this manner enabled us to more clearly observe the flagellum motion of a Dinoflagellate moving in circles near the fluid surface compared to the observations possible using conventional microfluidic chips. We believe that CYTOP microfluidic chips made using this new method may allow more detailed analysis of various cell migrations near solid boundaries.

  18. Route to one-step microstructure mold fabrication for PDMS microfluidic chip

    Lv, Xiaoqing; Geng, Zhaoxin; Fan, Zhiyuan; Wang, Shicai; Su, Yue; Fang, Weihao; Pei, Weihua; Chen, Hongda

    2018-04-01

    The microstructure mold fabrication for PDMS microfluidic chip remains complex and time-consuming process requiring special equipment and protocols: photolithography and etching. Thus, a rapid and cost-effective method is highly needed. Comparing with the traditional microfluidic chip fabricating process based on the micro-electromechanical system (MEMS), this method is simple and easy to implement, and the whole fabrication process only requires 1-2 h. Different size of microstructure from 100 to 1000 μm was fabricated, and used to culture four kinds of breast cancer cell lines. Cell viability and morphology was assessed when they were cultured in the micro straight channels, micro square holes and the bonding PDMS-glass microfluidic chip. The experimental results indicate that the microfluidic chip is good and meet the experimental requirements. This method can greatly reduce the process time and cost of the microfluidic chip, and provide a simple and effective way for the structure design and in the field of biological microfabrications and microfluidic chips.

  19. Integration of microelectronic chips in microfluidic systems on printed circuit board

    Burdallo, I; Jimenez-Jorquera, C; Fernández-Sánchez, C; Baldi, A

    2012-01-01

    A new scheme for the integration of small semiconductor transducer chips with microfluidic structures on printed circuit board (PCB) is presented. The proposed approach is based on a packaging technique that yields a large and flat area with small and shallow (∼44 µm deep) openings over the chips. The photocurable encapsulant material used, based on a diacrylate bisphenol A polymer, enables irreversible bonding of polydimethylsiloxane microfluidic structures at moderate temperatures (80 °C). This integration scheme enables the insertion of transducer chips in microfluidic systems with a lower added volume than previous schemes. Leakage tests have shown that the bonded structures withstand more than 360 kPa of pressure. A prototype microfluidic system with two detection chips, including one inter-digitated electrode (IDE) chip for conductivity and one ion selective field effect transistor (ISFET) chip for pH, has been implemented and characterized. Good electrical insulation of the chip contacts and silicon edge surfaces from the solution in the microchannels has been achieved. This integration procedure opens the door to the low-cost fabrication of complex analytical microsystems that combine the extraordinary potential of both the microfluidics and silicon microtechnology fields. (paper)

  20. One-step fabrication of microfluidic chips with in-plane, adhesive-free interconnections

    Sabourin, David; Dufva, Martin; Jensen, Thomas Glasdam

    2010-01-01

    A simple method for creating interconnections to a common microfluidic device material, poly(methyl methacrylate) (PMMA), is presented. A press-fit interconnection is created between oversized, deformable tubing and complementary, undersized semi-circular ports fabricated into PMMA bonding surfac...

  1. A novel bonding method for large scale poly(methyl methacrylate) micro- and nanofluidic chip fabrication

    Qu, Xingtian; Li, Jinlai; Yin, Zhifu

    2018-04-01

    Micro- and nanofluidic chips are becoming increasing significance for biological and medical applications. Future advances in micro- and nanofluidics and its utilization in commercial applications depend on the development and fabrication of low cost and high fidelity large scale plastic micro- and nanofluidic chips. However, the majority of the present fabrication methods suffer from a low bonding rate of the chip during thermal bonding process due to air trapping between the substrate and the cover plate. In the present work, a novel bonding technique based on Ar plasma and water treatment was proposed to fully bond the large scale micro- and nanofluidic chips. The influence of Ar plasma parameters on the water contact angle and the effect of bonding conditions on the bonding rate and the bonding strength of the chip were studied. The fluorescence tests demonstrate that the 5 × 5 cm2 poly(methyl methacrylate) chip with 180 nm wide and 180 nm deep nanochannels can be fabricated without any block and leakage by our newly developed method.

  2. Prototyping chips in minutes: Direct Laser Plotting (DLP) of functional microfluidic structures

    Wang, Limu

    2013-10-10

    We report a fast and simple prototyping method to fabricate polymer-based microfluidic chips using Direct Laser Plotting (DLP) technique, by which various functional micro-structures can be realized within minutes, in a mask-free and out-of-cleanroom fashion. A 2D Computer-Aid-Design (CAD) software was employed to layout the required micro-structures and micro-channels, a CO2 laser plotter was then used to construct the microstructures. The desired patterns can be plotted directly on PDMS substrates and bio-compatible polymer films by manipulating the strength and density of laser pulses. With the DLP technique, chip-embedded micro-electrodes, micro-mixers and 3D microfluidic chips with 5 layers, which normally require several days of work in a cleanroom facility, can be fabricated in minutes in common laboratory. This novel method can produce microfluidic channels with average feature size of 100 μm, while feature size of 50 μm or smaller is achievable by making use of the interference effect from laser impulsion. In this report, we present the optimized parameters for successful fabrication of 3D microchannels, micro-mixers and microfluidic chips for protein concentration measurements (Bovine Serum Albumine (BSA) test), and a novel procedure to pattern flexible embedding electrodes on PDMS-based microfluidic chips. DLP offers a convenient and low cost alternative to conventional microfluidic channel fabrication technique which relies on complicated and hazardous soft lithography process.

  3. In situ ZnO-PVA nanocomposite coated microfluidic chips for biosensing

    Habouti, Salah; Kunstmann-Olsen, Casper; Hoyland, James D.; Rubahn, Horst-Günter; Es-Souni, Mohammed

    2014-05-01

    Microfluidic chips with integrated fluid and optical connectors have been generated via a simple PDMS master-mould technique. In situ coating using a Zinc oxide polyvinylalcohol based sol-gel method results in ultrathin nanocomposite layers on the fluid channels, which makes them strongly hydrophilic and minimizes auto contamination of the chips by injected fluorescent biomarkers.

  4. Prototyping chips in minutes: Direct Laser Plotting (DLP) of functional microfluidic structures

    Wang, Limu; Kodzius, Rimantas; Yi, Xin; Li, Shunbo; Hui, Yu Sanna; Wen, Weijia

    2013-01-01

    and bio-compatible polymer films by manipulating the strength and density of laser pulses. With the DLP technique, chip-embedded micro-electrodes, micro-mixers and 3D microfluidic chips with 5 layers, which normally require several days of work in a

  5. In situ photo-immobilised pH gradient isoelectric focusing and zone electrophoresis integrated two-dimensional microfluidic chip electrophoresis for protein separation

    Lin, Fengmin; Yu, Shiyong; Gu, Le; Zhu, Xuetao; Wang, Jianshe; Zhu, Han; Lu, Yi; Wang, Yihua; Deng, Yulin; Geng, Lina

    2015-01-01

    A method is introduced for open-column photo-induced site-selective immobilization of pH gradients in a layer of PEG-methacrylate in a multi-dimensional microfluidic chip for use in electrophoresis. It has several attractive features: (a) mixtures of fluorescently labelled proteins carbonic anhydrase, catalase and myoglobin in their native state can be separated by pH-gradient isoelectric focusing (IEF) and zone electrophoresis (CZE) using integrated 2D chip electrophoresis; (b) compared to strip packing or monolithic photo-immobilization, it overcomes the shortcomings of free carrier ampholyte-based 2D chip electrophoresis in an easy way; (c) larger amount of sample can be loaded into the open column-mode electrophoresis (d) immobilized pH gradients can be re-used and the chip can be recycled; (e) a multilayer 3D pH gradient is established by a layer-by-layer assembly technique to further increase the separation capacity. In our perception, this strategy has a large potential in microfluidic chip-based separation schemes because of its simplicity, separation power, re-usability, and separation capacity. (author)

  6. Hydrophobic coating of microfluidic chips structured by SU-8 polymer for segmented flow operation

    Schumacher, J T; Grodrian, A; Metze, J; Kremin, C; Hoffmann, M

    2008-01-01

    We present a hydrophobization procedure for SU-8-based microfluidic chips on borofloat substrates. Different layouts of gold electrodes passivated by the polymer have been investigated. The chips are used for segmented flow in a two-fluid mode that requires a distinct hydrophobicity of the channel walls which is generated by the use of specific silane. In this paper we describe the production and silanization of the chips and demonstrate segmented flow operation

  7. IFSA: a microfluidic chip-platform for frit-based immunoassay protocols

    Hlawatsch, Nadine; Bangert, Michael; Miethe, Peter; Becker, Holger; Gärtner, Claudia

    2013-03-01

    Point-of-care diagnostics (POC) is one of the key application fields for lab-on-a-chip devices. While in recent years much of the work has concentrated on integrating complex molecular diagnostic assays onto a microfluidic device, there is a need to also put comparatively simple immunoassay-type protocols on a microfluidic platform. In this paper, we present the development of a microfluidic cartridge using an immunofiltration approach. In this method, the sandwich immunoassay takes place in a porous frit on which the antibodies have immobilized. The device is designed to be able to handle three samples in parallel and up to four analytical targets per sample. In order to meet the critical cost targets for the diagnostic market, the microfluidic chip has been designed and manufactured using high-volume manufacturing technologies in mind. Validation experiments show comparable sensitivities in comparison with conventional immunofiltration kits.

  8. Thin film metal sensors in fusion bonded glass chips for high-pressure microfluidics

    Andersson, Martin; Ek, Johan; Hedman, Ludvig; Johansson, Fredrik; Sehlstedt, Viktor; Stocklassa, Jesper; Snögren, Pär; Pettersson, Victor; Larsson, Jonas; Vizuete, Olivier; Hjort, Klas; Klintberg, Lena

    2017-01-01

    High-pressure microfluidics offers fast analyses of thermodynamic parameters for compressed process solvents. However, microfluidic platforms handling highly compressible supercritical CO 2 are difficult to control, and on-chip sensing would offer added control of the devices. Therefore, there is a need to integrate sensors into highly pressure tolerant glass chips. In this paper, thin film Pt sensors were embedded in shallow etched trenches in a glass wafer that was bonded with another glass wafer having microfluidic channels. The devices having sensors integrated into the flow channels sustained pressures up to 220 bar, typical for the operation of supercritical CO 2 . No leakage from the devices could be found. Integrated temperature sensors were capable of measuring local decompression cooling effects and integrated calorimetric sensors measured flow velocities over the range 0.5–13.8 mm s −1 . By this, a better control of high-pressure microfluidic platforms has been achieved. (paper)

  9. PEGylation of magnetic poly(glycidyl methacrylate) microparticles for microfluidic bioassays

    Kucerova, Jana; Svobodova, Zuzana; Knotek, Petr; Palarcik, Jiri; Vlcek, Milan; Kincl, Miloslav; Horak, Daniel; Autebert, Julien; Viovy, Jean-Louis; Bilkova, Zuzana

    2014-01-01

    In this study, magnetic poly(glycidyl methacrylate) microparticles containing carboxyl groups (PGMA-COOH) were coated using highly hydrophilic polymer poly(ethylene glycol) (PEG). PEG was used to reduce nonspecific interactions with proteins and cells while decreasing adhesion of particles to the walls of a microfluidic devices from poly(dimethylsiloxane) (PDMS) and cyclic olefin copolymer (COC). Zeta potential measurement, infrared spectroscopy, scanning electron microscopy, anti-PEG ELISA assay, and bioaffinity interactions between biotin and streptavidin-HRP successfully proved the presence of PEG on the surface of microspheres. Both neat and PEGylated microspheres were then incubated with the inert protein bovine serum albumin or cells to evaluate the rate of nonspecific adsorption (NSA). PEG with Mr of 30,000 Da was responsible for 45% reduction in NSA of proteins and 74% for cells compared to neat particles. The microspheres' behavior in PDMS and COC microchannels was then evaluated. Aggregation and adhesion of PEGylated microspheres significantly decreased compared to neat particles. Finally, the model enzyme horseradish peroxidase was immobilized on the microspheres through the heterobifunctional PEG chain. The possibility for subsequent covalent coupling of the ligand of interest was confirmed. Such PEGylated microparticles can be efficiently used in PDMS microchips as a carrier for bioaffinity separation or of enzyme for catalysis. - Highlights: • Magnetic polymer microspheres with highly hydrophilic PEG coating were prepared. • PEG reduced microsphere adhesion in microchannels versus neat particles. • Suitability of methods for detecting PEG on magnetic microspheres was investigated. • PEG on microsphere surfaces decreased nonspecific adsorption of proteins and cells

  10. PEGylation of magnetic poly(glycidyl methacrylate) microparticles for microfluidic bioassays

    Kucerova, Jana; Svobodova, Zuzana [Department of Biological and Biochemical Sciences, Faculty of Chemical Technology, University of Pardubice, Studentska 573, 53210 Pardubice (Czech Republic); Knotek, Petr [Joint Laboratory of Solid State Chemistry of IMC and University of Pardubice, Faculty of Chemical Technology, University of Pardubice, Studentska 573, 53210 Pardubice (Czech Republic); Palarcik, Jiri [Institute of Environmental and Chemical Engineering, Faculty of Chemical Technology, University of Pardubice, Studentska 573, 53210 Pardubice (Czech Republic); Vlcek, Milan; Kincl, Miloslav; Horak, Daniel [Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovsky Sq. 2, 16206 Prague 6 (Czech Republic); Autebert, Julien; Viovy, Jean-Louis [Macromolecules and Microsystems in Biology and Medicine, Institute Curie, UMR 168, 26 Rue d' Ulm, 75005 Paris (France); Bilkova, Zuzana, E-mail: zuzana.bilkova@upce.cz [Department of Biological and Biochemical Sciences, Faculty of Chemical Technology, University of Pardubice, Studentska 573, 53210 Pardubice (Czech Republic)

    2014-07-01

    In this study, magnetic poly(glycidyl methacrylate) microparticles containing carboxyl groups (PGMA-COOH) were coated using highly hydrophilic polymer poly(ethylene glycol) (PEG). PEG was used to reduce nonspecific interactions with proteins and cells while decreasing adhesion of particles to the walls of a microfluidic devices from poly(dimethylsiloxane) (PDMS) and cyclic olefin copolymer (COC). Zeta potential measurement, infrared spectroscopy, scanning electron microscopy, anti-PEG ELISA assay, and bioaffinity interactions between biotin and streptavidin-HRP successfully proved the presence of PEG on the surface of microspheres. Both neat and PEGylated microspheres were then incubated with the inert protein bovine serum albumin or cells to evaluate the rate of nonspecific adsorption (NSA). PEG with Mr of 30,000 Da was responsible for 45% reduction in NSA of proteins and 74% for cells compared to neat particles. The microspheres' behavior in PDMS and COC microchannels was then evaluated. Aggregation and adhesion of PEGylated microspheres significantly decreased compared to neat particles. Finally, the model enzyme horseradish peroxidase was immobilized on the microspheres through the heterobifunctional PEG chain. The possibility for subsequent covalent coupling of the ligand of interest was confirmed. Such PEGylated microparticles can be efficiently used in PDMS microchips as a carrier for bioaffinity separation or of enzyme for catalysis. - Highlights: • Magnetic polymer microspheres with highly hydrophilic PEG coating were prepared. • PEG reduced microsphere adhesion in microchannels versus neat particles. • Suitability of methods for detecting PEG on magnetic microspheres was investigated. • PEG on microsphere surfaces decreased nonspecific adsorption of proteins and cells.

  11. Chip-olate’ and dry-film resists for efficient fabrication, singulation and sealing of microfluidic chips

    Temiz, Yuksel; Delamarche, Emmanuel

    2014-09-01

    This paper describes a technique for high-throughput fabrication and efficient singulation of chips having closed microfluidic structures and takes advantage of dry-film resists (DFRs) for efficient sealing of capillary systems. The technique is illustrated using 4-inch Si/SiO2 wafers. Wafers carrying open microfluidic structures are partially diced to about half of their thickness. Treatments such as surface cleaning are done at wafer-level, then the structures are sealed using low-temperature (45 °C) lamination of a DFR that is pre-patterned using a craft cutter, and ready-to-use chips are finally separated manually like a chocolate bar by applying a small force (≤ 4 N). We further show that some DFRs have low auto-fluorescence at wavelengths typically used for common fluorescent dyes and that mechanical properties of some DFRs allow for the lamination of 200 μm wide microfluidic structures with negligible sagging (~1 μm). The hydrophilicity (advancing contact angle of ~60°) of the DFR supports autonomous capillary-driven flow without the need for additional surface treatment of the microfluidic chips. Flow rates from 1 to 5 µL min-1 are generated using different geometries of channels and capillary pumps. In addition, the ‘chip-olate’ technique is compatible with the patterning of capture antibodies on DFR for use in immunoassays. We believe this technique to be applicable to the fabrication of a wide range of microfluidic and lab-on-a-chip devices and to offer a viable alternative to many labor-intensive processes that are currently based on wafer bonding techniques or on the molding of poly(dimethylsiloxane) (PDMS) layers.

  12. Chip-olate’ and dry-film resists for efficient fabrication, singulation and sealing of microfluidic chips

    Temiz, Yuksel; Delamarche, Emmanuel

    2014-01-01

    This paper describes a technique for high-throughput fabrication and efficient singulation of chips having closed microfluidic structures and takes advantage of dry-film resists (DFRs) for efficient sealing of capillary systems. The technique is illustrated using 4-inch Si/SiO 2 wafers. Wafers carrying open microfluidic structures are partially diced to about half of their thickness. Treatments such as surface cleaning are done at wafer-level, then the structures are sealed using low-temperature (45 °C) lamination of a DFR that is pre-patterned using a craft cutter, and ready-to-use chips are finally separated manually like a chocolate bar by applying a small force (≤ 4 N). We further show that some DFRs have low auto-fluorescence at wavelengths typically used for common fluorescent dyes and that mechanical properties of some DFRs allow for the lamination of 200 μm wide microfluidic structures with negligible sagging (∼1 μm). The hydrophilicity (advancing contact angle of ∼60°) of the DFR supports autonomous capillary-driven flow without the need for additional surface treatment of the microfluidic chips. Flow rates from 1 to 5 µL min -1 are generated using different geometries of channels and capillary pumps. In addition, the ‘chip-olate’ technique is compatible with the patterning of capture antibodies on DFR for use in immunoassays. We believe this technique to be applicable to the fabrication of a wide range of microfluidic and lab-on-a-chip devices and to offer a viable alternative to many labor-intensive processes that are currently based on wafer bonding techniques or on the molding of poly(dimethylsiloxane) (PDMS) layers. (technical note)

  13. Rapid fabrication of microfluidic chips based on the simplest LED lithography

    Li, Yue; Wu, Ping; Luo, Zhaofeng; Ren, Yuxuan; Liao, Meixiang; Feng, Lili; Li, Yuting; He, Liqun

    2015-05-01

    Microfluidic chips are generally fabricated by a soft lithography method employing commercial lithography equipment. These heavy machines require a critical room environment and high lamp power, and the cost remains too high for most normal laboratories. Here we present a novel microfluidics fabrication method utilizing a portable ultraviolet (UV) LED as an alternative UV source for photolithography. With this approach, we can repeat several common microchannels as do these conventional commercial exposure machines, and both the verticality of the channel sidewall and lithography resolution are proved to be acceptable. Further microfluidics applications such as mixing, blood typing and microdroplet generation are implemented to validate the practicability of the chips. This simple but innovative method decreases the cost and requirement of chip fabrication dramatically and may be more popular with ordinary laboratories.

  14. Rapid fabrication of microfluidic chips based on the simplest LED lithography

    Li, Yue; Wu, Ping; Liao, Meixiang; Feng, Lili; Li, Yuting; He, Liqun; Luo, Zhaofeng; Ren, Yuxuan

    2015-01-01

    Microfluidic chips are generally fabricated by a soft lithography method employing commercial lithography equipment. These heavy machines require a critical room environment and high lamp power, and the cost remains too high for most normal laboratories. Here we present a novel microfluidics fabrication method utilizing a portable ultraviolet (UV) LED as an alternative UV source for photolithography. With this approach, we can repeat several common microchannels as do these conventional commercial exposure machines, and both the verticality of the channel sidewall and lithography resolution are proved to be acceptable. Further microfluidics applications such as mixing, blood typing and microdroplet generation are implemented to validate the practicability of the chips. This simple but innovative method decreases the cost and requirement of chip fabrication dramatically and may be more popular with ordinary laboratories. (paper)

  15. Integration of Curved D-Type Optical Fiber Sensor with Microfluidic Chip.

    Sun, Yung-Shin; Li, Chang-Jyun; Hsu, Jin-Cherng

    2016-12-30

    A curved D-type optical fiber sensor (OFS) combined with a microfluidic chip is proposed. This OFS, based on surface plasmon resonance (SPR) of the Kretchmann's configuration, is applied as a biosensor to measure the concentrations of different bio-liquids such as ethanol, methanol, and glucose solutions. The SPR phenomenon is attained by using the optical fiber to guide the light source to reach the side-polished, gold-coated region. Integrating this OFS with a polymethylmethacrylate (PMMA)-based microfluidic chip, the SPR spectra for liquids with different refractive indices are recorded. Experimentally, the sensitivity of the current biosensor was calculated to be in the order of 10 -5 RIU. This microfluidic chip-integrated OFS could be valuable for monitoring subtle changes in biological samples such as blood sugar, allergen, and biomolecular interactions.

  16. Integration of Curved D-Type Optical Fiber Sensor with Microfluidic Chip

    Yung-Shin Sun

    2016-12-01

    Full Text Available A curved D-type optical fiber sensor (OFS combined with a microfluidic chip is proposed. This OFS, based on surface plasmon resonance (SPR of the Kretchmann’s configuration, is applied as a biosensor to measure the concentrations of different bio-liquids such as ethanol, methanol, and glucose solutions. The SPR phenomenon is attained by using the optical fiber to guide the light source to reach the side-polished, gold-coated region. Integrating this OFS with a polymethylmethacrylate (PMMA-based microfluidic chip, the SPR spectra for liquids with different refractive indices are recorded. Experimentally, the sensitivity of the current biosensor was calculated to be in the order of 10−5 RIU. This microfluidic chip-integrated OFS could be valuable for monitoring subtle changes in biological samples such as blood sugar, allergen, and biomolecular interactions.

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

    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. Recent progress in preparation and application of microfluidic chip electrophoresis

    Cong, Hailin; Xu, Xiaodan; Yu, Bing; Yuan, Hua; Peng, Qiaohong; Tian, Chao

    2015-01-01

    Since its discovery in 1990, microfluidic chip electrophoresis (MCE) has allowed the development of applications with small size, fast analysis, low cost, high integration density and automatic level, which are easy to carry and have made commercialization efficient. MCE has been widely used in the areas of environmental protection, biochemistry, medicine and health, clinical testing, judicial expertise, food sanitation, pharmaceutical checking, drug testing, agrochemistry, biomedical engineering and life science. As one of the foremost fields in the research of capillary electrophoresis, MCE is the ultimate frontier to develop the miniaturized, integrated, automated all-in-one instruments needed in modern analytical chemistry. By adopting the advanced technologies of micro-machining, lasers and microelectronics, and the latest research achievements in analytical chemistry and biochemistry, the sampling, separation and detection systems of commonly used capillary electrophoresis are integrated with high densities onto glass, quartz, silicon or polymer wafers to form the MCE, which can finish the analysis of multi-step operations such as injection, enrichment, reaction, derivatization, separation, and collection of samples in a portable, efficient and super high speed manner. With reference to the different technological achievements in this area, the latest developments in MCE are reviewed in this article. The preparation mechanisms, surface modifications, and properties of different materials in MCE are compared, and the different sampling, separation and detection systems in MCE are summarized. The performance of MCE in analysis of fluorescent substance, metallic ion, sugar, medicine, nucleic acid, DNA, amino acid, polypeptide and protein is discussed, and the future direction of development is forecast. (topical review)

  19. Recent progress in preparation and application of microfluidic chip electrophoresis

    Cong, Hailin; Xu, Xiaodan; Yu, Bing; Yuan, Hua; Peng, Qiaohong; Tian, Chao

    2015-05-01

    Since its discovery in 1990, microfluidic chip electrophoresis (MCE) has allowed the development of applications with small size, fast analysis, low cost, high integration density and automatic level, which are easy to carry and have made commercialization efficient. MCE has been widely used in the areas of environmental protection, biochemistry, medicine and health, clinical testing, judicial expertise, food sanitation, pharmaceutical checking, drug testing, agrochemistry, biomedical engineering and life science. As one of the foremost fields in the research of capillary electrophoresis, MCE is the ultimate frontier to develop the miniaturized, integrated, automated all-in-one instruments needed in modern analytical chemistry. By adopting the advanced technologies of micro-machining, lasers and microelectronics, and the latest research achievements in analytical chemistry and biochemistry, the sampling, separation and detection systems of commonly used capillary electrophoresis are integrated with high densities onto glass, quartz, silicon or polymer wafers to form the MCE, which can finish the analysis of multi-step operations such as injection, enrichment, reaction, derivatization, separation, and collection of samples in a portable, efficient and super high speed manner. With reference to the different technological achievements in this area, the latest developments in MCE are reviewed in this article. The preparation mechanisms, surface modifications, and properties of different materials in MCE are compared, and the different sampling, separation and detection systems in MCE are summarized. The performance of MCE in analysis of fluorescent substance, metallic ion, sugar, medicine, nucleic acid, DNA, amino acid, polypeptide and protein is discussed, and the future direction of development is forecast.

  20. 3D-printed microfluidic chips with patterned, cell-laden hydrogel constructs.

    Knowlton, Stephanie; Yu, Chu Hsiang; Ersoy, Fulya; Emadi, Sharareh; Khademhosseini, Ali; Tasoglu, Savas

    2016-06-20

    Three-dimensional (3D) printing offers potential to fabricate high-throughput and low-cost fabrication of microfluidic devices as a promising alternative to traditional techniques which enables efficient design iterations in the development stage. In this study, we demonstrate a single-step fabrication of a 3D transparent microfluidic chip using two alternative techniques: a stereolithography-based desktop 3D printer and a two-step fabrication using an industrial 3D printer based on polyjet technology. This method, compared to conventional fabrication using relatively expensive materials and labor-intensive processes, presents a low-cost, rapid prototyping technique to print functional 3D microfluidic chips. We enhance the capabilities of 3D-printed microfluidic devices by coupling 3D cell encapsulation and spatial patterning within photocrosslinkable gelatin methacryloyl (GelMA). The platform presented here serves as a 3D culture environment for long-term cell culture and growth. Furthermore, we have demonstrated the ability to print complex 3D microfluidic channels to create predictable and controllable fluid flow regimes. Here, we demonstrate the novel use of 3D-printed microfluidic chips as controllable 3D cell culture environments, advancing the applicability of 3D printing to engineering physiological systems for future applications in bioengineering.

  1. Organ/body-on-a-chip based on microfluidic technology for drug discovery.

    Kimura, Hiroshi; Sakai, Yasuyuki; Fujii, Teruo

    2018-02-01

    Although animal experiments are indispensable for preclinical screening in the drug discovery process, various issues such as ethical considerations and species differences remain. To solve these issues, cell-based assays using human-derived cells have been actively pursued. However, it remains difficult to accurately predict drug efficacy, toxicity, and organs interactions, because cultivated cells often do not retain their original organ functions and morphologies in conventional in vitro cell culture systems. In the μTAS research field, which is a part of biochemical engineering, the technologies of organ-on-a-chip, based on microfluidic devices built using microfabrication, have been widely studied recently as a novel in vitro organ model. Since it is possible to physically and chemically mimic the in vitro environment by using microfluidic device technology, maintenance of cellular function and morphology, and replication of organ interactions can be realized using organ-on-a-chip devices. So far, functions of various organs and tissues, such as the lung, liver, kidney, and gut have been reproduced as in vitro models. Furthermore, a body-on-a-chip, integrating multi organ functions on a microfluidic device, has also been proposed for prediction of organ interactions. We herein provide a background of microfluidic systems, organ-on-a-chip, Body-on-a-chip technologies, and their challenges in the future. Copyright © 2017 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

  2. Manually operatable on-chip bistable pneumatic microstructures for microfluidic manipulations.

    Chen, Arnold; Pan, Tingrui

    2014-09-07

    Bistable microvalves are of particular interest because of their distinct nature of requiring energy consumption only during the transition between the open and closed states. This characteristic can be highly advantageous in reducing the number of external inputs and the complexity of control circuitries since microfluidic devices as contemporary lab-on-a-chip platforms are transferring from research settings to low-resource environments with high integrability and a small form factor. In this paper, we first present manually operatable, on-chip bistable pneumatic microstructures (BPMs) for microfluidic manipulation. The structural design and operation of the BPM devices can be readily integrated into any pneumatically powered microfluidic network consisting of pneumatic and fluidic channels. It is mainly composed of a vacuum activation chamber (VAC) and a pressure release chamber (PRC), of which users have direct control through finger pressing to switch either to the bistable vacuum state (VS) or the atmospheric state (AS). We have integrated multiple BPM devices into a 4-to-1 microfluidic multiplexor to demonstrate on-chip digital flow switching from different sources. Furthermore, we have shown its clinical relevance in a point-of-care diagnostic chip that processes blood samples to identify the distinct blood types (A/B/O) on-chip.

  3. Monolithic integration of DUV-induced waveguides into plastic microfluidic chip for optical manipulation

    Khoury Arvelo, Maria; Vannahme, Christoph; Sørensen, Kristian Tølbøl

    2014-01-01

    A monolithic polymer optofluidic chip for manipulation of microbeads in flow is demonstrated. On this chip, polymer waveguides induced by Deep UV lithography are integrated with microfluidic channels. The optical propagation losses of the waveguides are measured to be 0.66±0.13 dB/mm at a wavelen......A monolithic polymer optofluidic chip for manipulation of microbeads in flow is demonstrated. On this chip, polymer waveguides induced by Deep UV lithography are integrated with microfluidic channels. The optical propagation losses of the waveguides are measured to be 0.66±0.13 d......B/mm at a wavelength of λ = 808 nm. An optimized bead tracking algorithm is implemented, allowing for determination of the optical forces acting on the particles. The algorithm features a spatio-temporal mapping of coordinates for uniting partial trajectories, without increased processing time. With an external laser...

  4. Inkjet 3D printing of microfluidic structures—on the selection of the printer towards printing your own microfluidic chips

    Walczak, Rafał; Adamski, Krzysztof

    2015-01-01

    This article reports, for the first time, the results of detailed research on the application of inkjet 3D printing for the fabrication of microfluidic structures. CAD designed test structures were printed with four different printers. Dimensional fidelity, shape conformity, and surface roughness were studied for each printout. It was found that the minimum dimension (width or depth) for a properly printed microfluidic channel was approximately 200 μm. Although the nominal resolution of the printers was one order of magnitude better, smaller structures were significantly deformed or not printed at all. It was also found that a crucial step in one-step fabrication of embedded microchannels is the removal of the support material. We also discuss the source of print error and present a way to evaluate other printers. The printouts obtained from the four different printers were compared, and the optimal printing technique and printer were used to fabricate a microfluidic structure for the spectrophotometric characterisation of beverages. UV/VIS absorbance characteristics were collected using this microfluidic structure, demonstrating that the fabricated spectrophotometric chip operated properly. Thus, a proof-of-concept for using inkjet 3D printing for the fabrication of microfluidic structures was obtained. (paper)

  5. Nucleic acid and protein extraction from electropermeabilized E. coli cells on a microfluidic chip

    Matos, T.; Senkbeil, Silja; Mendonça, A.

    2013-01-01

    technique has been developed which is based on exposing E. coli cells to low voltages to allow extraction of nucleic acids and proteins. The flow-through electropermeability chip used consists of a microfluidic channel with integrated gold electrodes that promote cell envelope channel formation at low...

  6. Validation of a fully autonomous phosphate analyser based on a microfluidic lab-on-a-chip

    Slater, Conor; Cleary, J.; Lau, K.T.

    2010-01-01

    of long-term operation. This was proven by a bench top calibration of the analyser using standard solutions and also by comparing the analyser's performance to a commercially available phosphate monitor installed at a waste water treatment plant. The output of the microfluidic lab-on-a-chip analyser...

  7. A single microfluidic chip with dual surface properties for protein drug delivery.

    Bokharaei, Mehrdad; Saatchi, Katayoun; Häfeli, Urs O

    2017-04-15

    Principles of double emulsion generation were incorporated in a glass microfluidic chip fabricated with two different surface properties in order to produce protein loaded polymer microspheres. The microspheres were produced by integrating two microfluidic flow focusing systems and a multi-step droplet splitting and mixing system into one chip. The chip consists of a hydrophobic and a hydrophilic section with two different heights, 12μm and 45μm, respectively. As a result, the protein is homogenously distributed throughout the polymer microsphere matrix, not just in its center (which has been studied before). In our work, the inner phase was bovine serum albumin (BSA) in phosphate buffered saline, the disperse phase was poly (lactic acid) in chloroform and the continuous phase was an aqueous solution of poly(vinyl alcohol). After solvent removal, BSA loaded microspheres with an encapsulation efficiency of up to 96% were obtained. Our results show the feasibility of producing microspheres loaded with a hydrophilic drug in a microfluidic system that integrates different microfluidic units into one chip. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. In situ ZnO-PVA nanocomposite coated microfluidic chips for biosensing

    Habouti, S.; Kunstmann-Olsen, C.; Hoyland, J. D.

    2014-01-01

    Microfluidic chips with integrated fluid and optical connectors have been generated via a simple PDMS master-mould technique. In situ coating using a Zinc oxide polyvinylalcohol based sol-gel method results in ultrathin nanocomposite layers on the fluid channels, which makes them strongly...

  9. Scheduling and Fluid Routing for Flow-Based Microfluidic Laboratories-on-a-Chip

    Minhass, Wajid Hassan; McDaniel, Jeffrey; Raagaard, Michael Lander

    2017-01-01

    Microfluidic laboratories-on-chip (LoCs) are replacing the conventional biochemical analyzers and are able to integrate the necessary functions for biochemical analysis onchip. There are several types of LoCs, each having its advantages and limitations. In this paper we are interested in flow-bas...

  10. Extraction, amplification and detection of DNA in microfluidic chip-based assays

    Wu, Jinbo

    2013-12-20

    This review covers three aspects of PCR-based microfluidic chip assays: sample preparation, target amplification, and product detection. We also discuss the challenges related to the miniaturization and integration of each assay and make a comparison between conventional and microfluidic schemes. In order to accomplish these essential assays without human intervention between individual steps, the micro-components for fluid manipulation become critical. We therefore summarize and discuss components such as microvalves (for fluid regulation), pumps (for fluid driving) and mixers (for blending fluids). By combining the above assays and microcomponents, DNA testing of multi-step bio-reactions in microfluidic chips may be achieved with minimal external control. The combination of assay schemes with the use of micro-components also leads to rapid methods for DNA testing via multi-step bioreactions. Contains 259 references.

  11. Study of a Microfluidic Chip Integrating Single Cell Trap and 3D Stable Rotation Manipulation

    Liang Huang

    2016-08-01

    Full Text Available Single cell manipulation technology has been widely applied in biological fields, such as cell injection/enucleation, cell physiological measurement, and cell imaging. Recently, a biochip platform with a novel configuration of electrodes for cell 3D rotation has been successfully developed by generating rotating electric fields. However, the rotation platform still has two major shortcomings that need to be improved. The primary problem is that there is no on-chip module to facilitate the placement of a single cell into the rotation chamber, which causes very low efficiency in experiment to manually pipette single 10-micron-scale cells into rotation position. Secondly, the cell in the chamber may suffer from unstable rotation, which includes gravity-induced sinking down to the chamber bottom or electric-force-induced on-plane movement. To solve the two problems, in this paper we propose a new microfluidic chip with manipulation capabilities of single cell trap and single cell 3D stable rotation, both on one chip. The new microfluidic chip consists of two parts. The top capture part is based on the least flow resistance principle and is used to capture a single cell and to transport it to the rotation chamber. The bottom rotation part is based on dielectrophoresis (DEP and is used to 3D rotate the single cell in the rotation chamber with enhanced stability. The two parts are aligned and bonded together to form closed channels for microfluidic handling. Using COMSOL simulation and preliminary experiments, we have verified, in principle, the concept of on-chip single cell traps and 3D stable rotation, and identified key parameters for chip structures, microfluidic handling, and electrode configurations. The work has laid a solid foundation for on-going chip fabrication and experiment validation.

  12. Cerenkov radiation imaging as a method for quantitative measurements of beta particles in a microfluidic chip

    Cho, Jennifer S; Taschereau, Richard; Olma, Sebastian; Liu Kan; Chen Yichun; Shen, Clifton K-F; Van Dam, R Michael; Chatziioannou, Arion F

    2009-01-01

    It has been observed that microfluidic chips used for synthesizing 18 F-labeled compounds demonstrate visible light emission without nearby scintillators or fluorescent materials. The origin of the light was investigated and found to be consistent with the emission characteristics from Cerenkov radiation. Since 18 F decays through the emission of high-energy positrons, the energy threshold for beta particles, i.e. electrons or positrons, to generate Cerenkov radiation was calculated for water and polydimethylsiloxane (PDMS), the most commonly used polymer-based material for microfluidic chips. Beta particles emitted from 18 F have a continuous energy spectrum, with a maximum energy that exceeds this energy threshold for both water and PDMS. In addition, the spectral characteristics of the emitted light from 18 F in distilled water were also measured, yielding a broad distribution from 300 nm to 700 nm, with higher intensity at shorter wavelengths. A photograph of the 18 F solution showed a bluish-white light emitted from the solution, further suggesting Cerenkov radiation. In this study, the feasibility of using this Cerenkov light emission as a method for quantitative measurements of the radioactivity within the microfluidic chip in situ was evaluated. A detector previously developed for imaging microfluidic platforms was used. The detector consisted of a charge-coupled device (CCD) optically coupled to a lens. The system spatial resolution, minimum detectable activity and dynamic range were evaluated. In addition, the calibration of a Cerenkov signal versus activity concentration in the microfluidic chip was determined. This novel method of Cerenkov radiation measurements will provide researchers with a simple yet robust quantitative imaging tool for microfluidic applications utilizing beta particles.

  13. Science Issues Associated with the Use of a Microfluidic Chip Designed Specifically for Protein Crystallization

    Holmes, Anna M.; Monaco, Lisa; Barnes, Cindy; Spearing, Scott; Jenkins, Andy; Johnson, Todd; Mayer, Derek; Cole, Helen

    2003-01-01

    The Iterative Biological Crystallization team in partnership with Caliper Technologies has produced a prototype microfluidic chip for batch crystallization that has been designed and tested. The chip is designed for the mixing and dispensing of up to five solutions with possible variation of the recipe being delivered to two growth wells. Developments that have led to the successful on-chip crystallization of a few model proteins have required investigative insight into many different areas, including fluid mixing dynamics, surface treatments, quantification and fidelity of reagent delivery. This presentation will encompass the ongoing studies and data accumulated toward these efforts.

  14. A PDMS-Based Microfluidic Hanging Drop Chip for Embryoid Body Formation.

    Wu, Huei-Wen; Hsiao, Yi-Hsing; Chen, Chih-Chen; Yet, Shaw-Fang; Hsu, Chia-Hsien

    2016-07-06

    The conventional hanging drop technique is the most widely used method for embryoid body (EB) formation. However, this method is labor intensive and limited by the difficulty in exchanging the medium. Here, we report a microfluidic chip-based approach for high-throughput formation of EBs. The device consists of microfluidic channels with 6 × 12 opening wells in PDMS supported by a glass substrate. The PDMS channels were fabricated by replicating polydimethyl-siloxane (PDMS) from SU-8 mold. The droplet formation in the chip was tested with different hydrostatic pressures to obtain optimal operation pressures for the wells with 1000 μm diameter openings. The droplets formed at the opening wells were used to culture mouse embryonic stem cells which could subsequently developed into EBs in the hanging droplets. This device also allows for medium exchange of the hanging droplets making it possible to perform immunochemistry staining and characterize EBs on chip.

  15. A PDMS-Based Microfluidic Hanging Drop Chip for Embryoid Body Formation

    Huei-Wen Wu

    2016-07-01

    Full Text Available The conventional hanging drop technique is the most widely used method for embryoid body (EB formation. However, this method is labor intensive and limited by the difficulty in exchanging the medium. Here, we report a microfluidic chip-based approach for high-throughput formation of EBs. The device consists of microfluidic channels with 6 × 12 opening wells in PDMS supported by a glass substrate. The PDMS channels were fabricated by replicating polydimethyl-siloxane (PDMS from SU-8 mold. The droplet formation in the chip was tested with different hydrostatic pressures to obtain optimal operation pressures for the wells with 1000 μm diameter openings. The droplets formed at the opening wells were used to culture mouse embryonic stem cells which could subsequently developed into EBs in the hanging droplets. This device also allows for medium exchange of the hanging droplets making it possible to perform immunochemistry staining and characterize EBs on chip.

  16. Identification of microfluidic two-phase flow patterns in lab-on-chip devices.

    Yang, Zhaochu; Dong, Tao; Halvorsen, Einar

    2014-01-01

    This work describes a capacitive sensor for identification of microfluidic two-phase flow in lab-on-chip devices. With interdigital electrodes and thin insulation layer utilized, this sensor is capable of being integrated with the microsystems easily. Transducing principle and design considerations are presented with respect to the microfluidic gas/liquid flow patterns. Numerical simulation results verify the operational principle. And the factors affecting the performance of the sensor are discussed. Besides, a feasible process flow for the fabrication is also proposed.

  17. Fast prototyping of injection molded polymer microfluidic chips

    Hansen, Thomas Steen; Selmeczi, David; Larsen, Niels Bent

    2010-01-01

    We present fast prototyping of injection molding tools by the definition of microfluidic structures in a light-curable epoxy (SU-8) directly on planar nickel mold inserts. Optimized prototype mold structures could withstand injection molding of more than 300 replicas in cyclic olefin copolymer (COC...

  18. Microfluidic organ-on-chip technology for blood-brain barrier research.

    van der Helm, Marinke W; van der Meer, Andries D; Eijkel, Jan C T; van den Berg, Albert; Segerink, Loes I

    2016-01-01

    Organs-on-chips are a new class of microengineered laboratory models that combine several of the advantages of current in vivo and in vitro models. In this review, we summarize the advances that have been made in the development of organ-on-chip models of the blood-brain barrier (BBBs-on-chips) and the challenges that are still ahead. The BBB is formed by specialized endothelial cells and separates blood from brain tissue. It protects the brain from harmful compounds from the blood and provides homeostasis for optimal neuronal function [corrected]. Studying BBB function and dysfunction is important for drug development and biomedical research. Microfluidic BBBs-on-chips enable real-time study of (human) cells in an engineered physiological microenvironment, for example incorporating small geometries and fluid flow as well as sensors. Examples of BBBs-on-chips in literature already show the potential of more realistic microenvironments and the study of organ-level functions. A key challenge in the field of BBB-on-chip development is the current lack of standardized quantification of parameters such as barrier permeability and shear stress. This limits the potential for direct comparison of the performance of different BBB-on-chip models to each other and existing models. We give recommendations for further standardization in model characterization and conclude that the rapidly emerging field of BBB-on-chip models holds great promise for further studies in BBB biology and drug development.

  19. Droplet-based Biosensing for Lab-on-a-Chip, Open Microfluidics Platforms

    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.

  20. Real-time tunability of chip-based light source enabled by microfluidic mixing

    Olsen, Brian Bilenberg; Rasmussen, Torben; Balslev, Søren

    2006-01-01

    We demonstrate real-time tunability of a chip-based liquid light source enabled by microfluidic mixing. The mixer and light source are fabricated in SU-8 which is suitable for integration in SU-8-based laboratory-on-a-chip microsystems. The tunability of the light source is achieved by changing...... the concentration of rhodamine 6G dye inside two integrated vertical resonators, since both the refractive index and the gain profile are influenced by the dye concentration. The effect on the refractive index and the gain profile of rhodamine 6G in ethanol is investigated and the continuous tuning of the laser...

  1. A microfluidic chip for blood plasma separation using electro-osmotic flow control

    Jiang, Hai; Weng, Xuan; Chon, Chan Hee; Wu, Xudong; Li, Dongqing

    2011-01-01

    In this paper, a microfluidic-based chip with two straight microchannels and five branch microchannels was designed and tested to separate blood plasma from a small sample of fresh human blood. The electro-osmotic flow method was used to control the separation of blood plasma. Blood cell removal and blood plasma extraction were realized in experiments. The efficiency of extracting blood plasma can be as high as 26%

  2. Pyrolyzed Photoresist Electrodes for Integration in Microfluidic Chips for Transmitter Detection from Biological Cells

    Larsen, Simon Tylsgaard; Argyraki, Aikaterini; Amato, Letizia

    2013-01-01

    In this study, we show how pyrolyzed photoresist carbon electrodes can be used for amperometric detection of potassium-induced transmitter release from large groups of neuronal PC 12 cells. This opens the way for the use of carbon film electrodes in microfabricated devices for neurochemical drug ...... by the difference in photoresist viscosity. By adding a soft bake step to the fabrication procedure, the flatness of pyrolyzed AZ 5214 electrodes could be improved which would facilitate their integration in microfluidic chip devices....

  3. Chemiluminescence generation and detection in a capillary-driven microfluidic chip

    Ramon, Charlotte; Temiz, Yuksel; Delamarche, Emmanuel

    2017-02-01

    The use of microfluidic technology represents a strong opportunity for providing sensitive, low-cost and rapid diagnosis at the point-of-care and such a technology might therefore support better, faster and more efficient diagnosis and treatment of patients at home and in healthcare settings both in developed and developing countries. In this work, we consider luminescence-based assays as an alternative to well-established fluorescence-based systems because luminescence does not require a light source or expensive optical components and is therefore a promising detection method for point-of-care applications. Here, we show a proof-of-concept of chemiluminescence (CL) generation and detection in a capillary-driven microfluidic chip for potential immunoassay applications. We employed a commercial acridan-based reaction, which is catalyzed by horseradish peroxidase (HRP). We investigated CL generation under flow conditions using a simplified immunoassay model where HRP is used instead of the complete sandwich immunocomplex. First, CL signals were generated in a capillary microfluidic chip by immobilizing HRP on a polydimethylsiloxane (PDMS) sealing layer using stencil deposition and flowing CL substrate through the hydrophilic channels. CL signals were detected using a compact (only 5×5×2.5 cm3) and custom-designed scanner, which was assembled for less than $30 and comprised a 128×1 photodiode array, a mini stepper motor, an Arduino microcontroller, and a 3D-printed housing. In addition, microfluidic chips having specific 30-μm-deep structures were fabricated and used to immobilize ensembles of 4.50 μm beads functionalized with HRP so as to generate high CL signals from capillary-driven chips.

  4. Thermal activation of catalytic microjets in blood samples using microfluidic chips.

    Soler, Lluís; Martínez-Cisneros, Cynthia; Swiersy, Anka; Sánchez, Samuel; Schmidt, Oliver G

    2013-11-21

    We demonstrate that catalytic microjet engines can out-swim high complex media composed of red blood cells and serum. Despite the challenge presented by the high viscosity of the solution at room temperature, the catalytic microjets can be activated at physiological temperature and, consequently, self-propel in diluted solutions of blood samples. We prove that these microjets self-propel in 10× diluted blood samples using microfluidic chips.

  5. Cytotoxicity of cadmium-containing quantum dots based on a study using a microfluidic chip

    Zheng Xiannuo; Weng Lixing; Tian Jing; Wang Lianhui; Wu Lei; Jin Qinghui; Zhao Jianlong

    2012-01-01

    There is a lack of reliable nanotoxicity assays available for monitoring and quantifying multiple cellular events in cultured cells. In this study, we used a microfluidic chip to systematically investigate the cytotoxicity of three kinds of well-characterized cadmium-containing quantum dots (QDs) with the same core but different shell structures, including CdTe core QDs, CdTe/CdS core–shell QDs, and CdTe/CdS/ZnS core–shell–shell QDs, in HEK293 cells. Using the microfluidic chip combined with fluorescence microscopy, multiple QD-induced cellular events including cell morphology, viability, proliferation, and QD uptake were simultaneously analysed. The three kinds of QDs showed significantly different cytotoxicities. The CdTe QDs, which are highly toxic to HEK293 cells, resulted in remarkable cellular and nuclear morphological changes, a dose-dependent decrease in cell viability, and strong inhibition of cell proliferation; the CdTe/CdS QDs were moderately toxic but did not significantly affect the proliferation of HEK293 cells; while the CdTe/CdS/ZnS QDs had no detectable influence on cytotoxicity with respect to cell morphology, viability, and proliferation. Our data indicated that QD cytotoxicity was closely related to their surface structures and specific physicochemical properties. This study also demonstrated that the microfluidic chip could serve as a powerful tool to systematically evaluate the cytotoxicity of nanoparticles in multiple cellular events. (paper)

  6. Cytotoxicity of cadmium-containing quantum dots based on a study using a microfluidic chip

    Zheng, Xiannuo; Tian, Jing; Weng, Lixing; Wu, Lei; Jin, Qinghui; Zhao, Jianlong; Wang, Lianhui

    2012-02-01

    There is a lack of reliable nanotoxicity assays available for monitoring and quantifying multiple cellular events in cultured cells. In this study, we used a microfluidic chip to systematically investigate the cytotoxicity of three kinds of well-characterized cadmium-containing quantum dots (QDs) with the same core but different shell structures, including CdTe core QDs, CdTe/CdS core-shell QDs, and CdTe/CdS/ZnS core-shell-shell QDs, in HEK293 cells. Using the microfluidic chip combined with fluorescence microscopy, multiple QD-induced cellular events including cell morphology, viability, proliferation, and QD uptake were simultaneously analysed. The three kinds of QDs showed significantly different cytotoxicities. The CdTe QDs, which are highly toxic to HEK293 cells, resulted in remarkable cellular and nuclear morphological changes, a dose-dependent decrease in cell viability, and strong inhibition of cell proliferation; the CdTe/CdS QDs were moderately toxic but did not significantly affect the proliferation of HEK293 cells; while the CdTe/CdS/ZnS QDs had no detectable influence on cytotoxicity with respect to cell morphology, viability, and proliferation. Our data indicated that QD cytotoxicity was closely related to their surface structures and specific physicochemical properties. This study also demonstrated that the microfluidic chip could serve as a powerful tool to systematically evaluate the cytotoxicity of nanoparticles in multiple cellular events.

  7. Absolute quantification of DNA methylation using microfluidic chip-based digital PCR.

    Wu, Zhenhua; Bai, Yanan; Cheng, Zule; Liu, Fangming; Wang, Ping; Yang, Dawei; Li, Gang; Jin, Qinghui; Mao, Hongju; Zhao, Jianlong

    2017-10-15

    Hypermethylation of CpG islands in the promoter region of many tumor suppressor genes downregulates their expression and in a result promotes tumorigenesis. Therefore, detection of DNA methylation status is a convenient diagnostic tool for cancer detection. Here, we reported a novel method for the integrative detection of methylation by the microfluidic chip-based digital PCR. This method relies on methylation-sensitive restriction enzyme HpaII, which cleaves the unmethylated DNA strands while keeping the methylated ones intact. After HpaII treatment, the DNA methylation level is determined quantitatively by the microfluidic chip-based digital PCR with the lower limit of detection equal to 0.52%. To validate the applicability of this method, promoter methylation of two tumor suppressor genes (PCDHGB6 and HOXA9) was tested in 10 samples of early stage lung adenocarcinoma and their adjacent non-tumorous tissues. The consistency was observed in the analysis of these samples using our method and a conventional bisulfite pyrosequencing. Combining high sensitivity and low cost, the microfluidic chip-based digital PCR method might provide a promising alternative for the detection of DNA methylation and early diagnosis of epigenetics-related diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. A review of digital microfluidics as portable platforms for lab-on a-chip applications.

    Samiei, Ehsan; Tabrizian, Maryam; Hoorfar, Mina

    2016-07-07

    Following the development of microfluidic systems, there has been a high tendency towards developing lab-on-a-chip devices for biochemical applications. A great deal of effort has been devoted to improve and advance these devices with the goal of performing complete sets of biochemical assays on the device and possibly developing portable platforms for point of care applications. Among the different microfluidic systems used for such a purpose, digital microfluidics (DMF) shows high flexibility and capability of performing multiplex and parallel biochemical operations, and hence, has been considered as a suitable candidate for lab-on-a-chip applications. In this review, we discuss the most recent advances in the DMF platforms, and evaluate the feasibility of developing multifunctional packages for performing complete sets of processes of biochemical assays, particularly for point-of-care applications. The progress in the development of DMF systems is reviewed from eight different aspects, including device fabrication, basic fluidic operations, automation, manipulation of biological samples, advanced operations, detection, biological applications, and finally, packaging and portability of the DMF devices. Success in developing the lab-on-a-chip DMF devices will be concluded based on the advances achieved in each of these aspects.

  9. Integrating Carbon Nanotubes into Microfluidic Chip for Separating Biochemical Compounds

    Chen, Miaoxiang Max; Mogensen, Klaus Bo; Bøggild, Peter

    2012-01-01

    We present a new type of device to separate biochemical compounds wherein carbon nanotubes (CNTs) are integrated as chromatographic stationary phase. The CNTs were directly grown on the bottom of microfluidic channels on Si/SiO2 substrates by chemical vapor deposition (CVD). Acetylene was used...... as carbon source and Ni was employed as catalyst. For electrokinetic separations, higher electrical field strength is usually required; therefore, the CNTs were constructed in pillar-array-form by patterning the catalyst layer. Electrical field strength of 2.0 kV/cm has been realized, which is more than one...

  10. PEGylation of magnetic poly(glycidyl methacrylate) microparticles for microfluidic bioassays

    Kučerová, J.; Svobodová, Z.; Knotek, P.; Palarčik, J.; Vlček, Milan; Kincl, Miloslav; Horák, Daniel; Autebert, J.; Viovy, J.-L.; Bílková, Z.

    2014-01-01

    Roč. 40, 1 July (2014), s. 308-315 ISSN 0928-4931 R&D Projects: GA MŠk 7E12053; GA MŠk 7E09109 EU Projects: European Commission(XE) 246513 - NADINE; European Commission(XE) 228980 - CAMINEMS Institutional support: RVO:61389013 Keywords : PEGylation * magnetic microscopy * microfluidics Subject RIV: CE - Biochemistry

  11. Epoxy Chip-in-Carrier Integration and Screen-Printed Metalization for Multichannel Microfluidic Lab-on-CMOS Microsystems.

    Li, Lin; Yin, Heyu; Mason, Andrew J

    2018-04-01

    The integration of biosensors, microfluidics, and CMOS instrumentation provides a compact lab-on-CMOS microsystem well suited for high throughput measurement. This paper describes a new epoxy chip-in-carrier integration process and two planar metalization techniques for lab-on-CMOS that enable on-CMOS electrochemical measurement with multichannel microfluidics. Several design approaches with different fabrication steps and materials were experimentally analyzed to identify an ideal process that can achieve desired capability with high yield and low material and tool cost. On-chip electrochemical measurements of the integrated assembly were performed to verify the functionality of the chip-in-carrier packaging and its capability for microfluidic integration. The newly developed CMOS-compatible epoxy chip-in-carrier process paves the way for full implementation of many lab-on-CMOS applications with CMOS ICs as core electronic instruments.

  12. A microfluidic chip for direct and rapid trapping of white blood cells from whole blood

    Chen, Jingdong; Chen, Di; Yuan, Tao; Xie, Yao; Chen, Xiang

    2013-01-01

    Blood analysis plays a major role in medical and science applications and white blood cells (WBCs) are an important target of analysis. We proposed an integrated microfluidic chip for direct and rapid trapping WBCs from whole blood. The microfluidic chip consists of two basic functional units: a winding channel to mix and arrays of two-layer trapping structures to trap WBCs. Red blood cells (RBCs) were eliminated through moving the winding channel and then WBCs were trapped by the arrays of trapping structures. We fabricated the PDMS (polydimethylsiloxane) chip using soft lithography and determined the critical flow velocities of tartrazine and brilliant blue water mixing and whole blood and red blood cell lysis buffer mixing in the winding channel. They are 0.25 μl/min and 0.05 μl/min, respectively. The critical flow velocity of the whole blood and red blood cell lysis buffer is lower due to larger volume of the RBCs and higher kinematic viscosity of the whole blood. The time taken for complete lysis of whole blood was about 85 s under the flow velocity 0.05 μl/min. The RBCs were lysed completely by mixing and the WBCs were trapped by the trapping structures. The chip trapped about 2.0 × 103 from 3.3 × 103 WBCs. PMID:24404026

  13. Rotational microfluidic motor for on-chip microcentrifugation

    Shilton, Richie J.; Glass, Nick R.; Chan, Peggy; Yeo, Leslie Y.; Friend, James R.

    2011-06-01

    We report on the design of a surface acoustic wave (SAW) driven fluid-coupled micromotor which runs at high rotational velocities. A pair of opposing SAWs generated on a lithium niobate substrate are each obliquely passed into either side of a fluid drop to drive rotation of the fluid, and the thin circular disk set on the drop. Using water for the drop, a 5 mm diameter disk was driven with rotation speeds and start-up torques up to 2250 rpm and 60 nN m, respectively. Most importantly for lab-on-a-chip applications, radial accelerations of 172 m/s2 was obtained, presenting possibilities for microcentrifugation, flow sequencing, assays, and cell culturing in truly microscale lab-on-a-chip devices.

  14. Imaging through scattering microfluidic channels by digital holography for information recovery in lab on chip.

    Bianco, V; Paturzo, M; Gennari, O; Finizio, A; Ferraro, P

    2013-10-07

    We tackle the problem of information recovery and imaging through scattering microfluidic chips by means of digital holography (DH). In many cases the chip can become opalescent due to residual deposits settling down the inner channel faces, biofilm formation, scattering particle uptake by the channel cladding or its damaging by corrosive substances, or even by condensing effect on the exterior channels walls. In these cases white-light imaging is severely degraded and no information is obtainable at all about the flowing samples. Here we investigate the problem of counting and estimating velocity of cells flowing inside a scattering chip. Moreover we propose and test a method based on the recording of multiple digital holograms to retrieve improved phase-contrast images despite the strong scattering effect. This method helps, thanks to DH, to recover information which, otherwise, would be completely lost.

  15. Fluorimetric urease inhibition assay on a multilayer microfluidic chip with immunoaffinity immobilized enzyme reactors.

    Zhang, Qin; Tang, Xiuwen; Hou, Fenghua; Yang, Jianping; Xie, Zhiyong; Cheng, Zhiyi

    2013-10-01

    We fabricated a three-layer polydimethylsiloxane (PDMS)-based microfluidic chip for realizing urease inhibition assay with sensitive fluorescence detection. Procedures such as sample prehandling, enzyme reaction, reagent mixing, fluorescence derivatization, and detection can be readily carried out. Urease reactors were prepared by adsorption of rabbit immunoglobulin G (IgG) and immunoreaction with urease-conjugated goat anti-rabbit IgG. Acetohydroxamic acid (AHA) as a competitive inhibitor of urease was tested on the chip. Microfluidically generated gradient concentrations of AHA with substrate (urea) were loaded into urease reactors. After incubation, the produced ammonia was transported out of reactors and then reacted with o-phthalaldehyde (OPA) to generate fluorescent products. Urease inhibition was indicated by a decrease in fluorescence signal detected by microplate reader. The IC50 value of AHA was determined and showed good agreement with that obtained in microplate. The presented device combines several steps of the analytical process with advantages of low reagent consumption, reduced analysis time, and ease of manipulation. This microfluidic approach can be extended to the screening of inhibitory compounds in drug discovery. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Moving-part-free microfluidic systems for lab-on-a-chip

    Luo, J K; Fu, Y Q; Du, X Y; Flewitt, A J; Milne, W I; Li, Y; Walton, A J

    2009-01-01

    Microfluidic systems are part of an emerging technology which deals with minute amounts of liquids (biological samples and reagents) on a small scale. They are fast, compact and can be made into a highly integrated system to deliver sample purification, separation, reaction, immobilization, labelling, as well as detection, thus are promising for applications such as lab-on-a-chip and handheld healthcare devices. Miniaturized micropumps typically consist of a moving-part component, such as a membrane structure, to deliver liquids, and are often unreliable, complicated in structure and difficult to be integrated with other control electronics circuits. The trend of new-generation micropumps is moving-part-free micropumps operated by advanced techniques, such as electrokinetic force, surface tension/energy, acoustic waves. This paper reviews the development and advances of relevant technologies, and introduces electrowetting-on-dielectrics and acoustic wave-based microfluidics. The programmable electrowetting micropump has been realized to dispense and manipulate droplets in 2D with up to 1000 addressable electrodes and electronics built underneath. The acoustic wave-based microfluidics can be used not only for pumping, mixing and droplet generation but also for biosensors, suitable for single-mechanism-based lab-on-a-chip applications

  17. A single-walled carbon nanotube thin film-based pH-sensing microfluidic chip.

    Li, Cheng Ai; Han, Kwi Nam; Pham, Xuan-Hung; Seong, Gi Hun

    2014-04-21

    A novel microfluidic pH-sensing chip was developed based on pH-sensitive single-walled carbon nanotubes (SWCNTs). In this study, the SWCNT thin film acted both as an electrode and a pH-sensitive membrane. The potentiometric pH response was observed by electronic structure changes in the semiconducting SWCNTs in response to the pH level. In a microfluidic chip consisting of a SWCNT pH-sensing working electrode and an Ag/AgCl reference electrode, the calibration plot exhibited promising pH-sensing performance with an ideal Nernstian response of 59.71 mV pH(-1) between pH 3 and 11 (standard deviation of the sensitivity is 1.5 mV pH(-1), R(2) = 0.985). Moreover, the SWCNT electrode in the microfluidic device showed no significant variation at any pH value in the range of the flow rate between 0.1 and 15 μl min(-1). The selectivity coefficients of the SWCNT electrode revealed good selectivity against common interfering ions.

  18. Fast Prototyping of Sensorized Cell Culture Chips and Microfluidic Systems with Ultrashort Laser Pulses

    Sebastian M. Bonk

    2015-03-01

    Full Text Available We developed a confined microfluidic cell culture system with a bottom plate made of a microscopic slide with planar platinum sensors for the measurement of acidification, oxygen consumption, and cell adhesion. The slides were commercial slides with indium tin oxide (ITO plating or were prepared from platinum sputtering (100 nm onto a 10-nm titanium adhesion layer. Direct processing of the sensor structures (approximately three minutes per chip by an ultrashort pulse laser facilitated the production of the prototypes. pH-sensitive areas were produced by the sputtering of 60-nm Si3N4 through a simple mask made from a circuit board material. The system body and polydimethylsiloxane (PDMS molding forms for the microfluidic structures were manufactured by micromilling using a printed circuit board (PCB milling machine for circuit boards. The microfluidic structure was finally imprinted in PDMS. Our approach avoided the use of photolithographic techniques and enabled fast and cost-efficient prototyping of the systems. Alternatively, the direct production of metallic, ceramic or polymeric molding tools was tested. The use of ultrashort pulse lasers improved the precision of the structures and avoided any contact of the final structures with toxic chemicals and possible adverse effects for the cell culture in lab-on-a-chip systems.

  19. Immuno-capture and in situ detection of Salmonella typhimurium on a novel microfluidic chip

    Wang, Renjie, E-mail: 1058464972@qq.com [College of Chemistry and Chemical Engineering, Chongqing University, No. 174, St. Shazheng, Shapingba District, Chongqing (China); Ni, Yanan, E-mail: 468885029@qq.com [College of Chemistry and Chemical Engineering, Chongqing University, No. 174, St. Shazheng, Shapingba District, Chongqing (China); Xu, Yi, E-mail: xuyibbd@sina.com [College of Chemistry and Chemical Engineering, Chongqing University, No. 174, St. Shazheng, Shapingba District, Chongqing (China); National Center for International Research of Micro/Nano-System and New Material Technology, No. 174, St. Shazhengjie, Shapingba District, Chongqing (China); Key Laboratory of Fundamental Science of Micro/Nano-Device and System Technology for National Defense, Chongqing (China); Jiang, Yan, E-mail: 919865356@qq.com [College of Chemistry and Chemical Engineering, Chongqing University, No. 174, St. Shazheng, Shapingba District, Chongqing (China); Dong, Chunyan, E-mail: 774176325@qq.com [College of Chemistry and Chemical Engineering, Chongqing University, No. 174, St. Shazheng, Shapingba District, Chongqing (China); Chuan, Na, E-mail: 814859441@qq.com [College of Chemistry and Chemical Engineering, Chongqing University, No. 174, St. Shazheng, Shapingba District, Chongqing (China)

    2015-01-01

    Highlights: • A novel microfluidic chip and a LIF microsystem were designed and fabricated. • Salmonella typhimurium was captured and labeled by specific immuno-capture on chip. • CdSe/ZnS quantum dots-labeled bacteria were detected by in situ analysis using LIF microsystem. • The proposed method has potential application in practice. - Abstract: The new method presented in this article achieved the goal of capturing Salmonella typhimurium via immunoreaction and rapid in situ detection of the CdSe/ZnS quantum dots (QDs) labeled S. typhimurium by self-assembly light-emitting diode-induced fluorescence detection (LIF) microsystem on a specially designed multichannel microfluidic chip. CdSe/ZnS QDs were used as fluorescent markers improving detection sensitivity. The microfluidic chip developed in this study was composed of 12 sample channels, 3 mixing zones, and 6 immune reaction zones, which also acted as fluorescence detection zones. QDs–IgG–primary antibody complexes were generated by mixing CdSe/ZnS QDs conjugated secondary antibody (QDs–IgG) and S. typhimurium antibody (primary antibody) in mixing zones. Then, the complexes went into immune reaction zones to label previously captured S. typhimurium in the sandwich mode. The capture rate of S. typhimurium in each detection zone was up to 70%. The enriched QDs-labeled S. typhimurium was detected using a self-assembly LIF microsystem. A good linear relationship was obtained in the range from 3.7 × 10 to 3.7 × 10{sup 5} cfu mL{sup −1} using the equation I = 0.1739 log (C) − 0.1889 with R{sup 2} = 0.9907, and the detection limit was down to 37 cfu mL{sup −1}. The proposed method of online immunolabeling with QDs for in situ fluorescence detection on the designed multichannel microfluidic chip had been successfully used to detect S. typhimurium in pork sample, and it has shown potential advantages in practice.

  20. Ultrasensitive microfluidic solid-phase ELISA using an actuatable microwell-patterned PDMS chip.

    Wang, Tanyu; Zhang, Mohan; Dreher, Dakota D; Zeng, Yong

    2013-11-07

    Quantitative detection of low abundance proteins is of significant interest for biological and clinical applications. Here we report an integrated microfluidic solid-phase ELISA platform for rapid and ultrasensitive detection of proteins with a wide dynamic range. Compared to the existing microfluidic devices that perform affinity capture and enzyme-based optical detection in a constant channel volume, the key novelty of our design is two-fold. First, our system integrates a microwell-patterned assay chamber that can be pneumatically actuated to significantly reduce the volume of chemifluorescent reaction, markedly improving the sensitivity and speed of ELISA. Second, monolithic integration of on-chip pumps and the actuatable assay chamber allow programmable fluid delivery and effective mixing for rapid and sensitive immunoassays. Ultrasensitive microfluidic ELISA was demonstrated for insulin-like growth factor 1 receptor (IGF-1R) across at least five orders of magnitude with an extremely low detection limit of 21.8 aM. The microwell-based solid-phase ELISA strategy provides an expandable platform for developing the next-generation microfluidic immunoassay systems that integrate and automate digital and analog measurements to further improve the sensitivity, dynamic ranges, and reproducibility of proteomic analysis.

  1. Microfluidic Fabrication of Morphology-Controlled Polymeric Microspheres of Blends of Poly(4-butyltriphenylamine and Poly(methyl methacrylate

    Saki Yoshida

    2018-04-01

    Full Text Available Multicomponent polymer particles with specific morphology are promising materials exhibiting novel functionality which cannot be obtained with single-component polymer particles. Particularly, the preparation of such kinds of polymer particles involving electrically or optically active conjugated polymers with uniform size is a challenging subject due to their intense demands. Here, microspheres of binary polymer blend consisting of poly(4-butyltriphenylamine (PBTPA/poly(methyl methacrylate (PMMA (1:1 in weight were produced via a microfluidic emulsification with a Y-shaped microreactor, and a subsequent solvent evaporation method. The flow rate of the dispersed phase (polymer solution was fixed to 7 µL/min, and 140 or 700 µL/min of the flow rate of the continuous phase (aqueous 0.6 wt % of poly(vinyl alcohol (PVA solution was utilized to produce the dispersion with different diameter. The concentration of dispersed phase was adjusted to 0.1 or 1.0 w/v%. Core-shell, Janus and dumbbell type microspheres were obtained dependent on the flow rate of continuous phase. Incomplete core-shell type microspheres were produced for the blend involving low molecular weight PMMA. Complex Janus and core-shell type microspheres were fabricated by the addition of sodium dodecyl sulfate (SDS to continuous phase. It is found that final morphologies are strongly dependent on the initial conditions of dispersion including the particle size suggesting that the morphologies are governed by the kinetical factors together with the conventionally accepted thermodynamic ones.

  2. Microfluidic Organ/Body-on-a-Chip Devices at the Convergence of Biology and Microengineering

    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.

  3. Microfluidic Organ/Body-on-a-Chip Devices at the Convergence of Biology and Microengineering

    Perestrelo, Ana Rubina; Águas, Ana C. P.; Rainer, Alberto; Forte, Giancarlo

    2015-01-01

    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. PMID:26690442

  4. Multiple and high-throughput droplet reactions via combination of microsampling technique and microfluidic chip

    Wu, Jinbo

    2012-11-20

    Microdroplets offer unique compartments for accommodating a large number of chemical and biological reactions in tiny volume with precise control. A major concern in droplet-based microfluidics is the difficulty to address droplets individually and achieve high throughput at the same time. Here, we have combined an improved cartridge sampling technique with a microfluidic chip to perform droplet screenings and aggressive reaction with minimal (nanoliter-scale) reagent consumption. The droplet composition, distance, volume (nanoliter to subnanoliter scale), number, and sequence could be precisely and digitally programmed through the improved sampling technique, while sample evaporation and cross-contamination are effectively eliminated. Our combined device provides a simple model to utilize multiple droplets for various reactions with low reagent consumption and high throughput. © 2012 American Chemical Society.

  5. Tunable-angle wedge transducer for improved acoustophoretic control in a microfluidic chip

    Iranmanesh, I.; Barnkob, Rune; Bruus, Henrik

    2012-01-01

    We present a tunable-angle wedge ultrasound transducer for improved control of microparticle acoustophoresis in a microfluidic chip. The transducer is investigated by analyzing the pattern of aligned particles and induced acoustic energy density while varying the system geometry, transducer...... in geometry and that the coupling angle may be used as an additional tuning parameter for improved acoustophoretic control with single-frequency actuation. Further, we find that frequency-modulation actuation is suitable for diminishing such tuning effects and that it is a robust method to produce uniform...... coupling angle, and transducer actuation method (single-frequency actuation or frequency-modulation actuation). The energy-density analysis is based on measuring the transmitted light intensity through a microfluidic channel filled with a suspension of 5-μm-diameter beads and the results with the tunable-angle...

  6. Tunable-angle wedge transducer for improved acoustophoretic control in a microfluidic chip

    Iranmanesh, I.; Barnkob, Rune; Bruus, Henrik

    2013-01-01

    We present a tunable-angle wedge ultrasound transducer for improved control of microparticle acoustophoresis in a microfluidic chip. The transducer is investigated by analyzing the pattern of aligned particles and induced acoustic energy density while varying the transducer geometry, transducer...... change in geometry and that the coupling angle may be used as an additional tuning parameter for improved acoustophoretic control with single-frequency actuation. Further, we find that frequency-modulation actuation is suitable for diminishing such tuning effects and that it is a robust method to produce...... coupling angle, and transducer actuation method (single-frequency actuation or frequency-modulation actuation). The energy-density analysis is based on measuring the transmitted light intensity through a microfluidic channel filled with a suspension of 5 µm diameter beads and the results with the tunable-angle...

  7. Polydimethylsiloxane-integratable micropressure sensor for microfluidic chips

    Wang, Limu

    2009-09-17

    A novel microfluidicpressuresensor which can be fully integrated into polydimethylsiloxane(PDMS) is reported. The sensor produces electrical signals directly. We integrated PDMS-based conductive composites into a 30 μm thick membrane and bonded it to the microchannel side wall. The response time of the sensor is approximately 100 ms and can work within a pressure range as wide as 0–100 kPa. The resolution of this micropressure sensor is generally 0.1 kPa but can be increased to 0.01 kPa at high pressures as a result of the quadratic relationship between resistance and pressure. The PDMS-based nature of the sensor ensures its perfect bonding with PDMS chips, and the standard photolithographic process of the sensor allows one-time fabrication of three dimensional structures or even microsensor arrays. The theoretical calculations are in good agreement with experimental observations.

  8. Miniature interferometer for refractive index measurement in microfluidic chip

    Chen, Minghui; Geiser, Martial; Truffer, Frederic; Song, Chengli

    2012-12-01

    The design and development of the miniaturized interferometer for measurement of the refractive index or concentration of sub-microliter volume aqueous solution in microfludic chip is presented. It is manifested by a successful measurement of the refractive index of sugar-water solution, by utilizing a laser diode for light source and the small robust instrumentation for practical implementation. Theoretically, the measurement principle and the feasibility of the system are analyzed. Experimental device is constructed with a diode laser, lens, two optical plate and a complementary metal oxide semiconductor (CMOS). Through measuring the positional changes of the interference fringes, the refractive index change are retrieved. A refractive index change of 10-4 is inferred from the measured image data. The entire system is approximately the size of half and a deck of cards and can operate on battery power for long time.

  9. Polydimethylsiloxane-integratable micropressure sensor for microfluidic chips

    Wang, Limu; Zhang, Mengying; Yang, Min; Zhu, Weiming; Wu, Jinbo; Gong, Xiuqing; Wen, Weijia

    2009-01-01

    A novel microfluidicpressuresensor which can be fully integrated into polydimethylsiloxane(PDMS) is reported. The sensor produces electrical signals directly. We integrated PDMS-based conductive composites into a 30 μm thick membrane and bonded it to the microchannel side wall. The response time of the sensor is approximately 100 ms and can work within a pressure range as wide as 0–100 kPa. The resolution of this micropressure sensor is generally 0.1 kPa but can be increased to 0.01 kPa at high pressures as a result of the quadratic relationship between resistance and pressure. The PDMS-based nature of the sensor ensures its perfect bonding with PDMS chips, and the standard photolithographic process of the sensor allows one-time fabrication of three dimensional structures or even microsensor arrays. The theoretical calculations are in good agreement with experimental observations.

  10. A one-step strategy for ultra-fast and low-cost mass production of plastic membrane microfluidic chips.

    Hu, Chong; Lin, Sheng; Li, Wanbo; Sun, Han; Chen, Yangfan; Chan, Chiu-Wing; Leung, Chung-Hang; Ma, Dik-Lung; Wu, Hongkai; Ren, Kangning

    2016-10-05

    An ultra-fast, extremely cost-effective, and environmentally friendly method was developed for fabricating flexible microfluidic chips with plastic membranes. With this method, we could fabricate plastic microfluidic chips rapidly (within 12 seconds per piece) at an extremely low cost (less than $0.02 per piece). We used a heated perfluoropolymer perfluoroalkoxy (often called Teflon PFA) solid stamp to press a pile of two pieces of plastic membranes, low density polyethylene (LDPE) and polyethylene terephthalate (PET) coated with an ethylene-vinyl acetate copolymer (EVA). During the short period of contact with the heated PFA stamp, the pressed area of the membranes permanently bonded, while the LDPE membrane spontaneously rose up at the area not pressed, forming microchannels automatically. These two regions were clearly distinguishable even at the micrometer scale so we were able to fabricate microchannels with widths down to 50 microns. This method combines the two steps in the conventional strategy for microchannel fabrication, generating microchannels and sealing channels, into a single step. The production is a green process without using any solvent or generating any waste. Also, the chips showed good resistance against the absorption of Rhodamine 6G, oligonucleotides, and green fluorescent protein (GFP). We demonstrated some typical microfluidic manipulations with the flexible plastic membrane chips, including droplet formation, on-chip capillary electrophoresis, and peristaltic pumping for quantitative injection of samples and reagents. In addition, we demonstrated convenient on-chip detection of lead ions in water samples by a peristaltic-pumping design, as an example of the application of the plastic membrane chips in a resource-limited environment. Due to the high speed and low cost of the fabrication process, this single-step method will facilitate the mass production of microfluidic chips and commercialization of microfluidic technologies.

  11. Invited Article: Terahertz microfluidic chips sensitivity-enhanced with a few arrays of meta-atoms

    Serita, Kazunori; Matsuda, Eiki; Okada, Kosuke; Murakami, Hironaru; Kawayama, Iwao; Tonouchi, Masayoshi

    2018-05-01

    We present a nonlinear optical crystal (NLOC)-based terahertz (THz) microfluidic chip with a few arrays of split ring resonators (SRRs) for ultra-trace and quantitative measurements of liquid solutions. The proposed chip operates on the basis of near-field coupling between the SRRs and a local emission of point like THz source that is generated in the process of optical rectification in NLOCs on a sub-wavelength scale. The liquid solutions flowing inside the microchannel modify the resonance frequency and peak attenuation in the THz transmission spectra. In contrast to conventional bio-sensing with far/near-field THz waves, our technique can be expected to compactify the chip design as well as realize high sensitive near-field measurement of liquid solutions without any high-power optical/THz source, near-field probes, and prisms. Using this chip, we have succeeded in observing the 31.8 fmol of ion concentration in actual amount of 318 pl water solutions from the shift of the resonance frequency. The technique opens the door to microanalysis of biological samples with THz waves and accelerates development of THz lab-on-chip devices.

  12. Invited Article: Terahertz microfluidic chips sensitivity-enhanced with a few arrays of meta-atoms

    Kazunori Serita

    2018-05-01

    Full Text Available We present a nonlinear optical crystal (NLOC-based terahertz (THz microfluidic chip with a few arrays of split ring resonators (SRRs for ultra-trace and quantitative measurements of liquid solutions. The proposed chip operates on the basis of near-field coupling between the SRRs and a local emission of point like THz source that is generated in the process of optical rectification in NLOCs on a sub-wavelength scale. The liquid solutions flowing inside the microchannel modify the resonance frequency and peak attenuation in the THz transmission spectra. In contrast to conventional bio-sensing with far/near-field THz waves, our technique can be expected to compactify the chip design as well as realize high sensitive near-field measurement of liquid solutions without any high-power optical/THz source, near-field probes, and prisms. Using this chip, we have succeeded in observing the 31.8 fmol of ion concentration in actual amount of 318 pl water solutions from the shift of the resonance frequency. The technique opens the door to microanalysis of biological samples with THz waves and accelerates development of THz lab-on-chip devices.

  13. Determination of Apparent Amylose Content in Rice by Using Paper-Based Microfluidic Chips.

    Hu, Xianqiao; Lu, Lin; Fang, Changyun; Duan, Binwu; Zhu, Zhiwei

    2015-11-11

    Determination of apparent amylose content in rice is a key function for rice research and the rice industry. In this paper, a novel approach with paper-based microfluidic chip is reported to determine apparent amylose content in rice. The conventional color reaction between amylose and iodine was employed. Blue color of amylose-iodine complex generated on-chip was converted to gray and measured with Photoshop after the colored chip was scanned. The method for preparation of the paper chip is described. In situ generation of iodine for on-chip color reaction was designed, and factors influencing color reaction were investigated in detail. Elimination of yellow color interference of excess iodine by exploiting color removal function of Photoshop was presented. Under the optimized conditions, apparent amylose content in rice ranging from 1.5 to 26.4% can be determined, and precision was 6.3%. The analytical results obtained with the developed approach were in good agreement with those with the continuous flow analyzer method.

  14. A Novel Electrochemical Microfluidic Chip Combined with Multiple Biomarkers for Early Diagnosis of Gastric Cancer

    Xie, Yao; Zhi, Xiao; Su, Haichuan; Wang, Kan; Yan, Zhen; He, Nongyue; Zhang, Jingpu; Chen, Di; Cui, Daxiang

    2015-12-01

    Early diagnosis is very important to improve the survival rate of patients with gastric cancer and to understand the biology of cancer. In order to meet the clinical demands for early diagnosis of gastric cancer, we developed a disposable easy-to-use electrochemical microfluidic chip combined with multiple antibodies against six kinds of biomarkers (carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), Helicobacter pylori CagA protein (H.P.), P53oncoprotein (P53), pepsinogen I (PG I), and PG-II). The six kinds of biomarkers related to gastric cancer can be detected sensitively and synchronously in a short time. The specially designed three electrodes system enables cross-contamination to be avoided effectively. The linear ranges of detection of the electrochemical microfluidic chip were as follows: 0.37-90 ng mL-1 for CEA, 10.75-172 U mL-1 for CA19-9, 10-160 U L-1 for H.P., 35-560 ng mL-1 for P53, 37.5-600 ng mL-1 for PG I, and 2.5-80 ng mL-1for PG II. This method owns better sensitivity compared with enzyme-linked immunosorbent assay (ELISA) results of 394 specimens of gastric cancer sera. Furthermore, we established a multi-index prediction model based on the six kinds of biomarkers for predicting risk of gastric cancer. In conclusion, the electrochemical microfluidic chip for detecting multiple biomarkers has great potential in applications such as early screening of gastric cancer patients, and therapeutic evaluation, and real-time dynamic monitoring the progress of gastric cancer in near future.

  15. High-throughput particle manipulation by hydrodynamic, electrokinetic, and dielectrophoretic effects in an integrated microfluidic chip

    Li, Shunbo; Li, Ming; Bougot-Robin, Kristelle; Cao, Wenbin; Yeung Yeung Chau, Irene; Li, Weihua; Wen, Weijia

    2013-01-01

    Integrating different steps on a chip for cell manipulations and sample preparation is of foremost importance to fully take advantage of microfluidic possibilities, and therefore make tests faster, cheaper and more accurate. We demonstrated particle manipulation in an integrated microfluidic device by applying hydrodynamic, electroosmotic (EO), electrophoretic (EP), and dielectrophoretic (DEP) forces. The process involves generation of fluid flow by pressure difference, particle trapping by DEP force, and particle redirect by EO and EP forces. Both DC and AC signals were applied, taking advantages of DC EP, EO and AC DEP for on-chip particle manipulation. Since different types of particles respond differently to these signals, variations of DC and AC signals are capable to handle complex and highly variable colloidal and biological samples. The proposed technique can operate in a high-throughput manner with thirteen independent channels in radial directions for enrichment and separation in microfluidic chip. We evaluated our approach by collecting Polystyrene particles, yeast cells, and E. coli bacteria, which respond differently to electric field gradient. Live and dead yeast cells were separated successfully, validating the capability of our device to separate highly similar cells. Our results showed that this technique could achieve fast pre-concentration of colloidal particles and cells and separation of cells depending on their vitality. Hydrodynamic, DC electrophoretic and DC electroosmotic forces were used together instead of syringe pump to achieve sufficient fluid flow and particle mobility for particle trapping and sorting. By eliminating bulky mechanical pumps, this new technique has wide applications for in situ detection and analysis.

  16. High-throughput particle manipulation by hydrodynamic, electrokinetic, and dielectrophoretic effects in an integrated microfluidic chip

    Li, Shunbo

    2013-03-20

    Integrating different steps on a chip for cell manipulations and sample preparation is of foremost importance to fully take advantage of microfluidic possibilities, and therefore make tests faster, cheaper and more accurate. We demonstrated particle manipulation in an integrated microfluidic device by applying hydrodynamic, electroosmotic (EO), electrophoretic (EP), and dielectrophoretic (DEP) forces. The process involves generation of fluid flow by pressure difference, particle trapping by DEP force, and particle redirect by EO and EP forces. Both DC and AC signals were applied, taking advantages of DC EP, EO and AC DEP for on-chip particle manipulation. Since different types of particles respond differently to these signals, variations of DC and AC signals are capable to handle complex and highly variable colloidal and biological samples. The proposed technique can operate in a high-throughput manner with thirteen independent channels in radial directions for enrichment and separation in microfluidic chip. We evaluated our approach by collecting Polystyrene particles, yeast cells, and E. coli bacteria, which respond differently to electric field gradient. Live and dead yeast cells were separated successfully, validating the capability of our device to separate highly similar cells. Our results showed that this technique could achieve fast pre-concentration of colloidal particles and cells and separation of cells depending on their vitality. Hydrodynamic, DC electrophoretic and DC electroosmotic forces were used together instead of syringe pump to achieve sufficient fluid flow and particle mobility for particle trapping and sorting. By eliminating bulky mechanical pumps, this new technique has wide applications for in situ detection and analysis.

  17. Numerical study on fabricating rectangle microchannel in microfluidic chips by glass molding process

    Wang, Tao; Chen, Jing; Zhou, Tianfeng

    2017-09-01

    This paper studied the glass molding process (GMP) for fabricating a typical microstructure of glass microfluidic chips, i. e., rectangle microchannel, on soda-lime glass by finite element method. More than 100 models were established on the platform of Abaqus/Standard. The influence of parameters, i. e., temperature, aspect ratio, side wall angle and friction coefficient on deformation were studied, and the predicted morphology of the molded microchannel were presented as well. The research could provide fundamental experience for optimizing GMP process in the future.

  18. Ion and electron beam assisted fabrication of nanostructures integrated in microfluidic chips

    Evstrapov, A.A.; Mukhin, I.S.; Bukatin, A.S.; Kukhtevich, I.V.

    2012-01-01

    In present work we have designed and fabricated microfluidic chips (MFC) with integrated nets of nanochannels and whisker nanostructures in microchannels for investigation of biological samples in their native environment. We have designed a number of MFC topologies: (a) hydrodynamic traps with nanoscale channels which link microchannels; (b) a structure with regular vertical nanorod (nanowhisker) array, which could be used as a sensitive element. These topologies were created by means of ion and electron beam assisted techniques. These MFCs allow to investigate biological objects by means of high resolution microscopy. Fabricated MFCs were investigated with emulator of biological objects in different buffer solutions.

  19. On-chip gradient generation in 256 microfluidic cell cultures: simulation and experimental validation.

    Somaweera, Himali; Haputhanthri, Shehan O; Ibraguimov, Akif; Pappas, Dimitri

    2015-08-07

    A microfluidic diffusion diluter was used to create a stable concentration gradient for dose response studies. The microfluidic diffusion diluter used in this study consisted of 128 culture chambers on each side of the main fluidic channel. A calibration method was used to find unknown concentrations with 12% error. Flow rate dependent studies showed that changing the flow rates generated different gradient patterns. Mathematical simulations using COMSOL Multi-physics were performed to validate the experimental data. The experimental data obtained for the flow rate studies agreed with the simulation results. Cells could be loaded into culture chambers using vacuum actuation and cultured for long times under low shear stress. Decreasing the size of the culture chambers resulted in faster gradient formation (20 min). Mass transport into the side channels of the microfluidic diffusion diluter used in this study is an important factor in creating the gradient using diffusional mixing as a function of the distance. To demonstrate the device's utility, an H2O2 gradient was generated while culturing Ramos cells. Cell viability was assayed in the 256 culture chambers, each at a discrete H2O2 concentration. As expected, the cell viability for the high concentration side channels increased (by injecting H2O2) whereas the cell viability in the low concentration side channels decreased along the chip due to diffusional mixing as a function of distance. COMSOL simulations were used to identify the effective concentration of H2O2 for cell viability in each side chamber at 45 min. The gradient effects were confirmed using traditional H2O2 culture experiments. Viability of cells in the microfluidic device under gradient conditions showed a linear relationship with the viability of the traditional culture experiment. Development of the microfluidic device used in this study could be used to study hundreds of concentrations of a compound in a single experiment.

  20. Metaphase FISH on a Chip: Miniaturized Microfluidic Device for Fluorescence in situ Hybridization

    Vedarethinam, Indumathi; Shah, Pranjul Jaykumar; Dimaki, Maria

    2010-01-01

    -FISH, the process continues to be a manual, labour intensive, expensive and time consuming technique, often taking over 3-5 days, even in dedicated labs. We have developed a novel microFISH device to perform metaphase FISH on a chip which overcomes many shortcomings of the current laboratory protocols. This work...... also introduces a novel splashing device for preparing metaphase spreads on a microscope glass slide, followed by a rapid adhesive tape-based bonding protocol leading to rapid fabrication of the microFISH device. The microFISH device allows for an optimized metaphase FISH protocol on a chip with over...... a 20-fold reduction in the reagent volume. This is the first demonstration of metaphase FISH on a microfluidic device and offers a possibility of automation and significant cost reduction of many routine diagnostic tests of genetic anomalies....

  1. Implementation of Microfluidic Chip Electrophoresis for the Detection of B-cell Clonality

    Vazan M

    2016-04-01

    Full Text Available Introduction: A clonal population of B-cells is defined as those cells arising from the mitotic division of a single somatic cell with the same rearrangement of immunoglobulin genes. This gives rise to DNA markers for each individual lymphoid cell and its progenies and enables us to study clonality in different B-cell malignancies using multiplex polymerase chain reaction - PCR. The BIOMED-2 protocol has been implemented for clonality detection in lymphoproliferative diseases and exploits multiplex PCR reaction, subsequently analyzed by heteroduplex analysis (HDA using polyacrylamide gel electrophoresis (PAGE. With the advent of miniaturization and automation of molecular biology methods, lab-on-chip technologies were developed and replace partially the conventional approaches. We tested device for microfluidic chip, which is used for B-cells clonality analysis, using a PCR reaction for three subregions called frameworks (FR of the immunoglobulin heavy locus (IGH gene.

  2. Microfluidic Devices for Terahertz Spectroscopy of Live Cells Toward Lab-on-a-Chip Applications

    Qi Tang

    2016-04-01

    Full Text Available THz spectroscopy is an emerging technique for studying the dynamics and interactions of cells and biomolecules, but many practical challenges still remain in experimental studies. We present a prototype of simple and inexpensive cell-trapping microfluidic chip for THz spectroscopic study of live cells. Cells are transported, trapped and concentrated into the THz exposure region by applying an AC bias signal while the chip maintains a steady temperature at 37 °C by resistive heating. We conduct some preliminary experiments on E. coli and T-cell solution and compare the transmission spectra of empty channels, channels filled with aqueous media only, and channels filled with aqueous media with un-concentrated and concentrated cells.

  3. Microfluidic Arrayed Lab-On-A-Chip for Electrochemical Capacitive Detection of DNA Hybridization Events.

    Ben-Yoav, Hadar; Dykstra, Peter H; Bentley, William E; Ghodssi, Reza

    2017-01-01

    A microfluidic electrochemical lab-on-a-chip (LOC) device for DNA hybridization detection has been developed. The device comprises a 3 × 3 array of microelectrodes integrated with a dual layer microfluidic valved manipulation system that provides controlled and automated capabilities for high throughput analysis of microliter volume samples. The surface of the microelectrodes is functionalized with single-stranded DNA (ssDNA) probes which enable specific detection of complementary ssDNA targets. These targets are detected by a capacitive technique which measures dielectric variation at the microelectrode-electrolyte interface due to DNA hybridization events. A quantitative analysis of the hybridization events is carried out based on a sensing modeling that includes detailed analysis of energy storage and dissipation components. By calculating these components during hybridization events the device is able to demonstrate specific and dose response sensing characteristics. The developed microfluidic LOC for DNA hybridization detection offers a technology for real-time and label-free assessment of genetic markers outside of laboratory settings, such as at the point-of-care or in-field environmental monitoring.

  4. Isolation of cells for selective treatment and analysis using a magnetic microfluidic chip

    Yassine, Omar

    2014-05-01

    This study describes the development and testing of a magnetic microfluidic chip (MMC) for trapping and isolating cells tagged with superparamagnetic beads (SPBs) in a microfluidic environment for selective treatment and analysis. The trapping and isolation are done in two separate steps; first, the trapping of the tagged cells in a main channel is achieved by soft ferromagnetic disks and second, the transportation of the cells into side chambers for isolation is executed by tapered conductive paths made of Gold (Au). Numerical simulations were performed to analyze the magnetic flux and force distributions of the disks and conducting paths, for trapping and transporting SPBs. The MMC was fabricated using standard microfabrication processes. Experiments were performed with E. coli (K12 strand) tagged with 2.8 μm SPBs. The results showed that E. coli can be separated from a sample solution by trapping them at the disk sites, and then isolated into chambers by transporting them along the tapered conducting paths. Once the E. coli was trapped inside the side chambers, two selective treatments were performed. In one chamber, a solution with minimal nutrition content was added and, in another chamber, a solution with essential nutrition was added. The results showed that the growth of bacteria cultured in the second chamber containing nutrient was significantly higher, demonstrating that the E. coli was not affected by the magnetically driven transportation and the feasibility of performing different treatments on selectively isolated cells on a single microfluidic platform.

  5. Ultrasmall volume molecular isothermal amplification in microfluidic chip with advanced surface processing

    Huang Guoliang; Yang Xiaoyong; Ma Li; Yang Xu

    2011-01-01

    In this paper, we developed a metal micro-fluidic chip with advanced surface processing for ultra-small volume molecular isothermal amplification. This method takes advantages of the nucleic acid amplification with good stability and consistency, high sensitivity about 31 genomic DNA copies and bacteria specific gene identification. Based on the advanced surface processing, the bioreaction assays of nucleic acid amplification was dropped about 392nl in volume. A high numerical aperture confocal optical detection system was advanced to sensitively monitor the DNA amplification with low noise and high power collecting fluorescence near to the optical diffraction limit. A speedy nucleic acid isothermal amplification was performed in the ultra-small volume microfluidic chip, where the time at the inflexions of second derivative to DNA exponential amplified curves was brought forward and the sensitivity was improved about 65 folds to that of in current 25μl Ep-tube amplified reaction, which indicates a promising clinic molecular diagnostics in the droplet amplification.

  6. Study on Improving Thickness Uniformity of Microfluidic Chip Mold in the Electroforming Process

    Liqun Du

    2016-01-01

    Full Text Available Electroformed microfluidic chip mold faces the problem of uneven thickness, which decreases the dimensional accuracy of the mold, and increases the production cost. To fabricate a mold with uniform thickness, two methods are investigated. Firstly, experiments are carried out to study how the ultrasonic agitation affects the thickness uniformity of the mold. It is found that the thickness uniformity is maximally improved by about 30% after 2 h electroforming under 200 kHz and 500 W ultrasonic agitation. Secondly, adding a second cathode, a method suitable for long-time electroforming is studied by numerical simulation. The simulation results show that with a 4 mm width second cathode used, the thickness uniformity is improved by about 30% after 2 h of electroforming, and that with electroforming time extended, the thickness uniformity is improved more obviously. After 22 h electroforming, the thickness uniformity is increased by about 45%. Finally, by comparing two methods, the method of adding a second cathode is chosen, and a microfluidic chip mold is made with the help of a specially designed second cathode. The result shows that the thickness uniformity of the mold is increased by about 50%, which is in good agreement with the simulation results.

  7. Screening reactive oxygen species scavenging properties of platinum nanoparticles on a microfluidic chip.

    Zheng, Wenfu; Jiang, Bo; Hao, Yi; Zhao, Yuyun; Zhang, Wei; Jiang, Xingyu

    2014-09-12

    Hyperglycemia, hyperlipidemia and inflammation are key risk factors for atherosclerosis and can lead to overproduction of reactive oxygen species (ROS), which plays a critical role in vascular endothelial dysfunction and subsequent progress of atherosclerosis. However, there is currently a lack of effective drugs that deal with ROS. Platinum nanoparticles (Pt-NPs) have proven to be promising antioxidant drugs in vitro and in vivo. To optimize the efficacy of Pt-NP based drugs, we synthesized and characterized the ROS scavenging properties of three kinds of small molecules that capped Pt-NPs (Pt-AMP-NPs, Pt-ATT-NPs, Pt-MI-NPs) on a blood vessel-mimicking microfluidic chip. The Pt-NPs showed superior superoxide dismutase (SOD)-like functions and can scavenge ROS and recover compromised cell-cell junctions under hyperglycemic, hyperlipidemic and proinflammatory conditions. Amongst these NPs, Pt-AMP-NPs showed the most superior antioxidant properties, suggesting its potency to serve as a novel drug to treat vascular diseases such as atherosclerosis. Our microfluidic chip, providing physiological hemodynamic conditions for the experiments, is potentially a promising tool for a wide range of biological research on the vascular system.

  8. Prototyping of thermoplastic microfluidic chips and their application in high-performance liquid chromatography separations of small molecules.

    Wouters, Sam; De Vos, Jelle; Dores-Sousa, José Luís; Wouters, Bert; Desmet, Gert; Eeltink, Sebastiaan

    2017-11-10

    The present paper discusses practical aspects of prototyping of microfluidic chips using cyclic olefin copolymer as substrate and the application in high-performance liquid chromatography. The developed chips feature a 60mm long straight separation channel with circular cross section (500μm i.d.) that was created using a micromilling robot. To irreversibly seal the top and bottom chip substrates, a solvent-vapor-assisted bonding approach was optimized, allowing to approximate the ideal circular channel geometry. Four different approaches to establish the micro-to-macro interface were pursued. The average burst pressure of the microfluidic chips in combination with an encasing holder was established at 38MPa and the maximum burst pressure was 47MPa, which is believed to be the highest ever report for these polymer-based microfluidic chips. Porous polymer monolithic frits were synthesized in-situ via UV-initiated polymerization and their locations were spatially controlled by the application of a photomask. Next, high-pressure slurry packing was performed to introduce 3μm silica reversed-phase particles as the stationary phase in the separation channel. Finally, the application of the chip technology is demonstrated for the separation of alkyl phenones in gradient mode yielding baseline peak widths of 6s by applying a steep gradient of 1.8min at a flow rate of 10μL/min. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. A Microfluidic Chip Based on Localized Surface Plasmon Resonance for Real-Time Monitoring of Antigen-Antibody Reactions

    Hiep, Ha Minh; Nakayama, Tsuyoshi; Saito, Masato; Yamamura, Shohei; Takamura, Yuzuru; Tamiya, Eiichi

    2008-02-01

    Localized surface plasmon resonance (LSPR) connecting to noble metal nanoparticles is an important issue for many analytical and biological applications. Therefore, the development of microfluidic LSPR chip that allows studying biomolecular interactions becomes an essential requirement for micro total analysis systems (µTAS) integration. However, miniaturized process of the conventional surface plasmon resonance system has been faced with some limitations, especially with the usage of Kretschmann configuration in total internal reflection mode. In this study, we have tried to solve this problem by proposing a novel microfluidic LSPR chip operated with a simple collinear optical system. The poly(dimethylsiloxane) (PDMS) based microfluidic chip was fabricated by soft-lithography technique and enables to interrogate specific insulin and anti-insulin antibody reaction in real-time after immobilizing antibody on its surface. Moreover, the sensing ability of microfluidic LSPR chip was also evaluated with various glucose concentrations. The kinetic constant of insulin and anti-insulin antibody was determined and the detection limit of 100 ng/mL insulin was archived.

  10. Flow-orthogonal bead oscillation in a microfluidic chip with a magnetic anisotropic flux-guide array

    Van Pelt, Stijn; Derks, Roy; Matteucci, Marco

    2011-01-01

    A new concept for the manipulation of superparamagnetic beads inside a microfluidic chip is presented in this paper. The concept allows for bead actuation orthogonal to the flow direction inside a microchannel. Basic manipulation functionalities were studied by means of finite element simulations...

  11. From bioseparation to artificial micro-organs: microfluidic chip based particle manipulation techniques

    Stelzle, Martin

    2010-02-01

    Microfluidic device technology provides unique physical phenomena which are not available in the macroscopic world. These may be exploited towards a diverse array of applications in biotechnology and biomedicine ranging from bioseparation of particulate samples to the assembly of cells into structures that resemble the smallest functional unit of an organ. In this paper a general overview of chip-based particle manipulation and separation is given. In the state of the art electric, magnetic, optical and gravitational field effects are utilized. Also, mechanical obstacles often in combination with force fields and laminar flow are employed to achieve separation of particles or molecules. In addition, three applications based on dielectrophoretic forces for particle manipulation in microfluidic systems are discussed in more detail. Firstly, a virus assay is demonstrated. There, antibody-loaded microbeads are used to bind virus particles from a sample and subsequently are accumulated to form a pico-liter sized aggregate located at a predefined position in the chip thus enabling highly sensitive fluorescence detection. Secondly, subcellular fractionation of mitochondria from cell homogenate yields pure samples as was demonstrated by Western Blot and 2D PAGE analysis. Robust long-term operation with complex cell homogenate samples while avoiding electrode fouling is achieved by a set of dedicated technical means. Finally, a chip intended for the dielectrophoretic assembly of hepatocytes and endothelial cells into a structure resembling a liver sinusoid is presented. Such "artificial micro organs" are envisioned as substance screening test systems providing significantly higher predictability with respect to the in vivo response towards a substance under test.

  12. Characterizations of gas purge valves for liquid alignment and gas removal in a microfluidic chip

    Chuang, Han-Sheng; Thakur, Raviraj; Wereley, Steven T

    2012-01-01

    Two polydimethylsiloxane (PDMS) gas purge valves for excessive gas removal in general lab-on-a-chip applications are presented in this paper. Both valves are devised based on a three-layer configuration comprising a top layer for liquid channels, a membrane and a bottom layer for gas channels. The pneumatic valves work as a normal gateway for fluids when the membrane is bulged down (open state) by vacuum or pushed up (closed state) by pressure. In the closed state, the air in front of a liquid can be removed through a small notch or a permeable PDMS membrane by compressing the liquid. The purge valve with a small notch across its valve seat, termed surface-tension (ST) valve, can be operated with pressure under 11.5 kPa. The liquid is mainly retained by the surface tension resulting from the hydrophobic channel walls. In contrast, the purge valve with vacuum-filled grooves adjacent to a liquid channel, termed gas-permeation (GP) valve, can be operated at pressure above 5.5 kPa. Based on the principle of gas permeation, the excessive air can be slowly removed through the vent grooves. Detailed evaluations of both valves in a pneumatically driven microfluidic chip were conducted. Specifically, the purge valves enable users to remove gas and passively align liquids at desired locations without using sensing devices or feedback circuits. Finally, a rapid mixing reaction was successfully performed with the GP valves, showing their practicability as incorporated in a microfluidic chip. (paper)

  13. Nanophotonic lab-on-a-chip platforms including novel bimodal interferometers, microfluidics and grating couplers.

    Duval, Daphné; González-Guerrero, Ana Belén; Dante, Stefania; Osmond, Johann; Monge, Rosa; Fernández, Luis J; Zinoviev, Kirill E; Domínguez, Carlos; Lechuga, Laura M

    2012-05-08

    One of the main limitations for achieving truly lab-on-a-chip (LOC) devices for point-of-care diagnosis is the incorporation of the "on-chip" detection. Indeed, most of the state-of-the-art LOC devices usually require complex read-out instrumentation, losing the main advantages of portability and simplicity. In this context, we present our last advances towards the achievement of a portable and label-free LOC platform with highly sensitive "on-chip" detection by using nanophotonic biosensors. Bimodal waveguide interferometers fabricated by standard silicon processes have been integrated with sub-micronic grating couplers for efficient light in-coupling, showing a phase resolution of 6.6 × 10(-4)× 2π rad and a limit of detection of 3.3 × 10(-7) refractive index unit (RIU) in bulk. A 3D network of SU-8 polymer microfluidics monolithically assembled at the wafer-level was included, ensuring perfect sealing and compact packaging. To overcome some of the drawbacks inherent to interferometric read-outs, a novel all-optical wavelength modulation system has been implemented, providing a linear response and a direct read-out of the phase variation. Sensitivity, specificity and reproducibility of the wavelength modulated BiMW sensor has been demonstrated through the label-free immunodetection of the human hormone hTSH at picomolar level using a reliable biofunctionalization process.

  14. A simple method for preparation of macroporous polydimethylsiloxane membrane for microfluidic chip-based isoelectric focusing applications

    Ou Junjie [Department of Mechanical and Mechatronics Engineering, University of Waterloo, 200 University Ave West, Waterloo, Ontario, N2L 3G1 (Canada); Department of Chemistry, University of Waterloo, 200 University Ave West, Waterloo, Ontario, N2L 3G1 (Canada); Ren, Carolyn L., E-mail: c3ren@mecheng1.uwaterloo.ca [Department of Mechanical and Mechatronics Engineering, University of Waterloo, 200 University Ave West, Waterloo, Ontario, N2L 3G1 (Canada); Pawliszyn, Janusz [Department of Chemistry, University of Waterloo, 200 University Ave West, Waterloo, Ontario, N2L 3G1 (Canada)

    2010-03-10

    A new, simple method was reported to prepare PDMS membranes with micrometer size pores for microfluidic chip applications. The pores were formed by adding polystyrene and toluene into PDMS prepolymer solution prior to spin-coating and curing. The resulting PDMS membrane has a thickness of around 10 {mu}m and macropores with a diameter ranging from 1 to 2 {mu}m measured using scanning electron microscope (SEM) imaging. This PDMS membrane was validated by integrating it with PDMS microfluidic chips for protein separation using isoelectric focusing mechanism coupled with whole channel imaging detection (IEF-WCID). It has been shown that five standard pI markers and a mixture of two proteins, myoglobin and {beta}-lactoglobulin, can be separated using these chips. The results indicated that this macroporous PDMS membrane can replace the dialysis membrane in PDMS chips for the IEF-WCID technique. The preparation method of macroporous PDMS membrane may be potentially applied in other fields of microfluidic chips.

  15. Isotachophoresis of proteins in a networked microfluidic chip: experiment and 2-D simulation.

    Cui, Huanchun; Dutta, Prashanta; Ivory, Cornelius F

    2007-04-01

    This paper reports both the experimental application and 2-D simulation of ITP of proteins in a networked microfluidic chip. Experiments demonstrate that a mixture of three fluorescent proteins can be concentrated and stacked into adjacent zones of pure protein under a constant voltage of 100 V over a 2 cm long microchannel. Measurements of the isotachophoretic velocity of the moving zones demonstrates that, during ITP under a constant voltage, the zone velocity decreases as more of the channel is occupied by the terminating electrolyte. A 2-D ITP model based on the Nernst-Planck equations illustrates the stacking and separation features of ITP using simulations of three virtual proteins. The self-sharpening behavior of ITP zones dispersed by a T-junction is clearly demonstrated both by experiment and by simulation. Comparison of 2-D simulations of ITP and zone electrophoresis (ZE) confirms that ZE lacks the ability to resharpen protein zones after they pass through a T-junction.

  16. Microfluidic chips with multi-junctions: an advanced tool in recovering proteins from inclusion bodies.

    Yamaguchi, Hiroshi; Miyazaki, Masaya

    2015-01-01

    Active recombinant proteins are used for studying the biological functions of genes and for the development of therapeutic drugs. Overexpression of recombinant proteins in bacteria often results in the formation of inclusion bodies, which are protein aggregates with non-native conformations. Protein refolding is an important process for obtaining active recombinant proteins from inclusion bodies. However, the conventional refolding method of dialysis or dilution is time-consuming and recovered active protein yields are often low, and a cumbersome trial-and-error process is required to achieve success. To circumvent these difficulties, we used controllable diffusion through laminar flow in microchannels to regulate the denaturant concentration. This method largely aims at reducing protein aggregation during the refolding procedure. This Commentary introduces the principles of the protein refolding method using microfluidic chips and the advantage of our results as a tool for rapid and efficient recovery of active recombinant proteins from inclusion bodies.

  17. A piezo-ring-on-chip microfluidic device for simple and low-cost mass spectrometry interfacing.

    Tsao, Chia-Wen; Lei, I-Chao; Chen, Pi-Yu; Yang, Yu-Liang

    2018-02-12

    Mass spectrometry (MS) interfacing technology provides the means for incorporating microfluidic processing with post MS analysis. In this study, we propose a simple piezo-ring-on-chip microfluidic device for the controlled spraying of MALDI-MS targets. This device uses a low-cost, commercially-available ring-shaped piezoelectric acoustic atomizer (piezo-ring) directly integrated into a polydimethylsiloxane microfluidic device to spray the sample onto the MS target substrate. The piezo-ring-on-chip microfluidic device's design, fabrication, and actuation, and its pulsatile pumping effects were evaluated. The spraying performance was examined by depositing organic matrix samples onto the MS target substrate by using both an automatic linear motion motor, and manual deposition. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) was performed to analyze the peptide samples on the MALDI target substrates. Using our technique, model peptides with 10 -6 M concentration can be successfully detected. The results also indicate that the piezo-ring-on-chip approach forms finer matrix crystals and presents better MS signal uniformity with little sample consumption compared to the conventional pipetting method.

  18. A multiple biomarker assay for quality assessment of botanical drugs using a versatile microfluidic chip.

    Li, Zhen-Hao; Ai, Ni; Yu, Lawrence X; Qian, Zhong-Zhi; Cheng, Yi-Yu

    2017-09-25

    Quality control is critical for ensuring the safety and effectiveness of drugs. Current quality control method for botanical drugs is mainly based on chemical testing. However, chemical testing alone may not be sufficient as it may not capture all constituents of botanical drugs. Therefore, it is necessary to establish a bioassay correlating with the drug's known mechanism of action to ensure its potency and activity. Herein we developed a multiple biomarker assay to assess the quality of botanicals using microfluidics, where enzyme inhibition was employed to indicate the drug's activity and thereby evaluate biological consistency. This approach was exemplified on QiShenYiQi Pills using thrombin and angiotensin converting enzyme as "quality biomarkers". Our results demonstrated that there existed variations in potency across different batches of the intermediates and preparations. Compared with chromatographic fingerprinting, the bioassay provided better discrimination ability for some abnormal samples. Moreover, the chip could function as "affinity chromatography" to identify bioactive phytochemicals bound to the enzymes. This work proposed a multiple-biomarker strategy for quality assessment of botanical drugs, while demonstrating for the first time the feasibility of microfluidics in this field.

  19. A microfluidic chip containing multiple 3D nanofibrous scaffolds for culturing human pluripotent stem cells

    Wertheim, Lior; Shapira, Assaf; Amir, Roey J.; Dvir, Tal

    2018-04-01

    In microfluidics-based lab-on-a-chip systems, which are used for investigating the effect of drugs and growth factors on cells, the latter are usually cultured within the device’s channels in two-dimensional, and not in their optimal three-dimensional (3D) microenvironment. Herein, we address this shortfall by designing a microfluidic system, comprised of two layers. The upper layer of the system consists of multiple channels generating a gradient of soluble factors. The lower layer is comprised of multiple wells, each deposited with 3D, nanofibrous scaffold. We first used a mathematical model to characterize the fluid flow within the system. We then show that induced pluripotent stem cells can be seeded within the 3D scaffolds and be exposed to a well-mixed gradient of soluble factors. We believe that utilizing such system may enable in the future to identify new differentiation factors, investigate drug toxicity, and eventually allow to perform analyses on patient-specific tissues, in order to fit the appropriate combination and concentration of drugs.

  20. High-performance fluorescence-encoded magnetic microbeads as microfluidic protein chip supports for AFP detection

    Gong, Xiaoqun [School of Life Sciences, Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Collaborative Innovation Center of Chemical Science and Engineering, Tianjin University, Tianjin 300072 (China); Yan, Huan; Yang, Jiumin [Department of Laboratory Medicine, Tianjin Medical University General Hospital, Tianjin, 300052 (China); Wu, Yudong; Zhang, Jian; Yao, Yingyi [School of Life Sciences, Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Collaborative Innovation Center of Chemical Science and Engineering, Tianjin University, Tianjin 300072 (China); Liu, Ping [Bioscience (Tianjin) Diagnostic Technology CO., LTD, Tianjin, 300300 (China); Wang, Huiquan [Department of Biomedical Engineering, School of Electronics and Information Engineering, Tianjin Polytechnic University, Tianjin, 300387 (China); Hu, Zhidong, E-mail: huzhidong27@163.com [Department of Laboratory Medicine, Tianjin Medical University General Hospital, Tianjin, 300052 (China); Chang, Jin, E-mail: jinchang@tju.edu.cn [School of Life Sciences, Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Collaborative Innovation Center of Chemical Science and Engineering, Tianjin University, Tianjin 300072 (China)

    2016-10-05

    Fluorescence-encoded magnetic microbeads (FEMMs), with the fluorescence encoding ability of quantum dots (QDs) and magnetic enrichment and separation functions of Fe{sub 3}O{sub 4} nanoparticles, have been widely used for multiple biomolecular detection as microfluidic protein chip supports. However, the preparation of FEMMs with long-term fluorescent encoding and immunodetection stability is still a challenge. In this work, we designed a novel high-temperature chemical swelling strategy. The QDs and Fe{sub 3}O{sub 4} nanoparticles were effectively packaged into microbeads via the thermal motion of the polymer chains and the hydrophobic interaction between the nanoparticles and microbeads. The FEMMs obtained a highly uniform fluorescent property and long-term encoding and immunodetection stability and could be quickly magnetically separated and enriched. Then, the QD-encoded magnetic microbeads were applied to alpha fetoprotein (AFP) detection via sandwich immunoreaction. The properties of the encoded microspheres were characterized using a self-designed detecting apparatus, and the target molecular concentration in the sample was also quantified. The results suggested that the high-performance FEMMs have great potential in the field of biomolecular detection. - Graphical abstract: We designed a novel strategy to prepare a kind of high-performance fluorescence-encoded magnetic microbeads as microfluidic protein chip support with long-time fluorescent encoding and immunodetection stability for AFP detection. - Highlights: • A novel strategy combined the high temperature with chemical swelling technology is designed. • Based on hydrophobic interaction and polymer thermal motion, QDs and Fe{sub 3}O{sub 4} were effectively packaged into microbeads. • The fluorescence-encoded magnetic microbeads show long-term fluorescent encoding and immunodetection stability.

  1. A self-contained fully-enclosed microfluidic cartridge for lab on a chip.

    Yobas, Levent; Cheow, Lih Feng; Tang, Kum-Cheong; Yong, Shien-Eit; Ong, Eleana Kye-Zheng; Wong, Lionel; Teo, William Cheng-Yong; Ji, Hongmiao; Rafeah, Siti; Yu, Chen

    2009-12-01

    We describe a self-contained fully-enclosed cartridge for lab-on-a-chip applications where sample and reagents can be applied sequentially as is performed in a heterogeneous immunoassay, or nucleic acid extraction. Both the self-contained and fully-enclosed features of the cartridge are sought to ensure its safe use in the field by unskilled staff. Simplicity in cartridge design and operation is obtained via adopting a valveless concept whereby reagents are stored and used in the form of liquid plugs isolated by air spacers around a fluidic loop. Functional components integrated in the loop include a microfluidic chip specific to the target application, a novel peristaltic pump to displace the liquid plugs, and a pair of removable tubing segments where one is used to introduce biological sample and while the other is to collect eluant. The novel pump is fabricated through soft-lithography technique and works by pinching a planar channel under stainless-steel ball bearings that have been magnetically loaded. The utility of the cartridge is demonstrated for automated extraction and purification of nucleic acids (DNA) from a cell lysate on a battery-operated portable system. The cartridge shown here can be further extended to sample-in-answer-out diagnostic tests.

  2. A simple method for fabricating multi-layer PDMS structures for 3D microfluidic chips

    Zhang, Mengying

    2010-01-01

    We report a simple methodology to fabricate PDMS multi-layer microfluidic chips. A PDMS slab was surface-treated by trichloro (1H,1H,2H,2H-perfluorooctyl) silane, and acts as a reusable transferring layer. Uniformity of the thickness of the patterned PDMS layer and the well-alignment could be achieved due to the transparency and proper flexibility of this transferring layer. Surface treatment results are confirmed by XPS and contact angle testing, while bonding forces between different layers were measured for better understanding of the transferring process. We have also designed and fabricated a few simple types of 3D PDMS chip, especially one consisting of 6 thin layers (each with thickness of 50 μm), to demonstrate the potential utilization of this technique. 3D fluorescence images were taken by a confocal microscope to illustrate the spatial characters of essential parts. This fabrication method is confirmed to be fast, simple, repeatable, low cost and possible to be mechanized for mass production. © The Royal Society of Chemistry 2010.

  3. Metaphase FISH on a Chip: Miniaturized Microfluidic Device for Fluorescence in situ Hybridization

    Niels Tommerup

    2010-11-01

    Full Text Available Fluorescence in situ Hybridization (FISH is a major cytogenetic technique for clinical genetic diagnosis of both inherited and acquired chromosomal abnormalities. Although FISH techniques have evolved and are often used together with other cytogenetic methods like CGH, PRINS and PNA-FISH, the process continues to be a manual, labour intensive, expensive and time consuming technique, often taking over 3–5 days, even in dedicated labs. We have developed a novel microFISH device to perform metaphase FISH on a chip which overcomes many shortcomings of the current laboratory protocols. This work also introduces a novel splashing device for preparing metaphase spreads on a microscope glass slide, followed by a rapid adhesive tape-based bonding protocol leading to rapid fabrication of the microFISH device. The microFISH device allows for an optimized metaphase FISH protocol on a chip with over a 20-fold reduction in the reagent volume. This is the first demonstration of metaphase FISH on a microfluidic device and offers a possibility of automation and significant cost reduction of many routine diagnostic tests of genetic anomalies.

  4. Automated electric valve for electrokinetic separation in a networked microfluidic chip.

    Cui, Huanchun; Huang, Zheng; Dutta, Prashanta; Ivory, Cornelius F

    2007-02-15

    This paper describes an automated electric valve system designed to reduce dispersion and sample loss into a side channel when an electrokinetically mobilized concentration zone passes a T-junction in a networked microfluidic chip. One way to reduce dispersion is to control current streamlines since charged species are driven along them in the absence of electroosmotic flow. Computer simulations demonstrate that dispersion and sample loss can be reduced by applying a constant additional electric field in the side channel to straighten current streamlines in linear electrokinetic flow (zone electrophoresis). This additional electric field was provided by a pair of platinum microelectrodes integrated into the chip in the vicinity of the T-junction. Both simulations and experiments of this electric valve with constant valve voltages were shown to provide unsatisfactory valve performance during nonlinear electrophoresis (isotachophoresis). On the basis of these results, however, an automated electric valve system was developed with improved valve performance. Experiments conducted with this system showed decreased dispersion and increased reproducibility as protein zones isotachophoretically passed the T-junction. Simulations of the automated electric valve offer further support that the desired shape of current streamlines was maintained at the T-junction during isotachophoresis. Valve performance was evaluated at different valve currents based on statistical variance due to dispersion. With the automated control system, two integrated microelectrodes provide an effective way to manipulate current streamlines, thus acting as an electric valve for charged species in electrokinetic separations.

  5. On-Chip Microfluidic Components for In Situ Analysis, Separation, and Detection of Amino Acids

    Zheng, Yun; Getty, Stephanie; Dworkin, Jason; Balvin, Manuel; Kotecki, Carl

    2013-01-01

    The Astrobiology Analytical Laboratory at GSFC has identified amino acids in meteorites and returned cometary samples by using liquid chromatography-electrospray ionization time-of-flight mass spectrometry (LCMS). These organic species are key markers for life, having the property of chirality that can be used to distinguish biological from non-biological amino acids. One of the critical components in the benchtop instrument is liquid chromatography (LC) analytical column. The commercial LC analytical column is an over- 250-mm-long and 4.6-mm-diameter stainless steel tube filled with functionized microbeads as stationary phase to separate the molecular species based on their chemistry. Miniaturization of this technique for spaceflight is compelling for future payloads for landed missions targeting astrobiology objectives. A commercial liquid chromatography analytical column consists of an inert cylindrical tube filled with a stationary phase, i.e., microbeads, that has been functionalized with a targeted chemistry. When analyte is sent through the column by a pressurized carrier fluid (typically a methanol/ water mixture), compounds are separated in time due to differences in chemical interactions with the stationary phase. Different species of analyte molecules will interact more strongly with the column chemistry, and will therefore take longer to traverse the column. In this way, the column will separate molecular species based on their chemistry. A lab-on-chip liquid analysis tool was developed. The microfluidic analytical column is capable of chromatographically separating biologically relevant classes of molecules based on their chemistry. For this analytical column, fabrication, low leak rate, and stationary phase incorporation of a serpentine microchannel were demonstrated that mimic the dimensions of a commercial LC column within a 5 10 1 mm chip. The microchannel in the chip has a 75- micrometer-diameter oval-shaped cross section. The serpentine

  6. Fabrication of a microfluidic chip by UV bonding at room temperature for integration of temperature-sensitive layers

    Schlautmann, S.; Besselink, G. A. J.; Radhakrishna Prabhu, G.; Schasfoort, R. B. M.

    2003-07-01

    A method for the bonding of a microfluidic device at room temperature is presented. The wafer with the fluidic structures was bonded to a sensor wafer with gold pads by means of adhesive bonding, utilizing an UV-curable glue layer. To avoid filling the fluidic channels with the glue, a stamping process was developed which allows the selective application of a thin glue layer. In this way a microfluidic glass chip was fabricated that could be used for performing surface plasmon resonance measurements without signs of leakage. The advantage of this method is the possibility of integration of organic layers as well as other temperature-sensitive layers into a microfluidic glass device.

  7. Integration of micro-optics and microfluidics in a glass chip by fs-laser for optofluidic applications

    Osellame, Roberto; Martinez, Rebeca; Laporta, Paolo; Ramponi, Roberta; Cerullo, Giulio

    2009-02-01

    A lab-on-a-chip (LOC) is a device that incorporates in a single substrate the functionalities of a biological laboratory, i.e. a network of fluidic channels, reservoirs, valves, pumps and sensors, all with micrometer dimensions. Its main advantages are the possibility of working with small samples quantities (from nano- to picoliters), high sensitivity, speed of analysis and the possibility of measurement automation and standardization. They are becoming the most powerful tools of analytical chemistry with a broad application in life sciences, biotechnology and drug development. The next technological challenge of LOCs is direct on-chip integration of photonic functionalities for sensing of biomolecules flowing in the microchannels. Ultrafast laser processing of the bulk of a dielectric material is a very flexible and simple method to produce photonic devices inside microfluidic chips for capillary electrophoresis (CE) or chemical microreactors. By taking advantage of the unique three-dimensional capabilities of this fabrication technique, more complex functionalities, such as splitters or Mach-Zehnder interferometers, can be implemented. In this work we report on the use of femtosecond laser pulses to fabricate photonic devices (as waveguides, splitters and interferometers) inside commercial CE chips, without affecting the manufacturing procedure of the microfluidic part of the device. The fabrication of single waveguides intersecting the channels allows one to perform absorption or Laser Induced Fluorescence (LIF) sensing of the molecules separated inside the microchannels. Waveguide splitters are used for multipoint excitation of the microfluidic channel for parallel or higher sensitivity measurements. Finally, Mach-Zehnder interferometers are used for label-free sensing of the samples flowing in the microfluidic channels by means of refractive index changes detection.

  8. Simultaneous detection of multiple HPV DNA via bottom-well microfluidic chip within an infra-red PCR platform.

    Liu, Wenjia; Warden, Antony; Sun, Jiahui; Shen, Guangxia; Ding, Xianting

    2018-03-01

    Portable Polymerase Chain Reaction (PCR) devices combined with microfluidic chips or lateral flow stripes have shown great potential in the field of point-of-need testing (PoNT) as they only require a small volume of patient sample and are capable of presenting results in a short time. However, the detection for multiple targets in this field leaves much to be desired. Herein, we introduce a novel PCR platform by integrating a bottom-well microfluidic chip with an infra-red (IR) excited temperature control method and fluorescence co-detection of three PCR products. Microfluidic chips are utilized to partition different samples into individual bottom-wells. The oil phase in the main channel contains multi-walled carbon nanotubes which were used as a heat transfer medium that absorbs energy from the IR-light-emitting diode (LED) and transfers heat to the water phase below. Cyclical rapid heating and cooling necessary for PCR are achieved by alternative power switching of the IR-LED and Universal Serial Bus (USB) mini-fan with a pulse width modulation scheme. This design of the IR-LED PCR platform is economic, compact, and fully portable, making it a promising application in the field of PoNT. The bottom-well microfluidic chip and IR-LED PCR platform were combined to fulfill a three-stage thermal cycling PCR for 40 cycles within 90 min for Human Papilloma Virus (HPV) detection. The PCR fluorescent signal was successfully captured at the end of each cycle. The technique introduced here has broad applications in nucleic acid amplification and PoNT devices.

  9. Paper-Based Digital Microfluidic Chip for Multiple Electrochemical Assay Operated by a Wireless Portable Control System

    Ruecha, Nipapan; Lee, Jumi; Chae, Heedo

    2017-01-01

    for multiple analysis assays are fabricated by affordable printing techniques. For enhanced sensitivity of the sensor, the working electrode is modified through the electrochemical method, namely by reducing graphene with voltammetry and coating gold nanoparticles by amperometry. Detachable sensor and absorber...... designed portable power supply and wireless control system, the active paper-based chip platform can be utilized as an advanced point-of-care device for multiple assays in digital microfluidics....

  10. Can we get a better knowledge on dissolution processes in chalk by using microfluidic chips?

    Neuville, Amélie; Minde, Mona; Renaud, Louis; Vinningland, Jan Ludvig; Dysthe, Dag Kristian; Hiorth, Aksel

    2017-04-01

    mostly occurs at the surface of the sample. The reacting chalk surface is observed in situ by stereomicroscopy and by interferometry. The dissolution velocities are highly heterogeneous. To identify the mineral change of the surface, a posteriori measurements using field emission scanning electron microscopy (FE-SEM), and energy dispersive X-ray spectroscopy (EDS). [1] Neuville et al, 2016, Xurography for microfluidics on a reactive solid, Lab on Chip, DOI: 10.1039/c6lc01253a

  11. Rapid and Low-Cost CRP Measurement by Integrating a Paper-Based Microfluidic Immunoassay with Smartphone (CRP-Chip)

    Dong, Meili; Wu, Jiandong; Ma, Zimin; Peretz-Soroka, Hagit; Zhang, Michael; Komenda, Paul; Tangri, Navdeep; Liu, Yong; Rigatto, Claudio; Lin, Francis

    2017-01-01

    Traditional diagnostic tests for chronic diseases are expensive and require a specialized laboratory, therefore limiting their use for point-of-care (PoC) testing. To address this gap, we developed a method for rapid and low-cost C-reactive protein (CRP) detection from blood by integrating a paper-based microfluidic immunoassay with a smartphone (CRP-Chip). We chose CRP for this initial development because it is a strong biomarker of prognosis in chronic heart and kidney disease. The microfluidic immunoassay is realized by lateral flow and gold nanoparticle-based colorimetric detection of the target protein. The test image signal is acquired and analyzed using a commercial smartphone with an attached microlens and a 3D-printed chip–phone interface. The CRP-Chip was validated for detecting CRP in blood samples from chronic kidney disease patients and healthy subjects. The linear detection range of the CRP-Chip is up to 2 μg/mL and the detection limit is 54 ng/mL. The CRP-Chip test result yields high reproducibility and is consistent with the standard ELISA kit. A single CRP-Chip can perform the test in triplicate on a single chip within 15 min for less than 50 US cents of material cost. This CRP-Chip with attractive features of low-cost, fast test speed, and integrated easy operation with smartphones has the potential to enable future clinical PoC chronic disease diagnosis and risk stratification by parallel measurements of a panel of protein biomarkers. PMID:28346363

  12. Microfluidics and photonics for Bio-System-on-a-Chip: a review of advancements in technology towards a microfluidic flow cytometry chip.

    Godin, Jessica; Chen, Chun-Hao; Cho, Sung Hwan; Qiao, Wen; Tsai, Frank; Lo, Yu-Hwa

    2008-10-01

    Microfluidics and photonics come together to form a field commonly referred to as 'optofluidics'. Flow cytometry provides the field with a technology base from which both microfluidic and photonic components be developed and integrated into a useful device. This article reviews some of the more recent developments to familiarize a reader with the current state of the technologies and also highlights the requirements of the device and how researchers are working to meet these needs.

  13. Self-driven filter-based blood plasma separator microfluidic chip for point-of-care testing

    Madadi, Hojjat; Casals-Terré, Jasmina; Mohammadi, Mahdi

    2015-01-01

    There is currently a growing need for lab-on-a-chip devices for use in clinical analysis and diagnostics, especially in the area of patient care. The first step in most blood assays is plasma extraction from whole blood. This paper presents a novel, self-driven blood plasma separation microfluidic chip, which can extract more than 0.1 μl plasma from a single droplet of undiluted fresh human blood (∼5 μl). This volume of blood plasma is extracted from whole blood with high purity (more than 98%) in a reasonable time frame (3 to 5 min), and without the need for any external force. This would be the first step towards the realization of a single-use, self-blood test that does not require any external force or power source to deliver and analyze a fresh whole-blood sample, in contrast to the existing time-consuming conventional blood analysis. The prototypes are manufactured in polydimethylsiloxane that has been modified with a strong nonionic surfactant (Silwet L-77) to achieve hydrophilic behavior. The main advantage of this microfluidic chip design is the clogging delay in the filtration area, which results in an increased amount of extracted plasma (0.1 μl). Moreover, the plasma can be collected in one or more 10 μm-deep channels to facilitate the detection and readout of multiple blood assays. This high volume of extracted plasma is achieved thanks to a novel design that combines maximum pumping efficiency without disturbing the red blood cells’ trajectory through the use of different hydrodynamic principles, such as a constriction effect and a symmetrical filtration mode. To demonstrate the microfluidic chip’s functionality, we designed and fabricated a novel hybrid microdevice that exhibits the benefits of both microfluidics and lateral flow immunochromatographic tests. The performance of the presented hybrid microdevice is validated using rapid detection of thyroid stimulating hormone within a single droplet of whole blood. (paper)

  14. Determination of aminoglycoside antibiotics using an on-chip microfluidic device with chemiluminescence detection

    Sierra-Rodero, M.; Fernandez-Romero, J.M.; Gomez-Hens, A.

    2012-01-01

    We describe an on-chip microflow injection (μFI) approach for the determination of aminoglycoside antibiotics using chemiluminescence (CL) detection. The method is based on the inhibition of the Cu(II)-catalyzed CL reaction of luminol and hydrogen peroxide by the aminoglycosides due to the formation of a complex between the antibiotic and Cu(II). The main features of the method include small sample volumes and a fast response. Syringe pumps were used to insert the sample and the reagents into the microfluidic device. CL was collected using a fiber optic bundle connected to a luminescence detector. All instrumental, hydrodynamic and chemical variables involved in the system were optimized using neomycin as the aminoglycoside model. Inhibition is proportional to the concentration of the antibiotics. The dynamic ranges of the calibration graphs obtained for neomycin, streptomycin and amikacin are 0.3-3.3, 0.9-13.7, and 0.8-8.5 μmol L -1 , and the detection limits are 0.09, 0.28 and 0.24 μmol L -1 , respectively. The precision of the methods, expressed as relative standard deviation, is in the range from 0.8 to 5.0 %. The method was successfully applied to the determination of neomycin in water samples, with recoveries ranging from 80 to 120 %. (author)

  15. The Optimization of Electrophoresis on a Glass Microfluidic Chip and its Application in Forensic Science.

    Han, Jun P; Sun, Jing; Wang, Le; Liu, Peng; Zhuang, Bin; Zhao, Lei; Liu, Yao; Li, Cai X

    2017-11-01

    Microfluidic chips offer significant speed, cost, and sensitivity advantages, but numerous parameters must be optimized to provide microchip electrophoresis detection. Experiments were conducted to study the factors, including sieving matrices (the concentration and type), surface modification, analysis temperature, and electric field strengths, which all impact the effectiveness of microchip electrophoresis detection of DNA samples. Our results showed that the best resolution for ssDNA was observed using 4.5% w/v (7 M urea) lab-fabricated LPA gel, dynamic wall coating of the microchannel, electrophoresis temperatures between 55 and 60°C, and electrical fields between 350 and 450 V/cm on the microchip-based capillary electrophoresis (μCE) system. One base-pair resolution could be achieved in the 19-cm-length microchannel. Furthermore, both 9947A standard genomic DNA and DNA extracted from blood spots were demonstrated to be successfully separated with well-resolved DNA peaks in 8 min. Therefore, the microchip electrophoresis system demonstrated good potential for rapid forensic DNA analysis. © 2017 American Academy of Forensic Sciences.

  16. Development of micropump-actuated negative pressure pinched injection for parallel electrophoresis on array microfluidic chip.

    Li, Bowei; Jiang, Lei; Xie, Hua; Gao, Yan; Qin, Jianhua; Lin, Bingcheng

    2009-09-01

    A micropump-actuated negative pressure pinched injection method is developed for parallel electrophoresis on a multi-channel LIF detection system. The system has a home-made device that could individually control 16-port solenoid valves and a high-voltage power supply. The laser beam is excitated and distributes to the array separation channels for detection. The hybrid Glass-PDMS microfluidic chip comprises two common reservoirs, four separation channels coupled to their respective pneumatic micropumps and two reference channels. Due to use of pressure as a driving force, the proposed method has no sample bias effect for separation. There is only one high-voltage supply needed for separation without relying on the number of channels, which is significant for high-throughput analysis, and the time for sample loading is shortened to 1 s. In addition, the integrated micropumps can provide the versatile interface for coupling with other function units to satisfy the complicated demands. The performance is verified by separation of DNA marker and Hepatitis B virus DNA samples. And this method is also expected to show the potential throughput for the DNA analysis in the field of disease diagnosis.

  17. NeuroChip: a microfluidic electrophysiological device for genetic and chemical biology screening of Caenorhabditis elegans adult and larvae.

    Chunxiao Hu

    Full Text Available Genetic and chemical biology screens of C. elegans have been of enormous benefit in providing fundamental insight into neural function and neuroactive drugs. Recently the exploitation of microfluidic devices has added greater power to this experimental approach providing more discrete and higher throughput phenotypic analysis of neural systems. Here we make a significant addition to this repertoire through the design of a semi-automated microfluidic device, NeuroChip, which has been optimised for selecting worms based on the electrophysiological features of the pharyngeal neural network. We demonstrate this device has the capability to sort mutant from wild-type worms based on high definition extracellular electrophysiological recordings. NeuroChip resolves discrete differences in excitatory, inhibitory and neuromodulatory components of the neural network from individual animals. Worms may be fed into the device consecutively from a reservoir and recovered unharmed. It combines microfluidics with integrated electrode recording for sequential trapping, restraining, recording, releasing and recovering of C. elegans. Thus mutant worms may be selected, recovered and propagated enabling mutagenesis screens based on an electrophysiological phenotype. Drugs may be rapidly applied during the recording thus permitting compound screening. For toxicology, this analysis can provide a precise description of sub-lethal effects on neural function. The chamber has been modified to accommodate L2 larval stages showing applicability for small size nematodes including parasitic species which otherwise are not tractable to this experimental approach. We also combine NeuroChip with optogenetics for targeted interrogation of the function of the neural circuit. NeuroChip thus adds a new tool for exploitation of C. elegans and has applications in neurogenetics, drug discovery and neurotoxicology.

  18. Microfluidic Lab-on-a-Chip Platforms: Requirements, Characteristics and Applications

    Mark, D.; Haeberle, S.; Roth, G.; von Stetten, F.; Zengerle, R.

    This review summarizes recent developments in microfluidic platform approaches. In contrast to isolated application-specific solutions, a microfluidic platform provides a set of fluidic unit operations, which are designed for easy combination within a well-defined fabrication technology. This allows the implementation of different application-specific (bio-) chemical processes, automated by microfluidic process integration [1]. A brief introduction into technical advances, major market segments and promising applications is followed by a detailed characterization of different microfluidic platforms, comprising a short definition, the functional principle, microfluidic unit operations, application examples as well as strengths and limitations. The microfluidic platforms in focus are lateral flow tests, linear actuated devices, pressure driven laminar flow, microfluidic large scale integration, segmented flow microfluidics, centrifugal microfluidics, electro-kinetics, electrowetting, surface acoustic waves, and systems for massively parallel analysis. The review concludes with the attempt to provide a selection scheme for microfluidic platforms which is based on their characteristics according to key requirements of different applications and market segments. Applied selection criteria comprise portability, costs of instrument and disposable, sample throughput, number of parameters per sample, reagent consumption, precision, diversity of microfluidic unit operations and the flexibility in programming different liquid handling protocols.

  19. Lab-on-chip system combining a microfluidic-ELISA with an array of amorphous silicon photosensors for the detection of celiac disease epitopes

    Francesca Costantini

    2015-12-01

    Full Text Available This work presents a lab-on-chip system, which combines a glass-polydimethilsiloxane microfluidic network and an array of amorphous silicon photosensors for the diagnosis and follow-up of Celiac disease. The microfluidic chip implements an on-chip enzyme-linked immunosorbent assay (ELISA, relying on a sandwich immunoassay between antibodies against gliadin peptides (GPs and a secondary antibody marked with horseradish peroxidase (Ig-HRP. This enzyme catalyzes a chemiluminescent reaction, whose light intensity is detected by the amorphous silicon photosensors and transduced into an electrical signal that can be processed to recognize the presence of antibodies against GPs in the serum of people affected by Celiac syndrome.The correct operation of the developed lab-on-chip has been demonstrated using rabbit serum in the microfluidic ELISA. In particular, optimizing the dilution factors of both sera and Ig-HRP samples in the flowing solutions, the specific and non-specific antibodies against GPs can be successfully distinguished, showing the suitability of the presented device to effectively screen celiac disease epitopes. Keywords: Lab-on-chip, Celiac disease, Microfluidics, On-chip detection, ELISA, Amorphous silicon photosensors

  20. Bioprinting cell-laden matrigel for radioprotection study of liver by pro-drug conversion in a dual-tissue microfluidic chip

    Snyder, J E; Hamid, Q; Wang, C; Chang, R; Sun, W; Emami, K; Wu, H

    2011-01-01

    The objective of this paper is to introduce a novel cell printing and microfluidic system to serve as a portable ground model for the study of drug conversion and radiation protection of living liver tissue analogs. The system is applied to study behavior in ground models of space stress, particularly radiation. A microfluidic environment is engineered by two cell types to prepare an improved higher fidelity in vitro micro-liver tissue analog. Cell-laden Matrigel printing and microfluidic chips were used to test radiation shielding to liver cells by the pro-drug amifostine. In this work, the sealed microfluidic chip regulates three variables of interest: radiation exposure, anti-radiation drug treatment and single- or dual-tissue culture environments. This application is intended to obtain a scientific understanding of the response of the multi-cellular biological system for long-term manned space exploration, disease models and biosensors.

  1. Bioprinting cell-laden matrigel for radioprotection study of liver by pro-drug conversion in a dual-tissue microfluidic chip

    Snyder, J E; Hamid, Q; Wang, C; Chang, R; Sun, W [Department of Mechanical Engineering, Drexel University, Philadelphia, PA 19104 (United States); Emami, K; Wu, H, E-mail: sunwei@drexel.edu, E-mail: weisun@tsinghua.edu.cn [Radiation Biophysics Lab, NASA Johnson Space Center, Houston, TX 77586 (United States)

    2011-09-15

    The objective of this paper is to introduce a novel cell printing and microfluidic system to serve as a portable ground model for the study of drug conversion and radiation protection of living liver tissue analogs. The system is applied to study behavior in ground models of space stress, particularly radiation. A microfluidic environment is engineered by two cell types to prepare an improved higher fidelity in vitro micro-liver tissue analog. Cell-laden Matrigel printing and microfluidic chips were used to test radiation shielding to liver cells by the pro-drug amifostine. In this work, the sealed microfluidic chip regulates three variables of interest: radiation exposure, anti-radiation drug treatment and single- or dual-tissue culture environments. This application is intended to obtain a scientific understanding of the response of the multi-cellular biological system for long-term manned space exploration, disease models and biosensors.

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

    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.

  3. Dopamine-functionalized InP/ZnS quantum dots as fluorescence probes for the detection of adenosine in microfluidic chip.

    Ankireddy, Seshadri Reddy; Kim, Jongsung

    2015-01-01

    Microbeads are frequently used as solid supports for biomolecules such as proteins and nucleic acids in heterogeneous microfluidic assays. Chip-based, quantum dot (QD)-bead-biomolecule probes have been used for the detection of various types of DNA. In this study, we developed dopamine (DA)-functionalized InP/ZnS QDs (QDs-DA) as fluorescence probes for the detection of adenosine in microfluidic chips. The photoluminescence (PL) intensity of the QDs-DA is quenched by Zn(2+) because of the strong coordination interactions. In the presence of adenosine, Zn(2+) cations preferentially bind to adenosine, and the PL intensity of the QDs-DA is recovered. A polydimethylsiloxane-based microfluidic chip was fabricated, and adenosine detection was confirmed using QDs-DA probes.

  4. Active metamaterial: Gain and stability, and microfluidic chip for THz cell spectroscopy

    Tang, Qi

    . THz spectroscopy becomes an emerging technique for studying the dynamics and interactions of cells and biomolecules, but many practical challenges still remain in experimental studies. We present a prototype of simple and inexpensive cell-trapping microfluidic chip for THz spectroscopic study of live cells. Cells are transported, trapped and concentrated into the THz exposure region by applying an AC bias signal while the chip maintains a steady temperature at 37 ?C by resistive heating. We conduct some preliminary experiments on E. coli and T cell solution and compare the transmission spectra of empty channels, channels filled with aqueous media only, and channels filled with aqueous medium with un-concentrated and concentrated cells.

  5. Identifying EGFR-Expressed Cells and Detecting EGFR Multi-Mutations at Single-Cell Level by Microfluidic Chip

    Li, Ren; Zhou, Mingxing; Li, Jine; Wang, Zihua; Zhang, Weikai; Yue, Chunyan; Ma, Yan; Peng, Hailin; Wei, Zewen; Hu, Zhiyuan

    2018-03-01

    EGFR mutations companion diagnostics have been proved to be crucial for the efficacy of tyrosine kinase inhibitor targeted cancer therapies. To uncover multiple mutations occurred in minority of EGFR-mutated cells, which may be covered by the noises from majority of un-mutated cells, is currently becoming an urgent clinical requirement. Here we present the validation of a microfluidic-chip-based method for detecting EGFR multi-mutations at single-cell level. By trapping and immunofluorescently imaging single cells in specifically designed silicon microwells, the EGFR-expressed cells were easily identified. By in situ lysing single cells, the cell lysates of EGFR-expressed cells were retrieved without cross-contamination. Benefited from excluding the noise from cells without EGFR expression, the simple and cost-effective Sanger's sequencing, but not the expensive deep sequencing of the whole cell population, was used to discover multi-mutations. We verified the new method with precisely discovering three most important EGFR drug-related mutations from a sample in which EGFR-mutated cells only account for a small percentage of whole cell population. The microfluidic chip is capable of discovering not only the existence of specific EGFR multi-mutations, but also other valuable single-cell-level information: on which specific cells the mutations occurred, or whether different mutations coexist on the same cells. This microfluidic chip constitutes a promising method to promote simple and cost-effective Sanger's sequencing to be a routine test before performing targeted cancer therapy.[Figure not available: see fulltext.

  6. A full-wafer fabrication process for glass microfluidic chips with integrated electroplated electrodes by direct bonding of dry film resist

    Vulto, Paul; Urban, G A; Huesgen, Till; Albrecht, Björn

    2009-01-01

    A full-wafer process is presented for fast and simple fabrication of glass microfluidic chips with integrated electroplated electrodes. The process employs the permanent dry film resist (DFR) Ordyl SY300 to create microfluidic channels, followed by electroplating of silver and subsequent chlorination. The dry film resist is bonded directly to a second substrate, without intermediate gluing layers, only by applying pressure and moderate heating. The process of microfluidic channel fabrication, electroplating and wafer bonding can be completed within 1 day, thus making it one of the fastest and simplest full-wafer fabrication processes. (note)

  7. Rapid and simple half-quantitative measurement alpha-fetoprotein by poly(dimethylsiloxane) microfluidic chip immunochromatographic assay

    Tong, Chao; Jin, Qinghui; Zhao, Jianlong

    2008-03-01

    In this article, a kind of microfluidic method based on MEMS technology combined with gold immunochromatographic assay (GICA) is developed and discussed. Compared to the traditional GICA, this method supplies us convenient, multi-channel, in-parallel, low cost and similar efficiency approach in the fields of alpha-fetopro-tei (AFP)detection. Firstly, we improved the adhesion between the model material SU-8 and Silicon wafer, optimized approaches of the fabrication of the SU-8 model systematically, and fabricate the PDMS micro fluid chip with good reproduction successfully. Secondly, Surface modification and antibody immobilization methods with the GICA on the PDMS micro fluid analysis chip are studied, we choose the PDMS material and transfer GICA to the PDMS micro fluid chip successfully after researching the antibody immobilization efficiency of different materials utilized in fabrication of the micro fluid chip. In order to improve the reaction efficiency of the immobilized antibody, we studied the characteristics of micro fluid without the gas drive, and the fluid velocity control in our design; we also design structure of grove to strengthen the ability of immobilizing the antibody. The stimulation of the structure shows that it achieves great improvement and experiments prove the design is feasible.

  8. A 3D Microfluidic Chip for Electrochemical Detection of Hydrolysed Nucleic Bases by a Modified Glassy Carbon Electrode

    Jana Vlachova

    2015-01-01

    Full Text Available Modification of carbon materials, especially graphene-based materials, has wide applications in electrochemical detection such as electrochemical lab-on-chip devices. A glassy carbon electrode (GCE modified with chemically alternated graphene oxide was used as a working electrode (glassy carbon modified by graphene oxide with sulphur containing compounds and Nafion for detection of nucleobases in hydrolysed samples (HCl pH = 2.9, 100 °C, 1 h, neutralization by NaOH. It was found out that modification, especially with trithiocyanuric acid, increased the sensitivity of detection in comparison with pure GCE. All processes were finally implemented in a microfluidic chip formed with a 3D printer by fused deposition modelling technology. As a material for chip fabrication, acrylonitrile butadiene styrene was chosen because of its mechanical and chemical stability. The chip contained the one chamber for the hydrolysis of the nucleic acid and another for the electrochemical detection by the modified GCE. This chamber was fabricated to allow for replacement of the GCE.

  9. A 3D microfluidic chip for electrochemical detection of hydrolysed nucleic bases by a modified glassy carbon electrode.

    Vlachova, Jana; Tmejova, Katerina; Kopel, Pavel; Korabik, Maria; Zitka, Jan; Hynek, David; Kynicky, Jindrich; Adam, Vojtech; Kizek, Rene

    2015-01-22

    Modification of carbon materials, especially graphene-based materials, has wide applications in electrochemical detection such as electrochemical lab-on-chip devices. A glassy carbon electrode (GCE) modified with chemically alternated graphene oxide was used as a working electrode (glassy carbon modified by graphene oxide with sulphur containing compounds and Nafion) for detection of nucleobases in hydrolysed samples (HCl pH = 2.9, 100 °C, 1 h, neutralization by NaOH). It was found out that modification, especially with trithiocyanuric acid, increased the sensitivity of detection in comparison with pure GCE. All processes were finally implemented in a microfluidic chip formed with a 3D printer by fused deposition modelling technology. As a material for chip fabrication, acrylonitrile butadiene styrene was chosen because of its mechanical and chemical stability. The chip contained the one chamber for the hydrolysis of the nucleic acid and another for the electrochemical detection by the modified GCE. This chamber was fabricated to allow for replacement of the GCE.

  10. Quantitative evaluation of radiation dose by γ-H2AX on a microfluidic chip in a miniature fluorescence cytometer

    Wang, Junsheng; Song, Wendong; Song, Yongxin; Xu, Dan; Zhang, Min; Pan, Xinxiang; Sun, Yeqing; Li, Dongqing

    2014-01-01

    Evaluation of radiation dose is very important for the detection of radiation damage. γ-H2AX is a popular biological dosimeter to evaluate the radiation effect. Typically, bulky and expensive commercial flow cytometers are used to detect γ-H2AX. This paper presents a miniaturized and high sensitive cytometer using a microfluidic chip for evaluating the radiation dose by detecting the mean immunofluorescence intensity of γ-H2AX. A compact optical focusing system and a shift-phase differential amplifier are designed to improve the detection sensitivity. Sample lymphocyte cells are stained by FITC fluorescent dye after being irradiated by UVC. Comparison experiments between the developed miniature cytometer and a commercial flow cytometer were conducted under different radiation doses. The developed microfluidic cytometer also demonstrates a good linear correlation between the measured fluorescence intensity and the irradiation dose with a detection limit similar to that of the commercial flow cytometer. The developed cytometer can evaluate quantitatively the radiation dose by the mean fluorescence intensity of γ-H2AX with a significantly smaller amount of blood samples than a commercial flow cytometer. - Highlights: • A new microfluidic cytometer for evaluating irradiation dose was developed. • The utility of this biosensor is verified by comparison experiments using FCM. • The developed cytometer is small size, high sensitivity, low cost, and simple. • The cytometer can dramatically reduce sample consumption and analysis time

  11. A coral-on-a-chip microfluidic platform enabling live-imaging microscopy of reef-building corals

    Shapiro, Orr H.; Kramarsky-Winter, Esti; Gavish, Assaf R.; Stocker, Roman; Vardi, Assaf

    2016-01-01

    Coral reefs, and the unique ecosystems they support, are facing severe threats by human activities and climate change. Our understanding of these threats is hampered by the lack of robust approaches for studying the micro-scale interactions between corals and their environment. Here we present an experimental platform, coral-on-a-chip, combining micropropagation and microfluidics to allow direct microscopic study of live coral polyps. The small and transparent coral micropropagates are ideally suited for live-imaging microscopy, while the microfluidic platform facilitates long-term visualization under controlled environmental conditions. We demonstrate the usefulness of this approach by imaging coral micropropagates at previously unattainable spatio-temporal resolutions, providing new insights into several micro-scale processes including coral calcification, coral–pathogen interaction and the loss of algal symbionts (coral bleaching). Coral-on-a-chip thus provides a powerful method for studying coral physiology in vivo at the micro-scale, opening new vistas in coral biology. PMID:26940983

  12. A compound magnetic field generating system for targeted killing of Staphylococcus aureus by magnetotactic bacteria in a microfluidic chip

    Chen, Linjie; Chen, Changyou [Beijing Key Laboratory of Bioelectromagnetism, Institute of Electrical Engineering, Chinese Academy of Sciences, Beijing 100190 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); France-China Bio-Mineralization and Nano-Structures Laboratory, Beijing (China); Wang, Pingping; Chen, Chuanfang [Beijing Key Laboratory of Bioelectromagnetism, Institute of Electrical Engineering, Chinese Academy of Sciences, Beijing 100190 (China); France-China Bio-Mineralization and Nano-Structures Laboratory, Beijing (China); Wu, Long-Fei [Beijing Key Laboratory of Bioelectromagnetism, Institute of Electrical Engineering, Chinese Academy of Sciences, Beijing 100190 (China); Laboratoire de Chimie Bactérienne, UMR7283, Aix-Marseille University, Institut de Microbiologie de la Méditerranée, CNRS, Marseille (France); Song, Tao, E-mail: songtao@mail.iee.ac.cn [Beijing Key Laboratory of Bioelectromagnetism, Institute of Electrical Engineering, Chinese Academy of Sciences, Beijing 100190 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); France-China Bio-Mineralization and Nano-Structures Laboratory, Beijing (China)

    2017-04-01

    A compound magnetic field generating system was built to kill Staphylococcus aureus (S. aureus) by magnetotactic bacteria (MTB) in a microfluidic chip in this paper. The system was consisted of coil pairs, a switch circuit, a control program and controllable electrical sources. It could produce a guiding magnetic field (gMF) of ±1 mT along arbitrary direction in the horizontal plane, a rotating magnetic field (rMF) and a swing magnetic field (sMF, 2 Hz, 10 mT) by controlling the currents. The gMF was used to guide MTB swimming to the S. aureus pool in the microfluidic chip, and then the rMF enhanced the mixture of S. aureus and MTB cells, therefore beneficial to the attachments of them. Finally, the sMF was used to induce the death of S. aureus via MTB. The results showed that MTB could be navigated by the gMF and that 47.1% of S. aureus were killed when exposed to the sMF. It provides a new solution for the targeted treatment of infected diseases and even cancers. - Highlights: • We built a system which generated a compound magnetic field in one device. • The compoud magnetic field includes guiding, rotating and swing magnetic fields. • MTB was guided and S. aureus attached to MTB was killed in the same device.

  13. 3D-printed, sugar cube-size microplasma on a hybrid chip used as a spectral lamp to characterize UV-Vis transmission characteristics of polycarbonate chips for microfluidic applications

    Devathasan, D.; Trebych, K.; Karanassios, Vassili

    2013-05-01

    A 3d-printed, solar-powered, battery-operated, atmospheric-pressure, self-igniting microplasma the size of a sugar-cube has been used as light source to document the Ultra Violet (UV) and visible transmission characteristics of differentthickness polycarbonate chips that are often used for microfluidic applications. The hybrid microplasma chip was fitted with a quartz plate because quartz is transparent to UV.

  14. Microgels produced using microfluidic on-chip polymer blending for controlled released of VEGF encoding lentivectors.

    Madrigal, Justin L; Sharma, Shonit N; Campbell, Kevin T; Stilhano, Roberta S; Gijsbers, Rik; Silva, Eduardo A

    2018-03-15

    Alginate hydrogels are widely used as delivery vehicles due to their ability to encapsulate and release a wide range of cargos in a gentle and biocompatible manner. The release of encapsulated therapeutic cargos can be promoted or stunted by adjusting the hydrogel physiochemical properties. However, the release from such systems is often skewed towards burst-release or lengthy retention. To address this, we hypothesized that the overall magnitude of burst release could be adjusted by combining microgels with distinct properties and release behavior. Microgel suspensions were generated using a process we have termed on-chip polymer blending to yield composite suspensions of a range of microgel formulations. In this manner, we studied how alginate percentage and degradation relate to the release of lentivectors. Whereas changes in alginate percentage had a minimal impact on lentivector release, microgel degradation led to a 3-fold increase, and near complete release, over 10 days. Furthermore, by controlling the amount of degradable alginate present within microgels the relative rate of release can be adjusted. A degradable formulation of microgels was used to deliver vascular endothelial growth factor (VEGF)-encoding lentivectors in the chick chorioallantoic membrane (CAM) assay and yielded a proangiogenic response in comparison to the same lentivectors delivered in suspension. The utility of blended microgel suspensions may provide an especially appealing platform for the delivery of lentivectors or similarly sized therapeutics. Genetic therapeutics hold considerable potential for the treatment of diseases and disorders including ischemic cardiovascular diseases. To realize this potential, genetic vectors must be precisely and efficiently delivered to targeted regions of the body. However, conventional methods of delivery do not provide sufficient spatial and temporal control. Here, we demonstrate how alginate microgels provide a basis for developing systems for

  15. Microfluidic organ-on-chip technology for blood-brain barrier research

    van der Helm, Marieke Willemijn; van der Meer, Andries Dirk; Eijkel, Jan C.T.; van den Berg, Albert; Segerink, Loes Irene

    2016-01-01

    Organs-on-chips are a new class of microengineered laboratory models that combine several of the advantages of current in vivo and in vitro models. In this review, we summarize the advances that have been made in the development of organ-on-chip models of the blood-brain barrier (BBBs-on-chips) and

  16. A novel microfluidic chip electrophoresis strategy for simultaneous, label-free, multi-protein detection based on a graphene energy transfer biosensor.

    Lin, Fengming; Zhao, Xiaochao; Wang, Jianshe; Yu, Shiyong; Deng, Yulin; Geng, Lina; Li, HuanJun

    2014-06-07

    A new type of high-throughput and parallel optical sensing platform with a single-color probe based on microfluidic chip electrophoresis combined with aptamer-carboxyfluorescein/graphene oxide energy transfer is reported here. Label-free protein multi-targets were detected, even in challenging complex samples without any pre-treatment.

  17. Molecular Structure Effects of [NR,222][Tf2N] Ionic Liquids on Their Flow Properties in the Microfluidic Chip Reactor – a Complete Validation Study.

    Klusoň, Petr; Stavárek, Petr; Pěnkavová, Věra; Vychodilová, Hana; Hejda, Stanislav; Vlček, Dalibor; Bendová, Magdalena

    2017-01-01

    Roč. 111, JAN (2017), s. 57-66 ISSN 0255-2701 R&D Projects: GA ČR GA15-04790S Institutional support: RVO:67985858 Keywords : ionic liquids * microfluidic chip * reynolds number Subject RIV: CI - Industrial Chemistry, Chemical Engineering OBOR OECD: Chemical process engineering Impact factor: 2.234, year: 2016

  18. Microfluidic Chip Reactor and the Stereoselective Hydrogenation of Methylacetoacetate over (R)-Ru-BINAP in the [N8222][Tf2N]/Methanol/ Water Mixed Phase.

    Klusoň, Petr; Stavárek, Petr; Pěnkavová, Věra; Vychodilová, Hana; Hejda, Stanislav; Bendová, Magdalena

    2017-01-01

    Roč. 115, May (2017), s. 39-46 ISSN 0255-2701 R&D Projects: GA ČR GA15-04790S Institutional support: RVO:67985858 Keywords : stereoselectivity * microfluidic chip * ionic liquids Subject RIV: CI - Industrial Chemistry, Chemical Engineering OBOR OECD: Chemical process engineering Impact factor: 2.234, year: 2016

  19. Gas-liquid-liquid three-phase flow pattern and pressure drop in a microfluidic chip : similarities with gas-liquid/liquid-liquid flows

    Yue, J.; Rebrov, E.; Schouten, J.C.

    2014-01-01

    We report a three-phase slug flow and parallel-slug flow as two major flow patterns found under the nitrogen-decane-water flow through a glass microfluidic chip which features a long microchannel with a hydraulic diameter of 98 µm connected to a cross-flow mixer. The three-phase slug flow pattern is

  20. Microfluidic on-chip biomimicry for 3D cell culture: a fit-for-purpose investigation from the end user standpoint.

    Liu, Ye; Gill, Elisabeth; Shery Huang, Yan Yan

    2017-06-01

    A plethora of 3D and microfluidics-based culture models have been demonstrated in the recent years with the ultimate aim to facilitate predictive in vitro models for pharmaceutical development. This article summarizes to date the progress in the microfluidics-based tissue culture models, including organ-on-a-chip and vasculature-on-a-chip. Specific focus is placed on addressing the question of what kinds of 3D culture and system complexities are deemed desirable by the biological and biomedical community. This question is addressed through analysis of a research survey to evaluate the potential use of microfluidic cell culture models among the end users. Our results showed a willingness to adopt 3D culture technology among biomedical researchers, although a significant gap still exists between the desired systems and existing 3D culture options. With these results, key challenges and future directions are highlighted.

  1. Microfluidic on-chip biomimicry for 3D cell culture: a fit-for-purpose investigation from the end user standpoint

    Liu, Ye; Gill, Elisabeth; Shery Huang, Yan Yan

    2017-01-01

    A plethora of 3D and microfluidics-based culture models have been demonstrated in the recent years with the ultimate aim to facilitate predictive in vitro models for pharmaceutical development. This article summarizes to date the progress in the microfluidics-based tissue culture models, including organ-on-a-chip and vasculature-on-a-chip. Specific focus is placed on addressing the question of what kinds of 3D culture and system complexities are deemed desirable by the biological and biomedical community. This question is addressed through analysis of a research survey to evaluate the potential use of microfluidic cell culture models among the end users. Our results showed a willingness to adopt 3D culture technology among biomedical researchers, although a significant gap still exists between the desired systems and existing 3D culture options. With these results, key challenges and future directions are highlighted. PMID:28670465

  2. Cobalt hexacyanoferrate modified multi-walled carbon nanotubes/graphite composite electrode as electrochemical sensor on microfluidic chip

    Li Xinchun; Chen Zuanguang; Zhong Yuwen; Yang Fan; Pan Jianbin; Liang Yajing

    2012-01-01

    Highlights: ► CoHCF nanoparticles modified MWCNTs/graphite electrode use for electrochemistry on electrophoresis microchip for the first time. ► Simultaneous, rapid, and sensitive electrochemical detection of hydrazine and isoniazid in real samples. ► An exemplary work of CME sensor assembly onto microchip for determination of analytes with environmental significance. ► Manifestation of the applicability and flexibility of CME sensor for electroanalysis on microfluidic chip. - Abstract: Nanomaterial-based electrochemical sensor has received significant interest. In this work, cobalt hexacyanoferrate modified multi-walled carbon nanotubes/graphite composite electrode was electrochemically prepared and exploited as an amperometric detector for microchip electrophoresis. The prepared sensor displayed rapid and sensitive response towards hydrazine and isoniazid oxidation, which was attributed to synergetic electrocatalytic effect of cobalt hexacyanoferrate and multi-walled carbon nanotubes. The sensitivity enhancement with nearly two orders of magnitude was gained, compared with the bare carbon paste electrode, with the detection limit of 0.91 μM (S/N = 3) for hydrazine. Acceptable repeatability of the microanalysis system was verified by consecutive eleven injections of hydrazine without chip and electrode treatments, the RSDs for peak current and migration time were 3.4% and 2.1%, respectively. Meanwhile, well-shaped electrophoretic peaks were observed, mainly due to fast electron transfer of electroactive species on the modified electrode. The developed microchip-electrochemistry setup was successfully applied to the determination of hydrazine and isoniazid in river water and pharmaceutical preparation, respectively. Several merits of the novel electrochemical sensor coupled with microfluidic platform, such as comparative stability, easy fabrication and high sensitivity, hold great potential for hydrazine compounds assay in the lab-on-a-chip system.

  3. Cobalt hexacyanoferrate modified multi-walled carbon nanotubes/graphite composite electrode as electrochemical sensor on microfluidic chip

    Li Xinchun [School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan East Road of Higher Education Mega Centre, Guangzhou 510006 (China); Chen Zuanguang, E-mail: chenzg@mail.sysu.edu.cn [School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan East Road of Higher Education Mega Centre, Guangzhou 510006 (China); Zhong Yuwen, E-mail: yu0106@163.com [Center for Disease Control and Prevention of Guangdong Province, 176 Xingangxi, Guangzhou 510300 (China); Yang Fan; Pan Jianbin; Liang Yajing [School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan East Road of Higher Education Mega Centre, Guangzhou 510006 (China)

    2012-01-13

    Highlights: Black-Right-Pointing-Pointer CoHCF nanoparticles modified MWCNTs/graphite electrode use for electrochemistry on electrophoresis microchip for the first time. Black-Right-Pointing-Pointer Simultaneous, rapid, and sensitive electrochemical detection of hydrazine and isoniazid in real samples. Black-Right-Pointing-Pointer An exemplary work of CME sensor assembly onto microchip for determination of analytes with environmental significance. Black-Right-Pointing-Pointer Manifestation of the applicability and flexibility of CME sensor for electroanalysis on microfluidic chip. - Abstract: Nanomaterial-based electrochemical sensor has received significant interest. In this work, cobalt hexacyanoferrate modified multi-walled carbon nanotubes/graphite composite electrode was electrochemically prepared and exploited as an amperometric detector for microchip electrophoresis. The prepared sensor displayed rapid and sensitive response towards hydrazine and isoniazid oxidation, which was attributed to synergetic electrocatalytic effect of cobalt hexacyanoferrate and multi-walled carbon nanotubes. The sensitivity enhancement with nearly two orders of magnitude was gained, compared with the bare carbon paste electrode, with the detection limit of 0.91 {mu}M (S/N = 3) for hydrazine. Acceptable repeatability of the microanalysis system was verified by consecutive eleven injections of hydrazine without chip and electrode treatments, the RSDs for peak current and migration time were 3.4% and 2.1%, respectively. Meanwhile, well-shaped electrophoretic peaks were observed, mainly due to fast electron transfer of electroactive species on the modified electrode. The developed microchip-electrochemistry setup was successfully applied to the determination of hydrazine and isoniazid in river water and pharmaceutical preparation, respectively. Several merits of the novel electrochemical sensor coupled with microfluidic platform, such as comparative stability, easy fabrication and

  4. Extraction, amplification and detection of DNA in microfluidic chip-based assays

    Wu, Jinbo; Kodzius, Rimantas; Cao, Wenbin; Wen, Weijia

    2013-01-01

    comparison between conventional and microfluidic schemes. In order to accomplish these essential assays without human intervention between individual steps, the micro-components for fluid manipulation become critical. We therefore summarize and discuss

  5. Multiple and high-throughput droplet reactions via combination of microsampling technique and microfluidic chip

    Wu, Jinbo; Zhang, Mengying; Li, Xiaolin; Wen, Weijia

    2012-01-01

    Microdroplets offer unique compartments for accommodating a large number of chemical and biological reactions in tiny volume with precise control. A major concern in droplet-based microfluidics is the difficulty to address droplets individually

  6. Brain slice on a chip: opportunities and challenges of applying microfluidic technology to intact tissues.

    Huang, Yu; Williams, Justin C; Johnson, Stephen M

    2012-06-21

    Isolated brain tissue, especially brain slices, are valuable experimental tools for studying neuronal function at the network, cellular, synaptic, and single channel levels. Neuroscientists have refined the methods for preserving brain slice viability and function and converged on principles that strongly resemble the approach taken by engineers in developing microfluidic devices. With respect to brain slices, microfluidic technology may 1) overcome the traditional limitations of conventional interface and submerged slice chambers and improve oxygen/nutrient penetration into slices, 2) provide better spatiotemporal control over solution flow/drug delivery to specific slice regions, and 3) permit successful integration with modern optical and electrophysiological techniques. In this review, we highlight the unique advantages of microfluidic devices for in vitro brain slice research, describe recent advances in the integration of microfluidic devices with optical and electrophysiological instrumentation, and discuss clinical applications of microfluidic technology as applied to brain slices and other non-neuronal tissues. We hope that this review will serve as an interdisciplinary guide for both neuroscientists studying brain tissue in vitro and engineers as they further develop microfluidic chamber technology for neuroscience research.

  7. Theoretical microfluidics

    Bruus, Henrik

    Microfluidics is a young and rapidly expanding scientific discipline, which deals with fluids and solutions in miniaturized systems, the so-called lab-on-a-chip systems. It has applications in chemical engineering, pharmaceutics, biotechnology and medicine. As the lab-on-a-chip systems grow...

  8. Localized, stepwise template growth of functional nanowires from an amino acid-supported framework in a microfluidic chip.

    Puigmartí-Luis, Josep; Rubio-Martínez, Marta; Imaz, Inhar; Cvetković, Benjamin Z; Abad, Llibertat; Pérez Del Pino, Angel; Maspoch, Daniel; Amabilino, David B

    2014-01-28

    A spatially controlled synthesis of nanowire bundles of the functional crystalline coordination polymer (CP) Ag(I)TCNQ (tetracyanoquinodimethane) from previously fabricated and trapped monovalent silver CP (Ag(I)Cys (cysteine)) using a room-temperature microfluidic-assisted templated growth method is demonstrated. The incorporation of microengineered pneumatic clamps in a two-layer polydimethylsiloxane-based (PDMS) microfluidic platform was used. Apart from guiding the formation of the Ag(I)Cys coordination polymer, this microfluidic approach enables a local trapping of the in situ synthesized structures with a simple pneumatic clamp actuation. This method not only enables continuous and multiple chemical events to be conducted upon the trapped structures, but the excellent fluid handling ensures a precise chemical activation of the amino acid-supported framework in a position controlled by interface and clamp location that leads to a site-specific growth of Ag(I)TCNQ nanowire bundles. The synthesis is conducted stepwise starting with Ag(I)Cys CPs, going through silver metal, and back to a functional CP (Ag(I)TCNQ); that is, a novel microfluidic controlled ligand exchange (CP → NP → CP) is presented. Additionally, the pneumatic clamps can be employed further to integrate the conductive Ag(I)TCNQ nanowire bundles onto electrode arrays located on a surface, hence facilitating the construction of the final functional interfaced systems from solution specifically with no need for postassembly manipulation. This localized self-supported growth of functional matter from an amino acid-based CP shows how sequential localized chemistry in a fluid cell can be used to integrate molecular systems onto device platforms using a chip incorporating microengineered pneumatic tools. The control of clamp pressure and in parallel the variation of relative flow rates of source solutions permit deposition of materials at different locations on a chip that could be useful for device

  9. A microfluidic chip with a U-shaped microstructure array for multicellular spheroid formation, culturing and analysis

    Fu, Chien-Yu; Chang, Hwan-You; Tseng, Sheng-Yang; Yang, Shih-Mo; Hsu, Long; Liu, Cheng-Hsien

    2014-01-01

    Multicellular spheroids (MCS), formed by self-assembly of single cells, are commonly used as a three-dimensional cell culture model to bridge the gap between in vitro monolayer culture and in vivo tissues. However, current methods for MCS generation and analysis still suffer drawbacks such as being labor-intensive and of poor controllability, and are not suitable for high-throughput applications. This study demonstrates a novel microfluidic chip to facilitate MCS formation, culturing and analysis. The chip contains an array of U-shaped microstructures fabricated by photopolymerizing the poly(ethylene glycol) diacrylate hydrogel through defining the ultraviolet light exposure pattern with a photomask. The geometry of the U-shaped microstructures allowed trapping cells into the pocket through the actions of fluid flow and the force of gravity. The hydrogel is non-adherent for cells, promoting the formation of MCS. Its permselective property also facilitates exchange of nutrients and waste for MCS, while providing protection of MCS from shearing stress during the medium perfusion. Heterotypic MCS can be formed easily by manipulating the cell trapping steps. Subsequent drug susceptibility analysis and long-term culture could also be achieved within the same chip. This MCS formation and culture platform can be used as a micro-scale bioreactor and applied in many cell biology and drug testing studies. (paper)

  10. A dual-docking microfluidic cell migration assay (D2-Chip) for testing neutrophil chemotaxis and the memory effect.

    Yang, Ke; Wu, Jiandong; Xu, Guoqing; Xie, Dongxue; Peretz-Soroka, Hagit; Santos, Susy; Alexander, Murray; Zhu, Ling; Zhang, Michael; Liu, Yong; Lin, Francis

    2017-04-18

    Chemotaxis is a classic mechanism for guiding cell migration and an important topic in both fundamental cell biology and health sciences. Neutrophils are a widely used model to study eukaryotic cell migration and neutrophil chemotaxis itself can lead to protective or harmful immune actions to the body. While much has been learnt from past research about how neutrophils effectively navigate through a chemoattractant gradient, many interesting questions remain unclear. For example, while it is tempting to model neutrophil chemotaxis using the well-established biased random walk theory, the experimental proof was challenged by the cell's highly persistent migrating nature. A special experimental design is required to test the key predictions from the random walk model. Another question that has interested the cell migration community for decades concerns the existence of chemotactic memory and its underlying mechanism. Although chemotactic memory has been suggested in various studies, a clear quantitative experimental demonstration will improve our understanding of the migratory memory effect. Motivated by these questions, we developed a microfluidic cell migration assay (so-called dual-docking chip or D 2 -Chip) that can test both the biased random walk model and the memory effect for neutrophil chemotaxis on a single chip enabled by multi-region gradient generation and dual-region cell alignment. Our results provide experimental support for the biased random walk model and chemotactic memory for neutrophil chemotaxis. Quantitative data analyses provide new insights into neutrophil chemotaxis and memory by making connections to entropic disorder, cell morphology and oscillating migratory response.

  11. Research to Improve the Efficiency of Double Stereo PCR Microfluidic Chip by Passivating the Inner Surface of Steel Capillary with NOA61.

    Wu, Jian; Guo, Wei; Wang, Chunyan; Yu, Kuanxin; Ma, Ying; Chen, Tao; Li, Yinghui

    2015-06-01

    In this paper, we report the improvement of PCR microfluidic chip efficiency achieved by coating the inner surface of steel capillary microchannel with a 22-µm film of the ultraviolet-solidified NOA61 using a device invented by us. Our results indicate that with this treatment, the roughness of the inside wall of steel capillary was improved from Ra = 0.921 to Ra = 0.254. The contact angle was decreased from about 95° to 56°, and the surface hydrophobicity was also increased. The flow pressure for performing the real-time PCR in the microfluidic chip with modified surface was reduced by twofold (2.11/1) and that resulted in a substantially increased efficiency of PCR. A modification of the microchannel interior surface improved the quality of the on-chip integrated PCR procedure.

  12. Analysis of the Diffusion Process by pH Indicator in Microfluidic Chips for Liposome Production

    Elisabetta Bottaro

    2017-07-01

    Full Text Available In recent years, the development of nano- and micro-particles has attracted considerable interest from researchers and enterprises, because of the potential utility of such particles as drug delivery vehicles. Amongst the different techniques employed for the production of nanoparticles, microfluidic-based methods have proven to be the most effective for controlling particle size and dispersity, and for achieving high encapsulation efficiency of bioactive compounds. In this study, we specifically focus on the production of liposomes, spherical vesicles formed by a lipid bilayer encapsulating an aqueous core. The formation of liposomes in microfluidic devices is often governed by diffusive mass transfer of chemical species at the liquid interface between a solvent (i.e., alcohol and a non-solvent (i.e., water. In this work, we developed a new approach for the analysis of mixing processes within microfluidic devices. The method relies on the use of a pH indicator, and we demonstrate its utility by characterizing the transfer of ethanol and water within two different microfluidic architectures. Our approach represents an effective route to experimentally characterize diffusion and advection processes governing the formation of vesicular/micellar systems in microfluidics, and can also be employed to validate the results of numerical modelling.

  13. Fabrication of microfluidic architectures for optimal flow rate and concentration measurement for lab on chip application

    Adam, Tijjani; Hashim, U.

    2017-03-01

    Optimum flow in micro channel for sensing purpose is challenging. In this study, The optimizations of the fluid sample flows are made through the design and characterization of the novel microfluidics' architectures to achieve the optimal flow rate in the micro channels. The biocompatibility of the Polydimetylsiloxane (Sylgard 184 silicon elastomer) polymer used to fabricate the device offers avenue for the device to be implemented as the universal fluidic delivery system for bio-molecules sensing in various bio-medical applications. The study uses the following methodological approaches, designing a novel microfluidics' architectures by integrating the devices on a single 4 inches silicon substrate, fabricating the designed microfluidic devices using low-cost solution soft lithography technique, characterizing and validating the flow throughput of urine samples in the micro channels by generating pressure gradients through the devices' inlets. The characterization on the urine samples flow in the micro channels have witnessed the constant flow throughout the devices.

  14. Microfluidic Chip-based Nucleic Acid Testing using Gingival Crevicular Fluid as a New Technique for Detecting HIV-1 Infection

    Alex Willyandre

    2013-05-01

    Full Text Available Transmission of HIV-1 infection by individuals in window period who are tested negative in conventional HIV-1 detection would pose the community with serious problems. Several diagnostic tools require specific labora-tory equipment, perfect timing of diagnosis, antibody to HIV-1, and invasive technique to get sample for examination, until high amount of time to process the sample as well as accessibility of remote areas. Many attempts have been made to solve those problems to come to a new detection technique. This review aims to give information about the current development technique for detection of HIV infection. Microfluidic Chip-based Nucleic Acid Testing is currently introduced for detection of HIV-1 infection. This review also cover the possible usage of gingival crevicular fluid as sample specimen that could be taken noninvasively from the individual.DOI: 10.14693/jdi.v18i2.63

  15. Capacitance variation induced by microfluidic two-phase flow across insulated interdigital electrodes in lab-on-chip devices.

    Dong, Tao; Barbosa, Cátia

    2015-01-26

    Microfluidic two-phase flow detection has attracted plenty of interest in various areas of biology, medicine and chemistry. This work presents a capacitive sensor using insulated interdigital electrodes (IDEs) to detect the presence of droplets in a microchannel. This droplet sensor is composed of a glass substrate, patterned gold electrodes and an insulation layer. A polydimethylsiloxane (PDMS) cover bonded to the multilayered structure forms a microchannel. Capacitance variation induced by the droplet passage was thoroughly investigated with both simulation and experimental work. Olive oil and deionized water were employed as the working fluids in the experiments to demonstrate the droplet sensor. The results show a good sensitivity of the droplet with the appropriate measurement connection. This capacitive droplet sensor is promising to be integrated into a lab-on-chip device for in situ monitoring/counting of droplets or bubbles.

  16. Femtosecond laser microfabrication of optical waveguides in commercial microfluidic lab-on-a-chip

    Osellame, R.; Martinez-Vazquez, R.; Ramponi, R.; Cerullo, G.; Dongre, C.; Dekker, R.; Hoekstra, Hugo; Pollnau, Markus

    One of the main challenges of lab-on-a-chip technology is the on-chip integration of photonic functionalities by manufacturing optical waveguides for sensing biomolecules flowing in the microchannels. Such integrated approach has many advantages over traditional free-space optical sensing, such as

  17. Low-temperature bonded glass-membrane microfluidic device for in vitro organ-on-a-chip cell culture models

    Pocock, Kyall J.; Gao, Xiaofang; Wang, Chenxi; Priest, Craig; Prestidge, Clive A.; Mawatari, Kazuma; Kitamori, Takehiko; Thierry, Benjamin

    2015-12-01

    The integration of microfluidics with living biological systems has paved the way to the exciting concept of "organson- a-chip", which aims at the development of advanced in vitro models that replicate the key features of human organs. Glass based devices have long been utilised in the field of microfluidics but the integration of alternative functional elements within multi-layered glass microdevices, such as polymeric membranes, remains a challenge. To this end, we have extended a previously reported approach for the low-temperature bonding of glass devices that enables the integration of a functional polycarbonate porous membrane. The process was initially developed and optimised on specialty low-temperature bonding equipment (μTAS2001, Bondtech, Japan) and subsequently adapted to more widely accessible hot embosser units (EVG520HE Hot Embosser, EVG, Austria). The key aspect of this method is the use of low temperatures compatible with polymeric membranes. Compared to borosilicate glass bonding (650 °C) and quartz/fused silica bonding (1050 °C) processes, this method maintains the integrity and functionality of the membrane (Tg 150 °C for polycarbonate). Leak tests performed showed no damage or loss of integrity of the membrane for up to 150 hours, indicating sufficient bond strength for long term cell culture. A feasibility study confirmed the growth of dense and functional monolayers of Caco-2 cells within 5 days.

  18. Evaluation of the effect of the structure of bacterial cellulose on full thickness skin wound repair on a microfluidic chip.

    Li, Ying; Wang, Shiwen; Huang, Rong; Huang, Zhuo; Hu, Binfeng; Zheng, Wenfu; Yang, Guang; Jiang, Xingyu

    2015-03-09

    Bacterial cellulose (BC) is a kind of nanobiomaterial for tissue engineering. How the nanoscale structure of BC affects skin wound repair is unexplored. Here, the hierarchical structure of BC films and their different effects on skin wound healing were studied both in vitro and in vivo. The bottom side of the BC film had a larger pore size, and a looser and rougher structure than that of the top side. By using a microfluidics-based in vitro wound healing model, we revealed that the bottom side of the BC film can better promote the migration of cells to facilitate wound healing. Furthermore, the full-thickness skin wounds on Wistar rats demonstrated that, compared with gauze and the top side of the BC film, the wound covered by the bottom side of the BC film showed faster recovery rate and less inflammatory response. The results indicate that the platform based on the microfluidic chip provide a rapid, reliable, and repeatable method for wound dressing screening. As an excellent biomaterial for wound healing, the BC film displays different properties on different sides, which not only provides a method to optimize the biocompatibility of wound dressings but also paves a new way to building heterogeneous BC-based biomaterials for complex tissue engineering.

  19. Continuous Flow 1H and 13C NMR Spectroscopy in Microfluidic Stripline NMR Chips

    Oosthoek-de Vries, Anna Jo; Bart, Jacob; Tiggelaar, Roald M.; Janssen, Johannes W.G.; van Bentum, Jan (P.J.M.); Gardeniers, Han J.G.E.; Kentgens, Arno P.M.

    2017-01-01

    Microfluidic stripline NMR technology not only allows for NMR experiments to be performed on small sample volumes in the submicroliter range, but also experiments can easily be performed in continuous flow because of the stripline's favorable geometry. In this study we demonstrate the possibility of

  20. Microfluidics Integrated Biosensors: A Leading Technology towards Lab-on-a-Chip and Sensing Applications

    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

  1. Microfluidics Integrated Biosensors: A Leading Technology towards Lab-on-a-Chip and Sensing Applications

    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.

  2. Local modification and laser-welding production of functionalized microfluidic chips

    Rijo Carvalho, Rui

    2017-01-01

    The ability to locally functionalize the surface of glass and polymers allows for myriad biomedical and chemical applications. When we started this research enclosed surfaces such as microfluidic channels were not easily amenable to localized functionalization. Furthermore, pre-functionalization

  3. Drug Induced Sialorrhea and Microfluidic-Chip-Electrophoretic Analysis of Engorged Adult Female Tick Saliva of Haemaphysalis longicornis (Acari: Ixodidae

    Mohammad Saiful Islam

    2017-04-01

    Full Text Available Background: The aim of the present study was to induce salivation in Haemaphysalis longicornis to increase saliva production and to characterize the collection of proteins present in the collected saliva using on-chip-electrophoresis.Methods: Saliva of adult female engorged H. longicornis was collected by treatment with 0.2% dopamine hydrochlo­ride. All protein samples were characterized by SDS-PAGE electrophoresis using a microfluidic High Sensitiv­ity Protein Assay 250 kit by 2100 Bioanalyzer (Agilent Technologies, USA under non-reducing conditions.Results: The average salivary protein concentration was 0.169 µg/µl/tick and saliva secretion decreased with in­creased time of tick detachment from the host. Saliva secretion volume increased to 3.56 µl in the group of ticks with a body weight between 301–350 mg as compared to higher and lower body weight groups. On-chip-electrophoresis results show 13 distinct bands ranging from 9.9 to 294 kDa.Conclusion: Based on molecular weight, the putative salivary proteins are comprised of proline-rich proteins, tria­bin, apyrase members of the 12-kDa protein family, platelet inhibitors and anti-inflammatory proteins as tick saliva contains anti-inflammatory components.

  4. All-electronic droplet generation on-chip with real-time feedback control for EWOD digital microfluidics.

    Gong, Jian; Kim, Chang-Jin C J

    2008-06-01

    Electrowetting-on-dielectric (EWOD) actuation enables digital (or droplet) microfluidics where small packets of liquids are manipulated on a two-dimensional surface. Due to its mechanical simplicity and low energy consumption, EWOD holds particular promise for portable systems. To improve volume precision of the droplets, which is desired for quantitative applications such as biochemical assays, existing practices would require near-perfect device fabrication and operation conditions unless the droplets are generated under feedback control by an extra pump setup off of the chip. In this paper, we develop an all-electronic (i.e., no ancillary pumping) real-time feedback control of on-chip droplet generation. A fast voltage modulation, capacitance sensing, and discrete-time PID feedback controller are integrated on the operating electronic board. A significant improvement is obtained in the droplet volume uniformity, compared with an open loop control as well as the previous feedback control employing an external pump. Furthermore, this new capability empowers users to prescribe the droplet volume even below the previously considered minimum, allowing, for example, 1 : x (x < 1) mixing, in comparison to the previously considered n : m mixing (i.e., n and m unit droplets).

  5. ALL-ELECTRONIC DROPLET GENERATION ON-CHIP WITH REAL-TIME FEEDBACK CONTROL FOR EWOD DIGITIAL MICROFLUIDICS

    Gong, Jian; Kim, Chang-Jin “CJ”

    2009-01-01

    Electrowetting-on-dielectric (EWOD) actuation enables digital (or droplet) microfluidics where small packets of liquids are manipulated on a two-dimensional surface. Due to its mechanical simplicity and low energy consumption, EWOD holds particular promise for portable systems. To improve volume precision of the droplets, which is desired for quantitative applications such as biochemical assays, existing practices would require near-perfect device fabricaion and operation conditions unless the droplets are generated under feedback control by an extra pump setup off of the chip. In this paper, we develop an all-electronic (i.e., no ancillary pumping) real-time feedback control of on-chip droplet generation. A fast voltage modulation, capacitance sensing, and discrete-time PID feedback controller are integrated on the operating electronic board. A significant improvement is obtained in the droplet volume uniformity, compared with an open loop control as well as the previous feedback control employing an external pump. Furthermore, this new capability empowers users to prescribe the droplet volume even below the previously considered minimum, allowing, for example, 1:x (x < 1) mixing, in comparison to the previously considered n:m mixing (i.e., n and m unit droplets). PMID:18497909

  6. Influence of geometry on hydrodynamic focusing and long-range fluid behavior in PDMS microfluidic chips

    Kunstmann-Olsen, Casper; Hoyland, James; Rubahn, Horst-Günter

    2012-01-01

    Details of hydrodynamic focusing in a 2D microfluidic channel-junction are investigated experimentally and theoretically, especially the effect on the focusing width of volumetric flow ratio r between main and side channels, as well as angle θ between channels. A non-linear relationship is observed...... and it is observed that in the middle section of the channel, a smaller θ induces less divergence. This effect is of importance for microfluidic systems utilizing hydrodynamic focusing in long, straight channels....... where the focus width decreases rapidly with increasing r and levels off at higher values. For the dependence on θ, results from both experiments and modeling show that an increased focusing effect is obtained as θ approaches 90°. Long-range focusing is explored along a 1 cm long channel...

  7. Integrated Microfluidic Membrane Transistor Utilizing Chemical Information for On-Chip Flow Control

    Frank, Philipp; Schreiter, Joerg; Haefner, Sebastian; Paschew, Georgi; Voigt, Andreas; Richter, Andreas

    2016-01-01

    Microfluidics is a great enabling technology for biology, biotechnology, chemistry and general life sciences. Despite many promising predictions of its progress, microfluidics has not reached its full potential yet. To unleash this potential, we propose the use of intrinsically active hydrogels, which work as sensors and actuators at the same time, in microfluidic channel networks. These materials transfer a chemical input signal such as a substance concentration into a mechanical output. This way chemical information is processed and analyzed on the spot without the need for an external control unit. Inspired by the development electronics, our approach focuses on the development of single transistor-like components, which have the potential to be used in an integrated circuit technology. Here, we present membrane isolated chemical volume phase transition transistor (MIS-CVPT). The device is characterized in terms of the flow rate from source to drain, depending on the chemical concentration in the control channel, the source-drain pressure drop and the operating temperature. PMID:27571209

  8. Integrated Microfluidic Membrane Transistor Utilizing Chemical Information for On-Chip Flow Control.

    Frank, Philipp; Schreiter, Joerg; Haefner, Sebastian; Paschew, Georgi; Voigt, Andreas; Richter, Andreas

    2016-01-01

    Microfluidics is a great enabling technology for biology, biotechnology, chemistry and general life sciences. Despite many promising predictions of its progress, microfluidics has not reached its full potential yet. To unleash this potential, we propose the use of intrinsically active hydrogels, which work as sensors and actuators at the same time, in microfluidic channel networks. These materials transfer a chemical input signal such as a substance concentration into a mechanical output. This way chemical information is processed and analyzed on the spot without the need for an external control unit. Inspired by the development electronics, our approach focuses on the development of single transistor-like components, which have the potential to be used in an integrated circuit technology. Here, we present membrane isolated chemical volume phase transition transistor (MIS-CVPT). The device is characterized in terms of the flow rate from source to drain, depending on the chemical concentration in the control channel, the source-drain pressure drop and the operating temperature.

  9. Dopamine-functionalized InP/ZnS quantum dots as fluorescence probes for the detection of adenosine in microfluidic chip

    An, Seong Soo; Ankireddy,Seshadri Reddy; Kim,Jongsung

    2015-01-01

    Seshadri Reddy Ankireddy, Jongsung Kim Department of Chemical and Biological Engineering, Gachon University, Seongnam, Gyeonggi-Do, South Korea Abstract: Microbeads are frequently used as solid supports for biomolecules such as proteins and nucleic acids in heterogeneous microfluidic assays. Chip-based, quantum dot (QD)-bead-biomolecule probes have been used for the detection of various types of DNA. In this study, we developed dopamine (DA)-functionalized InP/ZnS QDs (QDs-DA) as fluorescen...

  10. High-throughput on-chip in vivo neural regeneration studies using femtosecond laser nano-surgery and microfluidics

    Rohde, Christopher B.; Zeng, Fei; Gilleland, Cody; Samara, Chrysanthi; Yanik, Mehmet F.

    2009-02-01

    In recent years, the advantages of using small invertebrate animals as model systems for human disease have become increasingly apparent and have resulted in three Nobel Prizes in medicine or chemistry during the last six years for studies conducted on the nematode Caenorhabditis elegans (C. elegans). The availability of a wide array of species-specific genetic techniques, along with the transparency of the worm and its ability to grow in minute volumes make C. elegans an extremely powerful model organism. We present a suite of technologies for complex high-throughput whole-animal genetic and drug screens. We demonstrate a high-speed microfluidic sorter that can isolate and immobilize C. elegans in a well-defined geometry, an integrated chip containing individually addressable screening chambers for incubation and exposure of individual animals to biochemical compounds, and a device for delivery of compound libraries in standard multiwell plates to microfluidic devices. The immobilization stability obtained by these devices is comparable to that of chemical anesthesia and the immobilization process does not affect lifespan, progeny production, or other aspects of animal health. The high-stability enables the use of a variety of key optical techniques. We use this to demonstrate femtosecond-laser nanosurgery and three-dimensional multiphoton microscopy. Used alone or in various combinations these devices facilitate a variety of high-throughput assays using whole animals, including mutagenesis and RNAi and drug screens at subcellular resolution, as well as high-throughput high-precision manipulations such as femtosecond-laser nanosurgery for large-scale in vivo neural degeneration and regeneration studies.

  11. Acoustic resonances in microfluidic chips: full-image micro-PIV experiments and numerical simulations.

    Hagsäter, S M; Jensen, T Glasdam; Bruus, H; Kutter, J P

    2007-10-01

    We show that full-image micro-PIV analysis in combination with images of transient particle motion is a powerful tool for experimental studies of acoustic radiation forces and acoustic streaming in microfluidic chambers under piezo-actuation in the MHz range. The measured steady-state motion of both large 5 microm and small 1 microm particles can be understood in terms of the acoustic eigenmodes or standing ultra-sound waves in the given experimental microsystems. This interpretation is supported by numerical solutions of the corresponding acoustic wave equation.

  12. Monolithic Chip System with a Microfluidic Channel for In Situ Electron Microscopy of Liquids

    Jensen, Eric; Burrows, Andrew; Mølhave, Kristian

    2014-01-01

    sandwiched microchips with thin membranes. We report on a new microfabricated chip system based on a monolithic design that enables membrane geometry on the scale of a few micrometers. The design is intended to reduce membrane deflection when the system is under pressure, a micro fluidic channel for improved...

  13. A microfluidic chip platform with electrochemical carbon nanotube electrodes for pre-clinical evaluation of antibiotics nanocapsules.

    Hong, Chien-Chong; Wang, Chih-Ying; Peng, Kuo-Ti; Chu, I-Ming

    2011-04-15

    This paper presents a microfluidic chip platform with electrochemical carbon nanotube electrodes for preclinical evaluation of antibiotics nanocapsules. Currently, there has been an increasing interest in the development of nanocapsules for drug delivery applications for localized treatments of diseases. So far, the methods to detect antibiotics are liquid chromatography (LC), high performance liquid chromatography (HPLC), mass spectroscopy (MS). These conventional instruments are bulky, expensive, not ease of access, and talented operator required. In order to help the development of nanocapsules and understand drug release profile before planning the clinical experiments, it is important to set up a biosensing platform which could monitor and evaluate the real-time drug release profile of nanocapsules with high sensitivity and long-term measurement ability. In this work, a microfluidic chip platform with electrochemical carbon nanotube electrodes has been developed and characterized for rapid detection of antibiotics teicoplanin nanocapsules. Multi-walled carbon nanotubes are used to modify the gold electrode surfaces to enhance the performance of the electrochemical biosensors. Experimental results show that the limit of detection of the developed platform using carbon nanotubes electrodes is 0.1 μg/ml with a linear range from 1 μg/ml to 10 μg/ml. The sensitivity of the developed system is 0.023 mA ml/μg at 37°C. The drug release profile of teicoplanin nanocapsules in PBS shows that the antibiotics nanocapsules significantly increased the release of drug on the 4th day, measuring 0.4858 μg/(ml hr). The release of drug from the antibiotics nanocapsules reached 34.98 μg/ml on the 7th day. The results showed a similar trend compared with the measurement result using the HPLC instrument. Compared with the traditional HPLC measurements, the electrochemical sensing platform we developed measures results with increased flexibility in controlling experimental

  14. Recent results of the investigation of a micro-fluidic sampling chip and sampling system for hot cell aqueous processing streams

    Tripp, J.; Smith, T.; Law, J.

    2013-01-01

    A Fuel Cycle Research and Development project has investigated an innovative sampling method that could evolve into the next generation sampling and analysis system for metallic elements present in aqueous processing streams. Initially sampling technologies were evaluated and micro-fluidic sampling chip technology was selected and tested. A conceptual design for a fully automated microcapillary-based system was completed and a robotic automated sampling system was fabricated. The mechanical and sampling operation of the completed sampling system was investigated. Different sampling volumes have been tested. It appears that the 10 μl volume has produced data that had much smaller relative standard deviations than the 2 μl volume. In addition, the production of a less expensive, mass produced sampling chip was investigated to avoid chip reuse thus increasing sampling reproducibility/accuracy. The micro-fluidic-based robotic sampling system's mechanical elements were tested to ensure analytical reproducibility and the optimum robotic handling of micro-fluidic sampling chips. (authors)

  15. Small systems, small sensors: Integrating sensing technologies into microfluidic and organ-on-a-chip devices

    Oomen, Pieter Edmond

    2016-01-01

    Pieter Oomen presenteert in zijn proefschrift verschillende microfluïdische systemen met geïntegreerde sensors voor biologische en chemische analyses. Deze geminiaturiseerde systemen kennen veel voordelen: reagentia- en monstergebruik worden verminderd, parallelle experimenten kunnen op een enkel apparaat worden gedaan en natuurlijke celomgevingen kunnen worden nagebootst in incubatiesystemen (orgaan-op-chip). Echter, om zulke systemen te controleren en systematisch te verbeteren gedurende de...

  16. Size-based cell sorting with a resistive pulse sensor and an electromagnetic pump in a microfluidic chip.

    Song, Yongxin; Li, Mengqi; Pan, Xinxiang; Wang, Qi; Li, Dongqing

    2015-02-01

    An electrokinetic microfluidic chip is developed to detect and sort target cells by size from human blood samples. Target-cell detection is achieved by a differential resistive pulse sensor (RPS) based on the size difference between the target cell and other cells. Once a target cell is detected, the detected RPS signal will automatically actuate an electromagnetic pump built in a microchannel to push the target cell into a collecting channel. This method was applied to automatically detect and sort A549 cells and T-lymphocytes from a peripheral fingertip blood sample. The viability of A549 cells sorted in the collecting well was verified by Hoechst33342 and propidium iodide staining. The results show that as many as 100 target cells per minute can be sorted out from the sample solution and thus is particularly suitable for sorting very rare target cells, such as circulating tumor cells. The actuation of the electromagnetic valve has no influence on RPS cell detection and the consequent cell-sorting process. The viability of the collected A549 cell is not impacted by the applied electric field when the cell passes the RPS detection area. The device described in this article is simple, automatic, and label-free and has wide applications in size-based rare target cell sorting for medical diagnostics. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Continuous Microfluidics (Ecology-on-a-Chip) Experiments for Long Term Observation of Bacteria at Liquid-Liquid Interfaces

    Miranda, Michael; White, Andrew; Jalali, Maryam; Sheng, Jian

    2017-11-01

    A microfluidic bioassay incorporating a peristaltic pump and chemostat capable of continuously culturing a bacterial suspension through a microchannel for an extended period of time relevant to ecological processes is presented. A single crude oil droplet is dispensed on-chip and subsequently pinned to the top and bottom surfaces of the microchannel to establish a vertical curved oil-water interface to observe bacteria without boundary interference. The accumulation of extracellular polymeric substances (EPS), microbial film formation, and aggregation is provided by DIC microscopy with an EMCCD camera at an interval of 30 sec. Cell-interface interactions such as cell translational and angular motilities as well as encountering, attachment, detachment to the interface are obtained by a high speed camera at 1000 fps with a sampling interval of 10 min. Experiments on Pseudomonas sp. (P62) and isolated EPS suspensions from Sagitulla Stelleta and Roseobacter show rapid formation of bacterial aggregates including EPS streamers stretching tens of drop diameters long. These results provide crucial insights into environmentally relevant processes such as the initiation of marine oil snow, an alternative mode of biodegradation to conventional bioconsumption. Funded by GoMRI, NSF, ARO.

  18. Real-time Image Processing for Microscopy-based Label-free Imaging Flow Cytometry in a Microfluidic Chip.

    Heo, Young Jin; Lee, Donghyeon; Kang, Junsu; Lee, Keondo; Chung, Wan Kyun

    2017-09-14

    Imaging flow cytometry (IFC) is an emerging technology that acquires single-cell images at high-throughput for analysis of a cell population. Rich information that comes from high sensitivity and spatial resolution of a single-cell microscopic image is beneficial for single-cell analysis in various biological applications. In this paper, we present a fast image-processing pipeline (R-MOD: Real-time Moving Object Detector) based on deep learning for high-throughput microscopy-based label-free IFC in a microfluidic chip. The R-MOD pipeline acquires all single-cell images of cells in flow, and identifies the acquired images as a real-time process with minimum hardware that consists of a microscope and a high-speed camera. Experiments show that R-MOD has the fast and reliable accuracy (500 fps and 93.3% mAP), and is expected to be used as a powerful tool for biomedical and clinical applications.

  19. Dielectrophoresis microjets: a merging of electromagnetics and microfluidics for on-chip technologies

    Hill, Kyle A.; Collier, Christopher M.; Holzman, Jonathan F.

    2014-05-01

    Digital (droplet-based) microfluidic systems apply electromagnetic characteristics as the fundamental fluid actuation mechanism. These systems are often implemented in two-dimensional architectures, overcoming one-dimensional continuous flow channel practical issues. The fundamental operation for digital microfluidics requires the creation of an electric field distribution to achieve desired fluid actuation. The electric field distribution is typically non-uniform, enabling creation of net dielectrophoresis (DEP) force. The DEP force magnitude is proportional to the difference between microdroplet and surrounding medium complex dielectric constants, and the gradient of the electric field magnitude squared. Force sign/direction can be manipulated to achieve a force towards higher (positive DEP) or lower (negative DEP) electrostatic energy by tailoring the relative difference between microdroplet and surrounding medium complex dielectric constants through careful selection of the devices fabrication materials. The DEP force magnitudes and directions are applied here for well-controlled and high-speed microdroplet actuation. Control and speed characteristics arise from significant differences in the microdroplet/medium conductivity and the use of a micropin architecture with strong electric field gradients. The implementation, referred to here as a DEP microjet, establishes especially strong axial propulsion forces. Single- and double-micropin topologies achieve strong axial propulsion force, but only the double-micropin topology creates transverse converging forces for stable and controlled microdroplet actuation. Electric field distributions for each topology are investigated and linked to axial and transverse forces. Experimental results are presented for both topologies. The double-micropin topology is tested with biological fluids. Microdroplet actuation speeds up to 25 cm/s are achieved—comparable to the fastest speeds to-date.

  20. Acinus-on-a-chip: a microfluidic platform for pulmonary acinar flows.

    Fishler, Rami; Mulligan, Molly K; Sznitman, Josué

    2013-11-15

    Convective respiratory flows in the pulmonary acinus and their influence on the fate of inhaled particles are typically studied using computational fluid dynamics (CFD) or scaled-up experimental models. However, experiments that replicate several generations of the acinar tree while featuring cyclic wall motion have not yet been realized. Moreover, current experiments generally capture only flow dynamics, without inhaled particle dynamics, due to difficulties in simultaneously matching flow and particle dynamics. In an effort to overcome these limitations, we introduce a novel microfluidic device mimicking acinar flow characteristics directly at the alveolar scale. The model features an anatomically-inspired geometry that expands and contracts periodically with five dichotomously branching airway generations lined with alveolar-like cavities. We use micro-particle image velocimetry with a glycerol solution as the carrying fluid to quantitatively characterize detailed flow patterns within the device and reveal experimentally for the first time a gradual transition of alveolar flow patterns along the acinar tree from recirculating to radial streamlines, in support of hypothesized predictions from past CFD simulations. The current measurements show that our microfluidic system captures the underlying characteristics of the acinar flow environment, including Reynolds and Womersley numbers as well as cyclic wall displacements and alveolar flow patterns at a realistic length scale. With the use of air as the carrying fluid, our miniaturized platform is anticipated to capture both particle and flow dynamics and serve in the near future as a promising in vitro tool for investigating the mechanisms of particle deposition deep in the lung. © 2013 Elsevier Ltd. All rights reserved.

  1. Fully Automated On-Chip Imaging Flow Cytometry System with Disposable Contamination-Free Plastic Re-Cultivation Chip

    Tomoyuki Kaneko

    2011-06-01

    Full Text Available We have developed a novel imaging cytometry system using a poly(methyl methacrylate (PMMA based microfluidic chip. The system was contamination-free, because sample suspensions contacted only with a flammable PMMA chip and no other component of the system. The transparency and low-fluorescence of PMMA was suitable for microscopic imaging of cells flowing through microchannels on the chip. Sample particles flowing through microchannels on the chip were discriminated by an image-recognition unit with a high-speed camera in real time at the rate of 200 event/s, e.g., microparticles 2.5 μm and 3.0 μm in diameter were differentiated with an error rate of less than 2%. Desired cells were separated automatically from other cells by electrophoretic or dielectrophoretic force one by one with a separation efficiency of 90%. Cells in suspension with fluorescent dye were separated using the same kind of microfluidic chip. Sample of 5 μL with 1 × 106 particle/mL was processed within 40 min. Separated cells could be cultured on the microfluidic chip without contamination. The whole operation of sample handling was automated using 3D micropipetting system. These results showed that the novel imaging flow cytometry system is practically applicable for biological research and clinical diagnostics.

  2. Formation of Linear Gradient of Antibiotics on Microfluidic Chips for High-throughput Antibiotic Susceptibility Testing

    Kim, Seunggyu; Lee, Seokhun; Jeon, Jessie S.

    2017-11-01

    To determine the most effective antimicrobial treatments of infectious pathogen, high-throughput antibiotic susceptibility test (AST) is critically required. However, the conventional AST requires at least 16 hours to reach the minimum observable population. Therefore, we developed a microfluidic system that allows maintenance of linear antibiotic concentration and measurement of local bacterial density. Based on the Stokes-Einstein equation, the flow rate in the microchannel was optimized so that linearization was achieved within 10 minutes, taking into account the diffusion coefficient of each antibiotic in the agar gel. As a result, the minimum inhibitory concentration (MIC) of each antibiotic against P. aeruginosa could be immediately determined 6 hours after treatment of the linear antibiotic concentration. In conclusion, our system proved the efficacy of a high-throughput AST platform through MIC comparison with Clinical and Laboratory Standards Institute (CLSI) range of antibiotics. This work was supported by the Climate Change Research Hub (Grant No. N11170060) of the KAIST and by the Brain Korea 21 Plus project.

  3. A microfabricated microfluidic bioMEMS device to model human brain aneurisms: the aneurysm-on-a-chip

    Reece, Lisa M.; Khor, Jian Wei; Thakur, Raviraj; Amin, Ahmed; Wereley, Steven T.; Leary, James F.

    2015-03-01

    Aneurysms are pockets of blood that collect outside blood vessel walls forming dilatations and leaving arterial walls very prone to rupture. There is little information concerning the causes of intracranial aneurysm formation, growth, and rupture. Current treatments include: (1) clipping, and (2) coil embolization, including stent-assisted coiling. Further, the evolution of any aneurysm is assumed to be caused by the remodeling of the affected blood vessel's material constituents (tunica intima, tunica media, or tunica adventitia). Velocity, pressure, and wall shear stresses aid in the disease development of aneurysmal growth, while the shear force mechanisms effecting wound closure are elusive. To study aneurysm pathogenesis, a lab-on-a-chip device is the key to discovering the underlying mechanisms of these lesions. A two-dimensional microfluidic model, the Aneurysm-on-a-Chip™ (AOC), was the logical answer to study particle flow within an aneurysm "sac". The AOC apparatus can track particles/cells when it is coupled to particle image velocimetry software (PIV) package. The AOC fluid flow was visualized using standard microscopy techniques with commercial microparticles and human aortic smooth muscle cells (HASMC). Images were taken during fluid flow experiments and PIV was utilized to monitor the flow of particles within the "sac" region, as well as particles entering and exiting the device. Quiver plots were generated from fluid flow experiments using standard 7 μm latex particles and fixed HASMC in PBS. PIV analysis shows that the particles flowed nicely from input to output. Wall shear stress provided evidence that there was some back flow at the edges of the "sac" - an indicator of aneurysm development in human patients.

  4. Air Quality Effects on Human Health and Approaches for Its Assessment through Microfluidic Chips.

    Schulze, Frank; Gao, Xinghua; Virzonis, Darius; Damiati, Samar; Schneider, Marlon R; Kodzius, Rimantas

    2017-09-27

    Air quality depends on the various gases and particles present in it. Both natural phenomena and human activities affect the cleanliness of air. In the last decade, many countries experienced an unprecedented industrial growth, resulting in changing air quality values, and correspondingly, affecting our life quality. Air quality can be accessed by employing microchips that qualitatively and quantitatively determine the present gases and dust particles. The so-called particular matter 2.5 (PM2.5) values are of high importance, as such small particles can penetrate the human lung barrier and enter the blood system. There are cancer cases related to many air pollutants, and especially to PM2.5, contributing to exploding costs within the healthcare system. We focus on various current and potential future air pollutants, and propose solutions on how to protect our health against such dangerous substances. Recent developments in the Organ-on-Chip (OoC) technology can be used to study air pollution as well. OoC allows determination of pollutant toxicity and speeds up the development of novel pharmaceutical drugs.

  5. On-chip mitochondrial assay microfluidic devices and protein nanopore/nanotube hybrid transistor

    Lim, Taesun

    Tremendous efforts to understand the cause, mechanism of development and the way to treat various diseases as well as an early diagnosis have been made so far and people are still working hardly on these researches. Even now, countless people are suffering from diseases such as Alzhemer's disease, Parkinson's disease, diabetes and cancer without knowing clues to cure their diseases completely. Generally speaking, we still have a long way to go through to comprehensively figure out these our long-lasting homeworks. One of possible solutions is to merge current advanced technology and science together to find a powerful synergetic effect for a specific purpose that can be tailored depending on user's need. Here this research tried to put nanotechnology and biological science together to find a way to resolve current challenges by developing a new generation of the analytical sensing device. Mitochondrial functions and biological roles in regulating life and death control will be discussed indicating mitochondrion is a crucial organism to monitor to obtain important information regarding degenerative diseases and aging process. On-chip mitochondrial functional assay microsensor that could facilitate the mitochondrial evaluation will be extensively demonstrated and discussed in both technical and biological perspectives. The novel fusion technological approach will be demonstrated by combining artificial cell membrane with carbon nanotube electronics to interrogate interactions between biomolecules and electronic circuitries. In addition, molecular dynamics at the cell membrane could be investigated closely which can help understand the cell-cell communication and the regulation of ion transport.

  6. Air Quality Effects on Human Health and Approaches for Its Assessment through Microfluidic Chips

    Frank Schulze

    2017-09-01

    Full Text Available Air quality depends on the various gases and particles present in it. Both natural phenomena and human activities affect the cleanliness of air. In the last decade, many countries experienced an unprecedented industrial growth, resulting in changing air quality values, and correspondingly, affecting our life quality. Air quality can be accessed by employing microchips that qualitatively and quantitatively determine the present gases and dust particles. The so-called particular matter 2.5 (PM2.5 values are of high importance, as such small particles can penetrate the human lung barrier and enter the blood system. There are cancer cases related to many air pollutants, and especially to PM2.5, contributing to exploding costs within the healthcare system. We focus on various current and potential future air pollutants, and propose solutions on how to protect our health against such dangerous substances. Recent developments in the Organ-on-Chip (OoC technology can be used to study air pollution as well. OoC allows determination of pollutant toxicity and speeds up the development of novel pharmaceutical drugs.

  7. Microfluidic chemical reaction circuits

    Lee, Chung-cheng [Irvine, CA; Sui, Guodong [Los Angeles, CA; Elizarov, Arkadij [Valley Village, CA; Kolb, Hartmuth C [Playa del Rey, CA; Huang, Jiang [San Jose, CA; Heath, James R [South Pasadena, CA; Phelps, Michael E [Los Angeles, CA; Quake, Stephen R [Stanford, CA; Tseng, Hsian-rong [Los Angeles, CA; Wyatt, Paul [Tipperary, IE; Daridon, Antoine [Mont-Sur-Rolle, CH

    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.

  8. Three-dimensional ordered titanium dioxide-zirconium dioxide film-based microfluidic device for efficient on-chip phosphopeptide enrichment.

    Zhao, De; He, Zhongyuan; Wang, Gang; Wang, Hongzhi; Zhang, Qinghong; Li, Yaogang

    2016-09-15

    Microfluidic technology plays a significant role in separating biomolecules, because of its miniaturization, integration, and automation. Introducing micro/nanostructured functional materials can improve the properties of microfluidic devices, and extend their application. Inverse opal has a three-dimensional ordered net-like structure. It possesses a large surface area and exhibits good mass transport, making it a good candidate for bio-separation. This study exploits inverse opal titanium dioxide-zirconium dioxide films for on-chip phosphopeptide enrichment. Titanium dioxide-zirconium dioxide inverse opal film-based microfluidic devices were constructed from templates of 270-, 340-, and 370-nm-diameter poly(methylmethacrylate) spheres. The phosphopeptide enrichments of these devices were determined by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. The device constructed from the 270-nm-diameter sphere template exhibited good comprehensive phosphopeptide enrichment, and was the best among these three devices. Because the size of opal template used in construction was the smallest, the inverse opal film therefore had the smallest pore sizes and the largest surface area. Enrichment by this device was also better than those of similar devices based on nanoparticle films and single component films. The titanium dioxide-zirconium dioxide inverse opal film-based device provides a promising approach for the efficient separation of various biomolecules. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Design, microfabrication, and characterization of a moulded PDMS/SU-8 inkjet dispenser for a Lab-on-a-Printer platform technology with disposable microfluidic chip.

    Bsoul, Anas; Pan, Sheng; Cretu, Edmond; Stoeber, Boris; Walus, Konrad

    2016-08-16

    In this paper, we present a disposable inkjet dispenser platform technology and demonstrate the Lab-on-a-Printer concept, an extension of the ubiquitous Lab-on-a-Chip concept, whereby microfluidic modules are directly integrated into the printhead. The concept is demonstrated here through the integration of an inkjet dispenser and a microfluidic mixer enabling control over droplet composition from a single nozzle in real-time during printing. The inkjet dispenser is based on a modular design platform that enables the low-cost microfluidic component and the more expensive actuation unit to be easily separated, allowing for the optional disposal of the former and reuse of the latter. To limit satellite droplet formation, a hydrophobic-coated and tapered micronozzle was microfabricated and integrated with the fluidics to realize the dispenser. The microfabricated devices generated droplets with diameters ranging from 150-220 μm, depending mainly on the orifice diameter, with printing rates up to 8000 droplets per second. The inkjet dispenser is capable of dispensing materials with a viscosity up to ∼19 mPa s. As a demonstration of the inkjet dispenser function and application, we have printed type I collagen seeded with human liver carcinoma cells (cell line HepG2), to form patterned biological structures.

  10. Clinical application of a microfluidic chip for immunocapture and quantification of circulating exosomes to assist breast cancer diagnosis and molecular classification.

    Fang, Shimeng; Tian, Hongzhu; Li, Xiancheng; Jin, Dong; Li, Xiaojie; Kong, Jing; Yang, Chun; Yang, Xuesong; Lu, Yao; Luo, Yong; Lin, Bingcheng; Niu, Weidong; Liu, Tingjiao

    2017-01-01

    Increasing attention has been attracted by exosomes in blood-based diagnosis because cancer cells release more exosomes in serum than normal cells and these exosomes overexpress a certain number of cancer-related biomarkers. However, capture and biomarker analysis of exosomes for clinical application are technically challenging. In this study, we developed a microfluidic chip for immunocapture and quantification of circulating exosomes from small sample volume and applied this device in clinical study. Circulating EpCAM-positive exosomes were measured in 6 cases breast cancer patients and 3 healthy controls to assist diagnosis. A significant increase in the EpCAM-positive exosome level in these patients was detected, compared to healthy controls. Furthermore, we quantified circulating HER2-positive exosomes in 19 cases of breast cancer patients for molecular classification. We demonstrated that the exosomal HER2 expression levels were almost consistent with that in tumor tissues assessed by immunohistochemical staining. The microfluidic chip might provide a new platform to assist breast cancer diagnosis and molecular classification.

  11. Microfluidics for chemical processing

    Gardeniers, Johannes G.E.

    2006-01-01

    Microfluidic systems, and more specifically, microfluidic chips, have a number of features that make them particularly useful for the study of chemical reactions on-line. The present paper will discuss two examples, the study of fluidic behaviour at high pressures and the excitation and detection of

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

    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.

  13. Rapid and Quantitative Detection of Vibrio parahemolyticus by the Mixed-Dye-Based Loop-Mediated Isothermal Amplification Assay on a Self-Priming Compartmentalization Microfluidic Chip.

    Pang, Bo; Ding, Xiong; Wang, Guoping; Zhao, Chao; Xu, Yanan; Fu, Kaiyue; Sun, Jingjing; Song, Xiuling; Wu, Wenshuai; Liu, Yushen; Song, Qi; Hu, Jiumei; Li, Juan; Mu, Ying

    2017-12-27

    Vibrio parahemolyticus (VP) mostly isolated from aquatic products is one of the major causes of bacterial food-poisoning events worldwide, which could be reduced using a promising on-site detection method. Herein, a rapid and quantitative method for VP detection was developed by applying a mixed-dye-loaded loop-mediated isothermal amplification (LAMP) assay on a self-priming compartmentalization (SPC) microfluidic chip, termed on-chip mixed-dye-based LAMP (CMD-LAMP). In comparison to conventional approaches, CMD-LAMP was advantageous on the limit of detection, which reached down to 1 × 10 3 CFU/mL in food-contaminated samples without the pre-enrichment of bacteria. Additionally, as a result of the use of a mixed dye and SPC chip, the quantitative result could be easily acquired, avoiding the requirement of sophisticated instruments and tedious operation. Also, CMD-LAMP was rapid and cost-effective. Conclusively, CMD-LAMP has great potential in realizing the on-site quantitative analysis of VP for food safety.

  14. Development and evaluation of a real-time fluorogenic loop-mediated isothermal amplification assay integrated on a microfluidic disc chip (on-chip LAMP) for rapid and simultaneous detection of ten pathogenic bacteria in aquatic animals.

    Zhou, Qian-Jin; Wang, Lei; Chen, Jiong; Wang, Rui-Na; Shi, Yu-Hong; Li, Chang-Hong; Zhang, De-Min; Yan, Xiao-Jun; Zhang, Yan-Jun

    2014-09-01

    Rapid, low-cost, and user-friendly strategies are urgently needed for early disease diagnosis and timely treatment, particularly for on-site screening of pathogens in aquaculture. In this study, we successfully developed a real-time fluorogenic loop-mediated isothermal amplification assay integrated on a microfluidic disc chip (on-chip LAMP), which was capable of simultaneously detecting 10 pathogenic bacteria in aquatic animals, i.e., Nocardia seriolae, Pseudomonas putida, Streptococcus iniae, Vibrio alginolyticus, Vibrio anguillarum, Vibrio fluvialis, Vibrio harveyi, Vibrio parahaemolyticus, Vibrio rotiferianus, and Vibrio vulnificus. The assay provided a nearly-automated approach, with only a single pipetting step per chip for sample dispensing. This technique could achieve limits of detection (LOD) ranging from 0.40 to 6.42pg per 1.414μL reaction in less than 30 min. The robust reproducibility was demonstrated by a little variation among duplications for each bacterium with the coefficient of variation (CV) for time to positive (Tp) value less than 0.10. The clinical sensitivity and specificity of this on-chip LAMP assay in detecting field samples were 96.2% and 93.8% by comparison with conventional microbiological methods. Compared with other well-known techniques, on-chip LAMP assay provides low sample and reagent consumption, ease-of-use, accelerated analysis, multiple bacteria and on-site detection, and high reproducibility, indicating that such a technique would be applicable for on-site detection and routine monitoring of multiple pathogens in aquaculture. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Microfluidics for medical applications

    van den Berg, Albert; van den Berg, A.; Segerink, L.I.; Segerink, Loes Irene; Unknown, [Unknown

    2015-01-01

    Lab-on-a-chip devices for point of care diagnostics have been present in clinics for several years now. Alongside their continual development, research is underway to bring the organs and tissue on-a-chip to the patient, amongst other medical applications of microfluidics. This book provides the

  16. Nanostructures for all-polymer microfluidic systems

    Matschuk, Maria; Bruus, Henrik; Larsen, Niels Bent

    2010-01-01

    antistiction coating was found to improve the replication fidelity (shape and depth) of nanoscale features substantially. Arrays of holes of 50 nm diameter/35 nm depth and 100 nm/100 nm diameter, respectively, were mass-produced in cyclic olefin copolymer (Topas 5013) by injection molding. Polymer microfluidic...... channel chip parts resulted from a separate injection molding process. The microfluidic chip part and the nanostructured chip part were successfully bonded to form a sealed microfluidic system using air plasma assisted thermal bonding....

  17. Microfluidic DNA microarrays in PMMA chips: streamlined fabrication via simultaneous DNA immobilization and bonding activation by brief UV exposure

    Sabourin, David; Petersen, J; Snakenborg, Detlef

    2010-01-01

    This report presents and describes a simple and scalable method for producing functional DNA microarrays within enclosed polymeric, PMMA, microfluidic devices. Brief (30 s) exposure to UV simultaneously immobilized poly(T)poly(C)-tagged DNA probes to the surface of unmodified PMMA and activated...... the surface for bonding below the glass transition temperature of the bulk PMMA. Functionality and validation of the enclosed PMMA microarrays was demonstrated as 18 patients were correctly genotyped for all eight mutation sites in the HBB gene interrogated. The fabrication process therefore produced probes...... with desired hybridization properties and sufficient bonding between PMMA layers to allow construction of microfluidic devices. The streamlined fabrication method is suited to the production of low-cost microfluidic microarray-based diagnostic devices and, as such, is equally applicable to the development...

  18. Construction of a microfluidic chip, using dried-down reagents, for LATE-PCR amplification and detection of single-stranded DNA.

    Jia, Yanwei; Mak, Pui-In; Massey, Conner; Martins, Rui P; Wangh, Lawrence J

    2013-12-07

    LATE-PCR is an advanced form of non-symmetric PCR that efficiently generates single-stranded DNA which can readily be characterized at the end of amplification by hybridization to low-temperature fluorescent probes. We demonstrate here for the first time that monoplex and duplex LATE-PCR amplification and probe target hybridization can be carried out in double layered PDMS microfluidics chips containing dried reagents. Addition of a set of reagents during dry down overcomes the common problem of single-stranded oligonucleotide binding to PDMS. These proof-of-principle results open the way to construction of inexpensive point-of-care devices that take full advantage of the analytical power of assays built using LATE-PCR and low-temperature probes.

  19. Room-temperature serial crystallography using a kinetically optimized microfluidic device for protein crystallization and on-chip X-ray diffraction

    Michael Heymann

    2014-09-01

    Full Text Available An emulsion-based serial crystallographic technology has been developed, in which nanolitre-sized droplets of protein solution are encapsulated in oil and stabilized by surfactant. Once the first crystal in a drop is nucleated, the small volume generates a negative feedback mechanism that lowers the supersaturation. This mechanism is exploited to produce one crystal per drop. Diffraction data are measured, one crystal at a time, from a series of room-temperature crystals stored on an X-ray semi-transparent microfluidic chip, and a 93% complete data set is obtained by merging single diffraction frames taken from different unoriented crystals. As proof of concept, the structure of glucose isomerase was solved to 2.1 Å, demonstrating the feasibility of high-throughput serial X-ray crystallography using synchrotron radiation.

  20. SAXS on a chip: from dynamics of phase transitions to alignment phenomena at interfaces studied with microfluidic devices.

    Silva, Bruno F B

    2017-09-13

    The field of microfluidics offers attractive possibilities to perform novel experiments that are difficult (or even impossible) to perform using conventional bulk and surface-based methods. Such attractiveness comes from several important aspects inherent to these miniaturized devices. First, the flow of fluids under submillimeter confinement typically leads to a drop of inertial forces, meaning that turbulence is practically suppressed. This leads to predictable and controllable flow profiles, along with well-defined chemical gradients and stress fields that can be used for controlled mixing and actuation on the micro and nanoscale. Secondly, intricate microfluidic device designs can be fabricated using cleanroom standard procedures. Such intricate geometries can take diverse forms, designed by researchers to perform complex tasks, that require exquisite control of flow of several components and gradients, or to mimic real world examples, facilitating the establishment of more realistic models. Thirdly, microfluidic devices are usually compatible with in situ or integrated characterization methods that allow constant real-time monitoring of the processes occurring inside the microchannels. This is very different from typical bulk-based methods, where usually one can only observe the final result, or otherwise, take quick snapshots of the evolving process or take aliquots to be analyzed separately. Altogether, these characteristics inherent to microfluidic devices provide researchers with a set of tools that allow not only exquisite control and manipulation of materials at the micro and nanoscale, but also observation of these effects. In this review, we will focus on the use and prospects of combining microfluidic devices with in situ small-angle X-ray scattering (and related techniques such as small-angle neutron scattering and X-ray photon correlation spectroscopy), and their enormous potential for physical-chemical research, mainly in self-assembly and phase

  1. Microfluidic Platform for the Long-Term On-Chip Cultivation of Mammalian Cells for Lab-On-A-Chip Applications.

    Bunge, Frank; Driesche, Sander van den; Vellekoop, Michael J

    2017-07-10

    Lab-on-a-Chip (LoC) applications for the long-term analysis of mammalian cells are still very rare due to the lack of convenient cell cultivation devices. The difficulties are the integration of suitable supply structures, the need of expensive equipment like an incubator and sophisticated pumps as well as the choice of material. The presented device is made out of hard, but non-cytotoxic materials (silicon and glass) and contains two vertical arranged membranes out of hydrogel. The porous membranes are used to separate the culture chamber from two supply channels for gases and nutrients. The cells are fed continuously by diffusion through the membranes without the need of an incubator and low requirements on the supply of medium to the assembly. The diffusion of oxygen is modelled in order to find the optimal dimensions of the chamber. The chip is connected via 3D-printed holders to the macroscopic world. The holders are coated with Parlyene C to ensure that only biocompatible materials are in contact with the culture medium. The experiments with MDCK-cells show the successful seeding inside the chip, culturing and passaging. Consequently, the presented platform is a step towards Lab-on-a-Chip applications that require long-term cultivation of mammalian cells.

  2. Inhibition of the Hedgehog Signaling Pathway Depresses the Cigarette Smoke-Induced Malignant Transformation of 16HBE Cells on a Microfluidic Chip.

    Qin, Yong-Xin; Yang, Zhi-Hui; Du, Xiao-Hui; Zhao, Hui; Liu, Yuan-Bin; Guo, Zhe; Wang, Qi

    2018-05-20

    The hedgehog signaling system (HHS) plays an important role in the regulation of cell proliferation and differentiation during the embryonic phases. However, little is known about the involvement of HHS in the malignant transformation of cells. This study aimed to detect the role of HHS in the malignant transformation of human bronchial epithelial (16HBE) cells. In this study, two microfluidic chips were designed to investigate cigarette smoke extract (CSE)-induced malignant transformation of cells. Chip A contained a concentration gradient generator, while chip B had four cell chambers with a central channel. The 16HBE cells cultured in chip A were used to determine the optimal concentration of CSE for inducing malignant transformation. The 16HBE cells in chip B were cultured with 12.25% CSE (Group A), 12.25% CSE + 5 μmol/L cyclopamine (Group B), or normal complete medium as control for 8 months (Group C), to establish the in vitro lung inflammatory-cancer transformation model. The transformed cells were inoculated into 20 nude mice as cells alone (Group 1) or cells with cyclopamine (Group 2) for tumorigenesis testing. Expression of HHS proteins was detected by Western blot. Data were expressed as mean ± standard deviation. The t-test was used for paired samples, and the difference among groups was analyzed using a one-way analysis of variance. The optimal concentration of CSE was 12.25%. Expression of HHS proteins increased during the process of malignant transformation (Group B vs. Group A, F = 7.65, P < 0.05). After CSE exposure for 8 months, there were significant changes in cellular morphology, which allowed the transformed cells to grow into tumors in 40 days after being inoculated into nude mice. Cyclopamine could effectively depress the expression of HHS proteins (Group C vs. Group B, F = 6.47, P < 0.05) and prevent tumor growth in nude mice (Group 2 vs. Group 1, t = 31.59, P < 0.01). The activity of HHS is upregulated during the CSE-induced malignant

  3. Fuel cell-powered microfluidic platform for lab-on-a-chip applications: Integration into an autonomous amperometric sensing device.

    Esquivel, J P; Colomer-Farrarons, J; Castellarnau, M; Salleras, M; del Campo, F J; Samitier, J; Miribel-Català, P; Sabaté, N

    2012-11-07

    The present paper reports for the first time the integration of a microfluidic system, electronics modules, amperometric sensor and display, all powered by a single micro direct methanol fuel cell. In addition to activating the electronic circuitry, the integrated power source also acts as a tuneable micropump. The electronics fulfil several functions. First, they regulate the micro fuel cell output power, which off-gas controls the flow rate of different solutions toward an electrochemical sensor through microfluidic channels. Secondly, as the fuel cell powers a three-electrode electrochemical cell, the electronics compare the working electrode output signal with a set reference value. Thirdly, if the concentration measured by the sensor exceeds this threshold value, the electronics switch on an integrated organic display. This integrated approach pushes forward the development of truly autonomous point-of-care devices relying on electrochemical detection.

  4. Geometrical effect characterization of femtosecond-laser manufactured glass microfluidic chips based on optical manipulation of submicroparticles

    Kotsifaki, Domna G.; Mackenzie, Mark D.; Polydefki, Georgia; Kar, Ajoy K.; Makropoulou, Mersini; Serafetinides, Alexandros A.

    2017-12-01

    Microfluidic devices provide a platform with wide ranging applications from environmental monitoring to disease diagnosis. They offer substantive advantages but are often not optimized or designed to be used by nonexpert researchers. Microchannels of a microanalysis platform and their geometrical characterization are of eminent importance when designing such devices. We present a method that is used to optimize each microchannel within a device using high-throughput particle manipulation. For this purpose, glass-based microfluidic devices, with three-dimensional channel networks of several geometrical sizes, were fabricated by employing laser fabrication techniques. The effect of channel geometry was investigated by employing an optical tweezer. The optical trapping force depends on the flow velocity that is associated with the dimensions of the microchannel. We observe a linear dependence of the trapping efficiency and of the fluid flow velocity, with the channel dimensions. We determined that the highest trapping efficiency was achieved for microchannels with aspect ratio equal to one. Numerical simulation validated the impact of the device design dimensions on the trapping efficiency. This investigation indicates that the geometrical characteristics, the flow velocity, and trapping efficiency are crucial and should be considered when fabricating microfluidic devices for cell studies.

  5. Finite element modeling simulation-assisted design of integrated microfluidic chips for heavy metal ion stripping analysis

    Hong, Ying; Zou, Jianhua; Ge, Gang; Xiao, Wanyue; Shao, Jinjun; Dong, Xiaochen; Gao, Ling

    2017-01-01

    In this article, a transparent integrated microfluidic device composed of a 3D-printed thin-layer flow cell (3D-PTLFC) and an S-shaped screen-printed electrode (SPE) has been designed and fabricated for heavy metal ion stripping analysis. A finite element modeling (FEM) simulation is employed to optimize the shape of the electrode, the direction of the inlet pipeline, the thin-layer channel height and the sample flow rate to enhance the electron-enrichment efficiency for stripping analysis. The results demonstrate that the S-shaped SPE configuration matches the channel in 3D-PTLFC perfectly for the anodic stripping behavior of the heavy metal ions. Under optimized conditions, a wide linear range of 1–80 µ g l −1 is achieved for Pb 2+ detection with a limit of 0.3 µ g l −1 for the microfluidic device. Thus, the obtained integrated microfluidic device proves to be a promising approach for heavy metal ions stripping analysis with low cost and high performance. (paper)

  6. Interconnection blocks: a method for providing reusable, rapid, multiple, aligned and planar microfluidic interconnections

    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 observ...

  7. Low-temperature, simple and fast integration technique of microfluidic chips by using a UV-curable adhesive

    Arayanarakool, Rerngchai; le Gac, Severine; van den Berg, Albert

    2010-01-01

    In the fields of MicroElectroMechanical Systems (MEMS) and Lab On a Chip (LOC), a device is often fabricated using diverse substrates which are processed separately and finally assembled together using a bonding process to yield the final device. Here we describe and demonstrate a novel

  8. Microfluidic liquid-air dual-gradient chip for synergic effect bio-evaluation of air pollutant.

    Liu, Xian-Jun; Hu, Shan-Wen; Xu, Bi-Yi; Zhao, Ge; Li, Xiang; Xie, Fu-Wei; Xu, Jing-Juan; Chen, Hong-Yuan

    2018-05-15

    In this paper, a novel prototype liquid-air dual gradient chip is introduced, which has paved the way for effective synergic effect bio-evaluation of air pollutant. The chip is composed of an array of the agarose liquid-air interfaces, top air gradient layer and bottom liquid gradient layer. The novel agarose liquid-air interface allows for non-biased exposure of cells to all the substances in the air and diffusive interactions with the liquid phase; while the dual liquid-air gradient provides powerful screening abilities, which well reduced errors, saved time and cost from repeated experiment. Coupling the two functions, the chip subsequently facilitates synergic effect evaluation of both liquid and air factors on cells. Here cigarette smoke was taken as the model air pollutant, and its strong synergic effects with inflammatory level of A549 lung cancer cells on their fate were successfully quantified for the first time. These results well testified that the proposed dual-gradient chip is powerful and indispensable for bio-evaluation of air pollutant. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Fiber free plug and play on-chip scattering cytometer module – for implementation in microfluidic point of care devices

    Jensen, Thomas Glasdam; Kutter, Jörg Peter

    2010-01-01

    In this paper, we report on recent progress toward the development of a plug and play on-chip cytometer based on light scattering. By developing a device that does not depend on the critical alignment and cumbersome handling of fragile optical fibers, we approach a device that is suitable for non...

  10. Study on the effect of surfactants on morphologies of trigonal selenium in microfluidic reactor

    Bian, Tian-bin [Institute of Microanalytical Systems, Department of Chemistry, Zhejiang University, Zheda Lu 38, Hangzhou 310027 (China); Yin, Xue-feng, E-mail: yinxf@zju.edu.cn [Institute of Microanalytical Systems, Department of Chemistry, Zhejiang University, Zheda Lu 38, Hangzhou 310027 (China); Fan, Jie [Institute of Catalysis, Department of Chemistry, Zhejiang University, Hangzhou 310027 (China); Liu, Jin-hua [College of Material Chemistry and Chemical Engineering, Hangzhou Normal University, Hangzhou 310036 (China)

    2010-02-15

    The influence of the surfactants on the morphologies of trigonal selenium (t-Se) submicrostructures was studied in a two-step microfluidic system, which is composed of a glass microchip for preparing spherical amorphous selenium (a-Se) colloids coupled with a poly(methyl methacrylate) microchip for transferring a-Se into its t-Se seeds under sonication. The selenious acid containing surfactants and hydrazine solutions were delivered through the two-inlets of the glass microfluidic chip. Submicro-rods, -wires as well as -tubes of t-Se were obtained by simply varying the coexisted surfactants. The as-synthesized products were characterized by powder X-ray diffraction (XRD), Raman spectrum, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and selected-area electron diffraction (SAED).

  11. An Impedance Aptasensor with Microfluidic Chips for Specific Detection of H5N1 Avian Influenza Virus

    Jacob Lum

    2015-07-01

    Full Text Available In this research a DNA aptamer, which was selected through SELEX (systematic evolution of ligands by exponential enrichment to be specific against the H5N1 subtype of the avian influenza virus (AIV, was used as an alternative reagent to monoclonal antibodies in an impedance biosensor utilizing a microfluidics flow cell and an interdigitated microelectrode for the specific detection of H5N1 AIV. The gold surface of the interdigitated microelectrode embedded in a microfluidics flow cell was modified using streptavidin. The biotinylated aptamer against H5N1 was then immobilized on the electrode surface using biotin–streptavidin binding. The target virus was captured on the microelectrode surface, causing an increase in impedance magnitude. The aptasensor had a detection time of 30 min with a detection limit of 0.0128 hemagglutinin units (HAU. Scanning electron microscopy confirmed the binding of the target virus onto the electrode surface. The DNA aptamer was specific to H5N1 and had no cross-reaction to other subtypes of AIV (e.g., H1N1, H2N2, H7N2. The newly developed aptasensor offers a portable, rapid, low-cost alternative to current methods with the same sensitivity and specificity.

  12. On-chip microfluidic systems for determination of L-glutamate based on enzymatic recycling of substrate

    Laiwattanapaisal, W.; Yakovleva, J.; Bengtsson, Martin

    2009-01-01

    Two microfluidic systems have been developed for specific analysis of L-glutamate in food based on substrate recycling fluorescence detection. L-glutamate dehydrogenase and a novel enzyme, D-phenylglycine aminotransferase, were covalently immobilized on (i) the surface of silicon microchips....... The reaction was accompanied by reduction of nicotinamide adenine dinucleotide (NAD(+)) to NADH, which was monitored by fluorescence detection (epsilon(ex)=340 nm, epsilon(em)=460 nm). First, the microchip-based system, L-glutamate was detected within a range of 3.1-50.0 mM. Second, to be automatically......). In the case of SIA, the beads were introduced and removed from the microchip automatically. The immobilized beads could be stored in a 20% glycerol and 0.5 mM ethylenediaminetetraacetic acid solution maintained at a pH of 7.0 using a phosphate buffer for at least 15 days with 72% of the activity remaining...

  13. Inhibitory effect of common microfluidic materials on PCR outcome

    Kodzius, Rimantas; Xiao, Kang; Wu, Jinbo; Yi, Xin; Gong, Xiuqing; Foulds, Ian G.; Wen, Weijia

    2012-01-01

    Microfluidic chips have a variety of applications in the biological sciences and medicine. In contrast with traditional experimental approaches, microfluidics entails lower sample and reagent consumption, allows faster reactions and enables

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

    Ahn, Chong H; Nevin, Joseph H; Beaucage, Gregory

    2005-01-01

    ... and reliable measurements of metabolic parameters from a human body with minimum invasion. The fully integrated disposable biochip is capable of precise volume control with smart microfluidic manipulation without costly on-chip microfluidic components...

  15. Microfluidic isotachophoresis: A review

    Smejkal, P.; Bottenus, D.; Breadmore, M. C.; Guijt, R. M.; Ivory, C. F.; Foret, František; Macka, M.

    2013-01-01

    Roč. 34, č. 11 (2013), s. 1493-1509 ISSN 0173-0835 R&D Projects: GA ČR(CZ) GAP301/11/2055 Institutional support: RVO:68081715 Keywords : chip * isotachophoresis * microfluidics * miniaturization Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 3.161, year: 2013

  16. Direct Surface and Droplet Microsampling for Electrospray Ionization Mass Spectrometry Analysis with an Integrated Dual-Probe Microfluidic Chip

    Huang, Cong-Min [Institute of Microanalytical; Zhu, Ying [Institute of Microanalytical; Jin, Di-Qiong [Institute of Microanalytical; Kelly, Ryan T. [Environmental; Fang, Qun [Institute of Microanalytical

    2017-08-15

    Ambient mass spectrometry (MS) has revolutionized the way of MS analysis and broadened its application in various fields. This paper describes the use of microfluidic techniques to simplify the setup and improve the functions of ambient MS by integrating the sampling probe, electrospray emitter probe, and online mixer on a single glass microchip. Two types of sampling probes, including a parallel-channel probe and a U-shaped channel probe, were designed for dryspot and liquid-phase droplet samples, respectively. We demonstrated that the microfabrication techniques not only enhanced the capability of ambient MS methods in analysis of dry-spot samples on various surfaces, but also enabled new applications in the analysis of nanoliter-scale chemical reactions in an array of droplets. The versatility of the microchip-based ambient MS method was demonstrated in multiple different applications including evaluation of residual pesticide on fruit surfaces, sensitive analysis of low-ionizable analytes using postsampling derivatization, and high-throughput screening of Ugi-type multicomponent reactions.

  17. A One-Square-Millimeter Compact Hollow Structure for Microfluidic Pumping on an All-Glass Chip

    Xing Yue (Larry Peng

    2016-04-01

    Full Text Available A micro surface tension pump is a new type of low-cost, built-in, all-glass, microfluidic pump on a glass microchip fabricated by one-step glass etching. However, geometric minimization and optimization for practical use are challenging. Here, we report a one-square-millimeter, built-in, all-glass pump controlled by two-way digital gas pressure. The pump consists simply of two joint chambers and a piston between two gas control channels. It does not require pre-perfusion for initialization, and can immediately begin to run when a liquid enters its inlet channel. It is also more reliable than conventional micro pumps for practical use due to its ability to restart after the formation of a blocking bubble, which can serve as a valuable troubleshooting procedure. Its volumetric pump output was 0.5–0.7 nL·s−1 under a pump head pressure of 300 Pa.

  18. Cell manipulation in microfluidics

    Yun, Hoyoung; Kim, Kisoo; Lee, Won Gu

    2013-01-01

    Recent advances in the lab-on-a-chip field in association with nano/microfluidics have been made for new applications and functionalities to the fields of molecular biology, genetic analysis and proteomics, enabling the expansion of the cell biology field. Specifically, microfluidics has provided promising tools for enhancing cell biological research, since it has the ability to precisely control the cellular environment, to easily mimic heterogeneous cellular environment by multiplexing, and to analyze sub-cellular information by high-contents screening assays at the single-cell level. Various cell manipulation techniques in microfluidics have been developed in accordance with specific objectives and applications. In this review, we examine the latest achievements of cell manipulation techniques in microfluidics by categorizing externally applied forces for manipulation: (i) optical, (ii) magnetic, (iii) electrical, (iv) mechanical and (v) other manipulations. We furthermore focus on history where the manipulation techniques originate and also discuss future perspectives with key examples where available. (topical review)

  19. Heteronuclear Micro-Helmholtz Coil Facilitates µm-Range Spatial and Sub-Hz Spectral Resolution NMR of nL-Volume Samples on Customisable Microfluidic Chips.

    Nils Spengler

    Full Text Available We present a completely revised generation of a modular micro-NMR detector, featuring an active sample volume of ∼ 100 nL, and an improvement of 87% in probe efficiency. The detector is capable of rapidly screening different samples using exchangeable, application-specific, MEMS-fabricated, microfluidic sample containers. In contrast to our previous design, the sample holder chips can be simply sealed with adhesive tape, with excellent adhesion due to the smooth surfaces surrounding the fluidic ports, and so withstand pressures of ∼2.5 bar, while simultaneously enabling high spectral resolution up to 0.62 Hz for H2O, due to its optimised geometry. We have additionally reworked the coil design and fabrication processes, replacing liquid photoresists by dry film stock, whose final thickness does not depend on accurate volume dispensing or precise levelling during curing. We further introduced mechanical alignment structures to avoid time-intensive optical alignment of the chip stacks during assembly, while we exchanged the laser-cut, PMMA spacers by diced glass spacers, which are not susceptible to melting during cutting. Doing so led to an overall simplification of the entire fabrication chain, while simultaneously increasing the yield, due to an improved uniformity of thickness of the individual layers, and in addition, due to more accurate vertical positioning of the wirebonded coils, now delimited by a post base plateau. We demonstrate the capability of the design by acquiring a 1H spectrum of ∼ 11 nmol sucrose dissolved in D2O, where we achieved a linewidth of 1.25 Hz for the TSP reference peak. Chemical shift imaging experiments were further recorded from voxel volumes of only ∼ 1.5 nL, which corresponded to amounts of just 1.5 nmol per voxel for a 1 M concentration. To extend the micro-detector to other nuclei of interest, we have implemented a trap circuit, enabling heteronuclear spectroscopy, demonstrated by two 1H/13C 2D HSQC

  20. Microfluidic redox battery.

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

    2013-07-07

    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.

  1. Highly efficient capture and harvest of circulating tumor cells on a microfluidic chip integrated with herringbone and micropost arrays.

    Xue, Peng; Wu, Yafeng; Guo, Jinhong; Kang, Yuejun

    2015-04-01

    Circulating tumor cells (CTCs), which are derived from primary tumor site and transported to distant organs, are considered as the major cause of metastasis. So far, various techniques have been applied for CTC isolation and enumeration. However, there exists great demand to improve the sensitivity of CTC capture, and it remains challenging to elute the cells efficiently from device for further biomolecular and cellular analyses. In this study, we fabricate a dual functional chip integrated with herringbone structure and micropost array to achieve CTC capture and elution through EpCAM-based immunoreaction. Hep3B tumor cell line is selected as the model of CTCs for processing using this device. The results demonstrate that the capture limit of Hep3B cells can reach up to 10 cells (per mL of sample volume) with capture efficiency of 80% on average. Moreover, the elution rate of the captured Hep3B cells can reach up to 69.4% on average for cell number ranging from 1 to 100. These results demonstrate that this device exhibits dual functions with considerably high capture rate and elution rate, indicating its promising capability for cancer diagnosis and therapeutics.

  2. Particle concentrating and sorting under a rotating electric field by direct optical-liquid heating in a microfluidics chip.

    Chen, Yu-Liang; Jiang, Hong-Ren

    2017-05-01

    We demonstrate a functional rotating electrothermal technique for rapidly concentrating and sorting a large number of particles on a microchip by the combination of particle dielectrophoresis (DEP) and inward rotating electrothermal (RET) flows. Different kinds of particles can be attracted (positive DEP) to or repelled (negative DEP) from electrode edges, and then the n-DEP responsive particles are further concentrated in the heated region by RET flows. The RET flows arise from the spatial inhomogeneous electric properties of fluid caused by direct infrared laser (1470 nm) heating of solution in a rotating electric field. The direction of the RET flows is radially inward to the heated region with a co-field (the same as the rotating electric field) rotation. Moreover, the velocity of the RET flows is proportional to the laser power and the square of the electric field strength. The RET flows are significant over a frequency range from 200 kHz to 5 MHz. The RET flows are generated by the simultaneous application of the infrared laser and the rotating electric field. Therefore, the location of particle concentrating can be controlled within the rotating electric field depending on the position of the laser spot. This multi-field technique can be operated in salt solutions and at higher frequency without external flow pressure, and thus it can avoid electrokinetic phenomena at low frequency to improve the manipulation accuracy for lab-on-chip applications.

  3. Mass-manufacturable polymer microfluidic device for dual fiber optical trapping.

    De Coster, Diane; Ottevaere, Heidi; Vervaeke, Michael; Van Erps, Jürgen; Callewaert, Manly; Wuytens, Pieter; Simpson, Stephen H; Hanna, Simon; De Malsche, Wim; Thienpont, Hugo

    2015-11-30

    We present a microfluidic chip in Polymethyl methacrylate (PMMA) for optical trapping of particles in an 80µm wide microchannel using two counterpropagating single-mode beams. The trapping fibers are separated from the sample fluid by 70µm thick polymer walls. We calculate the optical forces that act on particles flowing in the microchannel using wave optics in combination with non-sequential ray-tracing and further mathematical processing. Our results are compared with a theoretical model and the Mie theory. We use a novel fabrication process that consists of a premilling step and ultraprecision diamond tooling for the manufacturing of the molds and double-sided hot embossing for replication, resulting in a robust microfluidic chip for optical trapping. In a proof-of-concept demonstration, we show the trapping capabilities of the hot embossed chip by trapping spherical beads with a diameter of 6µm, 8µm and 10µm and use the power spectrum analysis of the trapped particle displacements to characterize the trap strength.

  4. Note: A portable Raman analyzer for microfluidic chips based on a dichroic beam splitter for integration of imaging and signal collection light paths

    Geng, Yijia; Xu, Shuping; Xu, Weiqing, E-mail: xuwq@jlu.edu.cn [State Key Laboratory of Supramolecular Structure and Materials, Institute of Theoretical Chemistry, Jilin University, Changchun 130012 (China); Chen, Lei [State Key Laboratory of Supramolecular Structure and Materials, Institute of Theoretical Chemistry, Jilin University, Changchun 130012 (China); College of Physics, Jilin University, Changchun 130012 (China); Chen, Gang [State Key Laboratory of Supramolecular Structure and Materials, Institute of Theoretical Chemistry, Jilin University, Changchun 130012 (China); College of Chemistry, Jilin University, Changchun 130012 (China); Bi, Wenbin [State Key Laboratory of Supramolecular Structure and Materials, Institute of Theoretical Chemistry, Jilin University, Changchun 130012 (China); School of Chemistry and Environmental Engineering, Changchun University of Science and Technology, Changchun 130022 (China); Cui, Haining [College of Physics, Jilin University, Changchun 130012 (China)

    2015-05-15

    An integrated and portable Raman analyzer featuring an inverted probe fixed on a motor-driving adjustable optical module was designed for the combination of a microfluidic system. It possesses a micro-imaging function. The inverted configuration is advantageous to locate and focus microfluidic channels. Different from commercial micro-imaging Raman spectrometers using manual switchable light path, this analyzer adopts a dichroic beam splitter for both imaging and signal collection light paths, which avoids movable parts and improves the integration and stability of optics. Combined with surface-enhanced Raman scattering technique, this portable Raman micro-analyzer is promising as a powerful tool for microfluidic analytics.

  5. Optial sensing systems for microfluidic devices: a review

    Kuswandi, Bambang; Nuriman, [Unknown; Huskens, Jurriaan; Verboom, Willem

    2007-01-01

    This review deals with the application of optical sensing systems for microfluidic devices. In the “off-chip approach” macro-scale optical infrastructure is coupled, while the “on-chip approach” comprises the integration of micro-optical functions into microfluidic devices. The current progress of

  6. Design and Characterization of a Sensorized Microfluidic Cell-Culture System with Electro-Thermal Micro-Pumps and Sensors for Cell Adhesion, Oxygen, and pH on a Glass Chip

    Sebastian M. Bonk

    2015-07-01

    Full Text Available We combined a multi-sensor glass-chip with a microfluidic channel grid for the characterization of cellular behavior. The grid was imprinted in poly-dimethyl-siloxane. Mouse-embryonal/fetal calvaria fibroblasts (MC3T3-E1 were used as a model system. Thin-film platinum (Pt sensors for respiration (amperometric oxygen electrode, acidification (potentiometric pH electrodes and cell adhesion (interdigitated-electrodes structures, IDES allowed us to monitor cell-physiological parameters as well as the cell-spreading behavior. Two on-chip electro-thermal micro-pumps (ETμPs permitted the induction of medium flow in the system, e.g., for medium mixing and drug delivery. The glass-wafer technology ensured the microscopic observability of the on-chip cell culture. Connecting Pt structures were passivated by a 1.2 μm layer of silicon nitride (Si3N4. Thin Si3N4 layers (20 nm or 60 nm were used as the sensitive material of the pH electrodes. These electrodes showed a linear behavior in the pH range from 4 to 9, with a sensitivity of up to 39 mV per pH step. The oxygen sensors were circular Pt electrodes with a sensor area of 78.5 μm2. Their sensitivity was 100 pA per 1% oxygen increase in the range from 0% to 21% oxygen (air saturated. Two different IDES geometries with 30- and 50-μm finger spacings showed comparable sensitivities in detecting the proliferation rate of MC3T3 cells. These cells were cultured for 11 days in vitro to test the biocompatibility, microfluidics and electric sensors of our system under standard laboratory conditions.

  7. Microfluidic Apps for off-the-shelf instruments.

    Mark, Daniel; von Stetten, Felix; Zengerle, Roland

    2012-07-21

    Within the last decade a huge increase in research activity in microfluidics could be observed. However, despite several commercial success stories, microfluidic chips are still not sold in high numbers in mass markets so far. Here we promote a new concept that could be an alternative approach to commercialization: designing microfluidic chips for existing off-the-shelf instruments. Such "Microfluidic Apps" could significantly lower market entry barriers and provide many advantages: developers of microfluidic chips make use of existing equipment or platforms and do not have to develop instruments from scratch; end-users can profit from microfluidics without the need to invest in new equipment; instrument manufacturers benefit from an expanded customer base due to the new applications that can be implemented in their instruments. Microfluidic Apps could be considered as low-cost disposables which can easily be distributed globally via web-shops. Therefore they could be a door-opener for high-volume mass markets.

  8. Preface book Microfluidics for medical applications

    van den Berg, Albert; Segerink, Loes Irene

    2015-01-01

    This book presents an overview of the major microfluidics techniques and platforms used for medicine and medical applications, providing the reader with an overview of the recent developments in this field. It is divided in three parts: (1) tissue and organs on-chip, (2) microfluidics for medicine

  9. Cell Culture Microfluidic Biochips: Experimental Throughput Maximization

    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....

  10. Automated microfluidic devices integrating solid-phase extraction, fluorescent labeling, and microchip electrophoresis for preterm birth biomarker analysis.

    Sahore, Vishal; Sonker, Mukul; Nielsen, Anna V; Knob, Radim; Kumar, Suresh; Woolley, Adam T

    2018-01-01

    We have developed multichannel integrated microfluidic devices for automated preconcentration, labeling, purification, and separation of preterm birth (PTB) biomarkers. We fabricated multilayer poly(dimethylsiloxane)-cyclic olefin copolymer (PDMS-COC) devices that perform solid-phase extraction (SPE) and microchip electrophoresis (μCE) for automated PTB biomarker analysis. The PDMS control layer had a peristaltic pump and pneumatic valves for flow control, while the PDMS fluidic layer had five input reservoirs connected to microchannels and a μCE system. The COC layers had a reversed-phase octyl methacrylate porous polymer monolith for SPE and fluorescent labeling of PTB biomarkers. We determined μCE conditions for two PTB biomarkers, ferritin (Fer) and corticotropin-releasing factor (CRF). We used these integrated microfluidic devices to preconcentrate and purify off-chip-labeled Fer and CRF in an automated fashion. Finally, we performed a fully automated on-chip analysis of unlabeled PTB biomarkers, involving SPE, labeling, and μCE separation with 1 h total analysis time. These integrated systems have strong potential to be combined with upstream immunoaffinity extraction, offering a compact sample-to-answer biomarker analysis platform. Graphical abstract Pressure-actuated integrated microfluidic devices have been developed for automated solid-phase extraction, fluorescent labeling, and microchip electrophoresis of preterm birth biomarkers.

  11. Optimizing Polymer Lab-on-Chip Platforms for Ultrasonic Manipulation: Influence of the Substrate

    Itziar González

    2015-05-01

    Full Text Available The choice of substrate material in a chip that combines ultrasound with microfluidics for handling biological and synthetic microparticles can have a profound effect on the performance of the device. This is due to the high surface-to-volume ratio that exists within such small structures and acquires particular relevance in polymer-based resonators with 3D standing waves. This paper presents three chips developed to perform particle flow-through separation by ultrasound based on a polymeric SU-8 layer containing channelization over three different substrates: Polymethyl methacrylate (PMMA; Pyrex; and a cracked PMMA composite-like structure. Through direct observations of polystyrene microbeads inside the channel, the three checked chips exhibit their potential as disposable continuous concentration devices with different spatial pressure patterns at frequencies of resonance close to 1 Mhz. Chips with Pyrex and cracked PMMA substrates show restrictions on the number of pressure nodes established in the channel associated with the inhibition of 3D modes in the solid structure. The glass-substrate chip presents some advantages associated with lower energy requirements to collect particles. According to the results, the use of polymer-based chips with rigid substrates can be advantageous for applications that require short treatment times (clinical tests handling human samples and low-cost fabrication.

  12. Microfluidic fuel cells and batteries

    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

  13. Tunable on chip optofluidic laser

    Bakal, Avraham; Vannahme, Christoph; Kristensen, Anders

    2016-01-01

    On chip tunable laser is demonstrated by realizing a microfluidic droplet array. The periodicity is controlled by the pressure applied to two separate inlets, allowing to tune the lasing frequency over a broad spectral range.......On chip tunable laser is demonstrated by realizing a microfluidic droplet array. The periodicity is controlled by the pressure applied to two separate inlets, allowing to tune the lasing frequency over a broad spectral range....

  14. Rapid wasted-free microfluidic fabrication based on ink-jet approach for microfluidic sensing applications

    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. A Microfluidics-HPLC/Differential Mobility Spectrometer Macromolecular Detection System for Human and Robotic Missions

    Coy, S. L.; Killeen, K.; Han, J.; Eiceman, G. A.; Kanik, I.; Kidd, R. D.

    2011-01-01

    Our goal is to develop a unique, miniaturized, solute analyzer based on microfluidics technology. The analyzer consists of an integrated microfluidics High Performance Liquid Chromatographic chip / Differential Mobility Spectrometer (?HPLCchip/ DMS) detection system

  16. Fluorescence detection system for microfluidic droplets

    Chen, Binyu; Han, Xiaoming; Su, Zhen; Liu, Quanjun

    2018-05-01

    In microfluidic detection technology, because of the universality of optical methods in laboratory, optical detection is an attractive solution for microfluidic chip laboratory equipment. In addition, the equipment with high stability and low cost can be realized by integrating appropriate optical detection technology on the chip. This paper reports a detection system for microfluidic droplets. Photomultiplier tubes (PMT) is used as a detection device to improve the sensitivity of detection. This system improves the signal to noise ratio by software filtering and spatial filter. The fluorescence intensity is proportional to the concentration of the fluorescence and intensity of the laser. The fluorescence micro droplets of different concentrations can be distinguished by this system.

  17. Digital Microfluidics Sample Analyzer

    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.

  18. A microfluidic device with pillars

    2014-01-01

    The invention provides a microfluidic device for mixing liquid reagents, the device comprises, a chip forming at least one reaction chamber between a bottom and a top and extending between an inlet and an outlet. To enable manufacturing from less rigid materials, the device comprises pillars...

  19. Microfluidic Technologies for Synthetic Biology

    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.

  20. Analytical isotachophoresis of lactate in human serum using dry film photoresist microfluidic chips compatible with a commercially available field-deployable instrument platform

    Smejkal, P.; Breadmore, M. C.; Guijt, R. M.; Foret, František; Bek, F.; Macka, M.

    2013-01-01

    Roč. 803, NOV (2013), s. 135-142 ISSN 0003-2670 R&D Projects: GA ČR(CZ) GAP301/11/2055 Institutional support: RVO:68081715 Keywords : isotachophoresis * microfluidics * fluorescence * indirect detection * serum Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 4.517, year: 2013

  1. Microplasma fabrication: from semiconductor technology for 2D-chips and microfluidic channels to rapid prototyping and 3D-printing of microplasma devices

    Shatford, R.; Karanassios, Vassili

    2014-05-01

    Microplasmas are receiving attention in recent conferences and current scientific literature. In our laboratory, microplasmas-on-chips proved to be particularly attractive. The 2D- and 3D-chips we developed became hybrid because they were fitted with a quartz plate (quartz was used due to its transparency to UV). Fabrication of 2D- and 3D-chips for microplasma research is described. The fabrication methods described ranged from semiconductor fabrication technology, to Computer Numerical Control (CNC) machining, to 3D-printing. These methods may prove to be useful for those contemplating in entering microplasma research but have no access to expensive semiconductor fabrication equipment.

  2. Rapid mask prototyping for microfluidics.

    Maisonneuve, B G C; Honegger, T; Cordeiro, J; Lecarme, O; Thiry, T; Fuard, D; Berton, K; Picard, E; Zelsmann, M; Peyrade, D

    2016-03-01

    With the rise of microfluidics for the past decade, there has come an ever more pressing need for a low-cost and rapid prototyping technology, especially for research and education purposes. In this article, we report a rapid prototyping process of chromed masks for various microfluidic applications. The process takes place out of a clean room, uses a commercially available video-projector, and can be completed in less than half an hour. We quantify the ranges of fields of view and of resolutions accessible through this video-projection system and report the fabrication of critical microfluidic components (junctions, straight channels, and curved channels). To exemplify the process, three common devices are produced using this method: a droplet generation device, a gradient generation device, and a neuro-engineering oriented device. The neuro-engineering oriented device is a compartmentalized microfluidic chip, and therefore, required the production and the precise alignment of two different masks.

  3. Microfluidic immunomagnetic separation for enhanced bacterial detection

    Hoyland, James; Kunstmann-Olsen, Casper; Ahmed, Shakil

    A combined lab-on-a-chip approach combining immunomagnetic separation (IMS) and flow cytometry was developed for the enrichment and detection of salmonella contamination in food samples. Immunomagnetic beads were immobilized in chips consisting of long fractal meanders while contaminated samples...... to obtain maximum capturing efficiency. The effects of channel volume, path length and number of bends of microfluidic chip on IMS efficiency were also determined....

  4. Microfluidic electronics.

    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.

  5. Optical manipulation with two beam traps in microfluidic polymer systems

    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 microflui......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...

  6. Miniaturization of environmental chemical assays in flowing systems: The lab-on-a-valve approach vis-à-vis lab-on-a-chip microfluidic devices

    Miró, Manuel; Hansen, Elo Harald

    2007-01-01

    The analytical capabilities of the microminiaturised lab-on-a-valve (LOV) module integrated into a microsequential injection (muSI) fluidic system in terms of analytical chemical performance, microfluidic handling and on-line sample processing are compared to those of the micro total analysis...... and the kinetics of the chemical reactions at will, LOV allows accommodation of reactions which, at least at the present stage, are not feasible by application of microfluidic LOC systems. Thus, in LOV one may take advantage of kinetic discriminations schemes, where even subtle differences in reactions...... are utilized for analytical purposes. Furthemore, it is also feasible to handle multi-step sequential reactions of divergent kinetics; to conduct multi-parametric determinations without manifold reconfiguration by utilization of the inherent open architecture of the micromachined unit for the implementation...

  7. Spontaneous oscillations in microfluidic networks

    Case, Daniel; Angilella, Jean-Regis; Motter, Adilson

    2017-11-01

    Precisely controlling flows within microfluidic systems is often difficult which typically results in systems being heavily reliant on numerous external pumps and computers. Here, I present a simple microfluidic network that exhibits flow rate switching, bistablity, and spontaneous oscillations controlled by a single pressure. That is, by solely changing the driving pressure, it is possible to switch between an oscillating and steady flow state. Such functionality does not rely on external hardware and may even serve as an on-chip memory or timing mechanism. I use an analytic model and rigorous fluid dynamics simulations to show these results.

  8. Potentiometric chip-based multipumping flow system for the simultaneous determination of fluoride, chloride, pH, and redox potential in water samples.

    Chango, Gabriela; Palacio, Edwin; Cerdà, Víctor

    2018-08-15

    A simple potentiometric chip-based multipumping flow system (MPFS) has been developed for the simultaneous determination of fluoride, chloride, pH, and redox potential in water samples. The proposed system was developed by using a poly(methyl methacrylate) chip microfluidic-conductor using the advantages of flow techniques with potentiometric detection. For this purpose, an automatic system has been designed and built by optimizing the variables involved in the process, such as: pH, ionic strength, stirring and sample volume. This system was applied successfully to water samples getting a versatile system with an analysis frequency of 12 samples per hour. Good correlation between chloride and fluoride concentration measured with ISE and ionic chromatography technique suggests satisfactory reliability of the system. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Interfacing Lab-on-a-Chip Embryo Technology with High-Definition Imaging Cytometry.

    Zhu, Feng; Hall, Christopher J; Crosier, Philip S; Wlodkowic, Donald

    2015-08-01

    To spearhead deployment of zebrafish embryo biotests in large-scale drug discovery studies, automated platforms are needed to integrate embryo in-test positioning and immobilization (suitable for high-content imaging) with fluidic modules for continuous drug and medium delivery under microperfusion to developing embryos. In this work, we present an innovative design of a high-throughput three-dimensional (3D) microfluidic chip-based device for automated immobilization and culture and time-lapse imaging of developing zebrafish embryos under continuous microperfusion. The 3D Lab-on-a-Chip array was fabricated in poly(methyl methacrylate) (PMMA) transparent thermoplastic using infrared laser micromachining, while the off-chip interfaces were fabricated using additive manufacturing processes (fused deposition modelling and stereolithography). The system's design facilitated rapid loading and immobilization of a large number of embryos in predefined clusters of traps during continuous microperfusion of drugs/toxins. It was conceptually designed to seamlessly interface with both upright and inverted fluorescent imaging systems and also to directly interface with conventional microtiter plate readers that accept 96-well plates. Compared with the conventional Petri dish assays, the chip-based bioassay was much more convenient and efficient as only small amounts of drug solutions were required for the whole perfusion system running continuously over 72 h. Embryos were spatially separated in the traps that assisted tracing single embryos, preventing interembryo contamination and improving imaging accessibility.

  10. Plastic lab-on-a-chip for fluorescence excitation with integrated organic semiconductor lasers.

    Vannahme, Christoph; Klinkhammer, Sönke; Lemmer, Uli; Mappes, Timo

    2011-04-25

    Laser light excitation of fluorescent markers offers highly sensitive and specific analysis for bio-medical or chemical analysis. To profit from these advantages for applications in the field or at the point-of-care, a plastic lab-on-a-chip with integrated organic semiconductor lasers is presented here. First order distributed feedback lasers based on the organic semiconductor tris(8-hydroxyquinoline) aluminum (Alq3) doped with the laser dye 4-dicyanomethylene-2-methyl-6-(p-dimethylaminostyril)-4H-pyrane (DCM), deep ultraviolet induced waveguides, and a nanostructured microfluidic channel are integrated into a poly(methyl methacrylate) (PMMA) substrate. A simple and parallel fabrication process is used comprising thermal imprint, DUV exposure, evaporation of the laser material, and sealing by thermal bonding. The excitation of two fluorescent marker model systems including labeled antibodies with light emitted by integrated lasers is demonstrated.

  11. Generation of tunable and pulsatile concentration gradients via microfluidic network

    Zhou, Bingpu; Xu, Wei; Wang, Cong; Chau, Yeungyeung; Zeng, Xiping; Zhang, Xixiang; Shen, Rong; Wen, Weijia

    2014-01-01

    We demonstrate a compact Polydimethylsiloxane microfluidic chip which can quickly generate ten different chemical concentrations simultaneously. The concentration magnitude of each branch can be flexibly regulated based on the flow rate ratios

  12. Practical Packaging Technology for Microfluidic Systems

    Lee, Hwan Yong; Han, Song I; Han, Ki Ho

    2010-01-01

    This paper presents the technology for the design, fabrication, and characterization of a microfluidic system interface (MSI): the purpose of this technology is to enable the integration of complex microfluidic systems. The MSI technology can be applied in a simple manner for realizing complex arrangements of microfluidic interconnects, integrated microvalves for fluid control, and optical windows for on-chip optical processes. A microfluidic system for the preparation of genetic samples was used as the test vehicle to prove the effectiveness of the MSI technology for packaging complex microfluidic systems with multiple functionalities. The miniaturized genetic sample preparation system comprised several functional compartments, including compartments for cell purification, cell separation, cell lysis, solid-phase DNA extraction, polymerase chain reaction, and capillary electrophoresis. Additionally, the functional operation of the solid-phase extraction and PCR thermocycling compartments was demonstrated by using the MSI

  13. Manipulation of microfluidic droplets by electrorheological fluid

    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.

  14. Aptamer entrapment in microfluidic channel using one-step sol-gel process, in view of the integration of a new selective extraction phase for lab-on-a-chip.

    Perréard, Camille; d'Orlyé, Fanny; Griveau, Sophie; Liu, Baohong; Bedioui, Fethi; Varenne, Anne

    2017-10-01

    There is a great demand for integrating sample treatment into μTASs. In this context, we developed a new sol-gel phase for extraction of trace compounds in complex matrices. For this purpose, the incorporation of aptamers in silica-based gel within PDMS/glass microfluidic channels was performed for the first time by a one-step sol-gel process. The effective gel attachment onto microchannel walls and aptamer incorporation in the polymerized gel were evaluated using fluorescence microscopy. A good gel stability and aptamer incorporation inside the microchannel was demonstrated upon rinsing and over storage time. The ability of gel-encapsulated aptamers to interact with its specific target (either sulforhodamine B as model fluorescent target, or diclofenac, a pain killer drug) was assessed too. The binding capacity of entrapped aptamers was quantified (in the micromolar range) and the selectivity of the interaction was evidenced. Preservation of aptamers binding affinity to target molecules was therefore demonstrated. Dissociation constant of the aptamer-target complex and interaction selectivity were evaluated similar to those in bulk solution. This opens the way to new selective on-chip SPE techniques for sample pretreatment. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Integrated Microfluidic Sensor System with Magnetostrictive Resonators

    Liang, Cai; Kosel, Jü rgen; Gooneratne, Chinthaka

    2011-01-01

    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.

  16. Microfluidic device for acoustic cell lysis

    Branch, Darren W.; Cooley, Erika Jane; Smith, Gennifer Tanabe; James, Conrad D.; McClain, Jaime L.

    2015-08-04

    A microfluidic acoustic-based cell lysing device that can be integrated with on-chip nucleic acid extraction. Using a bulk acoustic wave (BAW) transducer array, acoustic waves can be coupled into microfluidic cartridges resulting in the lysis of cells contained therein by localized acoustic pressure. Cellular materials can then be extracted from the lysed cells. For example, nucleic acids can be extracted from the lysate using silica-based sol-gel filled microchannels, nucleic acid binding magnetic beads, or Nafion-coated electrodes. Integration of cell lysis and nucleic acid extraction on-chip enables a small, portable system that allows for rapid analysis in the field.

  17. Integrated Microfluidic Gas Sensors for Water Monitoring

    Zhu, L.; Sniadecki, N.; DeVoe, D. L.; Beamesderfer, M.; Semancik, S.; DeVoe, D. L.

    2003-01-01

    A silicon-based microhotplate tin oxide (SnO2) gas sensor integrated into a polymer-based microfluidic system for monitoring of contaminants in water systems is presented. This device is designed to sample a water source, control the sample vapor pressure within a microchannel using integrated resistive heaters, and direct the vapor past the integrated gas sensor for analysis. The sensor platform takes advantage of novel technology allowing direct integration of discrete silicon chips into a larger polymer microfluidic substrate, including seamless fluidic and electrical interconnects between the substrate and silicon chip.

  18. Integrated Microfluidic Sensor System with Magnetostrictive Resonators

    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.

  19. Magnetic separation in microfluidic systems

    Smistrup, Kristian

    2007-01-01

    to facilitate real-time monitoring of the experiments. The set-up and experimental protocol are described in detail. Results are presented for ’active’ magnetic bead separators, where on-chip microfabricated electromagnets supply the magnetic field and field gradients necessary for magnetic bead separation....... 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...

  20. Interconnection blocks: a method for providing reusable, rapid, multiple, aligned and planar microfluidic interconnections

    Sabourin, D; Snakenborg, D; Dufva, M

    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 observation. The interconnection block method is scalable, flexible and supports high interconnection density. The average pressure limit of the interconnection block was near 5.5 bar and all individual results were well above the 2 bar threshold considered applicable to most microfluidic applications

  1. Microfluidic Biochip Design

    Panzarella, Charles

    2004-01-01

    As humans prepare for the exploration of our solar system, there is a growing need for miniaturized medical and environmental diagnostic devices for use on spacecrafts, especially during long-duration space missions where size and power requirements are critical. In recent years, the biochip (or Lab-on-a- Chip) has emerged as a technology that might be able to satisfy this need. In generic terms, a biochip is a miniaturized microfluidic device analogous to the electronic microchip that ushered in the digital age. It consists of tiny microfluidic channels, pumps and valves that transport small amounts of sample fluids to biosensors that can perform a variety of tests on those fluids in near real time. It has the obvious advantages of being small, lightweight, requiring less sample fluids and reagents and being more sensitive and efficient than larger devices currently in use. Some of the desired space-based applications would be to provide smaller, more robust devices for analyzing blood, saliva and urine and for testing water and food supplies for the presence of harmful contaminants and microorganisms. Our group has undertaken the goal of adapting as well as improving upon current biochip technology for use in long-duration microgravity environments. In addition to developing computational models of the microfluidic channels, valves and pumps that form the basis of every biochip, we are also trying to identify potential problems that could arise in reduced gravity and develop solutions to these problems. One such problem is due to the prevalence of bubbly sample fluids in microgravity. A bubble trapped in a microfluidic channel could be detrimental to the operation of a biochip. Therefore, the process of bubble formation in microgravity needs to be studied, and a model of this process has been developed and used to understand how bubbles develop and move through biochip components. It is clear that some type of bubble filter would be necessary in Space, and

  2. Design of a microfluidic device with a non-traditional flow profile for on-chip damage to zebrafish sensory cells

    Kwon, Hyuck-Jin; Xu, Yuhao; Solovitz, Stephen A; Xue, Wei; Xu, Jie; Dimitrov, Alexander G; Coffin, Allison B

    2014-01-01

    Hearing loss affects millions of people worldwide and often results from the death of the sensory hair cells in the inner ear, and exposure to intense noise is one of the leading causes of hair cell damage. Recently, the zebrafish lateral line system has emerged as a powerful in vivo model for real-time studies of hair cell damage and protection. In this research, we designed a microfluidic device for inducing noise damage in hair cells of the zebrafish lateral line. As the first step, a 3D computational fluid dynamics (CFD) simulation was utilized to predict the flow pattern inside the device. An ideal flow pattern for our application should feature higher velocity near the sidewalls to over-stimulate the externally located hair cells, and minimum flow in the middle of the channel to protect the fish from high pressure on the head. Flow induced from ordinary channel geometry with a single inlet/outlet pair would not work because the parabolic velocity profile features the maximum flow speed in the middle of the channel. In order to achieve the desired flow pattern, sidewall inlet/outlet pairs were used to suppress the growth of boundary layers. CFD simulation was used to design parameters such as the dimensions of the microfluidic channel and the angle of the inlets and outlets. It was found that in the case of an empty 2.0 mm wide channel with the inlet/outlet pairs set to 45°, the flow velocity at the side of the channel would be 6.7 times faster than the velocity in the middle, approaching the optimal flow characteristics. In the case of a fish-loaded channel, simulation shows that a 1.0 mm wide channel with a 60° inlet/outlet angle creates the lowest pressure (0.3 Pa) on the fish head while maintaining a reasonably strong shear stress (1.9 Pa) on the lateral line hair cells. (technical note)

  3. Electromembrane extraction of biogenic amines in food samples by a microfluidic-chip system followed by dabsyl derivatization prior to high performance liquid chromatography analysis.

    Zarghampour, Fereshteh; Yamini, Yadollah; Baharfar, Mahroo; Faraji, Mohammad

    2018-06-29

    In the present research, an on-chip electromembrane extraction coupled with high performance liquid chromatography was developed for monitoring the trace levels of biogenic amines (BAs), including histamine, tryptamine, putrescine, cadaverine and spermidine in food samples. A porous polypropylene sheet membrane impregnated with an organic solvent was placed between the two parts of the chip device to separate the channels. Two platinum electrodes were mounted at the bottom of these channels, which were connected to a power supply, providing the electrical driving force for migration of ionized analytes from the sample solution through the porous sheet membrane into the acceptor phase. BAs were extracted from 2 mL aqueous sample solutions at neutral pH into 50 μL of acidified (HCl 90 mM) acceptor solution. Supported liquid membrane including NPOE containing 10% DEHP was used to ensure efficient extraction. Low voltage of 40 V was applied over the SLMs during extraction time. The influences of fundamental parameters affecting the transport of BAs were optimized. Under the optimized conditions, the relative standard deviations based on four replicate measurements were less than 8.0% and limit of detections were in range of 3.0-8.0 μg L -1 . Finally, the method was successfully applied to determinate BAs in the food samples and satisfactory results (recovery > 95.6) were obtained. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Immunodetection of salivary biomarkers by an optical microfluidic biosensor with polyethylenimine-modified polythiophene-C70 organic photodetectors.

    Dong, Tao; Pires, Nuno Miguel Matos

    2017-08-15

    This work reports a novel optical microfluidic biosensor with highly sensitive organic photodetectors (OPDs) for absorbance-based detection of salivary protein biomarkers at the point of care. The compact and miniaturized biosensor has comprised OPDs made of polythiophene-C 70 bulk heterojunction for the photoactive layer; whilst a calcium-free cathode interfacial layer, made of linear polyethylenimine, was incorporated to the photodetectors to enhance the low cost. The OPDs realized onto a glass chip were aligned to antibody-functionalized chambers of a poly(methyl methacrylate) microfluidic chip, in where immunogold-silver assays were conducted. The biosensor has detected IL-8, IL-1β and MMP-8 protein in spiked saliva with high detection specificity and short analysis time exhibiting detection limits between 80pgmL -1 and 120pgmL -1 . The result for IL-8 was below the clinical established cut-off of 600pgmL -1 , which revealed the potential of the biosensor to early detection of oral cancer. The detection limit was also comparable to other previously reported immunosensors performed with bulky instrumentation or using inorganic photodetectors. The optical detection sensitivity of the polythiophene-C 70 OPD was enhanced by optimizing the thickness of the photoactive layer and anode interfacial layer prior to the saliva immunoassays. Further, the biosensor was tested with unspiked human saliva samples, and the results of measuring IL-8 and IL-1β were in statistical agreement with those provided by two commercial assays of ELISA. The optical microfluidic biosensor reported hereby offers an attractive and cost-effective tool to diagnostics or screening purposes at the point of care. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Long-term brain slice culturing in a microfluidic platform

    Vedarethinam, Indumathi; Avaliani, N.; Tønnesen, J.

    2011-01-01

    In this work, we present the development of a transparent poly(methyl methacrylate) (PMMA) based microfluidic culture system for handling long-term brain slice cultures independent of an incubator. The different stages of system development have been validated by culturing GFP producing brain sli...

  6. Optical chromatography using a photonic crystal fiber with on-chip fluorescence excitation

    Ashok, AC

    2010-03-01

    Full Text Available The authors describe the realization of integrated optical chromatography, in conjunction with on-chip fluorescence excitation, in a monolithically fabricated poly-dimethylsiloxane (PDMS) microfluidic chip. The unique endlessly-single-mode guiding...

  7. Encapsulation of Fluidic Tubing and Microelectrodes in Microfluidic Devices: Integrating Off-Chip Process and Coupling Conventional Capillary Electrophoresis with Electrochemical Detection.

    Becirovic, Vedada; Doonan, Steven R; Martin, R Scott

    2013-08-21

    In this paper, an approach to fabricate epoxy or polystyrene microdevices with encapsulated tubing and electrodes is described. Key features of this approach include a fixed alignment between the fluidic tubing and electrodes, the ability to polish the device when desired, and the low dead volume nature of the fluidic interconnects. It is shown that a variety of tubing can be encapsulated with this approach, including fused silica capillary, polyetheretherketone (PEEK), and perfluoroalkoxy (PFA), with the resulting tubing/microchip interface not leading to significant band broadening or plug dilution. The applicability of the devices with embedded tubing is demonstrated by integrating several off-chip analytical methods to the microchip. This includes droplet transfer, droplet desegmentation, and microchip-based flow injection analysis. Off-chip generated droplets can be transferred to the microchip with minimal coalescence, while flow injection studies showed improved peak shape and sensitivity when compared to the use of fluidic interconnects with an appreciable dead volume. Importantly, it is shown that this low dead volume approach can be extended to also enable the integration of conventional capillary electrophoresis (CE) with electrochemical detection. This is accomplished by embedding fused silica capillary along with palladium (for grounding the electrophoresis voltage) and platinum (for detection) electrodes. With this approach, up to 128,000 theoretical plates for dopamine was possible. In all cases, the tubing and electrodes are housed in a rigid base; this results in extremely robust devices that will be of interest to researchers wanting to develop microchips for use by non-experts.

  8. Skin Diseases Modeling using Combined Tissue Engineering and Microfluidic Technologies.

    Mohammadi, Mohammad Hossein; Heidary Araghi, Behnaz; Beydaghi, Vahid; Geraili, Armin; Moradi, Farshid; Jafari, Parya; Janmaleki, Mohsen; Valente, Karolina Papera; Akbari, Mohsen; Sanati-Nezhad, Amir

    2016-10-01

    In recent years, both tissue engineering and microfluidics have significantly contributed in engineering of in vitro skin substitutes to test the penetration of chemicals or to replace damaged skins. Organ-on-chip platforms have been recently inspired by the integration of microfluidics and biomaterials in order to develop physiologically relevant disease models. However, the application of organ-on-chip on the development of skin disease models is still limited and needs to be further developed. The impact of tissue engineering, biomaterials and microfluidic platforms on the development of skin grafts and biomimetic in vitro skin models is reviewed. The integration of tissue engineering and microfluidics for the development of biomimetic skin-on-chip platforms is further discussed, not only to improve the performance of present skin models, but also for the development of novel skin disease platforms for drug screening processes. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Microfluidic CODES: a scalable multiplexed electronic sensor for orthogonal detection of particles in microfluidic channels.

    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.

  10. Light-responsive polymers for microfluidic applications

    ter Schiphorst, J.; Saez, J.; Diamond, D.; Benito-Lopez, F.; Schenning, A.P.H.J.

    2018-01-01

    While the microfluidic device itself may be small, often the equipment required to control fluidics in the chip unit is large e.g. pumps, valves and mixing units, which can severely limit practical use and functional scalability. In addition, components associated with fluidic control of the device,

  11. Tunable on chip optofluidic laser

    Bakal, Avraham; Vannahme, Christoph; Kristensen, Anders

    2015-01-01

    A chip scale tunable laser in the visible spectral band is realized by generating a periodic droplet array inside a microfluidic channel. Combined with a gain medium within the droplets, the periodic structure provides the optical feedback of the laser. By controlling the pressure applied to two...

  12. Pneumatic oscillator circuits for timing and control of integrated microfluidics.

    Duncan, Philip N; Nguyen, Transon V; Hui, Elliot E

    2013-11-05

    Frequency references are fundamental to most digital systems, providing the basis for process synchronization, timing of outputs, and waveform synthesis. Recently, there has been growing interest in digital logic systems that are constructed out of microfluidics rather than electronics, as a possible means toward fully integrated laboratory-on-a-chip systems that do not require any external control apparatus. However, the full realization of this goal has not been possible due to the lack of on-chip frequency references, thus requiring timing signals to be provided from off-chip. Although microfluidic oscillators have been demonstrated, there have been no reported efforts to characterize, model, or optimize timing accuracy, which is the fundamental metric of a clock. Here, we report pneumatic ring oscillator circuits built from microfluidic valves and channels. Further, we present a compressible-flow analysis that differs fundamentally from conventional circuit theory, and we show the utility of this physically based model for the optimization of oscillator stability. Finally, we leverage microfluidic clocks to demonstrate circuits for the generation of phase-shifted waveforms, self-driving peristaltic pumps, and frequency division. Thus, pneumatic oscillators can serve as on-chip frequency references for microfluidic digital logic circuits. On-chip clocks and pumps both constitute critical building blocks on the path toward achieving autonomous laboratory-on-a-chip devices.

  13. A microfluidic sub-critical water extraction instrument

    Sherrit, Stewart; Noell, Aaron C.; Fisher, Anita; Lee, Mike C.; Takano, Nobuyuki; Bao, Xiaoqi; Kutzer, Thomas C.; Grunthaner, Frank

    2017-11-01

    This article discusses a microfluidic subcritical water extraction (SCWE) chip for autonomous extraction of amino acids from astrobiologically interesting samples. The microfluidic instrument is composed of three major components. These include a mixing chamber where the soil sample is mixed and agitated with the solvent (water), a subcritical water extraction chamber where the sample is sealed with a freeze valve at the chip inlet after a vapor bubble is injected into the inlet channels to ensure the pressure in the chip is in equilibrium with the vapor pressure and the slurry is then heated to ≤200 °C in the SCWE chamber, and a filter or settling chamber where the slurry is pumped to after extraction. The extraction yield of the microfluidic SCWE chip process ranged from 50% compared to acid hydrolysis and 80%-100% compared to a benchtop microwave SCWE for low biomass samples.

  14. Optical calorimetry in microfluidic droplets.

    Chamoun, Jacob; Pattekar, Ashish; Afshinmanesh, Farzaneh; Martini, Joerg; Recht, Michael I

    2018-05-29

    A novel microfluidic calorimeter that measures the enthalpy change of reactions occurring in 100 μm diameter aqueous droplets in fluoropolymer oil has been developed. The aqueous reactants flow into a microfluidic droplet generation chip in separate fluidic channels, limiting contact between the streams until immediately before they form the droplet. The diffusion-driven mixing of reactants is predominantly restricted to within the droplet. The temperature change in droplets due to the heat of reaction is measured optically by recording the reflectance spectra of encapsulated thermochromic liquid crystals (TLC) that are added to one of the reactant streams. As the droplets travel through the channel, the spectral characteristics of the TLC represent the internal temperature, allowing optical measurement with a precision of ≈6 mK. The microfluidic chip and all fluids are temperature controlled, and the reaction heat within droplets raises their temperature until thermal diffusion dissipates the heat into the surrounding oil and chip walls. Position resolved optical temperature measurement of the droplets allows calculation of the heat of reaction by analyzing the droplet temperature profile over time. Channel dimensions, droplet generation rate, droplet size, reactant stream flows and oil flow rate are carefully balanced to provide rapid diffusional mixing of reactants compared to thermal diffusion, while avoiding thermal "quenching" due to contact between the droplets and the chip walls. Compared to conventional microcalorimetry, which has been used in this work to provide reference measurements, this new continuous flow droplet calorimeter has the potential to perform titrations ≈1000-fold faster while using ≈400-fold less reactants per titration.

  15. Microfluidic photoinduced chemical oxidation for Ru(bpy)33 + chemiluminescence - A comprehensive experimental comparison with on-chip direct chemical oxidation

    Kadavilpparampu, Afsal Mohammed; Al Lawati, Haider A. J.; Suliman, Fakhr Eldin O.

    2017-08-01

    For the first time, the analytical figures of merit in detection capabilities of the very less explored photoinduced chemical oxidation method for Ru(bpy)32 + CL has been investigated in detail using 32 structurally different analytes. It was carried out on-chip using peroxydisulphate and visible light and compared with well-known direct chemical oxidation approaches using Ce(IV). The analytes belong to various chemical classes such as tertiary amine, secondary amine, sulphonamide, betalactam, thiol and benzothiadiazine. Influence of detection environment on CL emission with respect to method of oxidation was evaluated by changing the buffers and pH. The photoinduced chemical oxidation exhibited more universal nature for Ru(bpy)32 + CL in detection towards selected analytes. No additional enhancers, reagents, or modification in instrumental configuration were required. Wide detectability and enhanced emission has been observed for analytes from all the chemical classes when photoinduced chemical oxidation was employed. Some of these analytes are reported for the first time under photoinduced chemical oxidation like compounds from sulphonamide, betalactam, thiol and benzothiadiazine class. On the other hand, many of the selected analytes including tertiary and secondary amines such as cetirizine, azithromycin fexofenadine and proline did not produced any analytically useful CL signal (S/N = 3 or above for 1 μgmL- 1 analyte) under chemical oxidation. The most fascinating observations was in the detection limits; for example ofloxacin was 15 times more intense with a detection limit of 5.81 × 10- 10 M compared to most lowest ever reported 6 × 10- 9 M. Earlier, penicillamine was detected at 0.1 μg mL- 1 after derivatization using photoinduced chemical oxidation, but in this study, we improved it to 5.82 ng mL- 1 without any prior derivatization. The detection limits of many other analytes were also found to be improved by several orders of magnitude under

  16. Bioanalysis in microfluidic devices.

    Khandurina, Julia; Guttman, András

    2002-01-18

    Microfabricated bioanalytical devices (also referred to as laboratory-on-a-chip or micro-TAS) offer highly efficient platforms for simultaneous analysis of a large number of biologically important molecules, possessing great potential for genome, proteome and metabolome studies. Development and implementation of microfluidic-based bioanalytical tools involves both established and evolving technologies, including microlithography, micromachining, micro-electromechanical systems technology and nanotechnology. This article provides an overview of the latest developments in the key device subject areas and the basic interdisciplinary technologies. Important aspects of DNA and protein analysis, interfacing issues and system integration are all thoroughly discussed, along with applications for this novel "synergized" technology in high-throughput separations of biologically important molecules. This review also gives a better understanding of how to utilize these technologies as well as to provide appropriate technical solutions to problems perceived as being more fundamental.

  17. Facile fabrication of microfluidic surface-enhanced Raman scattering devices via lift-up lithography

    Wu, Yuanzi; Jiang, Ye; Zheng, Xiaoshan; Jia, Shasha; Zhu, Zhi; Ren, Bin; Ma, Hongwei

    2018-04-01

    We describe a facile and low-cost approach for a flexibly integrated surface-enhanced Raman scattering (SERS) substrate in microfluidic chips. Briefly, a SERS substrate was fabricated by the electrostatic assembling of gold nanoparticles, and shaped into designed patterns by subsequent lift-up soft lithography. The SERS micro-pattern could be further integrated within microfluidic channels conveniently. The resulting microfluidic SERS chip allowed ultrasensitive in situ SERS monitoring from the transparent glass window. With its advantages in simplicity, functionality and cost-effectiveness, this method could be readily expanded into optical microfluidic fabrication for biochemical applications.

  18. Fast architecture-level synthesis of fault-tolerant flow-based microfluidic biochips

    Huang, Wei Lun; Gupta, Ankur; Roy, Sudip

    2017-01-01

    Microfluidic-based lab-on-a-chips have emerged as a popular technology for implementation of different biochemical test protocols used in medical diagnostics. However, in the manufacturing process or during operation of such chips, some faults may occur that leads to damage of the chip, which...

  19. Microfluidic photoinduced chemical oxidation for Ru(bpy)33+ chemiluminescence - A comprehensive experimental comparison with on-chip direct chemical oxidation.

    Kadavilpparampu, Afsal Mohammed; Al Lawati, Haider A J; Suliman, Fakhr Eldin O

    2017-08-05

    For the first time, the analytical figures of merit in detection capabilities of the very less explored photoinduced chemical oxidation method for Ru(bpy) 3 2+ CL has been investigated in detail using 32 structurally different analytes. It was carried out on-chip using peroxydisulphate and visible light and compared with well-known direct chemical oxidation approaches using Ce(IV). The analytes belong to various chemical classes such as tertiary amine, secondary amine, sulphonamide, betalactam, thiol and benzothiadiazine. Influence of detection environment on CL emission with respect to method of oxidation was evaluated by changing the buffers and pH. The photoinduced chemical oxidation exhibited more universal nature for Ru(bpy) 3 2+ CL in detection towards selected analytes. No additional enhancers, reagents, or modification in instrumental configuration were required. Wide detectability and enhanced emission has been observed for analytes from all the chemical classes when photoinduced chemical oxidation was employed. Some of these analytes are reported for the first time under photoinduced chemical oxidation like compounds from sulphonamide, betalactam, thiol and benzothiadiazine class. On the other hand, many of the selected analytes including tertiary and secondary amines such as cetirizine, azithromycin fexofenadine and proline did not produced any analytically useful CL signal (S/N=3 or above for 1μgmL -1 analyte) under chemical oxidation. The most fascinating observations was in the detection limits; for example ofloxacin was 15 times more intense with a detection limit of 5.81×10 -10 M compared to most lowest ever reported 6×10 -9 M. Earlier, penicillamine was detected at 0.1μgmL -1 after derivatization using photoinduced chemical oxidation, but in this study, we improved it to 5.82ngmL -1 without any prior derivatization. The detection limits of many other analytes were also found to be improved by several orders of magnitude under photoinduced

  20. Integrated lasers for polymer Lab-on-a-Chip systems

    Mappes, Timo; Vannahme, Christoph; Grosmann, Tobias

    2012-01-01

    We develop optical Lab-on-a-Chips on different platforms for marker-based and label-free biophotonic sensor applications. Our chips are based on polymers and fabricated by mass production technologies to integrate microfluidic channels, optical waveguides and miniaturized lasers.......We develop optical Lab-on-a-Chips on different platforms for marker-based and label-free biophotonic sensor applications. Our chips are based on polymers and fabricated by mass production technologies to integrate microfluidic channels, optical waveguides and miniaturized lasers....

  1. Microfluidic Devices for Forensic DNA Analysis: A Review.

    Bruijns, Brigitte; van Asten, Arian; Tiggelaar, Roald; Gardeniers, Han

    2016-08-05

    Microfluidic devices may offer various advantages for forensic DNA analysis, such as reduced risk of contamination, shorter analysis time and direct application at the crime scene. Microfluidic chip technology has already proven to be functional and effective within medical applications, such as for point-of-care use. In the forensic field, one may expect microfluidic technology to become particularly relevant for the analysis of biological traces containing human DNA. This would require a number of consecutive steps, including sample work up, DNA amplification and detection, as well as secure storage of the sample. This article provides an extensive overview of microfluidic devices for cell lysis, DNA extraction and purification, DNA amplification and detection and analysis techniques for DNA. Topics to be discussed are polymerase chain reaction (PCR) on-chip, digital PCR (dPCR), isothermal amplification on-chip, chip materials, integrated devices and commercially available techniques. A critical overview of the opportunities and challenges of the use of chips is discussed, and developments made in forensic DNA analysis over the past 10-20 years with microfluidic systems are described. Areas in which further research is needed are indicated in a future outlook.

  2. Valve Concepts for Microfluidic Cell Handling

    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.

  3. Microfluidic Device

    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.

  4. Integrated microchip incorporating atomic magnetometer and microfluidic channel for NMR and MRI

    Ledbetter, Micah P [Oakland, CA; Savukov, Igor M [Los Alamos, NM; Budker, Dmitry [El Cerrito, CA; Shah, Vishal K [Plainsboro, NJ; Knappe, Svenja [Boulder, CO; Kitching, John [Boulder, CO; Michalak, David J [Berkeley, CA; Xu, Shoujun [Houston, TX; Pines, Alexander [Berkeley, CA

    2011-08-09

    An integral microfluidic device includes an alkali vapor cell and microfluidic channel, which can be used to detect magnetism for nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI). Small magnetic fields in the vicinity of the vapor cell can be measured by optically polarizing and probing the spin precession in the small magnetic field. This can then be used to detect the magnetic field of in encoded analyte in the adjacent microfluidic channel. The magnetism in the microfluidic channel can be modulated by applying an appropriate series of radio or audio frequency pulses upstream from the microfluidic chip (the remote detection modality) to yield a sensitive means of detecting NMR and MRI.

  5. Materials for Microfluidic Immunoassays: A Review.

    Mou, Lei; Jiang, Xingyu

    2017-08-01

    Conventional immunoassays suffer from at least one of these following limitations: long processing time, high costs, poor user-friendliness, technical complexity, poor sensitivity and specificity. Microfluidics, a technology characterized by the engineered manipulation of fluids in channels with characteristic lengthscale of tens of micrometers, has shown considerable promise for improving immunoassays that could overcome these limitations in medical diagnostics and biology research. The combination of microfluidics and immunoassay can detect biomarkers with faster assay time, reduced volumes of reagents, lower power requirements, and higher levels of integration and automation compared to traditional approaches. This review focuses on the materials-related aspects of the recent advances in microfluidics-based immunoassays for point-of-care (POC) diagnostics of biomarkers. We compare the materials for microfluidic chips fabrication in five aspects: fabrication, integration, function, modification and cost, and describe their advantages and drawbacks. In addition, we review materials for modifying antibodies to improve the performance of the reaction of immunoassay. We also review the state of the art in microfluidic immunoassays POC platforms, from the laboratory to routine clinical practice, and also commercial products in the market. Finally, we discuss the current challenges and future developments in microfluidic immunoassays. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Micro-optics for microfluidic analytical applications.

    Yang, Hui; Gijs, Martin A M

    2018-02-19

    This critical review summarizes the developments in the integration of micro-optical elements with microfluidic platforms for facilitating detection and automation of bio-analytical applications. Micro-optical elements, made by a variety of microfabrication techniques, advantageously contribute to the performance of an analytical system, especially when the latter has microfluidic features. Indeed the easy integration of optical control and detection modules with microfluidic technology helps to bridge the gap between the macroscopic world and chip-based analysis, paving the way for automated and high-throughput applications. In our review, we start the discussion with an introduction of microfluidic systems and micro-optical components, as well as aspects of their integration. We continue with a detailed description of different microfluidic and micro-optics technologies and their applications, with an emphasis on the realization of optical waveguides and microlenses. The review continues with specific sections highlighting the advantages of integrated micro-optical components in microfluidic systems for tackling a variety of analytical problems, like cytometry, nucleic acid and protein detection, cell biology, and chemical analysis applications.

  7. Optical two-beam traps in microfluidic systems

    Berg-Sørensen, Kirstine

    2016-01-01

    An attractive solution for optical trapping and stretching by means of two counterpropagating laser beams is to embed waveguides or optical fibers in a microfluidic system. The microfluidic system can be constructed in different materials, ranging from soft polymers that may easily be cast...... written waveguides and in an injection molded polymer chip with grooves for optical fibers. (C) 2016 The Japan Society of Applied Physics....

  8. Applications of micro/nanoparticles in microfluidic sensors: a review.

    Jiang, Yusheng

    2014-04-21

    This paper reviews the applications of micro/nanoparticles in microfluidics device fabrication and analytical processing. In general, researchers have focused on two properties of particles--electric behavior and magnetic behavior. The applications of micro/nanoparticles could be summarized on the chip fabrication level and on the processing level. In the fabrication of microfluidic chips (chip fabrication level), particles are good additives in polydimethylsiloxane (PDMS) to prepare conductive or magnetic composites which have wide applications in sensors, valves and actuators. On the other hand, particles could be manipulated according to their electric and magnetic properties under external electric and magnetic fields when they are travelling in microchannels (processing level). Researchers have made a great progress in preparing modified PDMS and investigating the behaviors of particles in microchannels. This article attempts to present a discussion on the basis of particles applications in microfluidics.

  9. Design of a confocal microfluidic particle sorter using fluorescent photon burst detection

    Kunst, B.H.; Schots, A.; Visser, A.J.W.G.

    2004-01-01

    An instrumental system is described for detecting and sorting single fluorescent particles such as microspheres, bacteria, viruses, or even smaller macromolecules in a flowing liquid. The system consists of microfluidic chips (biochips), computer controlled high voltage power supplies, and a

  10. Control Synthesis for the Flow-Based Microfluidic Large-Scale Integration Biochips

    Minhass, Wajid Hassan; Pop, Paul; Madsen, Jan

    2013-01-01

    In this paper we are interested in flow-based microfluidic biochips, which are able to integrate the necessary functions for biochemical analysis on-chip. In these chips, the flow of liquid is manipulated using integrated microvalves. By combining severalmicrovalves, more complex units, such asmi......In this paper we are interested in flow-based microfluidic biochips, which are able to integrate the necessary functions for biochemical analysis on-chip. In these chips, the flow of liquid is manipulated using integrated microvalves. By combining severalmicrovalves, more complex units...

  11. Microfluidic interconnects

    Benett, William J.; Krulevitch, Peter A.

    2001-01-01

    A miniature connector for introducing microliter quantities of solutions into microfabricated fluidic devices. The fluidic connector, for example, joins standard high pressure liquid chromatography (HPLC) tubing to 1 mm diameter holes in silicon or glass, enabling ml-sized volumes of sample solutions to be merged with .mu.l-sized devices. The connector has many features, including ease of connect and disconnect; a small footprint which enables numerous connectors to be located in a small area; low dead volume; helium leak-tight; and tubing does not twist during connection. Thus the connector enables easy and effective change of microfluidic devices and introduction of different solutions in the devices.

  12. Soft tubular microfluidics for 2D and 3D applications

    Xi, Wang; Kong, Fang; Yeo, Joo Chuan; Yu, Longteng; Sonam, Surabhi; Dao, Ming; Gong, Xiaobo; Teck Lim, Chwee

    2017-10-01

    Microfluidics has been the key component for many applications, including biomedical devices, chemical processors, microactuators, and even wearable devices. This technology relies on soft lithography fabrication which requires cleanroom facilities. Although popular, this method is expensive and labor-intensive. Furthermore, current conventional microfluidic chips precludes reconfiguration, making reiterations in design very time-consuming and costly. To address these intrinsic drawbacks of microfabrication, we present an alternative solution for the rapid prototyping of microfluidic elements such as microtubes, valves, and pumps. In addition, we demonstrate how microtubes with channels of various lengths and cross-sections can be attached modularly into 2D and 3D microfluidic systems for functional applications. We introduce a facile method of fabricating elastomeric microtubes as the basic building blocks for microfluidic devices. These microtubes are transparent, biocompatible, highly deformable, and customizable to various sizes and cross-sectional geometries. By configuring the microtubes into deterministic geometry, we enable rapid, low-cost formation of microfluidic assemblies without compromising their precision and functionality. We demonstrate configurable 2D and 3D microfluidic systems for applications in different domains. These include microparticle sorting, microdroplet generation, biocatalytic micromotor, triboelectric sensor, and even wearable sensing. Our approach, termed soft tubular microfluidics, provides a simple, cheaper, and faster solution for users lacking proficiency and access to cleanroom facilities to design and rapidly construct microfluidic devices for their various applications and needs.

  13. Microfluidic process monitor for industrial solvent extraction system

    Gelis, Artem; Pereira, Candido; Nichols, Kevin Paul Flood

    2016-01-12

    The present invention provides a system for solvent extraction utilizing a first electrode with a raised area formed on its surface, which defines a portion of a microfluidic channel; a second electrode with a flat surface, defining another portion of the microfluidic channel that opposes the raised area of the first electrode; a reversibly deformable substrate disposed between the first electrode and second electrode, adapted to accommodate the raised area of the first electrode and having a portion that extends beyond the raised area of the first electrode, that portion defining the remaining portions of the microfluidic channel; and an electrolyte of at least two immiscible liquids that flows through the microfluidic channel. Also provided is a system for performing multiple solvent extractions utilizing several microfluidic chips or unit operations connected in series.

  14. Next generation, in-situ microfluidic flow control using stimuli responsive materials for biomemetic microfluicic platforms

    Coleman, Simon; Azouz, Aymen Ben; Schiphorst, Jeroen Ter; Saez, Janire; Whyte, Jeffrey; McCluskey, Peter; Kent, Nigel; Benito-Lopez, Fernando; Schenning, Albert; Diamond, Dermot

    2016-01-01

    The requirement of significant off-chip fluid manipulation using high-cost mechanical components has resulted in design limitations in microfluidic devices. We report the use of novel stimuli responsive polymer gel materials for a variety of bio-inspired processes to achieve in-situ microfluidic

  15. Merging microfluidics and sonochemistry: towards greener and more efficient micro-sono-reactors

    Fernandez Rivas, David; Cintas, P.; Gardeniers, Johannes G.E.

    2012-01-01

    Microfluidics enable the manipulation of chemical reactions using very small amounts of fluid, in channels with dimensions of tens to hundreds of micrometers; so-called microstructured devices, from which the iconic image of chips emerges. The immediate attraction of microfluidics lies in its

  16. Inkjet printing of UV-curable adhesive and dielectric inks for microfluidic devices.

    Hamad, E M; Bilatto, S E R; Adly, N Y; Correa, D S; Wolfrum, B; Schöning, M J; Offenhäusser, A; Yakushenko, A

    2016-01-07

    Bonding of polymer-based microfluidics to polymer substrates still poses a challenge for Lab-On-a-Chip applications. Especially, when sensing elements are incorporated, patterned deposition of adhesives with curing at ambient conditions is required. Here, we demonstrate a fabrication method for fully printed microfluidic systems with sensing elements using inkjet and stereolithographic 3D-printing.

  17. Routing-based Synthesis of Digital Microfluidic Biochips

    Maftei, Elena; Pop, Paul; Madsen, Jan

    2010-01-01

    Microfluidic biochips are replacing the conventional biochemical analyzers, and are able to integrate on-chip all the basic functsions for biochemical analysis. The "digital" microfluidic biochips are manipulating liquids not as a continuous flow, but as discrete droplets on a two-dimensional array...... of electrodes. Basic microfluidic operations, such as mixing and dilution, are performed on the array, by routing the corresponding droplets on a series of electrodes. So far, researchers have assumed that these operations are executed on rectangular virtual devices, formed by grouping several adjacent...

  18. Electrogates for stop-and-go control of liquid flow in microfluidics

    Arango, Y.; Temiz, Y.; Gökçe, O.; Delamarche, E.

    2018-04-01

    Diagnostics based on microfluidic devices necessitate specific reagents, flow conditions, and kinetics for optimal performance. Such an optimization is often achieved using assay-specific microfluidic chip designs or systems with external liquid pumps. Here, we present "electrogates" for stop-and-go control of flow of liquids in capillary-driven microfluidic chips by combining liquid pinning and electrowetting. Electrogates are simple to fabricate and efficient: a sample pipetted to a microfluidic chip flows autonomously in 15-μm-deep hydrophilic channels until the liquid meniscus is pinned at the edge of a 1.5-μm-deep trench patterned at the bottom of a rectangular microchannel. The flow can then be resumed by applying a DC voltage between the liquid and the trench via integrated electrodes. Using a trench geometry with a semicircular shape, we show that retention times longer than 30 min are achieved for various aqueous solutions such as biological buffers, artificial urine, and human serum. We studied the activation voltage and activation delay of electrogates using a chip architecture having 6 independent flow paths and experimentally showed that the flow can be resumed in less than 1 s for voltages smaller than 10 V, making this technique compatible with low-power and portable microfluidic systems. Electrogates therefore can make capillary-driven microfluidic chips very versatile by adding flow control in microfluidic channels in a flexible manner.

  19. Microfluidic Pumps Containing Teflon [Trademark] AF Diaphragms

    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.

  20. Designing Polymeric Microfluidic Platforms for Biomedical Applications

    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...... analyses systems in use today. The overall goal of this PhD project is to address two different areas using microfluidics : i) Chromosome analysis by metaphase FISH such a platform, if successful, can immediately substitute the routine, labor-intensive, glass slide-based FISH analyses in Clinical...... Cytogenetics laboratories. During the course of this project, initially the suitability of the polymeric chip substrate was tested and a microfluidic device was developed for performing interphase FISH analysis. With this device, the key factors involved in chromosome spreading crucial to FISH analysis were...

  1. "Connecting worlds - a view on microfluidics for a wider application".

    Fernandes, Ana C; Gernaey, Krist V; Krühne, Ulrich

    From its birth, microfluidics has been referenced as a revolutionary technology and the solution to long standing technological and sociological issues, such as detection of dilute compounds and personalized healthcare. Microfluidics has for example been envisioned as: (1) being capable of miniaturizing industrial production plants, thereby increasing their automation and operational safety at low cost; (2) being able to identify rare diseases by running bioanalytics directly on the patient's skin; (3) allowing health diagnostics in point-of-care sites through cheap lab-on-a-chip devices. However, the current state of microfluidics, although technologically advanced, has so far failed to reach the originally promised widespread use. In this paper, some of the aspects are identified and discussed that have prevented microfluidics from reaching its full potential, especially in the chemical engineering and biotechnology fields, focusing mainly on the specialization on a single target of most microfluidic devices and offering a perspective on the alternate, multi-use, "plug and play" approach. Increasing the flexibility of microfluidic platforms, by increasing their compatibility with different substrates, reactions and operation conditions, and other microfluidic systems is indeed of surmount importance and current academic and industrial approaches to modular microfluidics are presented. Furthermore, two views on the commercialization of plug-and-play microfluidics systems, leading towards improved acceptance and more widespread use, are introduced. A brief review of the main materials and fabrication strategies used in these fields, is also presented. Finally, a step-wise guide towards the development of microfluidic systems is introduced with special focus on the integration of sensors in microfluidics. The proposed guidelines are then applied for the development of two different example platforms, and to three examples taken from literature. With this work, we

  2. Macromolecular Crystal Growth by Means of Microfluidics

    vanderWoerd, Mark; Ferree, Darren; Spearing, Scott; Monaco, Lisa; Molho, Josh; Spaid, Michael; Brasseur, Mike; Curreri, Peter A. (Technical Monitor)

    2002-01-01

    We have performed a feasibility study in which we show that chip-based, microfluidic (LabChip(TM)) technology is suitable for protein crystal growth. This technology allows for accurate and reliable dispensing and mixing of very small volumes while minimizing bubble formation in the crystallization mixture. The amount of (protein) solution remaining after completion of an experiment is minimal, which makes this technique efficient and attractive for use with proteins, which are difficult or expensive to obtain. The nature of LabChip(TM) technology renders it highly amenable to automation. Protein crystals obtained in our initial feasibility studies were of excellent quality as determined by X-ray diffraction. Subsequent to the feasibility study, we designed and produced the first LabChip(TM) device specifically for protein crystallization in batch mode. It can reliably dispense and mix from a range of solution constituents into two independent growth wells. We are currently testing this design to prove its efficacy for protein crystallization optimization experiments. In the near future we will expand our design to incorporate up to 10 growth wells per LabChip(TM) device. Upon completion, additional crystallization techniques such as vapor diffusion and liquid-liquid diffusion will be accommodated. Macromolecular crystallization using microfluidic technology is envisioned as a fully automated system, which will use the 'tele-science' concept of remote operation and will be developed into a research facility for the International Space Station as well as on the ground.

  3. Microfluidic chips for clinical and forensic analysis

    Verpoorte, Elisabeth

    2002-01-01

    This review gives an overview of developments in the field of microchip analysis for clinical diagnostic and forensic applications. The approach chosen to review the literature is different from that in most microchip reviews to date, in that the information is presented in terms of analytes tested

  4. Production Quality Control Of Microfluidic Chip Designs

    Calaon, Matteo; Hansen, Hans Nørgaard; Tosello, Guido

    2012-01-01

    The challenge of fabricating geometries with critical dimensions ranging from few microns down to 10 nanometers with high production rate is delaying the development of nanotechnology based products. Diverse research works have shown the capability of technologies such as UV lithography, nano imp...

  5. Microfluidic Mixing Technology for a Universal Health Sensor

    Chan, Eugene Y.; Bae, Candice

    2009-01-01

    A highly efficient means of microfluidic mixing has been created for use with the rHEALTH sensor an elliptical mixer and passive curvilinear mixing patterns. The rHEALTH sensor provides rapid, handheld, complete blood count, cell differential counts, electrolyte measurements, and other lab tests based on a reusable, flow-based microfluidic platform. These geometries allow for cleaning in a reusable manner, and also allow for complete mixing of fluid streams. The microfluidic mixing is performed by flowing two streams of fluid into an elliptical or curvilinear design that allows the combination of the flows into one channel. The mixing is accomplished by either chaotic advection around micro - fluidic loops. All components of the microfluidic chip are flow-through, meaning that cleaning solution can be introduced into the chip to flush out cells, plasma proteins, and dye. Tests were performed on multiple chip geometries to show that cleaning is efficient in any flowthrough design. The conclusion from these experiments is that the chip can indeed be flushed out with microliter volumes of solution and biological samples are cleaned readily from the chip with minimal effort. The technology can be applied in real-time health monitoring at patient s bedside or in a doctor s office, and real-time clinical intervention in acute situations. It also can be used for daily measurement of hematocrit for patients on anticoagulant drugs, or to detect acute myocardial damage outside a hospital.

  6. On-chip integrated lasers for biophotonic applications

    Mappes, Timo; Wienhold, Tobias; Bog, Uwe

    Meeting the need of biomedical users, we develop disposable Lab-on-a-Chip systems based on commercially available polymers. We are combining passive microfluidics with active optical elements on-chip by integrating multiple solid-state and liquid-core lasers. While covering a wide range of laser ...

  7. Microfluidics for Antibiotic Susceptibility and Toxicity Testing

    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.

  8. Design of Microfluidic Biochips (Dagstuhl Seminar 15352)

    Chakrabarty, Krishnendu; Ho, Tsung-Yi; Wille, Robert

    2016-01-01

    Advances in microfluidic technologies have led to the emergence of biochip devices for automating laboratory procedures in biochemistry and molecular biology. Corresponding systems are revolutionizing a diverse range of applications, e.g.~air quality studies, point-of-care clinical diagnostics, drug discovery, and DNA sequencing -- with an increasing market. However, this continued growth depends on advances in chip integration and design-automation tools. Thus, there is a need to deliver the...

  9. Easy fabrication of high quality nickel mold for deep polymer microfluidic channels

    Wong, Ten It; Tan, Christina Yuan Ling; Zhou, Xiaodong; Limantoro, Julian; Fong, Kin Phang; Quan, Chenggen; Sun, Ling Ling

    2016-01-01

    Mass fabrication of disposable microfluidic chips with hot embossing is a key technology for microfluidic chip based biosensors. In this work, we develop a new method of fabricating high quality and highly durable nickel molds for hot embossing polymer chips. The process involves the addition of a thick, patterned layer of negative photoresist AZ-125nxT to a 4″ silicon wafer, followed by nickel electroplating and delamination of the nickel mold. Our investigations found that compared to a pillar mask, a hole mask can minimize the diffraction effect in photolithography of a thick photoresist, reduce the adhesion of the AZ-125nxT to the photomask in photolithography, and facilitate clean development of the photoresist patterns. By optimizing the hot embossing and chip bonding parameters, microfluidic chips with deep channels are achieved. (paper)

  10. A polymer chip-integrable piezoelectric micropump with low backpressure dependence

    Conde, A. J.; Bianchetti, A.; Veiras, F. E.

    2015-01-01

    We describe a piezoelectric micropump constructed in polymers with conventional machining methods. The micropump is self-contained and can be built as an independent device or as an on-chip module within laminated microfluidic chips. We demonstrate on-chip integrability by the fabrication and tes...

  11. Accelerated Biofluid Filling in Complex Microfluidic Networks by Vacuum-Pressure Accelerated Movement (V-PAM).

    Yu, Zeta Tak For; Cheung, Mei Ki; Liu, Shirley Xiaosu; Fu, Jianping

    2016-09-01

    Rapid fluid transport and exchange are critical operations involved in many microfluidic applications. However, conventional mechanisms used for driving fluid transport in microfluidics, such as micropumping and high pressure, can be inaccurate and difficult for implementation for integrated microfluidics containing control components and closed compartments. Here, a technology has been developed termed Vacuum-Pressure Accelerated Movement (V-PAM) capable of significantly enhancing biofluid transport in complex microfluidic environments containing dead-end channels and closed chambers. Operation of the V-PAM entails a pressurized fluid loading into microfluidic channels where gas confined inside can rapidly be dissipated through permeation through a thin, gas-permeable membrane sandwiched between microfluidic channels and a network of vacuum channels. Effects of different structural and operational parameters of the V-PAM for promoting fluid filling in microfluidic environments have been studied systematically. This work further demonstrates the applicability of V-PAM for rapid filling of temperature-sensitive hydrogels and unprocessed whole blood into complex irregular microfluidic networks such as microfluidic leaf venation patterns and blood circulatory systems. Together, the V-PAM technology provides a promising generic microfluidic tool for advanced fluid control and transport in integrated microfluidics for different microfluidic diagnosis, organs-on-chips, and biomimetic studies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Fully integrated optical system for lab-on-a-chip applications

    Balslev, Søren; Olsen, Brian Bilenberg; Geschke, Oliver

    2004-01-01

    We present a lab-on-a-chip device featuring a microfluidic dye laser, wave-guides, microfluidic components and photo-detectors integrated on the chip. The microsystem is designed for wavelength selective absorption measurements in the visible range on a fluidic sample, which can be prepared....../mixed on-chip. The laser structures, wave-guides and micro-fluidic handling system are defined in a single UV-lithography step on a 10 μm thick SU-8 layer on top of the substrate. The SU-8 structures are sealed by a Borofloat glass lid, using polymethylmethacrylate (PMMA) adhesive bonding....

  13. Desktop aligner for fabrication of multilayer microfluidic devices.

    Li, Xiang; Yu, Zeta Tak For; Geraldo, Dalton; Weng, Shinuo; Alve, Nitesh; Dun, Wu; Kini, Akshay; Patel, Karan; Shu, Roberto; Zhang, Feng; Li, Gang; Jin, Qinghui; Fu, Jianping

    2015-07-01

    Multilayer assembly is a commonly used technique to construct multilayer polydimethylsiloxane (PDMS)-based microfluidic devices with complex 3D architecture and connectivity for large-scale microfluidic integration. Accurate alignment of structure features on different PDMS layers before their permanent bonding is critical in determining the yield and quality of assembled multilayer microfluidic devices. Herein, we report a custom-built desktop aligner capable of both local and global alignments of PDMS layers covering a broad size range. Two digital microscopes were incorporated into the aligner design to allow accurate global alignment of PDMS structures up to 4 in. in diameter. Both local and global alignment accuracies of the desktop aligner were determined to be about 20 μm cm(-1). To demonstrate its utility for fabrication of integrated multilayer PDMS microfluidic devices, we applied the desktop aligner to achieve accurate alignment of different functional PDMS layers in multilayer microfluidics including an organs-on-chips device as well as a microfluidic device integrated with vertical passages connecting channels located in different PDMS layers. Owing to its convenient operation, high accuracy, low cost, light weight, and portability, the desktop aligner is useful for microfluidic researchers to achieve rapid and accurate alignment for generating multilayer PDMS microfluidic devices.

  14. Biosensors-on-chip: a topical review

    Chen, Sensen; Shamsi, Mohtashim H

    2017-01-01

    This review will examine the integration of two fields that are currently at the forefront of science, i.e. biosensors and microfluidics. As a lab-on-a-chip (LOC) technology, microfluidics has been enriched by the integration of various detection tools for analyte detection and quantitation. The application of such microfluidic platforms is greatly increased in the area of biosensors geared towards point-of-care diagnostics. Together, the merger of microfluidics and biosensors has generated miniaturized devices for sample processing and sensitive detection with quantitation. We believe that microfluidic biosensors (biosensors-on-chip) are essential for developing robust and cost effective point-of-care diagnostics. This review is relevant to a variety of disciplines, such as medical science, clinical diagnostics, LOC technologies including MEMs/NEMs, and analytical science. Specifically, this review will appeal to scientists working in the two overlapping fields of biosensors and microfluidics, and will also help new scientists to find their directions in developing point-of-care devices. (topical review)

  15. Microfluidic sieve valves

    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.

  16. Microfluidic Dye Lasers

    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...

  17. System-level modeling and simulation of the cell culture microfluidic biochip ProCell

    Minhass, Wajid Hassan; Pop, Paul; Madsen, Jan

    2010-01-01

    Microfluidic biochips offer a promising alternative to a conventional biochemical laboratory. There are two technologies for the microfluidic biochips: droplet-based and flow-based. In this paper we are interested in flow-based microfluidic biochips, where the liquid flows continuously through pre......-defined micro-channels using valves and pumps. We present an approach to the system-level modeling and simulation of a cell culture microfluidic biochip called ProCell, Programmable Cell Culture Chip. ProCell contains a cell culture chamber, which is envisioned to run 256 simultaneous experiments (viewed...

  18. A decade of microfluidic analysis coupled with electrospray mass spectrometry: An overview

    Koster, S.; Verpoorte, E.

    2007-01-01

    This review presents a thorough overview covering the period 1997-2006 of microfluidic chips coupled to mass spectrometry through an electrospray interface. The different types of fabrication processes and materials used to fabricate these chips throughout this period are discussed. Three 'eras' of

  19. A decade of microfluidic analysis coupled with electrospray mass spectrometry : An overview

    Koster, Sander; Verpoorte, Elisabeth

    2007-01-01

    This review presents a thorough overview covering the period 1997-2006 of microfluidic chips coupled to mass spectrometry through an electrospray interface. The different types of fabrication processes and materials used to fabricate these chips throughout this period are discussed. Three 'eras' of

  20. Fabrication and characterization of injection molded multi level nano and microfluidic systems

    Matteucci, Marco; Christiansen, Thomas Lehrmann; Tanzi, Simone

    2013-01-01

    We here present a method for fabrication of multi-level all-polymer chips by means of silicon dry etching, electroplating and injection molding. This method was used for successful fabrication of microfluidic chips for applications in the fields of electrochemistry, cell trapping and DNA elongati...

  1. Rapid photochemical surface patterning of proteins in thiol-ene based microfluidic devices

    Lafleur, Josiane P.; Kwapiszewski, Radoslaw; Jensen, Thomas Glasdam

    2012-01-01

    ” and “ene” monomers present in the microfluidic chip bulk material provides a simple and efficient way of tuning the chip’s surface chemistry. Here, thiol-ene chips displaying an excess of functional thiol groups at their surfaces are functionalized with biotin and streptavidin in a controlled fashion using...

  2. Microfluidic Devices for Drug Delivery Systems and Drug Screening

    Kompella, Uday B.; Damiati, Safa A.

    2018-01-01

    Microfluidic devices present unique advantages for the development of efficient drug carrier particles, cell-free protein synthesis systems, and rapid techniques for direct drug screening. Compared to bulk methods, by efficiently controlling the geometries of the fabricated chip and the flow rates of multiphase fluids, microfluidic technology enables the generation of highly stable, uniform, monodispersed particles with higher encapsulation efficiency. Since the existing preclinical models are inefficient drug screens for predicting clinical outcomes, microfluidic platforms might offer a more rapid and cost-effective alternative. Compared to 2D cell culture systems and in vivo animal models, microfluidic 3D platforms mimic the in vivo cell systems in a simple, inexpensive manner, which allows high throughput and multiplexed drug screening at the cell, organ, and whole-body levels. In this review, the generation of appropriate drug or gene carriers including different particle types using different configurations of microfluidic devices is highlighted. Additionally, this paper discusses the emergence of fabricated microfluidic cell-free protein synthesis systems for potential use at point of care as well as cell-, organ-, and human-on-a-chip models as smart, sensitive, and reproducible platforms, allowing the investigation of the effects of drugs under conditions imitating the biological system. PMID:29462948

  3. Hybrid Integrated Silicon Microfluidic Platform for Fluorescence Based Biodetection

    André Darveau

    2007-09-01

    Full Text Available The desideratum to develop a fully integrated Lab-on-a-chip device capable ofrapid specimen detection for high throughput in-situ biomedical diagnoses and Point-of-Care testing applications has called for the integration of some of the novel technologiessuch as the microfluidics, microphotonics, immunoproteomics and Micro ElectroMechanical Systems (MEMS. In the present work, a silicon based microfluidic device hasbeen developed for carrying out fluorescence based immunoassay. By hybrid attachment ofthe microfluidic device with a Spectrometer-on-chip, the feasibility of synthesizing anintegrated Lab-on-a-chip type device for fluorescence based biosensing has beendemonstrated. Biodetection using the microfluidic device has been carried out usingantigen sheep IgG and Alexafluor-647 tagged antibody particles and the experimentalresults prove that silicon is a compatible material for the present application given thevarious advantages it offers such as cost-effectiveness, ease of bulk microfabrication,superior surface affinity to biomolecules, ease of disposability of the device etc., and is thussuitable for fabricating Lab-on-a-chip type devices.

  4. A smartphone controlled handheld microfluidic liquid handling system.

    Li, Baichen; Li, Lin; Guan, Allan; Dong, Quan; Ruan, Kangcheng; Hu, Ronggui; Li, Zhenyu

    2014-10-21

    Microfluidics and lab-on-a-chip technologies have made it possible to manipulate small volume liquids with unprecedented resolution, automation and integration. However, most current microfluidic systems still rely on bulky off-chip infrastructures such as compressed pressure sources, syringe pumps and computers to achieve complex liquid manipulation functions. Here, we present a handheld automated microfluidic liquid handling system controlled by a smartphone, which is enabled by combining elastomeric on-chip valves and a compact pneumatic system. As a demonstration, we show that the system can automatically perform all the liquid handling steps of a bead-based HIV1 p24 sandwich immunoassay on a multi-layer PDMS chip without any human intervention. The footprint of the system is 6 × 10.5 × 16.5 cm, and the total weight is 829 g including battery. Powered by a 12.8 V 1500 mAh Li battery, the system consumed 2.2 W on average during the immunoassay and lasted for 8.7 h. This handheld microfluidic liquid handling platform is generally applicable to many biochemical and cell-based assays requiring complex liquid manipulation and sample preparation steps such as FISH, PCR, flow cytometry and nucleic acid sequencing. In particular, the integration of this technology with read-out biosensors may help enable the realization of the long-sought Tricorder-like handheld in vitro diagnostic (IVD) systems.

  5. Pin-count reduction for continuous flow microfluidic biochips

    Schneider, Alexander; Pop, Paul; Madsen, Jan

    2017-01-01

    Microfluidic biochips are replacing the conventional biochemical analyzers integrating the necessary functions on-chip. We are interested in flow-based biochips, where a continuous flow of liquid is manipulated using integrated microvalves, controlled from external pressure sources via off...

  6. Process for production of an alkyl methacrylate

    Eastham, Graham Ronald; Johnson, David William; Fraaije, Marco; Winter, Remko

    2015-01-01

    A process for the production of an alkyl methacrylate, particularly methyl methacrylate, is provided, in which a Baeyer-Villiger Monooxygenase enzyme is used to convert an alkylisopropenylketone substrate to the relevant alkyl methacrylate by abnormal asymmetric oxygen insertion. The invention

  7. Bottom-up on-crystal in-chip formation of a conducting salt and a view of its restructuring: From organic insulator to conducting >switch> through microfluidic manipulation

    Puigmartí-Luis, Josep; Paradinas, Markos; Bailo, Elena; Rodríguez-Trujillo, Romen; Pfattner, Raphael; Ocal, Carmen; Amabilino, David B.

    2015-01-01

    The chemical modification of an immobilized single crystal in a fluid cell is reported, whereby a material with switching functions is generated in situ by generating a chemical reagent in the flow. Crystals of the insulating organic crystal of TCNQ (tetracyanoquinodimethane) were grown in a microfluidic channel and were trapped using a pneumatic valve, a nascent technique for materials manipulation. They were subsequently reduced using solution-deposited silver to provide a conducting materi...

  8. Routing-based synthesis of digital microfluidic biochips

    Maftei, Elena; Pop, Paul; Madsen, Jan

    2012-01-01

    Microfluidic biochips are replacing the conventional biochemical analyzers, and are able to integrate on-chip all the necessary functions for biochemical analysis. The “digital” biochips are manipulating liquids as discrete droplets on a two-dimensional array of electrodes. Basic microfluidic...... electrodes are considered occupied during the operation execution, although the droplet uses only one electrode at a time. Moreover, the operations can actually be performed by routing the droplets on any sequence of electrodes on the microfluidic array. Hence, in this paper, we eliminate the concept...... on the surface of the microfluidic array. We have extended the GRASP-based algorithm to consider contamination avoidance during routing-based synthesis. Several real-life examples and synthetic benchmarks are used to evaluate the proposed approaches....

  9. A simple method of fabricating mask-free microfluidic devices for biological analysis.

    Yi, Xin

    2010-09-07

    We report a simple, low-cost, rapid, and mask-free method to fabricate two-dimensional (2D) and three-dimensional (3D) microfluidic chip for biological analysis researches. In this fabrication process, a laser system is used to cut through paper to form intricate patterns and differently configured channels for specific purposes. Bonded with cyanoacrylate-based resin, the prepared paper sheet is sandwiched between glass slides (hydrophilic) or polymer-based plates (hydrophobic) to obtain a multilayer structure. In order to examine the chip\\'s biocompatibility and applicability, protein concentration was measured while DNA capillary electrophoresis was carried out, and both of them show positive results. With the utilization of direct laser cutting and one-step gas-sacrificing techniques, the whole fabrication processes for complicated 2D and 3D microfluidic devices are shorten into several minutes which make it a good alternative of poly(dimethylsiloxane) microfluidic chips used in biological analysis researches.

  10. In search of low cost biological analysis: Wax or acrylic glue bonded paper microfluidic devices

    Kodzius, Rimantas

    2011-01-22

    In this body of work we have been developing and characterizing paper based microfluidic fabrication technologies to produce low cost biological analysis. Specifically we investigated the performance of paper microfluidics that had been bonded using wax or acrylic glue, and characterized the affect of these and other microfluidic materials on the polymerase chain reaction (PCR). 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 or cyanoacrylate-based resin 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 or simple cyanoacrylate-based resin can realize bridge bonding between various materials, for example, paper, polymethylmethacrylate film, glass sheets, or metal plate. The wax 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 evacuating the channels of adhesive material in a hot-water. We applied the wax-paper based microfluidic chip to HeLa cell electroporation. 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 recombinant 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. The chip bonded with cyanoacrylate-based resin was tested by measuring protein concentration and carrying out DNA capillary electrophoresis. To study the biocompatibility and applicability of our microfluidic chip fabrication technology, we tested the PCR compatibility of our chip materials along with various other common materials

  11. Hybrid Macro-Micro Fluidics System for a Chip-Based Biosensor

    Tamanaha, C. R; Whitman, L. J; Colton, R.J

    2002-01-01

    We describe the engineering of a hybrid fluidics platform for a chip-based biosensor system that combines high-performance microfluidics components with powerful, yet compact, millimeter-scale pump and valve actuators...

  12. Research of Dielectric Breakdown Micro fluidic Sampling Chip

    Jiang, F.; Lei, Y.; Yu, J.

    2013-01-01

    Micro fluidic chip is mainly driven electrically by external electrode and array electrode, but there are certain disadvantages in both of ways, which affect the promotion and application of micro fluidic technology. This paper discusses a scheme that uses the conductive solution in a microchannel made by PDMS, replacing electrodes and the way of dielectric breakdown to achieve microfluidic chip driver. It could reduce the driving voltage and simplify the chip production process. To prove the feasibility of this method, we produced a micro fluidic chip used in PDMS material with the lithography technology and experimented it. The results showed that using the dielectric breakdown to achieve microfluidic chip driver is feasible, and it has certain application prospect.

  13. Leveraging liquid dielectrophoresis for microfluidic applications

    Chugh, Dipankar; Kaler, Karan V I S

    2008-01-01

    Miniaturized fluidic systems have been developed in recent years and offer new and novel means of leveraging the domain of microfluidics for the development of micro-total analysis systems (μTAS). Initially, such systems employed closed microchannels in order to facilitate chip-based biochemical assays, requiring very small quantities of sample and/or reagents and furthermore providing rapid and low-cost analysis on a compact footprint. More recently, advancements in the domain of surface microfluidics have suggested that similar low volume sample handling and manipulation capabilities for bioassays can be attained by leveraging the phenomena of liquid dielectrophoresis and droplet dielectrophoresis (DEP), without the need for separate pumps or valves. Some of the key aspects of this surface microfluidic technology and its capabilities are discussed and highlighted in this paper. We, furthermore, examine the integration and utility of liquid DEP and droplet DEP in providing rapid and automated sample handling and manipulation capabilities on a compact chip-based platform

  14. Logic control of microfluidics with smart colloid

    Wang, Limu

    2010-01-01

    We report the successful realization of a microfluidic chip with switching and corresponding inverting functionalities. The chips are identical logic control components incorporating a type of smart colloid, giant electrorheological fluid (GERF), which possesses reversible characteristics via a liquid-solid phase transition under external electric field. Two pairs of electrodes embedded on the sides of two microfluidic channels serve as signal input and output, respectively. One, located in the GERF micro-channel is used to control the flow status of GERF, while another one in the ither micro-fluidic channel is used to detect the signal generated with a passing-by droplet (defined as a signal droplet). Switching of the GERF from the suspended state (off-state) to the flowing state (on-state) or vice versa in the micro-channel is controlled by the appearance of signal droplets whenever they pass through the detection electrode. The output on-off signals can be easily demonstrated, clearly matching with GERF flow status. Our results show that such a logic switch is also a logic IF gate, while its inverter functions as a NOT gate. © The Royal Society of Chemistry 2010.

  15. Microfluidics for single cell analysis

    Jensen, Marie Pødenphant

    Isolation and manipulation of single cells have gained an increasing interest from researchers because of the heterogeneity of cells from the same cell culture. Single cell analysis can ensure a better understanding of differences between individual cells and potentially solve a variety of clinical...... problems. In this thesis lab on a chip systems for rare single cell analysis are investigated. The focus was to develop a commercial, disposable device for circulating tumour cell (CTC) analysis. Such a device must be able to separate rare cells from blood samples and subsequently capture the specific...... cells, and simultaneously be fabricated and operated at low costs and be user-friendly. These challenges were addressed through development of two microfluidic devices, one for rare cell isolation based on pinched flow fractionation (PFF) and one for single cell capture based on hydrodynamic trapping...

  16. Organ-Tumor-on-a-Chip for Chemosensitivity Assay: A Critical Review

    Navid Kashaninejad; Mohammad Reza Nikmaneshi; Hajar Moghadas; Amir Kiyoumarsi Oskouei; Milad Rismanian; Maryam Barisam; Mohammad Said Saidi; Bahar Firoozabadi

    2016-01-01

    With a mortality rate over 580,000 per year, cancer is still one of the leading causes of death worldwide. However, the emerging field of microfluidics can potentially shed light on this puzzling disease. Unique characteristics of microfluidic chips (also known as micro-total analysis system) make them excellent candidates for biological applications. The ex vivo approach of tumor-on-a-chip is becoming an indispensable part of personalized medicine and can replace in vivo animal testing as we...

  17. Recent Advances in Magnetic Microfluidic Biosensors

    Ioanna Giouroudi

    2017-07-01

    Full Text Available The development of portable biosening devices for the detection of biological entities such as biomolecules, pathogens, and cells has become extremely significant over the past years. Scientific research, driven by the promise for miniaturization and integration of complex laboratory equipment on inexpensive, reliable, and accurate devices, has successfully shifted several analytical and diagnostic methods to the submillimeter scale. The miniaturization process was made possible with the birth of microfluidics, a technology that could confine, manipulate, and mix very small volumes of liquids on devices integrated on standard silicon technology chips. Such devices are then directly translating the presence of these entities into an electronic signal that can be read out with a portable instrumentation. For the aforementioned tasks, the use of magnetic markers (magnetic particles—MPs—functionalized with ligands in combination with the application of magnetic fields is being strongly investigated by research groups worldwide. The greatest merits of using magnetic fields are that they can be applied either externally or from integrated microconductors and they can be well-tuned by adjusting the applied current on the microconductors. Moreover, the magnetic markers can be manipulated inside microfluidic channels by high gradient magnetic fields that can in turn be detected by magnetic sensors. All the above make this technology an ideal candidate for the development of such microfluidic biosensors. In this review, focus is given only to very recent advances in biosensors that use microfluidics in combination with magnetic sensors and magnetic markers/nanoparticles.

  18. Revisiting lab-on-a-chip technology for drug discovery.

    Neuži, Pavel; Giselbrecht, Stefan; Länge, Kerstin; Huang, Tony Jun; Manz, Andreas

    2012-08-01

    The field of microfluidics or lab-on-a-chip technology aims to improve and extend the possibilities of bioassays, cell biology and biomedical research based on the idea of miniaturization. Microfluidic systems allow more accurate modelling of physiological situations for both fundamental research and drug development, and enable systematic high-volume testing for various aspects of drug discovery. Microfluidic systems are in development that not only model biological environments but also physically mimic biological tissues and organs; such 'organs on a chip' could have an important role in expediting early stages of drug discovery and help reduce reliance on animal testing. This Review highlights the latest lab-on-a-chip technologies for drug discovery and discusses the potential for future developments in this field.

  19. Rapid manufacturing for microfluidics

    Land, K

    2012-10-01

    Full Text Available for microfluidics K. LAND, S. HUGO, M MBANJWA, L FOURIE CSIR Materials Science and Manufacturing P O Box 395, Pretoria 0001, SOUTH AFRICA Email: kland@csir.co.za INTRODUCTION Microfluidics refers to the manipulation of very small volumes of fluid.... Microfluidics is at the forefront of developing solutions for drug discovery, diagnostics (from glucose tests to malaria and TB testing) and environmental diagnostics (E-coli monitoring of drinking water). In order to quickly implement new designs, a rapid...

  20. Commercialization of microfluidic devices.

    Volpatti, Lisa R; Yetisen, Ali K

    2014-07-01

    Microfluidic devices offer automation and high-throughput screening, and operate at low volumes of consumables. Although microfluidics has the potential to reduce turnaround times and costs for analytical devices, particularly in medical, veterinary, and environmental sciences, this enabling technology has had limited diffusion into consumer products. This article analyzes the microfluidics market, identifies issues, and highlights successful commercialization strategies. Addressing niche markets and establishing compatibility with existing workflows will accelerate market penetration. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Tunable Microfluidic Dye Laser

    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...

  2. Microfluidic PMMA interfaces for rectangular glass capillaries

    Evander, Mikael; Tenje, Maria

    2014-01-01

    We present the design and fabrication of a polymeric capillary fluidic interface fabricated by micro-milling. The design enables the use of glass capillaries with any kind of cross-section in complex microfluidic setups. We demonstrate two different designs of the interface; a double-inlet interface for hydrodynamic focusing and a capillary interface with integrated pneumatic valves. Both capillary interfaces are presented together with examples of practical applications. This communication shows the design optimization and presents details of the fabrication process. The capillary interface opens up for the use of complex microfluidic systems in single-use glass capillaries. They also enable simple fabrication of glass/polymer hybrid devices that can be beneficial in many research fields where a pure polymer chip negatively affects the device's performance, e.g. acoustofluidics. (technical note)

  3. Screening applications in drug discovery based on microfluidic technology.

    Eribol, P; Uguz, A K; Ulgen, K O

    2016-01-01

    Microfluidics has been the focus of interest for the last two decades for all the advantages such as low chemical consumption, reduced analysis time, high throughput, better control of mass and heat transfer, downsizing a bench-top laboratory to a chip, i.e., lab-on-a-chip, and many others it has offered. Microfluidic technology quickly found applications in the pharmaceutical industry, which demands working with leading edge scientific and technological breakthroughs, as drug screening and commercialization are very long and expensive processes and require many tests due to unpredictable results. This review paper is on drug candidate screening methods with microfluidic technology and focuses specifically on fabrication techniques and materials for the microchip, types of flow such as continuous or discrete and their advantages, determination of kinetic parameters and their comparison with conventional systems, assessment of toxicities and cytotoxicities, concentration generations for high throughput, and the computational methods that were employed. An important conclusion of this review is that even though microfluidic technology has been in this field for around 20 years there is still room for research and development, as this cutting edge technology requires ingenuity to design and find solutions for each individual case. Recent extensions of these microsystems are microengineered organs-on-chips and organ arrays.

  4. Screening applications in drug discovery based on microfluidic technology

    Eribol, P.; Uguz, A. K.; Ulgen, K. O.

    2016-01-01

    Microfluidics has been the focus of interest for the last two decades for all the advantages such as low chemical consumption, reduced analysis time, high throughput, better control of mass and heat transfer, downsizing a bench-top laboratory to a chip, i.e., lab-on-a-chip, and many others it has offered. Microfluidic technology quickly found applications in the pharmaceutical industry, which demands working with leading edge scientific and technological breakthroughs, as drug screening and commercialization are very long and expensive processes and require many tests due to unpredictable results. This review paper is on drug candidate screening methods with microfluidic technology and focuses specifically on fabrication techniques and materials for the microchip, types of flow such as continuous or discrete and their advantages, determination of kinetic parameters and their comparison with conventional systems, assessment of toxicities and cytotoxicities, concentration generations for high throughput, and the computational methods that were employed. An important conclusion of this review is that even though microfluidic technology has been in this field for around 20 years there is still room for research and development, as this cutting edge technology requires ingenuity to design and find solutions for each individual case. Recent extensions of these microsystems are microengineered organs-on-chips and organ arrays. PMID:26865904

  5. Diffusion dynamics in micro-fluidic dye lasers

    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...

  6. Fabricating process of hollow out-of-plane Ni microneedle arrays and properties of the integrated microfluidic device

    Zhu, Jun; Cao, Ying; Wang, Hong; Li, Yigui; Chen, Xiang; Chen, Di

    2013-07-01

    Although microfluidic devices that integrate microfluidic chips with hollow out-of-plane microneedle arrays have many advantages in transdermal drug delivery applications, difficulties exist in their fabrication due to the special three-dimensional structures of hollow out-of-plane microneedles. A new, cost-effective process for the fabrication of a hollow out-of-plane Ni microneedle array is presented. The integration of PDMS microchips with the Ni hollow microneedle array and the properties of microfluidic devices are also presented. The integrated microfluidic devices provide a new approach for transdermal drug delivery.

  7. Nanostructured surfaces for microfluidics and sensing applications.

    Picraux, Samuel Thomas (Arizona State University); Piech, Marcin (United Technologies Corp.); Schneider, John F.; Vail, Sean (Arizona State University); Hayes, Mark A. (Arizona State University); Garcia, Anthony A.; Bell, Nelson Simmons; Gust, D (Arizona State University); Yang, Dongqing (Arizona State University)

    2007-01-01

    The present work demonstrates the use of light to move liquids on a photoresponsive monolayer, providing a new method for delivering analyses in lab-on-chip environments for microfluidic systems. The light-driven motion of liquids was achieved on photoresponsive azobenzene modified surfaces. The surface energy components of azobenzene modified surfaces were calculated by Van Oss theory. The motion of the liquid was achieved by generation of a surface tension gradient by isomerization of azobenzene monolayers using UV and Visible light, thereby establishing a surface energy heterogeneity on the edge of the droplet. Contact angle measurements of various solvents were used to demonstrate the requirement for fluid motion.

  8. 40 CFR 721.10153 - Modified methyl methacrylate, 2-hydroxyethyl methacrylate polymer (generic).

    2010-07-01

    ...-hydroxyethyl methacrylate polymer (generic). 721.10153 Section 721.10153 Protection of Environment...-hydroxyethyl methacrylate polymer (generic). (a) Chemical substance and significant new uses subject to... methacrylate polymer (PMN P-08-6) is subject to reporting under this section for the significant new uses...

  9. A multi-staining chip using hydrophobic valves for exfoliative cytology in cancer

    Lee, Tae Hee; Bu, Jiyoon; Moon, Jung Eun; Kim, Young Jun; Kang, Yoon-Tae; Cho, Young-Ho; Kim, In Sik

    2017-07-01

    Exfoliative cytology is a highly established technique for the diagnosis of tumors. Various microfluidic devices have been developed to minimize the sample numbers by conjugating multiple antibodies in a single sample. However, the previous multi-staining devices require complex control lines and valves operated by external power sources, to deliver multiple antibodies separately for a single sample. In addition, most of these devices are composed of hydrophobic materials, causing unreliable results due to the non-specific binding of antibodies. Here, we present a multi-staining chip using hydrophobic valves, which is formed by the partial treatment of 2-hydroxyethyl methacrylate (HEMA). Our chip consists of a circular chamber, divided into six equal fan-shaped regions. Switchable injection ports are located at the center of the chamber and at the middle of the arc of each fan-shaped zone. Thus, our device is beneficial for minimizing the control lines, since pre-treatment solutions flow from the center to outer ports, while six different antibodies are introduced oppositely from the outer ports. Furthermore, hydrophobic narrow channels, connecting the central region and each of the six fan-shaped zones, are closed by capillary effect, thus preventing the fluidic mixing without external power sources. Meanwhile, HEMA treatment on the exterior region results in hydrophobic-to-hydrophilic transition and prevents the non-specific binding of antibodies. For the application, we measured the expression of six different antibodies in a single sample using our device. The expression levels of each antibody highly matched the conventional immunocytochemistry results. Our device enables cancer screening with a small number of antibodies for a single sample.

  10. A multi-staining chip using hydrophobic valves for exfoliative cytology in cancer

    Lee, Tae Hee; Bu, Jiyoon; Kim, Young Jun; Kang, Yoon-Tae; Cho, Young-Ho; Moon, Jung Eun; Kim, In Sik

    2017-01-01

    Exfoliative cytology is a highly established technique for the diagnosis of tumors. Various microfluidic devices have been developed to minimize the sample numbers by conjugating multiple antibodies in a single sample. However, the previous multi-staining devices require complex control lines and valves operated by external power sources, to deliver multiple antibodies separately for a single sample. In addition, most of these devices are composed of hydrophobic materials, causing unreliable results due to the non-specific binding of antibodies. Here, we present a multi-staining chip using hydrophobic valves, which is formed by the partial treatment of 2-hydroxyethyl methacrylate (HEMA). Our chip consists of a circular chamber, divided into six equal fan-shaped regions. Switchable injection ports are located at the center of the chamber and at the middle of the arc of each fan-shaped zone. Thus, our device is beneficial for minimizing the control lines, since pre-treatment solutions flow from the center to outer ports, while six different antibodies are introduced oppositely from the outer ports. Furthermore, hydrophobic narrow channels, connecting the central region and each of the six fan-shaped zones, are closed by capillary effect, thus preventing the fluidic mixing without external power sources. Meanwhile, HEMA treatment on the exterior region results in hydrophobic-to-hydrophilic transition and prevents the non-specific binding of antibodies. For the application, we measured the expression of six different antibodies in a single sample using our device. The expression levels of each antibody highly matched the conventional immunocytochemistry results. Our device enables cancer screening with a small number of antibodies for a single sample. (paper)

  11. Microfluidic systems with ion-selective membranes.

    Slouka, Zdenek; Senapati, Satyajyoti; Chang, Hsueh-Chia

    2014-01-01

    When integrated into microfluidic chips, ion-selective nanoporous polymer and solid-state membranes can be used for on-chip pumping, pH actuation, analyte concentration, molecular separation, reactive mixing, and molecular sensing. They offer numerous functionalities and are hence superior to paper-based devices for point-of-care biochips, with only slightly more investment in fabrication and material costs required. In this review, we first discuss the fundamentals of several nonequilibrium ion current phenomena associated with ion-selective membranes, many of them revealed by studies with fabricated single nanochannels/nanopores. We then focus on how the plethora of phenomena has been applied for transport, separation, concentration, and detection of biomolecules on biochips.

  12. Field-programmable lab-on-a-chip based on microelectrode dot array architecture.

    Wang, Gary; Teng, Daniel; Lai, Yi-Tse; Lu, Yi-Wen; Ho, Yingchieh; Lee, Chen-Yi

    2014-09-01

    The fundamentals of electrowetting-on-dielectric (EWOD) digital microfluidics are very strong: advantageous capability in the manipulation of fluids, small test volumes, precise dynamic control and detection, and microscale systems. These advantages are very important for future biochip developments, but the development of EWOD microfluidics has been hindered by the absence of: integrated detector technology, standard commercial components, on-chip sample preparation, standard manufacturing technology and end-to-end system integration. A field-programmable lab-on-a-chip (FPLOC) system based on microelectrode dot array (MEDA) architecture is presented in this research. The MEDA architecture proposes a standard EWOD microfluidic component called 'microelectrode cell', which can be dynamically configured into microfluidic components to perform microfluidic operations of the biochip. A proof-of-concept prototype FPLOC, containing a 30 × 30 MEDA, was developed by using generic integrated circuits computer aided design tools, and it was manufactured with standard low-voltage complementary metal-oxide-semiconductor technology, which allows smooth on-chip integration of microfluidics and microelectronics. By integrating 900 droplet detection circuits into microelectrode cells, the FPLOC has achieved large-scale integration of microfluidics and microelectronics. Compared to the full-custom and bottom-up design methods, the FPLOC provides hierarchical top-down design approach, field-programmability and dynamic manipulations of droplets for advanced microfluidic operations.

  13. Multichannel Mars Organic Analyzer (McMOA): Microfluidic Networks for the Automated In Situ Microchip Electrophoretic Analysis of Organic Biomarkers on Mars

    Chiesl, T. N.; Benhabib, M.; Stockton, A. M.; Mathies, R. A.

    2010-04-01

    We present the Multichannel Mars Organic Analyzer (McMOA) for the analysis of Amino Acids, PAHs, and Oxidized Carbon. Microfluidic architecures integrating automated metering, mixing, on chip reactions, and serial dilutions are also discussed.

  14. A low-cost 2D fluorescence detection system for mm sized beads on-chip

    Segerink, Loes Irene; Koster, Maarten J.; Sprenkels, A.J.; van den Berg, Albert

    2012-01-01

    In this paper we describe a compact fluorescence detection system for on-chip analysis of beads, comprising a low-cost optical HD-DVD pickup. The complete system consists of a fluorescence detection unit, a control unit and a microfluidic chip containing microchannels and optical markers. With these

  15. Development & Characterization of Multifunctional Microfluidic Materials

    Ucar, Ahmet Burak

    The field of microfluidics has been mostly investigated for miniaturized lab on a chip devices for analytical and clinical applications. However, there is an emerging class of "smart" microfluidic materials, combining microfluidics with soft polymers to yield new functionalities. The best inspiration for such materials found in nature is skin, whose functions are maintained and controlled by a vascular "microfluidic" network. We report here the development and characterization of a few new classes of microfluidic materials. First, we introduced microfluidic materials that can change their stiffness on demand. These materials were based on an engineered microchannel network embedded into a matrix of polydimethylsiloxane (PDMS), whose channels were filled with a liquid photoresist (SU- 8). The elastomer filled with the photoresist was initially soft. The materials were shaped into a desired geometry and then exposed to UV-light. Once photocured, the material preserved the defined shape and it could be bent, twisted or stretched with a very high recoverable strain. As soon as the external force was removed the material returned back to its predefined shape. Thus, the polymerized SU-8 acted as the 'endoskeleton' of the microfluidic network, which drastically increased the composite's elastic and bending moduli. Second, we demonstrated a class of simple and versatile soft microfluidic materials that can be turned optically transparent or colored on demand. These materials were made in the form of flexible sheets containing a microchannel network embedded in PDMS, similar to the photocurable materials. However, this time the channels were filled with a glycerolwater mixture, whose refractive index was matched with that of the PDMS matrix. By pumping such dye solutions into the channel network and consecutively replacing the medium, we showed that we can control the material's color and light transmittance in the visible and near-infrared regions, which can be used for

  16. Modular integration of electronics and microfluidic systems using flexible printed circuit boards.

    Wu, Amy; Wang, Lisen; Jensen, Erik; Mathies, Richard; Boser, Bernhard

    2010-02-21

    Microfluidic systems offer an attractive alternative to conventional wet chemical methods with benefits including reduced sample and reagent volumes, shorter reaction times, high-throughput, automation, and low cost. However, most present microfluidic systems rely on external means to analyze reaction products. This substantially adds to the size, complexity, and cost of the overall system. Electronic detection based on sub-millimetre size integrated circuits (ICs) has been demonstrated for a wide range of targets including nucleic and amino acids, but deployment of this technology to date has been limited due to the lack of a flexible process to integrate these chips within microfluidic devices. This paper presents a modular and inexpensive process to integrate ICs with microfluidic systems based on standard printed circuit board (PCB) technology to assemble the independently designed microfluidic and electronic components. The integrated system can accommodate multiple chips of different sizes bonded to glass or PDMS microfluidic systems. Since IC chips and flex PCB manufacturing and assembly are industry standards with low cost, the integrated system is economical for both laboratory and point-of-care settings.

  17. Microfluidic biolector-microfluidic bioprocess control in microtiter plates.

    Funke, Matthias; Buchenauer, Andreas; Schnakenberg, Uwe; Mokwa, Wilfried; Diederichs, Sylvia; Mertens, Alan; Müller, Carsten; Kensy, Frank; Büchs, Jochen

    2010-10-15

    In industrial-scale biotechnological processes, the active control of the pH-value combined with the controlled feeding of substrate solutions (fed-batch) is the standard strategy to cultivate both prokaryotic and eukaryotic cells. On the contrary, for small-scale cultivations, much simpler batch experiments with no process control are performed. This lack of process control often hinders researchers to scale-up and scale-down fermentation experiments, because the microbial metabolism and thereby the growth and production kinetics drastically changes depending on the cultivation strategy applied. While small-scale batches are typically performed highly parallel and in high throughput, large-scale cultivations demand sophisticated equipment for process control which is in most cases costly and difficult to handle. Currently, there is no technical system on the market that realizes simple process control in high throughput. The novel concept of a microfermentation system described in this work combines a fiber-optic online-monitoring device for microtiter plates (MTPs)--the BioLector technology--together with microfluidic control of cultivation processes in volumes below 1 mL. In the microfluidic chip, a micropump is integrated to realize distinct substrate flow rates during fed-batch cultivation in microscale. Hence, a cultivation system with several distinct advantages could be established: (1) high information output on a microscale; (2) many experiments can be performed in parallel and be automated using MTPs; (3) this system is user-friendly and can easily be transferred to a disposable single-use system. This article elucidates this new concept and illustrates applications in fermentations of Escherichia coli under pH-controlled and fed-batch conditions in shaken MTPs. Copyright 2010 Wiley Periodicals, Inc.

  18. Advances in Microfluidic Platforms for Analyzing and Regulating Human Pluripotent Stem Cells

    Qian, Tongcheng; Shusta, Eric V.; Palecek, Sean P.

    2015-01-01

    Microfluidic devices employ submillimeter length scale control of flow to achieve high-resolution spatial and temporal control over the microenvironment, providing powerful tools to elucidate mechanisms of human pluripotent stem cell (hPSC) regulation and to elicit desired hPSC fates. In addition, microfluidics allow control of paracrine and juxtracrine signaling, thereby enabling fabrication of microphysiological systems comprised of multiple cell types organized into organs-on-a-chip. Microfluidic cell culture systems can also be integrated with actuators and sensors, permitting construction of high-density arrays of cell-based biosensors for screening applications. This review describes recent advances in using microfluidics to understand mechanisms by which the microenvironment regulates hPSC fates and applications of microfluidics to realize the potential of hPSCs for in vitro modeling and screening applications. PMID:26313850

  19. An integrated microfluidic analysis microsystems with bacterial capture enrichment and in-situ impedance detection

    Liu, Hai-Tao; Wen, Zhi-Yu; Xu, Yi; Shang, Zheng-Guo; Peng, Jin-Lan; Tian, Peng

    2017-09-01

    In this paper, an integrated microfluidic analysis microsystems with bacterial capture enrichment and in-situ impedance detection was purposed based on microfluidic chips dielectrophoresis technique and electrochemical impedance detection principle. The microsystems include microfluidic chip, main control module, and drive and control module, and signal detection and processing modulet and result display unit. The main control module produce the work sequence of impedance detection system parts and achieve data communication functions, the drive and control circuit generate AC signal which amplitude and frequency adjustable, and it was applied on the foodborne pathogens impedance analysis microsystems to realize the capture enrichment and impedance detection. The signal detection and processing circuit translate the current signal into impendence of bacteria, and transfer to computer, the last detection result is displayed on the computer. The experiment sample was prepared by adding Escherichia coli standard sample into chicken sample solution, and the samples were tested on the dielectrophoresis chip capture enrichment and in-situ impedance detection microsystems with micro-array electrode microfluidic chips. The experiments show that the Escherichia coli detection limit of microsystems is 5 × 104 CFU/mL and the detection time is within 6 min in the optimization of voltage detection 10 V and detection frequency 500 KHz operating conditions. The integrated microfluidic analysis microsystems laid the solid foundation for rapid real-time in-situ detection of bacteria.

  20. The thermal degradation of poly(iso-butyl methacrylate and poly(sec-butyl methacrylate

    IVANKA G. POPOVIC

    2000-12-01

    Full Text Available The non-oxidative thermal degradation of poly(iso-butyl methacrylate and poly(sec-butyl methacrylate was investigated by studying changes in the polymer residue. Due to the different number of b-hydrogens in their ester substituents, these two polymeric isomers behave differently when subjected to elevated temperatures. Poly(iso-butyl methacrylate degrades quantitatively by depolymerisation with zip lengths of the same order of magnitude as those of poly(methyl methacrylate. Poly(sec-butyl methacrylate degrades by a combined degradation mechanism of depolymerisation and de-esterification. De-esterification becomes a significant thermolysis route at temperatures higher than 240°C.

  1. Technology Roadmap: Lab-on-a-Chip

    Pattharaporn Suntharasaj; Tugrul U Daim

    2010-01-01

    With the integration of microfluidic and MEMS technologies, biochips such as the lab-on-a-chip (LOC) devices are at the brink of revolutionizing the medical disease diagnostics industries. Remarkable advancements in the biochips industry are making products resembling Star Trek.s "tricorder" and handheld medical scanners a reality. Soon, doctors can screen for cancer at the molecular level without costly and cumbersome equipments, and discuss treatment plans based on immediate lab results. Th...

  2. Meta-atom microfluidic sensor for measurement of dielectric properties of liquids

    Awang, Robiatun A.; Tovar-Lopez, Francisco J.; Baum, Thomas; Sriram, Sharath; Rowe, Wayne S. T.

    2017-03-01

    High sensitivity microwave frequency microfluidic sensing is gaining popularity in chemical and biosensing applications for evaluating the dielectric properties of liquid samples. Here, we show that a tiny microfluidic channel positioned in the gaps of a dual-gap meta-atom split-ring resonator can exploit the electric field sensitivity to predict the dielectric properties of liquid samples. Employing an empirical relation between resonant characteristics of the fabricated sensor and the complex permittivity of water-ethanol or water-methanol mixtures produces good congruence to standardized values from the literature. This microfluidic sensor offers a potential lab-on-chip solution for liquid dielectric characterization without external electrical connections.

  3. A multi-scale PDMS fabrication strategy to bridge the size mismatch between integrated circuits and microfluidics.

    Muluneh, Melaku; Issadore, David

    2014-12-07

    In recent years there has been great progress harnessing the small-feature size and programmability of integrated circuits (ICs) for biological applications, by building microfluidics directly on top of ICs. However, a major hurdle to the further development of this technology is the inherent size-mismatch between ICs (~mm) and microfluidic chips (~cm). Increasing the area of the ICs to match the size of the microfluidic chip, as has often been done in previous studies, leads to a waste of valuable space on the IC and an increase in fabrication cost (>100×). To address this challenge, we have developed a three dimensional PDMS chip that can straddle multiple length scales of hybrid IC/microfluidic chips. This approach allows millimeter-scale ICs, with no post-processing, to be integrated into a centimeter-sized PDMS chip. To fabricate this PDMS chip we use a combination of soft-lithography and laser micromachining. Soft lithography was used to define micrometer-scale fluid channels directly on the surface of the IC, allowing fluid to be controlled with high accuracy and brought into close proximity to sensors for highly sensitive measurements. Laser micromachining was used to create ~50 μm vias to connect these molded PDMS channels to a larger PDMS chip, which can connect multiple ICs and house fluid connections to the outside world. To demonstrate the utility of this approach, we built and demonstrated an in-flow magnetic cytometer that consisted of a 5 × 5 cm(2) microfluidic chip that incorporated a commercial 565 × 1145 μm(2) IC with a GMR sensing circuit. We additionally demonstrated the modularity of this approach by building a chip that incorporated two of these GMR chips connected in series.

  4. Controlled and tunable polymer particles' production using a single microfluidic device

    Amoyav, Benzion; Benny, Ofra

    2018-04-01

    Microfluidics technology offers a new platform to control liquids under flow in small volumes. The advantage of using small-scale reactions for droplet generation along with the capacity to control the preparation parameters, making microfluidic chips an attractive technology for optimizing encapsulation formulations. However, one of the drawback in this methodology is the ability to obtain a wide range of droplet sizes, from sub-micron to microns using a single chip design. In fact, typically, droplet chips are used for micron-dimension particles, while nanoparticles' synthesis requires complex chips design (i.e., microreactors and staggered herringbone micromixer). Here, we introduce the development of a highly tunable and controlled encapsulation technique, using two polymer compositions, for generating particles ranging from microns to nano-size using the same simple single microfluidic chip design. Poly(lactic-co-glycolic acid) (PLGA 50:50) or PLGA/polyethylene glycol polymeric particles were prepared with focused-flow chip, yielding monodisperse particle batches. We show that by varying flow rate, solvent, surfactant and polymer composition, we were able to optimize particles' size and decrease polydispersity index, using simple chip designs with no further related adjustments or costs. Utilizing this platform, which offers tight tuning of particle properties, could offer an important tool for formulation development and can potentially pave the way towards a better precision nanomedicine.

  5. Transient deformation of a droplet near a microfluidic constriction: A quantitative analysis

    Trégouët, Corentin; Salez, Thomas; Monteux, Cécile; Reyssat, Mathilde

    2018-05-01

    We report on experiments that consist of deforming a collection of monodisperse droplets produced by a microfluidic chip through a flow-focusing device. We show that a proper numerical modeling of the flow is necessary to access the stress applied by the latter on the droplet along its trajectory through the chip. This crucial step enables the full integration of the differential equation governing the dynamical deformation, and consequently the robust measurement of the interfacial tension by fitting the experiments with the calculated deformation. Our study thus demonstrates the feasibility of quantitative in situ rheology in microfluidic flows involving, e.g., droplets, capsules, or cells.

  6. The MainSTREAM Component Platform: A Holistic Approach to Microfluidic System Design

    Sabourin, David; Skafte-Pedersen, Peder; Søe, Martin Jensen

    2013-01-01

    A microfluidic component library for building systems driving parallel or serial microfluidic-based assays is presented. The components are a miniaturized eight-channel peristaltic pump, an eight-channel valve, sample-to-waste liquid management, and interconnections. The library of components...... of reaction chips; (2) highly parallel pumping and routing/valving capability; (3) methods to interface pumps and chip-to-liquid management systems; (4) means to construct a portable system; (5) reconfigurability/flexibility in system design; (6) means to interface to microscopes; and (7) compatibility...

  7. Macromolecular Crystallization in Microfluidics for the International Space Station

    Monaco, Lisa A.; Spearing, Scott

    2003-01-01

    At NASA's Marshall Space Flight Center, the Iterative Biological Crystallization (IBC) project has begun development on scientific hardware for macromolecular crystallization on the International Space Station (ISS). Currently ISS crystallization research is limited to solution recipes that were prepared on the ground prior to launch. The proposed hardware will conduct solution mixing and dispensing on board the ISS, be fully automated, and have imaging functions via remote commanding from the ground. Utilizing microfluidic technology, IBC will allow for on orbit iterations. The microfluidics LabChip(R) devices that have been developed, along with Caliper Technologies, will greatly benefit researchers by allowing for precise fluid handling of nano/pico liter sized volumes. IBC will maximize the amount of science return by utilizing the microfluidic approach and be a valuable tool to structural biologists investigating medically relevant projects.

  8. Microfluidics to Mimic Blood Flow in Health and Disease

    Sebastian, Bernhard; Dittrich, Petra S.

    2018-01-01

    Throughout history, capillary systems have aided the establishment of the fundamental laws of blood flow and its non-Newtonian properties. The advent of microfluidics technology in the 1990s propelled the development of highly integrated lab-on-a-chip platforms that allow highly accurate replication of vascular systems' dimensions, mechanical properties, and biological complexity. Applications include the detection of pathological changes to red blood cells, white blood cells, and platelets at unparalleled sensitivity and the efficacy assessment of drug treatment. Recent efforts have aimed at the development of microfluidics-based tests usable in a clinial environment or the replication of more complex diseases such as thrombosis. These microfluidic disease models enable the study of onset and progression of disease as well as the identification of key players and risk factors, which have led to a spectrum of clinically relevant findings.

  9. Evaluation of microfluidic channels with optical coherence tomography

    Czajkowski, J.; Prykä ri, T.; Alarousu, E.; Lauri, J.; Myllylä , R.

    2010-01-01

    Application of time domain, ultra high resolution optical coherence tomography (UHR-OCT) in evaluation of microfluidic channels is demonstrated. Presented study was done using experimental UHR-OCT device based on a Kerr-lens mode locked Ti:sapphire femtosecond laser, a photonic crystal fibre and modified, free-space Michelson interferometer. To show potential of the technique, microfluidic chip fabricated by VTT Center for Printed Intelligence (Oulu, Finland) was measured. Ability for full volumetric reconstruction in non-contact manner enabled complete characterization of closed entity of a microfluidic channel without contamination and harm for the sample. Measurement, occurring problems, and methods of postprocessing for raw data are described. Results present completely resolved physical structure of the channel, its spatial dimensions, draft angles and evaluation of lamination quality.

  10. Evaluation of microfluidic channels with optical coherence tomography

    Czajkowski, J.

    2010-06-25

    Application of time domain, ultra high resolution optical coherence tomography (UHR-OCT) in evaluation of microfluidic channels is demonstrated. Presented study was done using experimental UHR-OCT device based on a Kerr-lens mode locked Ti:sapphire femtosecond laser, a photonic crystal fibre and modified, free-space Michelson interferometer. To show potential of the technique, microfluidic chip fabricated by VTT Center for Printed Intelligence (Oulu, Finland) was measured. Ability for full volumetric reconstruction in non-contact manner enabled complete characterization of closed entity of a microfluidic channel without contamination and harm for the sample. Measurement, occurring problems, and methods of postprocessing for raw data are described. Results present completely resolved physical structure of the channel, its spatial dimensions, draft angles and evaluation of lamination quality.

  11. Evaluation of microfluidic channels with optical coherence tomography

    Czajkowski, J.; Prykäri, T.; Alarousu, E.; Lauri, J.; Myllylä, R.

    2010-11-01

    Application of time domain, ultra high resolution optical coherence tomography (UHR-OCT) in evaluation of microfluidic channels is demonstrated. Presented study was done using experimental UHR-OCT device based on a Kerr-lens mode locked Ti:sapphire femtosecond laser, a photonic crystal fibre and modified, free-space Michelson interferometer. To show potential of the technique, microfluidic chip fabricated by VTT Center for Printed Intelligence (Oulu, Finland) was measured. Ability for full volumetric reconstruction in non-contact manner enabled complete characterization of closed entity of a microfluidic channel without contamination and harm for the sample. Measurement, occurring problems, and methods of postprocessing for raw data are described. Results present completely resolved physical structure of the channel, its spatial dimensions, draft angles and evaluation of lamination quality.

  12. Process for the production of methyl methacrylate

    Eastham, G.R.; Johnson, D.W.; Straathof, A.J.J.; Fraaije, Marco; Winter, Remko

    2015-01-01

    A process of producing methyl methacrylate or derivatives thereof is described. The process includes the steps of; (i) converting 2-butanone to methyl propionate using a Baeyer-Villiger monooxygenase, and (ii) treating the methyl propionate produced to obtain methyl methacrylate or derivatives

  13. Modular microfluidics for point-of-care protein purifications.

    Millet, L J; Lucheon, J D; Standaert, R F; Retterer, S T; Doktycz, M J

    2015-04-21

    Biochemical separations are the heart of diagnostic assays and purification methods for biologics. On-chip miniaturization and modularization of separation procedures will enable the development of customized, portable devices for personalized health-care diagnostics and point-of-use production of treatments. In this report, we describe the design and fabrication of miniature ion exchange, size exclusion and affinity chromatography modules for on-chip clean-up of recombinantly-produced proteins. Our results demonstrate that these common separations techniques can be implemented in microfluidic modules with performance comparable to conventional approaches. We introduce embedded 3-D microfluidic interconnects for integrating micro-scale separation modules that can be arranged and reconfigured to suit a variety of fluidic operations or biochemical processes. We demonstrate the utility of the modular approach with a platform for the enrichment of enhanced green fluorescent protein (eGFP) from Escherichia coli lysate through integrated affinity and size-exclusion chromatography modules.

  14. A modular microfluidic architecture for integrated biochemical analysis.

    Shaikh, Kashan A; Ryu, Kee Suk; Goluch, Edgar D; Nam, Jwa-Min; Liu, Juewen; Thaxton, C Shad; Chiesl, Thomas N; Barron, Annelise E; Lu, Yi; Mirkin, Chad A; Liu, Chang

    2005-07-12

    Microfluidic laboratory-on-a-chip (LOC) systems based on a modular architecture are presented. The architecture is conceptualized on two levels: a single-chip level and a multiple-chip module (MCM) system level. At the individual chip level, a multilayer approach segregates components belonging to two fundamental categories: passive fluidic components (channels and reaction chambers) and active electromechanical control structures (sensors and actuators). This distinction is explicitly made to simplify the development process and minimize cost. Components belonging to these two categories are built separately on different physical layers and can communicate fluidically via cross-layer interconnects. The chip that hosts the electromechanical control structures is called the microfluidic breadboard (FBB). A single LOC module is constructed by attaching a chip comprised of a custom arrangement of fluid routing channels and reactors (passive chip) to the FBB. Many different LOC functions can be achieved by using different passive chips on an FBB with a standard resource configuration. Multiple modules can be interconnected to form a larger LOC system (MCM level). We demonstrated the utility of this architecture by developing systems for two separate biochemical applications: one for detection of protein markers of cancer and another for detection of metal ions. In the first case, free prostate-specific antigen was detected at 500 aM concentration by using a nanoparticle-based bio-bar-code protocol on a parallel MCM system. In the second case, we used a DNAzyme-based biosensor to identify the presence of Pb(2+) (lead) at a sensitivity of 500 nM in <1 nl of solution.

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

    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

  16. Generation of tunable and pulsatile concentration gradients via microfluidic network

    Zhou, Bingpu

    2014-06-04

    We demonstrate a compact Polydimethylsiloxane microfluidic chip which can quickly generate ten different chemical concentrations simultaneously. The concentration magnitude of each branch can be flexibly regulated based on the flow rate ratios of the two injecting streams. The temporal/pulsatile concentration gradients are achieved by integrating on-chip pneumatic actuated valves controlled by the external signals. The temporal concentration gradients can also be tuned precisely by varying applied frequency and duty cycle of the trigger signal. It is believed that such microdevice will be potentially used for some application areas of producing stable chemical gradients as well as allowing fast, pulsatile gradient transformation in seconds.

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

    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.

  18. Microfluidic pressure sensing using trapped air compression.

    Srivastava, Nimisha; Burns, Mark A

    2007-05-01

    We have developed a microfluidic method for measuring the fluid pressure head experienced at any location inside a microchannel. The principal component is a microfabricated sealed chamber with a single inlet and no exit; the entrance to the single inlet is positioned at the location where pressure is to be measured. The pressure measurement is then based on monitoring the movement of a liquid-air interface as it compresses air trapped inside the microfabricated sealed chamber and calculating the pressure using the ideal gas law. The method has been used to measure the pressure of the air stream and continuous liquid flow inside microfluidic channels (d approximately 50 microm). Further, a pressure drop has also been measured using multiple microfabricated sealed chambers. For air pressure, a resolution of 700 Pa within a full-scale range of 700-100 kPa was obtained. For liquids, pressure drops as low as 70 Pa were obtained in an operating range from 70 Pa to 10 kPa. Since the method primarily uses a microfluidic sealed chamber, it does not require additional fabrication steps and may easily be incorporated in several lab-on-a-chip fluidic applications for laminar as well as turbulent flow conditions.

  19. Digital Microfluidic System with Vertical Functionality

    Brian F. Bender

    2015-11-01

    Full Text Available Digital (droplet microfluidics (DµF is a powerful platform for automated lab-on-a-chip procedures, ranging from quantitative bioassays such as RT-qPCR to complete mammalian cell culturing. The simple MEMS processing protocols typically employed to fabricate DµF devices limit their functionality to two dimensions, and hence constrain the applications for which these devices can be used. This paper describes the integration of vertical functionality into a DµF platform by stacking two planar digital microfluidic devices, altering the electrode fabrication process, and incorporating channels for reversibly translating droplets between layers. Vertical droplet movement was modeled to advance the device design, and three applications that were previously unachievable using a conventional format are demonstrated: (1 solutions of calcium dichloride and sodium alginate were vertically mixed to produce a hydrogel with a radially symmetric gradient in crosslink density; (2 a calcium alginate hydrogel was formed within the through-well to create a particle sieve for filtering suspensions passed from one layer to the next; and (3 a cell spheroid formed using an on-chip hanging-drop was retrieved for use in downstream processing. The general capability of vertically delivering droplets between multiple stacked levels represents a processing innovation that increases DµF functionality and has many potential applications.

  20. Microfluidic Fabrication of Conjugated Polymer Sensor Fibers

    Yoo, Imsung; Song, Simon [Hanyang University, Seoul (Korea, Republic of)

    2014-10-15

    We propose a fabrication method for polydiacetylene (PDA)-embedded hydrogel microfibers on a microfluidic chip. These fibers can be applied to the detection of cyclodextrines (CDs), which are a family of sugar and aluminum ions. PDA, a family of conjugated polymers, has unique characteristics when used for a sensor, because it undergoes a blue-to-red color transition and nonfluorescence-to-fluorescence transition in response to environmental stimulation. PDAs have different sensing characteristics depending on the head group of PCDA. By taking advantage of ionic crosslinking-induced hydrogel formation and the 3D hydrodynamic focusing effect on a microfluidic chip, PCDA-EDEA-derived diacetylene (DA) monomer-embedded microfibers were successfully fabricated. UV irradiation of the fibers afforded blue-colored PDA, and the resulting blue PDA fibers underwent a phase transition to red and emitted red fluorescence upon exposure to CDs and aluminum ions. Their fluorescence intensity varied depending on the CDs and aluminum ion concentrations. This phase transition was also observed when the fibers were dried.

  1. Synthesis of hexagonal gold nanoparticles using a microfluidic reaction system

    Weng, Chen-Hsun; Lee, Gwo-Bin; Huang, Chih-Chia; Yeh, Chen-Sheng; Lei, Huan-Yao

    2008-01-01

    A new microfluidic reaction system capable of mixing, transporting and reacting is developed for the synthesis of gold nanoparticles. It allows for a rapid and a cost-effective approach to accelerate the synthesis of gold nanoparticles. The microfluidic reaction chip is made from micro-electro-mechanical-system technologies which integrate a micro-mixer, micro-pumps, a micro-valve, micro-heaters and a micro temperature sensor on a single chip. Successful synthesis of dispersed gold nanoparticles has been demonstrated within a shorter period of time, as compared to traditional methods. It is experimentally found that precise control of the mixing/heating time for gold salts and reducing agents plays an essential role in the synthesis of gold nanoparticles. The growth process of hexagonal gold nanoparticles by a thermal aqueous approach is also systematically studied by using the same microfluidic reaction system. The development of the microfluidic reaction system could be promising for the synthesis of functional nanoparticles for future biomedical applications

  2. A Droplet Microfluidic Platform for Automating Genetic Engineering.

    Gach, Philip C; Shih, Steve C C; Sustarich, Jess; Keasling, Jay D; Hillson, Nathan J; Adams, Paul D; Singh, Anup K

    2016-05-20

    We present a water-in-oil droplet microfluidic platform for transformation, culture and expression of recombinant proteins in multiple host organisms including bacteria, yeast and fungi. The platform consists of a hybrid digital microfluidic/channel-based droplet chip with integrated temperature control to allow complete automation and integration of plasmid addition, heat-shock transformation, addition of selection medium, culture, and protein expression. The microfluidic format permitted significant reduction in consumption (100-fold) of expensive reagents such as DNA and enzymes compared to the benchtop method. The chip contains a channel to continuously replenish oil to the culture chamber to provide a fresh supply of oxygen to the cells for long-term (∼5 days) cell culture. The flow channel also replenished oil lost to evaporation and increased the number of droplets that could be processed and cultured. The platform was validated by transforming several plasmids into Escherichia coli including plasmids containing genes for fluorescent proteins GFP, BFP and RFP; plasmids with selectable markers for ampicillin or kanamycin resistance; and a Golden Gate DNA assembly reaction. We also demonstrate the applicability of this platform for transformation in widely used eukaryotic organisms such as Saccharomyces cerevisiae and Aspergillus niger. Duration and temperatures of the microfluidic heat-shock procedures were optimized to yield transformation efficiencies comparable to those obtained by benchtop methods with a throughput up to 6 droplets/min. The proposed platform offers potential for automation of molecular biology experiments significantly reducing cost, time and variability while improving throughput.

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

    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.

  4. Acoustofluidics 14: Applications of acoustic streaming in microfluidic devices.

    Wiklund, Martin; Green, Roy; Ohlin, Mathias

    2012-07-21

    In part 14 of the tutorial series "Acoustofluidics--exploiting ultrasonic standing wave forces and acoustic streaming in microfluidic systems for cell and particle manipulation", we provide a qualitative description of acoustic streaming and review its applications in lab-on-a-chip devices. The paper covers boundary layer driven streaming, including Schlichting and Rayleigh streaming, Eckart streaming in the bulk fluid, cavitation microstreaming and surface-acoustic-wave-driven streaming.

  5. Discrete microfluidics based on aluminum nitride surface acoustic wave devices

    Zhou, J.; Pang, H.F.; Garcia-Gancedo, L.; Iborra, E.; Clement, M.; De Miguel-Ramos, M.; Jin, H.; Luo, J.K.; Smith, S.; Dong, S.R.; Wang, D.M.; Fu, Y.Q.

    2015-01-01

    To date, most surface acoustic wave (SAW) devices have been made from bulk piezoelectric materials, such as quartz, lithium niobate or lithium tantalite. These bulk materials are brittle, less easily integrated with electronics for control and signal processing, and difficult to realize multiple wave modes or apply complex electrode designs. Using thin film SAWs makes it convenient to integrate microelectronics and multiple sensing or microfluidics techniques into a lab-on-a-chip with low cos...

  6. Dimensional metrology of lab-on-a-chip internal structures: a comparison of optical coherence tomography with confocal fluorescence microscopy.

    Reyes, D R; Halter, M; Hwang, J

    2015-07-01

    The characterization of internal structures in a polymeric microfluidic device, especially of a final product, will require a different set of optical metrology tools than those traditionally used for microelectronic devices. We demonstrate that optical coherence tomography (OCT) imaging is a promising technique to characterize the internal structures of poly(methyl methacrylate) devices where the subsurface structures often cannot be imaged by conventional wide field optical microscopy. The structural details of channels in the devices were imaged with OCT and analyzed with an in-house written ImageJ macro in an effort to identify the structural details of the channel. The dimensional values obtained with OCT were compared with laser-scanning confocal microscopy images of channels filled with a fluorophore solution. Attempts were also made using confocal reflectance and interferometry microscopy to measure the channel dimensions, but artefacts present in the images precluded quantitative analysis. OCT provided the most accurate estimates for the channel height based on an analysis of optical micrographs obtained after destructively slicing the channel with a microtome. OCT may be a promising technique for the future of three-dimensional metrology of critical internal structures in lab-on-a-chip devices because scans can be performed rapidly and noninvasively prior to their use. © 2015 The Authors Journal of Microscopy © 2015 Royal Microscopical Society.

  7. Lab-on-a-Chip: Frontier Science in the Classroom

    Wietsma, Jan Jaap; van der Veen, Jan T.; Buesink, Wilfred; van den Berg, Albert; Odijk, Mathieu

    2018-01-01

    Lab-on-a-chip technology is brought into the classroom through development of a lesson series with hands-on practicals. Students can discover the principles of microfluidics with different practicals covering laminar flow, micromixing, and droplet generation, as well as trapping and counting beads. A quite affordable novel production technique…

  8. A 3D Microfluidic Model to Recapitulate Cancer Cell Migration and Invasion

    Yi-Chin Toh

    2018-04-01

    Full Text Available We have developed a microfluidic-based culture chip to simulate cancer cell migration and invasion across the basement membrane. In this microfluidic chip, a 3D microenvironment is engineered to culture metastatic breast cancer cells (MX1 in a 3D tumor model. A chemo-attractant was incorporated to stimulate motility across the membrane. We validated the usefulness of the chip by tracking the motilities of the cancer cells in the system, showing them to be migrating or invading (akin to metastasis. It is shown that our system can monitor cell migration in real time, as compare to Boyden chambers, for example. Thus, the chip will be of interest to the drug-screening community as it can potentially be used to monitor the behavior of cancer cell motility, and, therefore, metastasis, in the presence of anti-cancer drugs.

  9. Fast infectious diseases diagnostics based on microfluidic biochip system

    Qin Huang

    2017-03-01

    Full Text Available Molecular diagnostics is one of the most important tools currently in use for clinical pathogen detection due to its high sensitivity, specificity, and low consume of sample and reagent is keyword to low cost molecular diagnostics. In this paper, a sensitive DNA isothermal amplification method for fast clinical infectious diseases diagnostics at aM concentrations of DNA was developed using a polycarbonate (PC microfluidic chip. A portable confocal optical fluorescence detector was specifically developed for the microfluidic chip that was capable of highly sensitive real-time detection of amplified products for sequence-specific molecular identification near the optical diffraction limit with low background. The molecular diagnostics of Listeria monocytogenes with nucleic acid extracted from stool samples was performed at a minimum DNA template concentration of 3.65aM, and a detection limit of less than five copies of genomic DNA. Contrast to the general polymerase chain reaction (PCR at eppendorf (EP tube, the detection time in our developed method was reduced from 1.5h to 45min for multi-target parallel detection, the consume of sample and reagent was dropped from 25μL to 1.45μL. This novel microfluidic chip system and method can be used to develop a micro total analysis system as a clinically relevant pathogen molecular diagnostics method via the amplification of targets, with potential applications in biotechnology, medicine, and clinical molecular diagnostics.

  10. In search of low cost biological analysis: Wax or acrylic glue bonded paper microfluidic devices

    Kodzius, Rimantas; Gong, Xiuqing; Li, Shunbo; Qin, Jianhua; Wen, Weijia; Wu, Jinbo; Xiao, Kang; Yi, Xin

    2011-01-01

    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 or cyanoacrylate-based resin 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 or simple cyanoacrylate-based resin can realize bridge bonding between various materials, for example, paper, polymethylmethacrylate film, glass sheets, or metal plate. The wax 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 evacuating the channels of adhesive material in a hot-water. We applied the wax-paper based microfluidic chip to HeLa cell electroporation. 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 recombinant 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. The chip bonded with cyanoacrylate-based resin was tested by measuring protein concentration and carrying out DNA capillary electrophoresis. To study the biocompatibility and applicability of our microfluidic chip fabrication technology, we tested the PCR compatibility of our chip materials along with various other common materials employed in the fabrication of microfluidic chips including: silicon, several kinds of silicon oxide, glasses, plastics, wax, and adhesives, etc. 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

  11. Microfluidic production of polymeric functional microparticles

    Jiang, Kunqiang

    This dissertation focuses on applying droplet-based microfluidics to fabricate new classes of polymeric microparticles with customized properties for various applications. The integration of microfluidic techniques with microparticle engineering allows for unprecedented control over particle size, shape, and functional properties. Specifically, three types of microparticles are discussed here: (1) Magnetic and fluorescent chitosan hydrogel microparticles and their in-situ assembly into higher-order microstructures; (2) Polydimethylsiloxane (PDMS) microbeads with phosphorescent properties for oxygen sensing; (3) Macroporous microparticles as biological immunosensors. First, we describe a microfluidic approach to generate monodisperse chitosan hydrogel microparticles that can be further connected in-situ into higher-order microstructures. Microparticles of the biopolymer chitosan are created continuously by contacting an aqueous solution of chitosan at a microfluidic T-junction with a stream of hexadecane containing a nonionic detergent, followed by downstream crosslinking of the generated droplets by a ternary flow of glutaraldehyde. Functional properties of the microparticles can be easily varied by introducing payloads such as magnetic nanoparticles and/or fluorescent dyes into the chitosan solution. We then use these prepared microparticles as "building blocks" and assemble them into high ordered microstructures, i.e. microchains with controlled geometry and flexibility. Next, we describe a new approach to produce monodisperse microbeads of PDMS using microfluidics. Using a flow-focusing configuration, a PDMS precursor solution is dispersed into microdroplets within an aqueous continuous phase. These droplets are collected and thermally cured off-chip into soft, solid microbeads. In addition, our technique allows for direct integration of payloads, such as an oxygen-sensitive porphyrin dye, into the PDMS microbeads. We then show that the resulting dye

  12. Phase holograms in polymethyl methacrylate

    Maker, P. D.; Muller, R. E.

    1992-01-01

    A procedure is described for the fabrication of complex computer-generated phase holograms in polymethyl methacrylate (PMMA) by means of partial-exposure e-beam lithography and subsequent carefully controlled partial development. Following the development, the pattern appears (rendered in relief) in the PMMA, which then acts as the phase-delay medium. The devices fabricated were designed with 16 equal phase steps per retardation cycle, were up to 3 mm square, and consisted of up to 10 millions of 0.3-2.0-micron square pixels. Data files were up to 60 Mb-long, and the exposure times ranged to several hours. A Fresnel phase lens was fabricated with a diffraction-limited optical performance of 83-percent efficiency.

  13. Microfluidic systems for stem cell-based neural tissue engineering.

    Karimi, Mahdi; Bahrami, Sajad; Mirshekari, Hamed; Basri, Seyed Masoud Moosavi; Nik, Amirala Bakhshian; Aref, Amir R; Akbari, Mohsen; Hamblin, Michael R

    2016-07-05

    Neural tissue engineering aims at developing novel approaches for the treatment of diseases of the nervous system, by providing a permissive environment for the growth and differentiation of neural cells. Three-dimensional (3D) cell culture systems provide a closer biomimetic environment, and promote better cell differentiation and improved cell function, than could be achieved by conventional two-dimensional (2D) culture systems. With the recent advances in the discovery and introduction of different types of stem cells for tissue engineering, microfluidic platforms have provided an improved microenvironment for the 3D-culture of stem cells. Microfluidic systems can provide more precise control over the spatiotemporal distribution of chemical and physical cues at the cellular level compared to traditional systems. Various microsystems have been designed and fabricated for the purpose of neural tissue engineering. Enhanced neural migration and differentiation, and monitoring of these processes, as well as understanding the behavior of stem cells and their microenvironment have been obtained through application of different microfluidic-based stem cell culture and tissue engineering techniques. As the technology advances it may be possible to construct a "brain-on-a-chip". In this review, we describe the basics of stem cells and tissue engineering as well as microfluidics-based tissue engineering approaches. We review recent testing of various microfluidic approaches for stem cell-based neural tissue engineering.

  14. Shannon Meets Fick on the Microfluidic Channel: Diffusion Limit to Sum Broadcast Capacity for Molecular Communication.

    Bicen, A Ozan; Lehtomaki, Janne J; Akyildiz, Ian F

    2018-03-01

    Molecular communication (MC) over a microfluidic channel with flow is investigated based on Shannon's channel capacity theorem and Fick's laws of diffusion. Specifically, the sum capacity for MC between a single transmitter and multiple receivers (broadcast MC) is studied. The transmitter communicates by using different types of signaling molecules with each receiver over the microfluidic channel. The transmitted molecules propagate through microfluidic channel until reaching the corresponding receiver. Although the use of different types of molecules provides orthogonal signaling, the sum broadcast capacity may not scale with the number of the receivers due to physics of the propagation (interplay between convection and diffusion based on distance). In this paper, the performance of broadcast MC on a microfluidic chip is characterized by studying the physical geometry of the microfluidic channel and leveraging the information theory. The convergence of the sum capacity for microfluidic broadcast channel is analytically investigated based on the physical system parameters with respect to the increasing number of molecular receivers. The analysis presented here can be useful to predict the achievable information rate in microfluidic interconnects for the biochemical computation and microfluidic multi-sample assays.

  15. Rapid prototyping of 2D glass microfluidic devices based on femtosecond laser assisted selective etching process

    Kim, Sung-Il; Kim, Jeongtae; Koo, Chiwan; Joung, Yeun-Ho; Choi, Jiyeon

    2018-02-01

    Microfluidics technology which deals with small liquid samples and reagents within micro-scale channels has been widely applied in various aspects of biological, chemical, and life-scientific research. For fabricating microfluidic devices, a silicon-based polymer, PDMS (Polydimethylsiloxane), is widely used in soft lithography, but it has several drawbacks for microfluidic applications. Glass has many advantages over PDMS due to its excellent optical, chemical, and mechanical properties. However, difficulties in fabrication of glass microfluidic devices that requires multiple skilled steps such as MEMS technology taking several hours to days, impedes broad application of glass based devices. Here, we demonstrate a rapid and optical prototyping of a glass microfluidic device by using femtosecond laser assisted selective etching (LASE) and femtosecond laser welding. A microfluidic droplet generator was fabricated as a demonstration of a microfluidic device using our proposed prototyping. The fabrication time of a single glass chip containing few centimeter long and complex-shaped microfluidic channels was drastically reduced in an hour with the proposed laser based rapid and simple glass micromachining and hermetic packaging technique.

  16. Fabricating and Characterizing the Microfluidic Solid Phase Extraction Module Coupling with Integrated ESI Emitters

    Hangbin Tang

    2018-05-01

    Full Text Available Microfluidic chips coupling with mass spectrometry (MS will be of great significance to the development of relevant instruments involving chemical and bio-chemical analysis, drug detection, food and environmental applications and so on. In our previous works, we proposed two types of microfluidic electrospray ionization (ESI chip coupling with MS: the two-phase flow focusing (FF ESI microfluidic chip and the corner-integrated ESI emitter, respectively. However the pretreatment module integrated with these ESI emitters is still a challenging problem. In this paper, we concentrated on integrating the solid phase micro-extraction (SPME module with our previous proposed on-chip ESI emitters; the fabrication processes of such SPME module are fully compatible with our previous proposed ESI emitters based on the multi-layer soft lithography. We optimized the structure of the integrated chip and characterized its performance using standard samples. Furthermore, we verified its abilities of salt removal, extraction of multiple analytes and separation through on-chip elution using mimic biological urine spiked with different drugs. The results indicated that our proposed integrated module with ESI emitters is practical and effective for real biological sample pretreatment and MS detection.

  17. A new UV-curing elastomeric substrate for rapid prototyping of microfluidic devices

    Alvankarian, Jafar; Yeop Majlis, Burhanuddin

    2012-03-01

    Rapid prototyping in the design cycle of new microfluidic devices is very important for shortening time-to-market. Researchers are facing the challenge to explore new and suitable substrates with simple and efficient microfabrication techniques. In this paper, we introduce and characterize a UV-curing elastomeric polyurethane methacrylate (PUMA) for rapid prototyping of microfluidic devices. The swelling and solubility of PUMA in different chemicals is determined. Time-dependent measurements of water contact angle show that the native PUMA is hydrophilic without surface treatment. The current monitoring method is used for measurement of the electroosmotic flow mobility in the microchannels made from PUMA. The optical, physical, thermal and mechanical properties of PUMA are evaluated. The UV-lithography and molding process is used for making micropillars and deep channel microfluidic structures integrated to the supporting base layer. Spin coating is characterized for producing different layer thicknesses of PUMA resin. A device is fabricated and tested for examining the strength of different bonding techniques such as conformal, corona treating and semi-curing of two PUMA layers in microfluidic application and the results show that the bonding strengths are comparable to that of PDMS. We also report fabrication and testing of a three-layer multi inlet/outlet microfluidic device including a very effective fluidic interconnect for application demonstration of PUMA as a promising new substrate. A simple micro-device is developed and employed for observing the pressure deflection of membrane made from PUMA as a very effective elastomeric valve in microfluidic devices.

  18. Chips 2020

    2016-01-01

    The release of this second volume of CHIPS 2020 coincides with the 50th anniversary of Moore’s Law, a critical year marked by the end of the nanometer roadmap and by a significantly reduced annual rise in chip performance. At the same time, we are witnessing a data explosion in the Internet, which is consuming 40% more electrical power every year, leading to fears of a major blackout of the Internet by 2020. The messages of the first CHIPS 2020, published in 2012, concerned the realization of quantum steps for improving the energy efficiency of all chip functions. With this second volume, we review these messages and amplify upon the most promising directions: ultra-low-voltage electronics, nanoscale monolithic 3D integration, relevant-data, brain- and human-vision-inspired processing, and energy harvesting for chip autonomy. The team of authors, enlarged by more world leaders in low-power, monolithic 3D, video, and Silicon brains, presents new vistas in nanoelectronics, promising  Moore-like exponential g...

  19. Low-cost rapid prototyping of flexible plastic paper based microfluidic devices

    Fan, Yiqiang

    2013-04-01

    This research presents a novel rapid prototyping method for paper-based flexible microfluidic devices. The microchannels were fabricated using laser ablation on a piece of plastic paper (permanent paper), the dimensions of the microchannels was carefully studied for various laser powers and scanning speeds. After laser ablation of the microchannels on the plastic paper, a transparent poly (methyl methacrylate)(PMMA) film was thermally bonded to the plastic paper to enclose the channels. After connection of tubing, the device was ready to use. An example microfluidic device (droplet generator) was also fabricated using this technique. Due to the flexibility of the fabricated device, this technique can be used to fabricate 3D microfluidic devices. The fabrication process was simple and rapid without any requirement of cleanroom facilities. © 2013 IEEE.

  20. Neural Stem Cell Differentiation Using Microfluidic Device-Generated Growth Factor Gradient.

    Kim, Ji Hyeon; Sim, Jiyeon; Kim, Hyun-Jung

    2018-04-11

    Neural stem cells (NSCs) have the ability to self-renew and differentiate into multiple nervous system cell types. During embryonic development, the concentrations of soluble biological molecules have a critical role in controlling cell proliferation, migration, differentiation and apoptosis. In an effort to find optimal culture conditions for the generation of desired cell types in vitro , we used a microfluidic chip-generated growth factor gradient system. In the current study, NSCs in the microfluidic device remained healthy during the entire period of cell culture, and proliferated and differentiated in response to the concentration gradient of growth factors (epithermal growth factor and basic fibroblast growth factor). We also showed that overexpression of ASCL1 in NSCs increased neuronal differentiation depending on the concentration gradient of growth factors generated in the microfluidic gradient chip. The microfluidic system allowed us to study concentration-dependent effects of growth factors within a single device, while a traditional system requires multiple independent cultures using fixed growth factor concentrations. Our study suggests that the microfluidic gradient-generating chip is a powerful tool for determining the optimal culture conditions.

  1. Computational analysis of integrated biosensing and shear flow in a microfluidic vascular model

    Wong, Jeremy F.; Young, Edmond W. K.; Simmons, Craig A.

    2017-11-01

    Fluid flow and flow-induced shear stress are critical components of the vascular microenvironment commonly studied using microfluidic cell culture models. Microfluidic vascular models mimicking the physiological microenvironment also offer great potential for incorporating on-chip biomolecular detection. In spite of this potential, however, there are few examples of such functionality. Detection of biomolecules released by cells under flow-induced shear stress is a significant challenge due to severe sample dilution caused by the fluid flow used to generate the shear stress, frequently to the extent where the analyte is no longer detectable. In this work, we developed a computational model of a vascular microfluidic cell culture model that integrates physiological shear flow and on-chip monitoring of cell-secreted factors. Applicable to multilayer device configurations, the computational model was applied to a bilayer configuration, which has been used in numerous cell culture applications including vascular models. Guidelines were established that allow cells to be subjected to a wide range of physiological shear stress while ensuring optimal rapid transport of analyte to the biosensor surface and minimized biosensor response times. These guidelines therefore enable the development of microfluidic vascular models that integrate cell-secreted factor detection while addressing flow constraints imposed by physiological shear stress. Ultimately, this work will result in the addition of valuable functionality to microfluidic cell culture models that further fulfill their potential as labs-on-chips.

  2. Detection of Plasmodium Aldolase Using a Smartphone and Microfluidic Enzyme Linked Immunosorbent Assay

    Nikhil S. Gopal

    2017-01-01

    Full Text Available Background. Malaria control efforts are limited in rural areas. A low-cost system to monitor response without the use of electricity is needed. Plasmodium aldolase is a malaria biomarker measured using enzyme linked immunosorbent assay (ELISA techniques. A three-part system using ELISA was developed consisting of a microfluidic chip, hand crank centrifuge, and a smartphone. Methods. A circular microfluidic chip was fabricated using clear acrylic and a CO2 laser. A series of passive valves released reagents at precise times based upon centrifugal force. Color change was measured via smartphone camera using an application programmed in Java. The microchip was compared to a standard 96-well sandwich ELISA. Results. Results from standard ELISA were compared to microchip at varying concentrations (1–10 ng/mL. Over 15 different microfluidic patterns were tested, and a final prototype of the chip was created. The prototype microchip was compared to standard sandwich ELISA (n=20 using samples of recombinant aldolase. Color readings of standard ELISA and microfluidic microchip showed similar results. Conclusion. A low-cost microfluidic system could detect and follow therapeutic outcomes in rural areas and identify resistant strains.

  3. Polymerization of sodium methacrylate induced by irradiation

    Galvan S, A.

    1998-01-01

    This work has two objectives, first: it is pretended to localize the lines of carbon links in its IR spectra, and second: following the polymerization of sodium methacrylate according to that it is irradiated with gamma rays. (Author)

  4. Integrated electrofluidic circuits: pressure sensing with analog and digital operation functionalities for microfluidics.

    Wu, Chueh-Yu; Lu, Jau-Ching; Liu, Man-Chi; Tung, Yi-Chung

    2012-10-21

    Microfluidic technology plays an essential role in various lab on a chip devices due to its desired advantages. An automated microfluidic system integrated with actuators and sensors can further achieve better controllability. A number of microfluidic actuation schemes have been well developed. In contrast, most of the existing sensing methods still heavily rely on optical observations and external transducers, which have drawbacks including: costly instrumentation, professional operation, tedious interfacing, and difficulties of scaling up and further signal processing. This paper reports the concept of electrofluidic circuits - electrical circuits which are constructed using ionic liquid (IL)-filled fluidic channels. The developed electrofluidic circuits can be fabricated using a well-developed multi-layer soft lithography (MSL) process with polydimethylsiloxane (PDMS) microfluidic channels. Electrofluidic circuits allow seamless integration of pressure sensors with analog and digital operation functions into microfluidic systems and provide electrical readouts for further signal processing. In the experiments, the analog operation device is constructed based on electrofluidic Wheatstone bridge circuits with electrical outputs of the addition and subtraction results of the applied pressures. The digital operation (AND, OR, and XOR) devices are constructed using the electrofluidic pressure controlled switches, and output electrical signals of digital operations of the applied pressures. The experimental results demonstrate the designed functions for analog and digital operations of applied pressures are successfully achieved using the developed electrofluidic circuits, making them promising to develop integrated microfluidic systems with capabilities of precise pressure monitoring and further feedback control for advanced lab on a chip applications.

  5. Organs-on-Chips in Drug Development: The Importance of Involving Stakeholders in Early Health Technology Assessment

    Middelkamp, Heleen H.T.; van der Meer, Andries Dirk; Hummel, J. Marjan; Stamatialis, Dimitrios; Mummery, Christine Lindsay; Passier, Petrus Christianus Johannes Josephus; IJzerman, Maarten Joost

    2016-01-01

    Organs-on-chips are three-dimensional, microfluidic cell culture systems that simulate the function of tissues and organ subunits. Organ-on-chip systems are expected to contribute to drug candidate screening and the reduction of animal tests in preclinical drug development and may increase

  6. Monitoring single-cell gene regulation under dynamically controllable conditions with integrated microfluidics and software

    Kaiser, Matthias; Jug, Florian; Julou, Thomas; Deshpande, S.R.; Pfohl, Thomas; Silander, Olin K.; Myers, Gene; Van Nimwegen, Erik

    2018-01-01

    Much is still not understood about how gene regulatory interactions control cell fate decisions in single cells, in part due to the difficulty of directly observing gene regulatory processes in vivo. We introduce here a novel integrated setup consisting of a microfluidic chip and accompanying

  7. Synthesis of Biochemical Applications on Flow-Based Microfluidic Biochips using Constraint Programming

    Minhass, Wajid Hassan; Pop, Paul; Madsen, Jan

    2012-01-01

    Microfluidic biochips are replacing the conventional biochemical analyzers and are able to integrate the necessary functions for biochemical analysis on-chip. In this paper we are interested in flow-based biochips, in which the flow of liquid is manipulated using integrated microvalves. By combin...

  8. A simple method of fabricating mask-free microfluidic devices for biological analysis.

    Yi, Xin; Kodzius, Rimantas; Gong, Xiuqing; Xiao, Kang; Wen, Weijia

    2010-01-01

    We report a simple, low-cost, rapid, and mask-free method to fabricate two-dimensional (2D) and three-dimensional (3D) microfluidic chip for biological analysis researches. In this fabrication process, a laser system is used to cut through paper

  9. A low-cost, manufacturable method for fabricating capillary and optical fiber interconnects for microfluidic devices.

    Hartmann, Daniel M; Nevill, J Tanner; Pettigrew, Kenneth I; Votaw, Gregory; Kung, Pang-Jen; Crenshaw, Hugh C

    2008-04-01

    Microfluidic chips require connections to larger macroscopic components, such as light sources, light detectors, and reagent reservoirs. In this article, we present novel methods for integrating capillaries, optical fibers, and wires with the channels of microfluidic chips. The method consists of forming planar interconnect channels in microfluidic chips and inserting capillaries, optical fibers, or wires into these channels. UV light is manually directed onto the ends of the interconnects using a microscope. UV-curable glue is then allowed to wick to the end of the capillaries, fibers, or wires, where it is cured to form rigid, liquid-tight connections. In a variant of this technique, used with light-guiding capillaries and optical fibers, the UV light is directed into the capillaries or fibers, and the UV-glue is cured by the cone of light emerging from the end of each capillary or fiber. This technique is fully self-aligned, greatly improves both the quality and the manufacturability of the interconnects, and has the potential to enable the fabrication of interconnects in a fully automated fashion. Using these methods, including a semi-automated implementation of the second technique, over 10,000 interconnects have been formed in almost 2000 microfluidic chips made of a variety of rigid materials. The resulting interconnects withstand pressures up to at least 800psi, have unswept volumes estimated to be less than 10 femtoliters, and have dead volumes defined only by the length of the capillary.

  10. Microfluidic Flame Barrier

    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.

  11. 40 CFR 721.9492 - Polymers of styrene, cyclohexyl methacrylate and substituted methacrylate.

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Polymers of styrene, cyclohexyl... Significant New Uses for Specific Chemical Substances § 721.9492 Polymers of styrene, cyclohexyl methacrylate...) The chemical substances identified generically as polymers of styrene, cyclohexyl methacrylate and...

  12. A microfluidic tubing method and its application for controlled synthesis of polymeric nanoparticles.

    Wang, Jidong; Chen, Wenwen; Sun, Jiashu; Liu, Chao; Yin, Qifang; Zhang, Lu; Xianyu, Yunlei; Shi, Xinghua; Hu, Guoqing; Jiang, Xingyu

    2014-05-21

    This report describes a straightforward but robust tubing method for connecting polydimethylsiloxane (PDMS) microfluidic devices to external equipment. The interconnection is irreversible and can sustain a pressure of up to 4.5 MPa that is characterized experimentally and theoretically. To demonstrate applications of this high-pressure tubing technique, we fabricate a semicircular microfluidic channel to implement a high-throughput, size-controlled synthesis of poly(lactic-co-glycolic acid) (PLGA) nanoparticles ranging from 55 to 135 nm in diameter. This microfluidic device allows for a total flow rate of 410 mL h(-1), resulting in enhanced convective mixing which can be utilized to precipitate small size nanoparticles with a good dispersion. We expect that this tubing technique would be widely used in microfluidic chips for nanoparticle synthesis, cell manipulation, and potentially nanofluidic applications.

  13. Contact allergy to epoxy (meth)acrylates.

    Aalto-Korte, Kristiina; Jungewelter, Soile; Henriks-Eckerman, Maj-Len; Kuuliala, Outi; Jolanki, Riitta

    2009-07-01

    Contact allergy to epoxy (meth)acrylates, 2,2-bis[4-(2-hydroxy-3-methacryloxypropoxy) phenyl]propane (bis-GMA), 2,2-bis[4-(2-hydroxy-3-acryloxypropoxy)phenyl]-propane (bis-GA), 2,2-bis[4-(methacryl-oxyethoxy)phenyl] propane (bis-EMA), 2,2-bis[4-(methacryloxy)phenyl]-propane (bis-MA), and glycidyl methacrylate (GMA) is often manifested together with contact allergy to diglycidyl ether of bisphenol A (DGEBA) epoxy resin. To analyse patterns of concomitant allergic reactions to the five epoxy (meth)acrylates in relation to exposure. We reviewed the 1994-2008 patch test files at the Finnish Institute of Occupational Health (FIOH) for reactions to the five epoxy (meth)acrylates, and examined the patients' medical records for exposure. Twenty-four patients had an allergic reaction to at least one of the studied epoxy (meth)acrylates, but specific exposure was found only in five patients: two bis-GMA allergies from dental products, two bis-GA allergies from UV-curable printing inks, and one bis-GA allergy from an anaerobic glue. Only 25% of the patients were negative to DGEBA epoxy resin. The great majority of allergic patch test reactions to bis-GMA, bis-GA, GMA and bis-EMA were not associated with specific exposure, and cross-allergy to DGEBA epoxy resin remained a probable explanation. However, independent reactions to bis-GA indicated specific exposure. Anaerobic sealants may induce sensitization not only to aliphatic (meth)acrylates but also to aromatic bis-GA.

  14. Simple approach to study biomolecule adsorption in polymeric microfluidic channels

    Gubala, Vladimir; Siegrist, Jonathan; Monaghan, Ruairi; O’Reilly, Brian; Gandhiraman, Ram Prasad; Daniels, Stephen; Williams, David E.; Ducrée, Jens

    2013-01-01

    Highlights: ► A simple tool to assess biomolecule adsorption onto the surfaces of microchannels. ► Development for dilution by surface-adsorption based depletion of protein samples. ► It can easily be done using a readily available apparatus like a spin-coater. ► The assessment tool is facile and quantitative. ► Straightforward comparison of different surface chemistries. - Abstract: Herein a simple analytical method is presented for the characterization of biomolecule adsorption on cyclo olefin polymer (COP, trade name: Zeonor ® ) substrates which are widely used in microfluidic lab-on-a-chip devices. These Zeonor ® substrates do not possess native functional groups for specific reactions with biomolecules. Therefore, depending on the application, such substrates must be functionalized by surface chemistry methods to either enhance or suppress biomolecular adsorption. This work demonstrates a microfluidic method for evaluating the adsorption of antibodies and oligonucleotides surfaces. The method uses centrifugal microfluidic flow-through chips and can easily be implemented using common equipment such as a spin coater. The working principle is very simple. The user adds 40 L of the solution containing the sample to the starting side of a microfluidic channel, where it is moved through by centrifugal force. Some molecules are adsorbed in the channel. The sample is then collected at the other end in a small reservoir and the biomolecule concentration is measured. As a pilot application, we characterized the adsorption of goat anti-human IgG and a 20-mer DNA on Zeonor ® , and on three types of functionalized Zeonor: 3-aminopropyltriethoxysilane (APTES) modified surface with mainly positive charge, negatively charged surface with immobilized bovine serum albumin (BSA), and neutral, hydrogel-like film with polyethylene glycol (PEG) characteristics. This simple analytical approach adds to the fundamental understanding of the interaction forces in real

  15. Simple approach to study biomolecule adsorption in polymeric microfluidic channels

    Gubala, Vladimir, E-mail: V.Gubala@kent.ac.uk [Biomedical Diagnostics Institute (BDI), National Centre for Sensor Research (NCSR), Dublin City University, Dublin 9 (Ireland); Medway School of Pharmacy, University of Kent, Central Avenue, Anson 120, Chatham Maritime, Kent ME4 4TB (United Kingdom); Siegrist, Jonathan; Monaghan, Ruairi; O' Reilly, Brian; Gandhiraman, Ram Prasad [Biomedical Diagnostics Institute (BDI), National Centre for Sensor Research (NCSR), Dublin City University, Dublin 9 (Ireland); Daniels, Stephen [Biomedical Diagnostics Institute (BDI), National Centre for Sensor Research (NCSR), Dublin City University, Dublin 9 (Ireland); National Centre for Plasma Science and Technology (NCPST), Dublin City University, Dublin 9 (Ireland); Williams, David E. [Biomedical Diagnostics Institute (BDI), National Centre for Sensor Research (NCSR), Dublin City University, Dublin 9 (Ireland); MacDiarmid Institute for Advanced Materials and Nanotechnology, School of Chemical Sciences, University of Auckland, Auckland 1142 (New Zealand); Ducree, Jens [Biomedical Diagnostics Institute (BDI), National Centre for Sensor Research (NCSR), Dublin City University, Dublin 9 (Ireland)

    2013-01-14

    Highlights: Black-Right-Pointing-Pointer A simple tool to assess biomolecule adsorption onto the surfaces of microchannels. Black-Right-Pointing-Pointer Development for dilution by surface-adsorption based depletion of protein samples. Black-Right-Pointing-Pointer It can easily be done using a readily available apparatus like a spin-coater. Black-Right-Pointing-Pointer The assessment tool is facile and quantitative. Black-Right-Pointing-Pointer Straightforward comparison of different surface chemistries. - Abstract: Herein a simple analytical method is presented for the characterization of biomolecule adsorption on cyclo olefin polymer (COP, trade name: Zeonor{sup Registered-Sign }) substrates which are widely used in microfluidic lab-on-a-chip devices. These Zeonor{sup Registered-Sign} substrates do not possess native functional groups for specific reactions with biomolecules. Therefore, depending on the application, such substrates must be functionalized by surface chemistry methods to either enhance or suppress biomolecular adsorption. This work demonstrates a microfluidic method for evaluating the adsorption of antibodies and oligonucleotides surfaces. The method uses centrifugal microfluidic flow-through chips and can easily be implemented using common equipment such as a spin coater. The working principle is very simple. The user adds 40 L of the solution containing the sample to the starting side of a microfluidic channel, where it is moved through by centrifugal force. Some molecules are adsorbed in the channel. The sample is then collected at the other end in a small reservoir and the biomolecule concentration is measured. As a pilot application, we characterized the adsorption of goat anti-human IgG and a 20-mer DNA on Zeonor{sup Registered-Sign }, and on three types of functionalized Zeonor: 3-aminopropyltriethoxysilane (APTES) modified surface with mainly positive charge, negatively charged surface with immobilized bovine serum albumin (BSA), and

  16. Numerical Optimization in Microfluidics

    Jensen, Kristian Ejlebjærg

    2017-01-01

    Numerical modelling can illuminate the working mechanism and limitations of microfluidic devices. Such insights are useful in their own right, but one can take advantage of numerical modelling in a systematic way using numerical optimization. In this chapter we will discuss when and how numerical...... optimization is best used....

  17. Enzyme detection by microfluidics

    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...

  18. Chemistry in Microfluidic Channels

    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…

  19. Enhanced physicochemical properties of polydimethylsiloxane based microfluidic devices and thin films by incorporating synthetic micro-diamond.

    Waheed, Sidra; Cabot, Joan M; Macdonald, Niall P; Kalsoom, Umme; Farajikhah, Syamak; Innis, Peter C; Nesterenko, Pavel N; Lewis, Trevor W; Breadmore, Michael C; Paull, Brett

    2017-11-08

    Synthetic micro-diamond-polydimethylsiloxane (PDMS) composite microfluidic chips and thin films were produced using indirect 3D printing and spin coating fabrication techniques. Microfluidic chips containing up to 60 wt% micro-diamond were successfully cast and bonded. Physicochemical properties, including the dispersion pattern, hydrophobicity, chemical structure, elasticity and thermal characteristics of both chip and films were investigated. Scanning electron microscopy indicated that the micro-diamond particles were embedded and interconnected within the bulk material of the cast microfluidic chip, whereas in the case of thin films their increased presence at the polymer surface resulted in a reduced hydrophobicity of the composite. The elastic modulus increased from 1.28 for a PDMS control, to 4.42 MPa for the 60 wt% composite, along with a three-fold increase in thermal conductivity, from 0.15 to 0.45 W m -1 K -1 . Within the fluidic chips, micro-diamond incorporation enhanced heat dissipation by efficient transfer of heat from within the channels to the surrounding substrate. At a flow rate of 1000 μL/min, the gradient achieved for the 60 wt% composite chip equalled a 9.8 °C drop across a 3 cm long channel, more than twice that observed with the PDMS control chip.

  20. Design of pressure-driven microfluidic networks using electric circuit analogy.

    Oh, Kwang W; Lee, Kangsun; Ahn, Byungwook; Furlani, Edward P

    2012-02-07

    This article reviews the application of electric circuit methods for the analysis of pressure-driven microfluidic networks with an emphasis on concentration- and flow-dependent systems. The application of circuit methods to microfluidics is based on the analogous behaviour of hydraulic and electric circuits with correlations of pressure to voltage, volumetric flow rate to current, and hydraulic to electric resistance. Circuit analysis enables rapid predictions of pressure-driven laminar flow in microchannels and is very useful for designing complex microfluidic networks in advance of fabrication. This article provides a comprehensive overview of the physics of pressure-driven laminar flow, the formal analogy between electric and hydraulic circuits, applications of circuit theory to microfluidic network-based devices, recent development and applications of concentration- and flow-dependent microfluidic networks, and promising future applications. The lab-on-a-chip (LOC) and microfluidics community will gain insightful ideas and practical design strategies for developing unique microfluidic network-based devices to address a broad range of biological, chemical, pharmaceutical, and other scientific and technical challenges.

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

    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. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. A disposable and multifunctional capsule for easy operation of microfluidic elastomer systems

    Thorslund, Sara; Läräng, Thomas; Kreuger, Johan; Nguyen, Hugo; Barkefors, Irmeli

    2011-01-01

    The global lab-on-chip and microfluidic markets for cell-based assays have been predicted to grow considerably, as novel microfluidic systems enable cell biologists to perform in vitro experiments at an unprecedented level of experimental control. Nevertheless, microfluidic assays must, in order to compete with conventional assays, be made available at easily affordable costs, and in addition be made simple to operate for users having no previous experience with microfluidics. We have to this end developed a multifunctional microfluidic capsule that can be mass-produced at low cost in thermoplastic material. The capsule enables straightforward operation of elastomer inserts of optional design, here exemplified with insert designs for molecular gradient formation in microfluidic cell culture systems. The integrated macro–micro interface of the capsule ensures reliable connection of the elastomer fluidic structures to an external perfusion system. A separate compartment in the capsule filled with superabsorbent material is used for internal waste absorption. The capsule assembly process is made easy by integrated snap-fits, and samples within the closed capsule can be analyzed using both inverted and upright microscopes. Taken together, the capsule concept presented here could help accelerate the use of microfluidic-based biological assays in the life science sector. (technical note)

  3. Quantum dot-based microfluidic biosensor for cancer detection

    Ghrera, Aditya Sharma; Pandey, Chandra Mouli; Ali, Md. Azahar; Malhotra, Bansi Dhar

    2015-05-01

    We report results of the studies relating to fabrication of an impedimetric microfluidic-based nucleic acid sensor for quantification of DNA sequences specific to chronic myelogenous leukemia (CML). The sensor chip is prepared by patterning an indium-tin-oxide (ITO) coated glass substrate via wet chemical etching method followed by sealing with polydimethylsiloxane (PDMS) microchannel for fluid control. The fabricated microfluidic chip comprising of a patterned ITO substrate is modified by depositing cadmium selenide quantum dots (QCdSe) via Langmuir-Blodgett technique. Further, the QCdSe surface has been functionalized with specific DNA probe for CML detection. The probe DNA functionalized QCdSe integrated miniaturized system has been used to monitor target complementary DNA concentration by measuring the interfacial charge transfer resistance via hybridization. The presence of complementary DNA in buffer solution significantly results in decreased electro-conductivity of the interface due to presence of a charge barrier for transport of the redox probe ions. The microfluidic DNA biosensor exhibits improved linearity in the concentration range of 10-15 M to 10-11 M.

  4. Recent Developments in Optical Detection Technologies in Lab-on-a-Chip Devices for Biosensing Applications

    Nuno Miguel Matos Pires

    2014-08-01

    Full Text Available The field of microfluidics has yet to develop practical devices that provide real clinical value. One of the main reasons for this is the difficulty in realizing low-cost, sensitive, reproducible, and portable analyte detection microfluidic systems. Previous research has addressed two main approaches for the detection technologies in lab-on-a-chip devices: (a study of the compatibility of conventional instrumentation with microfluidic structures, and (b integration of innovative sensors contained within the microfluidic system. Despite the recent advances in electrochemical and mechanical based sensors, their drawbacks pose important challenges to their application in disposable microfluidic devices. Instead, optical detection remains an attractive solution for lab-on-a-chip devices, because of the ubiquity of the optical methods in the laboratory. Besides, robust and cost-effective devices for use in the field can be realized by integrating proper optical detection technologies on chips. This review examines the recent developments in detection technologies applied to microfluidic biosensors, especially addressing several optical methods, including fluorescence, chemiluminescence, absorbance and surface plasmon resonance.

  5. A Transdermal Measurement Platform Based on Microfluidics

    Wen-Ying Huang

    2017-01-01

    Full Text Available The Franz diffusion cell is one of the most widely used devices to evaluate transdermal drug delivery. However, this static and nonflowing system has some limitations, such as a relatively large solution volume and skin area and the development of gas bubbles during sampling. To overcome these disadvantages, this study provides a proof of concept for miniaturizing models of transdermal delivery by using a microfluidic chip combined with a diffusion cell. The proposed diffusion microchip system requires only 80 μL of sample solution and provides flow circulation. Two model compounds, Coomassie Brilliant Blue G-250 and potassium ferricyanide, were successfully tested for transdermal delivery experiments. The diffusion rate is high for a high sample concentration or a large membrane pore size. The developed diffusion microchip system, which is feasible, can be applied for transdermal measurement in the future.

  6. Microfluidic Platform for Enzyme-Linked and Magnetic Particle-Based Immunoassay

    Dorota G. Pijanowska

    2013-06-01

    Full Text Available This article presents design and testing of a microfluidic platform for immunoassay. The method is based on sandwiched ELISA, whereby the primary antibody is immobilized on nitrocelluose and, subsequently, magnetic beads are used as a label to detect the analyte. The chip takes approximately 2 h and 15 min to complete the assay. A Hall Effect sensor using 0.35-μm BioMEMS TSMC technology (Taiwan Semiconductor Manufacturing Company Bio-Micro-Electro-Mechanical Systems was fabricated to sense the magnetic field from the beads. Furthermore, florescence detection and absorbance measurements from the chip demonstrate successful immunoassay on the chip. In addition, investigation also covers the Hall Effect simulations, mechanical modeling of the bead–protein complex, testing of the microfluidic platform with magnetic beads averaging 10 nm, and measurements with an inductor-based system.

  7. Methacrylate and acrylate allergy in dental personnel.

    Aalto-Korte, Kristiina; Alanko, Kristiina; Kuuliala, Outi; Jolanki, Riitta

    2007-11-01

    Methacrylates are important allergens in dentistry. The study aimed to analyse patch test reactivity to 36 acrylic monomers in dental personnel in relation to exposure. We reviewed the test files at the Finnish Institute of Occupational Health from 1994 to 2006 for allergic reactions to acrylic monomers in dental personnel and analysed the clinical records of the sensitized patients. 32 patients had allergic reactions to acrylic monomers: 15 dental nurses, 9 dentists, and 8 dental technicians. The dentists and dental nurses were most commonly exposed to 2-hydroxyethyl methacrylate (2-HEMA), triethyleneglycol dimethacrylate (TREGDMA), and 2,2-bis[4-(2-hydroxy-3-methacryloxypropoxy) phenyl]propane (bis-GMA). 8 dentists and 12 dental nurses were allergic to 2-HEMA. The remaining dentist was positive to bis-GMA and other epoxy acrylates. The remaining 3 dental nurses reacted to diethyleneglycol diacrylate (DEGDA) or triethyleneglycol diacrylate (TREGDA), but not to monofunctional and multifunctional methacrylates. Our dental technicians were mainly exposed and sensitized to methyl methacrylate (MMA) and ethyleneglycol dimethacrylate (EGDMA). 1 technician reacted only to 2-HEMA, and another to ethyl methacrylate (EMA) and ethyl acrylate (EA). 2-HEMA was the most important allergen in dentists and dental nurses, and MMA and EGDMA in dental technicians. Reactions to bis-GMA, DEGDA, TREGDA, EMA and EA were relevant in some patients.

  8. 78 FR 55644 - Styrene, Copolymers with Acrylic Acid and/or Methacrylic Acid; Tolerance Exemption

    2013-09-11

    ..., 3-sulfopropyl acrylate, 3-sulfopropyl methacrylate, hydroxypropyl methacrylate, hydroxypropyl acrylate, hydroxyethyl methacrylate, and/or hydroxyethyl acrylate; and its sodium, potassium, ammonium..., hydroxypropyl acrylate, hydroxyethyl methacrylate, and/or hydroxyethyl acrylate; and its sodium, potassium...

  9. Dielectrophoretic Microfluidic Device for in Vitro Fertilization

    Hong-Yuan Huang

    2018-03-01

    Full Text Available The aim of this work was to create a microfluidic platform that uses in vitro fertilization (IVF and avoids unnecessary damage to oocytes due to the dielectrophoretic force manipulation of the sperms and oocytes that occurs in a traditional IVF operation. The device from this research can serve also to decrease medium volumes, as well as the cost of cell culture under evaporation, and to prevent unnecessary risk in intracytoplasmic sperm injection (ICSI. To decrease the impact and destruction of the oocyte and the sperm, we adopted a positive dielectrophoretic force to manipulate both the sperms and the oocyte. The mouse oocytes were trapped with a positive dielectrophoretic (p-DEP force by using Indium Tin Oxide (ITO-glass electrodes; the ITO-glass electrode chip was fabricated by wet etching the ITO-glass. The polydimethylsiloxane (PDMS flow-focusing microfluidic device was used to generate microdroplets of micrometer size to contain the zygotes. The volume of the microdroplets was controlled by adjusting the flow rates of both inlets for oil and the DEP buffer. As a result, the rate of fertilization was increased by about 5% beyond that of the DEP treatment in traditional IVF, and more than 20% developed to the blastocyst stage with a low sperm-oocyte ratio.

  10. Printed microfluidic filter for heparinized blood.

    Bilatto, Stanley E R; Adly, Nouran Y; Correa, Daniel S; Wolfrum, Bernhard; Offenhäusser, Andreas; Yakushenko, Alexey

    2017-05-01

    A simple lab-on-a-chip method for blood plasma separation was developed by combining stereolithographic 3D printing with inkjet printing, creating a completely sealed microfluidic device. In some approaches, one dilutes the blood sample before separation, reducing the concentration of a target analyte and increasing a contamination risk. In this work, a single drop (8  μ l) of heparinized whole blood could be efficiently filtered using a capillary effect without any external driving forces and without dilution. The blood storage in heparin tubes during 24 h at 4 °C initiated the formation of small crystals that formed auto-filtration structures in the sample upon entering the 3D-printed device, with pores smaller than the red blood cells, separating plasma from the cellular content. The total filtration process took less than 10 s. The presented printed plasma filtration microfluidics fabricated with a rapid prototyping approach is a miniaturized, fast and easy-to-operate device that can be integrated into healthcare/portable systems for point-of-care diagnostics.

  11. PREFACE: Nano- and microfluidics Nano- and microfluidics

    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

  12. Magnetic particle mixing with magnetic micro-convection for microfluidics

    Kitenbergs, Guntars; Erglis, Kaspars; Perzynski, Régine; Cēbers, Andrejs

    2015-01-01

    In this paper we discuss the magnetic micro-convection phenomenon as a tool for mixing enhancement in microfluidics systems in cases when one of the miscible fluids is a magnetic particle colloid. A system of a water-based magnetic fluid and water is investigated experimentally under homogeneous magnetic field in a Hele–Shaw cell. Subsequent image analysis both qualitatively and quantitatively reveals the high enhancement of mixing efficiency provided by this method. The mixing efficiency dependence on the magnetic field and the physical limits is discussed. A suitable model for a continuous-flow microfluidics setup for mixing with magnetic micro-convection is also proposed and justified with an experiment. In addition, possible applications in improving the speed of ferrohydrodynamic sorting and magnetic label or selected tracer mixing in lab on a chip systems are noted. - Highlights: • We study the magnetic micro-convection as a mixing method in microfluidics. • We show that the method enhances mixing with magnetic field squared dependency. • We propose a flow cell setup for mixing and justify it with a sample experiment. • The mixing method can be easily implemented in an existing microfluidics setup

  13. Inhibitory effect of common microfluidic materials on PCR outcome

    Kodzius, Rimantas

    2012-02-20

    Microfluidic chips have a variety of applications in the biological sciences and medicine. In contrast with traditional experimental approaches, microfluidics entails lower sample and reagent consumption, allows faster reactions and enables efficient separation. Additionally microfluidics offers other advantages accruing from the fluids’ various distinct behaviors, such as energy dissipation, fluidic resistance, laminar flow, and surface tension. Biological molecules suspended in fluid and transported through microfluidics channels interact with the channel-wall material. This interaction is even stronger in high surface-area-to-volume ratio (SAVR) microfluidic channels. Adsorption and inhibition of biomolecules occur when these materials come in contact with biomolecular reaction components. Polymerase chain reaction (PCR) is a thermal cycling procedure for amplifying target DNA. The PCR compatibility of silicon, silicon dioxide (SiO2) and other surfaces have been studied; however the results are inconclusive. Usually for protein-surface interaction measurements, bulky and expensive equipment is used, such as Atomic Force Microscopy (AFM), Scanning or Transmission Electron Microscopy (SEM, TEM), spectrophotometric protein concentration measurement, Fourier transform infrared spectroscopy (FTIR) or X-Ray photoelectron spectroscopy (XPS). \\tThe PCR reaction components include the DNA template, primers, DNA polymerase (the main component), dNTPs, a buffer, divalent ions (MgCl2), and KCl. \\tWe designed a simple, relatively quick measurement that only requires a PCR cycler; thus it mimics actual conditions in PCR cycling. In our study, we evaluated the inhibitory affect of different materials on PCR, which is one of the most frequently used enzymatic reactions in microfluidics. PCR reaction optimization through choice of surface materials is of the upmost importance, as it enables and improves enzymatic reaction in microfluidics. Our assessment of the PCR

  14. Retention of krypton on polymethyl methacrylate

    Ciric, M.M.; Cvjeticanin, N.M.; Radak, B.B.

    1975-01-01

    Retention of krypton on polymethyl methacrylate was studied as a function of kryptonation pressure (P), temperature (T) and time (t). It was found that the dependence of the retained quantity on P, T, and t is in accordance with the diffusion theory. The optimum results (i.e., the maximum retained quantity and the best stability of the kryptonate) were obtained at elevated kryptonation temperatures (200 0 C). The diffusion coefficients of krypton in polymethyl methacrylate, determined from the dekryptonation process, vary from 1 x 10 -10 cm 2 /s to 0.2 x 10 -10 cm 2 /s for samples kryptonated at 20 0 C and 200 0 C respectively. The results have been discussed from the viewpoint of radiation and thermal stability of kryptonated polymethyl methacrylate. Inadequate radiation stability could be the main obstacle for practical purposes. (U.S.)

  15. Polymerization of novel methacrylated anthraquinone dyes

    Christian Dollendorf

    2013-02-01

    Full Text Available A new series of polymerizable methacrylated anthraquinone dyes has been synthesized by nucleophilic aromatic substitution reactions and subsequent methacrylation. Thereby, green 5,8-bis(4-(2-methacryloxyethylphenylamino-1,4-dihydroxyanthraquinone (2, blue 1,4-bis(4-((2-methacryloxyethyloxyphenylaminoanthraquinone (6 and red 1-((2-methacryloxy-1,1-dimethylethylaminoanthraquinone (12, as well as 1-((1,3-dimethacryloxy-2-methylpropan-2-ylaminoanthraquinone (15 were obtained. By mixing of these brilliant dyes in different ratios and concentrations, a broad color spectrum can be generated. After methacrylation, the monomeric dyes can be covalently emplaced into several copolymers. Due to two polymerizable functionalities, they can act as cross-linking agents. Thus, diffusion out of the polymer can be avoided, which increases the physiological compatibility and makes the dyes promising compounds for medical applications, such as iris implants.

  16. A self-contained, programmable microfluidic cell culture system with real-time microscopy access

    Skafte-Pedersen, Peder; Hemmingsen, Mette; Sabourin, David

    2011-01-01

    Utilizing microfluidics is a promising way for increasing the throughput and automation of cell biology research. We present a complete self-contained system for automated cell culture and experiments with real-time optical read-out. The system offers a high degree of user-friendliness, stability...... enables the system to perform parallel, programmable and multiconditional assays on a single chip. A modular approach provides system versatility and allows many different chips to be used dependent upon application. We validate the system's performance by demonstrating on-chip passive switching...... and mixing by peristaltically driven flows. Applicability for biological assays is demonstrated by on-chip cell culture including on-chip transfection and temporally programmable gene expression....

  17. Microfluidic device, and related methods

    Wong, Eric W. (Inventor)

    2010-01-01

    A method of making a microfluidic device is provided. The method features patterning a permeable wall on a substrate, and surrounding the permeable wall with a solid, non-permeable boundary structure to establish a microfluidic channel having a cross-sectional dimension less than 5,000 microns and a cross-sectional area at least partially filled with the permeable wall so that fluid flowing through the microfluidic channel at least partially passes through the permeable wall.

  18. Methyl methacrylate oligomerically-modified clay and its poly(methyl methacrylate) nanocomposites

    Zheng Xiaoxia; Jiang, David D.; Wilkie, Charles A.

    2005-01-01

    A methyl methacrylate oligomerically-modified clay was used to prepare poly(methyl methacrylate) clay nanocomposites by melt blending and the effect of the clay loading level on the modified clay and corresponding nanocomposite was studied. These nanocomposites were characterized by X-ray diffraction, transmission electron microscopy, thermogravimetric analysis and cone calorimetry. The results show a mixed intercalated/delaminated morphology with good nanodispersion. The compatibility between the methylacrylate-subsituted clay and poly(methyl methacrylate) (PMMA) are greatly improved compared to other oligomerically-modified clays

  19. Polymer microfluidic device replacing fluids using only capillary force

    Chung, Kwang Hyo; Lee, Dae Sik; Yang, Haesik; Kim, Sung Jin; Pyo, Hyun Bong

    2005-02-01

    A novel polymer microfluidic device for self-wash using only capillary force is presented. A liquid filled in a reaction chamber is replaced by another liquid with no external actuation. All the fluidic actuations in the device is pre-programmed about time and sequence, and accomplished by capillary force naturally. Careful design is necessary for exact actions. The fluidic conduits were designed by the newly derived theoretical equations about the capillary stop pressure and flow time. Simulations using CFD-ACE+ were conducted to check the validity of theory and the performance of the chip. These analytic results were consistent with experimental ones. The chip was made of polymers for the purpose of single use and low price. It was fabricated by sealing the hot-embossed PMMA substrate with a PET film. For simpler fabrication, the chip was of a single height. The embossing master was produced from a nickel-electroplating on a SU8-patterned Ni-plate followed by CMP. The contact angles of liquids on substrates were manipulated through the mixing of surfactants, and the temporal variations were monitored for a more exact design. The real actuation steps in experiment revealed the stable performance of selfwash, and coincided well with the designed ones. The presented microfluidic method can be applicable to other LOCs of special purposes through simple modification. For example, array or serial types would be possible for multiple selfwashes.

  20. Integrated bioassays in microfluidic devices: botulinum toxin assays.

    Mangru, Shakuntala; Bentz, Bryan L; Davis, Timothy J; Desai, Nitin; Stabile, Paul J; Schmidt, James J; Millard, Charles B; Bavari, Sina; Kodukula, Krishna

    2005-12-01

    A microfluidic assay was developed for screening botulinum neurotoxin serotype A (BoNT-A) by using a fluorescent resonance energy transfer (FRET) assay. Molded silicone microdevices with integral valves, pumps, and reagent reservoirs were designed and fabricated. Electrical and pneumatic control hardware were constructed, and software was written to automate the assay protocol and data acquisition. Detection was accomplished by fluorescence microscopy. The system was validated with a peptide inhibitor, running 2 parallel assays, as a feasibility demonstration. The small footprint of each bioreactor cell (0.5 cm2) and scalable fluidic architecture enabled many parallel assays on a single chip. The chip is programmable to run a dilution series in each lane, generating concentration-response data for multiple inhibitors. The assay results showed good agreement with the corresponding experiments done at a macroscale level. Although the system has been developed for BoNT-A screening, a wide variety of assays can be performed on the microfluidic chip with little or no modification.

  1. Methods of making microfluidic devices

    Buttner, Ulrich

    2017-06-01

    Microfluidics has advanced in terms of designs and structures, however, fabrication methods are either time consuming or expensive to produce, in terms of the facilities and equipment needed. A fast and economically viable method is provided to allow, for example, research groups to have access to microfluidic fabrication. Unlike most fabrication methods, a method is provided to fabricate a microfluidic device in one step. In an embodiment, a resolution of 50 micrometers was achieved by using maskless high-resolution digital light projection (MDLP). Bonding and channel fabrication of complex or simple structures can be rapidly incorporated to fabricate the microfluidic devices.

  2. The Use of Microfluidics in Cytotoxicity and Nanotoxicity Experiments

    Scott C. McCormick

    2017-04-01

    Full Text Available Many unique chemical compounds and nanomaterials are being developed, and each one requires a considerable range of in vitro and/or in vivo toxicity screening in order to evaluate their safety. The current methodology of in vitro toxicological screening on cells is based on well-plate assays that require time-consuming manual handling or expensive automation to gather enough meaningful toxicology data. Cost reduction; access to faster, more comprehensive toxicity data; and a robust platform capable of quantitative testing, will be essential in evaluating the safety of new chemicals and nanomaterials, and, at the same time, in securing the confidence of regulators and end-users. Microfluidic chips offer an alternative platform for toxicity screening that has the potential to transform both the rates and efficiency of nanomaterial testing, as reviewed here. The inherent advantages of microfluidic technologies offer high-throughput screening with small volumes of analytes, parallel analyses, and low-cost fabrication.

  3. Microfluidics and nanofluidics handbook chemistry, physics, and life science principles

    Mitra, Sushanta K

    2011-01-01

    The Microfluidics and Nanofluidics Handbook: Two-Volume Set comprehensively captures the cross-disciplinary breadth of the fields of micro- and nanofluidics, which encompass the biological sciences, chemistry, physics and engineering applications. To fill the knowledge gap between engineering and the basic sciences, the editors pulled together key individuals, well known in their respective areas, to author chapters that help graduate students, scientists, and practicing engineers understand the overall area of microfluidics and nanofluidics. Topics covered include Cell Lysis Techniques in Lab-on-a-Chip Technology Electrodics in Electrochemical Energy Conversion Systems: Microstructure and Pore-Scale Transport Microscale Gas Flow Dynamics and Molecular Models for Gas Flow and Heat Transfer Microscopic Hemorheology and Hemodynamics Covering physics and transport phenomena along with life sciences and related applications, Volume One: Chemistry, Physics, and Life Science Principles provides readers with the fun...

  4. Electrostatic charging and control of droplets in microfluidic devices.

    Zhou, Hongbo; Yao, Shuhuai

    2013-03-07

    Precharged droplets can facilitate manipulation and control of low-volume liquids in droplet-based microfluidics. In this paper, we demonstrate non-contact electrostatic charging of droplets by polarizing a neutral droplet and splitting it into two oppositely charged daughter droplets in a T-junction microchannel. We performed numerical simulation to analyze the non-contact charging process and proposed a new design with a notch at the T-junction in aid of droplet splitting for more efficient charging. We experimentally characterized the induced charge in droplets in microfabricated devices. The experimental results agreed well with the simulation. Finally, we demonstrated highly effective droplet manipulation in a path selection unit appending to the droplet charging. We expect our work could enable precision manipulation of droplets for more complex liquid handling in microfluidics and promote electric-force based manipulation in 'lab-on-a-chip' systems.

  5. Microfluidic mixing triggered by an external LED illumination.

    Venancio-Marques, Anna; Barbaud, Fanny; Baigl, Damien

    2013-02-27

    The mixing of confined liquids is a central yet challenging operation in miniaturized devices. Microfluidic mixing is usually achieved with passive mixers that are robust but poorly flexible, or active mixers that offer dynamic control but mainly rely on electrical or mechanical transducers, which increase the fragility, cost, and complexity of the device. Here, we describe the first remote and reversible control of microfluidic mixing triggered by a light illumination simply provided by an external LED illumination device. The approach is based on the light-induced generation of water microdroplets acting as reversible stirrers of two continuous oil phase flows containing samples to be mixed. We demonstrate many cycles of reversible photoinduced transitions between a nonmixing behavior and full homogenization of the two oil phases. The method is cheap, portable, and adaptable to many device configurations, thus constituting an essential brick for the generation of future all-optofluidic chip.

  6. High-Throughput Fabrication of Nanocone Substrates through Polymer Injection Moulding For SERS Analysis in Microfluidic Systems

    Viehrig, Marlitt; Matteucci, Marco; Thilsted, Anil H.

    analysis. Metal-capped silicon nanopillars, fabricated through a maskless ion etch, are state-of-the-art for on-chip SERS substrates. A dense cluster of high aspect ratio polymer nanocones was achieved by using high-throughput polymer injection moulding over a large area replicating a silicon nanopillar...... structure. Gold-capped polymer nanocones display similar SERS sensitivity as silicon nanopillars, while being easily integrable into a microfluidic chips....

  7. Microfluidic size separation of cells and particles using a swinging bucket centrifuge.

    Yeo, Joo Chuan; Wang, Zhiping; Lim, Chwee Teck

    2015-09-01

    Biomolecular separation is crucial for downstream analysis. Separation technique mainly relies on centrifugal sedimentation. However, minuscule sample volume separation and extraction is difficult with conventional centrifuge. Furthermore, conventional centrifuge requires density gradient centrifugation which is laborious and time-consuming. To overcome this challenge, we present a novel size-selective bioparticles separation microfluidic chip on a swinging bucket minifuge. Size separation is achieved using passive pressure driven centrifugal fluid flows coupled with centrifugal force acting on the particles within the microfluidic chip. By adopting centrifugal microfluidics on a swinging bucket rotor, we achieved over 95% efficiency in separating mixed 20 μm and 2 μm colloidal dispersions from its liquid medium. Furthermore, by manipulating the hydrodynamic resistance, we performed size separation of mixed microbeads, achieving size efficiency of up to 90%. To further validate our device utility, we loaded spiked whole blood with MCF-7 cells into our microfluidic device and subjected it to centrifugal force for a mere duration of 10 s, thereby achieving a separation efficiency of over 75%. Overall, our centrifugal microfluidic device enables extremely rapid and label-free enrichment of different sized cells and particles with high efficiency.

  8. Detachably assembled microfluidic device for perfusion culture and post-culture analysis of a spheroid array.

    Sakai, Yusuke; Hattori, Koji; Yanagawa, Fumiki; Sugiura, Shinji; Kanamori, Toshiyuki; Nakazawa, Kohji

    2014-07-01

    Microfluidic devices permit perfusion culture of three-dimensional (3D) tissue, mimicking the flow of blood in vascularized 3D tissue in our body. Here, we report a microfluidic device composed of a two-part microfluidic chamber chip and multi-microwell array chip able to be disassembled at the culture endpoint. Within the microfluidic chamber, an array of 3D tissue aggregates (spheroids) can be formed and cultured under perfusion. Subsequently, detailed post-culture analysis of the spheroids collected from the disassembled device can be performed. This device facilitates uniform spheroid formation, growth analysis in a high-throughput format, controlled proliferation via perfusion flow rate, and post-culture analysis of spheroids. We used the device to culture spheroids of human hepatocellular carcinoma (HepG2) cells under two controlled perfusion flow rates. HepG2 spheroids exhibited greater cell growth at higher perfusion flow rates than at lower perfusion flow rates, and exhibited different metabolic activity and mRNA and protein expression under the different flow rate conditions. These results show the potential of perfusion culture to precisely control the culture environment in microfluidic devices. The construction of spheroid array chambers allows multiple culture conditions to be tested simultaneously, with potential applications in toxicity and drug screening. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Capture and X-ray diffraction studies of protein microcrystals in a microfluidic trap array

    Lyubimov, Artem Y. [Stanford University, Stanford, CA 94305 (United States); Stanford University, Stanford, CA 94305 (United States); Stanford University, Stanford, CA 94305 (United States); Stanford University, Stanford, CA 94305 (United States); Stanford University, Stanford, CA 94305 (United States); Murray, Thomas D. [University of California, Berkeley, CA 94720 (United States); Johns Hopkins University School of Medicine, Baltimore, MD 21205 (United States); Koehl, Antoine [Stanford University, Stanford, CA 94305 (United States); Araci, Ismail Emre [Stanford University, Stanford, CA 94305 (United States); Stanford University, Stanford, CA 94305 (United States); Uervirojnangkoorn, Monarin; Zeldin, Oliver B. [Stanford University, Stanford, CA 94305 (United States); Stanford University, Stanford, CA 94305 (United States); Stanford University, Stanford, CA 94305 (United States); Stanford University, Stanford, CA 94305 (United States); Stanford University, Stanford, CA 94305 (United States); Cohen, Aina E.; Soltis, S. Michael; Baxter, Elizabeth L. [SLAC National Accelerator Laboratory, Stanford, CA 94305 (United States); Brewster, Aaron S.; Sauter, Nicholas K. [Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Brunger, Axel T., E-mail: brunger@stanford.edu [Stanford University, Stanford, CA 94305 (United States); Stanford University, Stanford, CA 94305 (United States); Stanford University, Stanford, CA 94305 (United States); Stanford University, Stanford, CA 94305 (United States); Stanford University, Stanford, CA 94305 (United States); Berger, James M., E-mail: brunger@stanford.edu [Johns Hopkins University School of Medicine, Baltimore, MD 21205 (United States); Stanford University, Stanford, CA 94305 (United States)

    2015-04-01

    A microfluidic platform has been developed for the capture and X-ray analysis of protein microcrystals, affording a means to improve the efficiency of XFEL and synchrotron experiments. X-ray free-electron lasers (XFELs) promise to enable the collection of interpretable diffraction data from samples that are refractory to data collection at synchrotron sources. At present, however, more efficient sample-delivery methods that minimize the consumption of microcrystalline material are needed to allow the application of XFEL sources to a wide range of challenging structural targets of biological importance. Here, a microfluidic chip is presented in which microcrystals can be captured at fixed, addressable points in a trap array from a small volume (<10 µl) of a pre-existing slurry grown off-chip. The device can be mounted on a standard goniostat for conducting diffraction experiments at room temperature without the need for flash-cooling. Proof-of-principle tests with a model system (hen egg-white lysozyme) demonstrated the high efficiency of the microfluidic approach for crystal harvesting, permitting the collection of sufficient data from only 265 single-crystal still images to permit determination and refinement of the structure of the protein. This work shows that microfluidic capture devices can be readily used to facilitate data collection from protein microcrystals grown in traditional laboratory formats, enabling analysis when cryopreservation is problematic or when only small numbers of crystals are available. Such microfluidic capture devices may also be useful for data collection at synchrotron sources.

  10. Microfluidic Diatomite Analytical Devices for Illicit Drug Sensing with ppb-Level Sensitivity.

    Kong, Xianming; Chong, Xinyuan; Squire, Kenny; Wang, Alan X

    2018-04-15

    The escalating research interests in porous media microfluidics, such as microfluidic paper-based analytical devices, have fostered a new spectrum of biomedical devices for point-of-care (POC) diagnosis and biosensing. In this paper, we report microfluidic diatomite analytical devices (μDADs), which consist of highly porous photonic crystal biosilica channels, as an innovative lab-on-a-chip platform to detect illicit drugs. The μDADs in this work are fabricated by spin-coating and tape-stripping diatomaceous earth on regular glass slides with cross section of 400×30µm 2 . As the most unique feature, our μDADs can simultaneously perform on-chip chromatography to separate small molecules from complex biofluidic samples and acquire the surface-enhanced Raman scattering spectra of the target chemicals with high specificity. Owing to the ultra-small dimension of the diatomite microfluidic channels and the photonic crystal effect from the fossilized diatom frustules, we demonstrate unprecedented sensitivity down to part-per-billion (ppb) level when detecting pyrene (1ppb) from mixed sample with Raman dye and cocaine (10 ppb) from human plasma. This pioneering work proves the exclusive advantage of μDADs as emerging microfluidic devices for chemical and biomedical sensing, especially for POC drug screening.

  11. Testing of a Microfluidic Sampling System for High Temperature Electrochemical MC&A

    Pereira, Candido [Argonne National Lab. (ANL), Argonne, IL (United States); Nichols, Kevin [Argonne National Lab. (ANL), Argonne, IL (United States)

    2013-11-27

    This report describes the preliminary validation of a high-temperature microfluidic chip system for sampling of electrochemical process salt. Electroanalytical and spectroscopic techniques are attractive candidates for improvement through high-throughput sample analysis via miniaturization. Further, microfluidic chip systems are amenable to micro-scale chemical processing such as rapid, automated sample purification to improve sensor performance. The microfluidic chip was tested to determine the feasibility of the system for high temperature applications and conditions under which microfluidic systems can be used to generate salt droplets at process temperature to support development of material balance and control systems in a used fuel treatment facility. In FY13, the project focused on testing a quartz microchip device with molten salts at near process temperatures. The equipment was installed in glove box and tested up to 400°C using commercial thermal transfer fluids as the carrier phase. Preliminary tests were carried out with a low-melting halide salt to initially characterize the properties of this novel liquid-liquid system and to investigate the operating regimes for inducing droplet flow within candidate carrier fluids. Initial results show that the concept is viable for high temperature sampling but further development is required to optimize the system to operate with process relevant molten salts.

  12. The Microfluidic Jukebox

    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.

  13. Comprehensive Study of Microgel Electrode for On-Chip Electrophoretic Cell Sorting

    Hattori, Akihiro; Yasuda, Kenji

    2010-06-01

    We have developed an on-chip cell sorting system and microgel electrode for applying electrostatic force in microfluidic pathways in the chip. The advantages of agarose electrodes are 1) current-driven electrostatic force generation, 2) stability against pH change and chemicals, and 3) no bubble formation caused by electrolysis. We examined the carrier ion type and concentration dependence of microgel electrode impedance, and found that CoCl2 has less than 1/10 of the impedance from NaCl, and the reduction of the impedance of NaCl gel electrode was plateaued at 0.5 M. The structure control of the microgel electrode exploiting the surface tension of sol-state agarose was also introduced. The addition of 1% (w/v) trehalose into the microgel electrode allowed the frozen storage of the microgel electrode chip. The experimental results demonstrate the potential of our system and microgel electrode for practical applications in microfluidic chips.

  14. Droplet based microfluidics

    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.

  15. A Microfluidic Cell Concentrator

    Warrick, Jay; Casavant, Ben; Frisk, Megan; Beebe, David

    2010-01-01

    Cell concentration via centrifugation is a ubiquitous step in many cell culture procedures. At the macroscale, centrifugation suffers from a number of limitations particularly when dealing with small numbers of cells (e.g., less than 50,000). On the other hand, typical microscale methods for cell concentration can affect cell physiology and bias readouts of cell behavior and function. In this paper, we present a microfluidic concentrator device that utilizes the effects of gravity to allow cells to gently settle out of a suspension into a collection region without the use of specific adhesion ligands. Dimensional analysis was performed to compare different device designs and was verified with flow modeling to optimize operational parameters. We are able to concentrate low-density cell suspensions in a microfluidic chamber, achieving a cell loss of only 1.1 ± 0.6% (SD, n=7) with no observed loss during a subsequent cell staining protocol which incorporates ~36 complete device volume replacements. This method provides a much needed interface between rare cell samples and microfluidic culture assays. PMID:20843010

  16. Microfluidics with fluid walls.

    Walsh, Edmond J; Feuerborn, Alexander; Wheeler, James H R; Tan, Ann Na; Durham, William M; Foster, Kevin R; Cook, Peter R

    2017-10-10

    Microfluidics has great potential, but the complexity of fabricating and operating devices has limited its use. Here we describe a method - Freestyle Fluidics - that overcomes many key limitations. In this method, liquids are confined by fluid (not solid) walls. Aqueous circuits with any 2D shape are printed in seconds on plastic or glass Petri dishes; then, interfacial forces pin liquids to substrates, and overlaying an immiscible liquid prevents evaporation. Confining fluid walls are pliant and resilient; they self-heal when liquids are pipetted through them. We drive flow through a wide range of circuits passively by manipulating surface tension and hydrostatic pressure, and actively using external pumps. Finally, we validate the technology with two challenging applications - triggering an inflammatory response in human cells and chemotaxis in bacterial biofilms. This approach provides a powerful and versatile alternative to traditional microfluidics.The complexity of fabricating and operating microfluidic devices limits their use. Walsh et al. describe a method in which circuits are printed as quickly and simply as writing with a pen, and liquids in them are confined by fluid instead of solid walls.

  17. A nonaqueous potentiometric titration study of the dissociation of t-butyl methacrylate-methacrylic acid copolymers.

    Nakatani, Kiyoharu; Yamashita, Jun; Sekine, Tomomi; Toriumi, Minoru; Itani, Toshiro

    2003-05-01

    The dissociation of t-butyl methacrylate-methacrylic acid copolymers in dimethyl sulfoxide was analyzed by a nonaqueous potentiometric titration technique. The negative logarithm of the dissociation constant of the monomer unit of a methacrylic acid (MAA) monotonously increased with the increasing degree of dissociation corresponding to the titrant/MAA amount ratio, and was highly influenced by the copolymerization ratio. The results are discussed in terms of the suppression of the dissociation of MAA by a neighboring charged methacrylate anion unit.

  18. Exploring chip-capillary electrophoresis-laser-induced fluorescence field-deployable platform flexibility: Separations of fluorescent dyes by chip-based non-aqueous capillary electrophoresis

    Nuchtavorn, N.; Smejkal, Petr; Breadmore, M. C.; Guijt, R. M.; Doble, P.; Bek, F.; Foret, František; Suntornsuk, L.; Macka, M.

    2013-01-01

    Roč. 1286, APR (2013), s. 216-221 ISSN 0021-9673 R&D Projects: GA ČR(CZ) GBP206/12/G014 Institutional support: RVO:68081715 Keywords : microfluidic chip CE * capillary electrophoresis * NACE * LIF detection Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 4.258, year: 2013

  19. A simple microfluidic platform for rapid and efficient production of the radiotracer [18F]fallypride.

    Zhang, Xin; Liu, Fei; Knapp, Karla-Anne; Nickels, Michael L; Manning, H Charles; Bellan, Leon M

    2018-05-01

    Herein, we report the development of a simple, high-throughput and efficient microfluidic system for synthesizing radioactive [18F]fallypride, a PET imaging radiotracer widely used in medical research. The microfluidic chip contains all essential modules required for the synthesis and purification of radioactive fallypride. The radiochemical yield of the tracer is sufficient for multiple animal injections for preclinical imaging studies. To produce the on-chip concentration and purification columns, we employ a simple "trapping" mechanism by inserting rows of square pillars with predefined gaps near the outlet of microchannel. Microspheres with appropriate functionality are suspended in solution and loaded into the microchannels to form columns for radioactivity concentration and product purification. Instead of relying on complicated flow control elements (e.g., micromechanical valves requiring complex external pneumatic actuation), external valves are utilized to control transfer of the reagents between different modules. The on-chip ion exchange column can efficiently capture [18F]fluoride with negligible loss (∼98% trapping efficiency), and subsequently release a burst of concentrated [18F]fluoride to the reaction cavity. A thin layer of PDMS with a small hole in the center facilitates rapid and reliable water evaporation (with the aid of azeotropic distillation and nitrogen flow) while reducing fluoride loss. During the solvent exchange and fluorination reaction, the entire chip is uniformly heated to the desired temperature using a hot plate. All aspects of the [18F]fallypride synthesis were monitored by high-performance liquid chromatography (HPLC) analysis, resulting in labelling efficiency in fluorination reaction ranging from 67-87% (n = 5). Moreover, after isolating unreacted [18F]fluoride, remaining fallypride precursor, and various by-products via an on-chip purification column, the eluted [18F]fallypride is radiochemically pure and of a sufficient

  20. Polymeric microbead arrays for microfluidic applications

    Thompson, Jason A; Du, Xiaoguang; Grogan, Joseph M; Schrlau, Michael G; Bau, Haim H

    2010-01-01

    Microbeads offer a convenient and efficient means of immobilizing biomolecules and capturing target molecules of interest in microfluidic immunoassay devices. In this study, hot embossing is used to form wells enabling the direct incorporation of a microbead array in a plastic substrate. We demonstrate two techniques to populate the well array with beads. In the first case, encoded beads with various functionalizations are distributed randomly among the wells and their position is registered by reading their encoding. Alternatively, beads are controllably placed at predetermined positions and decoding is not required. The random placement technique is demonstrated with two functionalized bead types that are distributed among the wells and then decoded to register their locations. The alternative, deliberate placement technique is demonstrated by controllably placing magnetic beads at selected locations in the array using a magnetic probe. As a proof of concept to illustrate the biosensing capability of the randomly assembled array, an on-chip, bead-based immunoassay is employed to detect the inflammatory protein Interleukin-8. The principle of the assay, however, can be extended to detect multiple targets simultaneously. Our method eliminates the need to interface silicon components with plastic devices to form microarrays containing individually addressable beads. This has the potential to reduce the cost and complexity of lab-on-chip devices for medical diagnosis, food and water quality inspection, and environmental monitoring