WorldWideScience

Sample records for flow-based microfluidic device

  1. Microfluidic Device

    Science.gov (United States)

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

    2017-01-01

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

  2. Commercialization of microfluidic devices.

    Science.gov (United States)

    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.

  3. Microfluidic Cell Culture Device

    Science.gov (United States)

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

    2014-01-01

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

  4. Modeling and Simulation Framework for Flow-Based Microfluidic Biochips

    DEFF Research Database (Denmark)

    Schmidt, Morten Foged; Minhass, Wajid Hassan; Pop, Paul

    2013-01-01

    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 fluidic flow is manipulated using integrated microvalves. By combining...... and error prone. In this paper, we present an Integrated Development Environment (IDE), which addresses (i) schematic capture of the biochip architecture and biochemical application, (ii) logic simulation of an application running on a biochip, and is able to integrate the high level synthesis tasks we have...

  5. Methods of making microfluidic devices

    KAUST Repository

    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.

  6. A network-flow based valve-switching aware binding algorithm for flow-based microfluidic biochips

    DEFF Research Database (Denmark)

    Tseng, Kai-Han; You, Sheng-Chi; Minhass, Wajid Hassan

    2013-01-01

    -flow based resource binding algorithm based on breadth-first search (BFS) and minimum cost maximum flow (MCMF) in architectural-level synthesis. The experimental results show that our methodology not only makes significant reduction of valve-switching activities but also diminishes the application completion......Designs of flow-based microfluidic biochips are receiving much attention recently because they replace conventional biological automation paradigm and are able to integrate different biochemical analysis functions on a chip. However, as the design complexity increases, a flow-based microfluidic...... biochip needs more chip-integrated micro-valves, i.e., the basic unit of fluid-handling functionality, to manipulate the fluid flow for biochemical applications. Moreover, frequent switching of micro-valves results in decreased reliability. To minimize the valve-switching activities, we develop a network...

  7. Mixing in a Microfluid Device

    DEFF Research Database (Denmark)

    Hjorth, Poul G.; Deryabin, Mikhail

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

  8. Microfluidic device for drug delivery

    Science.gov (United States)

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

    2010-01-01

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

  9. Diffusion phenomena of cells and biomolecules in microfluidic devices.

    Science.gov (United States)

    Yildiz-Ozturk, Ece; Yesil-Celiktas, Ozlem

    2015-09-01

    Biomicrofluidics is an emerging field at the cross roads of microfluidics and life sciences which requires intensive research efforts in terms of introducing appropriate designs, production techniques, and analysis. The ultimate goal is to deliver innovative and cost-effective microfluidic devices to biotech, biomedical, and pharmaceutical industries. Therefore, creating an in-depth understanding of the transport phenomena of cells and biomolecules becomes vital and concurrently poses significant challenges. The present article outlines the recent advancements in diffusion phenomena of cells and biomolecules by highlighting transport principles from an engineering perspective, cell responses in microfluidic devices with emphases on diffusion- and flow-based microfluidic gradient platforms, macroscopic and microscopic approaches for investigating the diffusion phenomena of biomolecules, microfluidic platforms for the delivery of these molecules, as well as the state of the art in biological applications of mammalian cell responses and diffusion of biomolecules.

  10. Microfluidic devices for droplet injection

    Science.gov (United States)

    Aubrecht, Donald; Akartuna, Ilke; Weitz, David

    2012-02-01

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

  11. Architectural Synthesis of Flow-Based Microfluidic Large-Scale Integration Biochips

    DEFF Research Database (Denmark)

    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......,we propose a top-down architectural synthesis methodology for the flow-based biochips. Starting from a given biochemical application and a microfluidic component library, we are interested in synthesizing a biochip architecture, i.e., performing component allocation from the library based on the biochemical...... application, generating the biochip schematic (netlist) and then performing physical synthesis (deciding the placement of the microfluidic components on the chip and performing routing of the microfluidic channels), such that the application completion time is minimized. We evaluate our proposed approach...

  12. Microfluidic devices for cell cultivation and proliferation

    OpenAIRE

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

    2013-01-01

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

  13. Microfluidic Devices for Blood Fractionation

    Directory of Open Access Journals (Sweden)

    Chwee Teck Lim

    2011-07-01

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

  14. Synthesis of Biochemical Applications on Flow-Based Microfluidic Biochips using Constraint Programming

    DEFF Research Database (Denmark)

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

    2012-01-01

    . By combining several microvalves, more complex units, such as micropumps, switches, mixers, and multiplexers, can be built. We propose a constraint programming (CP) based approach for the synthesis of biochemical applications on flow-based microfluidic biochips. We use a sequencing graph to model...

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

    DEFF Research Database (Denmark)

    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...

  16. Integrated lenses in polystyrene microfluidic devices

    KAUST Repository

    Fan, Yiqiang

    2013-04-01

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

  17. Enzymatic Reactions in Microfluidic Devices

    Science.gov (United States)

    Ristenpart, W. D.; Wan, J.; Stone, H. A.

    2008-11-01

    We establish simple scaling laws for enzymatic reactions in microfluidic devices, and we demonstrate that kinetic parameters obtained conventionally using multiple stop-flow experiments may instead be extracted from a single microfluidic experiment. Introduction of an enzyme and substrate species in different arms of a Y-shaped channel allows the two species to diffuse across the parallel streamlines and to begin reacting. Measurements of the product concentration versus distance down the channel provide information about the kinetics of the reaction. In the limit where the enzyme is much larger (and thus less diffusive) than the substrate, we show that near the entrance the total amount of product (P) formed varies as a power law in the distance x down the channel. For reactions that follow standard Michaelis-Menten kinetics, the power law takes the form P˜(Vmax/Km) x^5/2, where Vmax and Km are the maximum reaction rate and Michaelis constant respectively. If a large excess of substrate is used, then Km is identified by measuring Vmax far downstream where the different species are completely mixed by diffusion. Numerical simulations and experiments using the bioluminescent reaction between luciferase and ATP as a model system are both shown to accord with the model. We discuss the implications for significant savings in the amount of time and enzyme required for determination of kinetic parameters.

  18. System-Level Modeling and Synthesis of Flow-Based Microfluidic Biochips

    DEFF Research Database (Denmark)

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

    2011-01-01

    Microfluidic biochips are replacing the conventional biochemical analyzers and are able to integrate the necessary functions for biochemical analysis on-chip. There are several types of microfluidic biochips, each having its advantages and limitations. In this paper we are interested in flow......-based biochips, in which the flow of liquid is manipulated using integrated microvalves. By combining several microvalves, more complex units, such as micropumps, switches, mixers, and multiplexers, can be built. Although researchers have proposed significant work on the system-level synthesis of droplet......-based biochips, which manipulate droplets on a two-dimensional array of electrodes, no research on system-level synthesis of flow-based biochips has been reported so far. The focus has been on application modeling and component-level simulation. Therefore, for the first time to our knowledge, we propose a system...

  19. Microfluidic Devices in Advanced Caenorhabditis elegans Research

    Directory of Open Access Journals (Sweden)

    Muniesh Muthaiyan Shanmugam

    2016-08-01

    Full Text Available The study of model organisms is very important in view of their potential for application to human therapeutic uses. One such model organism is the nematode worm, Caenorhabditis elegans. As a nematode, C. elegans have ~65% similarity with human disease genes and, therefore, studies on C. elegans can be translated to human, as well as, C. elegans can be used in the study of different types of parasitic worms that infect other living organisms. In the past decade, many efforts have been undertaken to establish interdisciplinary research collaborations between biologists, physicists and engineers in order to develop microfluidic devices to study the biology of C. elegans. Microfluidic devices with the power to manipulate and detect bio-samples, regents or biomolecules in micro-scale environments can well fulfill the requirement to handle worms under proper laboratory conditions, thereby significantly increasing research productivity and knowledge. The recent development of different kinds of microfluidic devices with ultra-high throughput platforms has enabled researchers to carry out worm population studies. Microfluidic devices primarily comprises of chambers, channels and valves, wherein worms can be cultured, immobilized, imaged, etc. Microfluidic devices have been adapted to study various worm behaviors, including that deepen our understanding of neuromuscular connectivity and functions. This review will provide a clear account of the vital involvement of microfluidic devices in worm biology.

  20. Microfluidic devices for biological applications

    CSIR Research Space (South Africa)

    Potgieter, S

    2010-01-01

    Full Text Available , faster reaction times and process-specific designs. A microfluidic system typically consists of a series of channels with components like pumps, valves and actuators to control the flow of fluids. One of the applications being worked on is a microfluidic...

  1. 3D-printed microfluidic devices.

    Science.gov (United States)

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

    2016-06-20

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

  2. Biocompatible "click" wafer bonding for microfluidic devices

    OpenAIRE

    Saharil, Farizah; Carlborg, Carl Fredrik; Haraldsson, Tommy; van der Wijngaart, Wouter

    2012-01-01

    We introduce a novel dry wafer bonding concept designed for permanent attachment of micromolded polymer structures to surface functionalized silicon substrates. The method, designed for simultaneous fabrication of many lab-on-chip devices, utilizes a chemically reactive polymer microfluidic structure, which rapidly bonds to a functionalized substrate via "click" chemistry reactions. The microfluidic structure consists of an off-stoichiometry thiol-ene (OSTE) polymer with a very high density o...

  3. Microfluidic chip-capillary electrophoresis devices

    CERN Document Server

    Fung, Ying Sing; Du, Fuying; Guo, Wenpeng; Ma, Tongmei; Nie, Zhou; Sun, Hui; Wu, Ruige; Zhao, Wenfeng

    2015-01-01

    Capillary electrophoresis (CE) and microfluidic chip (MC) devices are relatively mature technologies, but this book demonstrates how they can be integrated into a single, revolutionary device that can provide on-site analysis of samples when laboratory services are unavailable. By introducing the combination of CE and MC technology, Microfluidic Chip-Capillary Electrophoresis Devices broadens the scope of chemical analysis, particularly in the biomedical, food, and environmental sciences.The book gives an overview of the development of MC and CE technology as well as technology that now allows

  4. A Pin-Count Reduction Algorithm for Flow-Based Microfluidic Biochips

    DEFF Research Database (Denmark)

    Schneider, Alexander Rüdiger; Pop, Paul; Madsen, Jan

    2016-01-01

    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......-chip control pins. Recent research has addressed the physical design of such biochips. However, such research has so far ignored the pin-count, which rises with the increase in the number of microvalves. Given a biochip architecture and a biochemical application, we propose an algorithm for reducing the number...

  5. Porous Microfluidic Devices - Fabrication adn Applications

    NARCIS (Netherlands)

    de Jong, J.; Geerken, M.J.; Lammertink, Rob G.H.; Wessling, Matthias

    2007-01-01

    The major part of microfluidic devices nowadays consists of a dense material that defines the fluidic structure. A generic fabrication method enabling the production of completely porous micro devices with user-defined channel networks is developed. The channel walls can be used as a (selective) bar

  6. MEMS and microfluidics for diagnostics devices.

    Science.gov (United States)

    Rosen, Y; Gurman, P

    2010-06-01

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

  7. Mixing in polymeric microfluidic devices.

    Energy Technology Data Exchange (ETDEWEB)

    Schunk, Peter Randall; Sun, Amy Cha-Tien; Davis, Robert H. (University of Colorado at Boulder, Boulder, CO); Brotherton, Christopher M. (University of Colorado at Boulder, Boulder, CO)

    2006-04-01

    This SAND report describes progress made during a Sandia National Laboratories sponsored graduate fellowship. The fellowship was funded through an LDRD proposal. The goal of this project is development and characterization of mixing strategies for polymeric microfluidic devices. The mixing strategies under investigation include electroosmotic flow focusing, hydrodynamic focusing, physical constrictions and porous polymer monoliths. For electroosmotic flow focusing, simulations were performed to determine the effect of electroosmotic flow in a microchannel with heterogeneous surface potential. The heterogeneous surface potential caused recirculations to form within the microchannel. These recirculations could then be used to restrict two mixing streams and reduce the characteristic diffusion length. Maximum mixing occurred when the ratio of the mixing region surface potential to the average channel surface potential was made large in magnitude and negative in sign, and when the ratio of the characteristic convection time to the characteristic diffusion time was minimized. Based on these results, experiments were performed to evaluate the manipulation of surface potential using living-radical photopolymerization. The material chosen to manipulate typically exhibits a negative surface potential. Using living-radical surface grafting, a positive surface potential was produced using 2-(Dimethylamino)ethyl methacrylate and a neutral surface was produced using a poly(ethylene glycol) surface graft. Simulations investigating hydrodynamic focusing were also performed. For this technique, mixing is enhanced by using a tertiary fluid stream to constrict the two mixing streams and reduce the characteristic diffusion length. Maximum mixing occurred when the ratio of the tertiary flow stream flow-rate to the mixing streams flow-rate was maximized. Also, like the electroosmotic focusing mixer, mixing was also maximized when the ratio of the characteristic convection time to the

  8. Micro-Fluidic Device for Drug Delivery

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

    Yuen, Po Ki

    2013-05-07

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

  10. Reaction and separation opportunities with microfluidic devices

    NARCIS (Netherlands)

    Kolfschoten, R.C.

    2011-01-01

    Microfluidic devices make precisely controlled processing of substances possible on a microliter level. The advantage is that, due to the small sizes, the driving forces for mass and heat transfer are high. The surface to volume ratios are also high, which can benefit many surface oriented processes

  11. Biocompatible "click" wafer bonding for microfluidic devices.

    Science.gov (United States)

    Saharil, Farizah; Carlborg, Carl Fredrik; Haraldsson, Tommy; van der Wijngaart, Wouter

    2012-09-07

    We introduce a novel dry wafer bonding concept designed for permanent attachment of micromolded polymer structures to surface functionalized silicon substrates. The method, designed for simultaneous fabrication of many lab-on-chip devices, utilizes a chemically reactive polymer microfluidic structure, which rapidly bonds to a functionalized substrate via"click" chemistry reactions. The microfluidic structure consists of an off-stoichiometry thiol-ene (OSTE) polymer with a very high density of surface bound thiol groups and the substrate is a silicon wafer that has been functionalized with common bio-linker molecules. We demonstrate here void free, and low temperature (silane functionalized silicon wafer.

  12. Nanoplasmonic and Microfluidic Devices for Biological Sensing

    KAUST Repository

    Perozziello, G.

    2017-02-16

    In this chapter we report about recent advances on the development and application of 2D and 3D plasmonic nanostructures used for sensing of biological samples by Raman spectroscopy at unprecedented resolution of analysis. Besides, we explain how the integration of these nanodevices in a microfluidic apparatus can simplify the analysis of biological samples. In the first part we introduce and motivate the convenience of using nanoplasmonic enhancers and Raman spectroscopy for biological sensing, describing the phenomena and the current approaches to fabricate nanoplasmonic structures. In the second part, we explain how specific multi-element devices produce the optimal enhancement of the Raman scattering. We report cases where biological sensing of DNA was performed at few molecules level with nanometer spatial resolutions. Finally, we show an example of microfluidic device integrating plasmonic nanodevices to sort and drive biological samples, like living cells, towards the optical probe in order to obtain optimal conditions of analysis.

  13. Tuning particle focusing in inertial microfluidic devices

    Science.gov (United States)

    Hood, Kaitlyn; Kahkeshani, Soroush; di Carlo, Dino; Roper, Marcus

    2014-11-01

    Particles in microfluidic devices at finite Reynolds number are subject to two forces: (i) inertial focusing and (ii) particle-particle interactions. Although microfluidic chips exploit these forces to manipulate particles for particle/cell sorting and high throughput flow cytometry, the forces are not understood well enough to allow rational design of devices that can tune and attenuate particle focusing. We present a mathematical model addressing both inertial focusing and particle interactions, and we apply our model to various channel geometries to determine the balance of forces. In addition, we present experimental data that illustrate the accuracy of our model. We will address the following questions: Why do high aspect ratio channels favor two equilibrium positions? Why do particle chains form?

  14. Fluid control structures in microfluidic devices

    Energy Technology Data Exchange (ETDEWEB)

    Mathies, Richard A.; Grover, William H.; Skelley, Alison; Lagally, Eric; Liu, Chung N.

    2017-05-09

    Methods and apparatus for implementing microfluidic analysis devices are provided. A monolithic elastomer membrane associated with an integrated pneumatic manifold allows the placement and actuation of a variety of fluid control structures, such as structures for pumping, isolating, mixing, routing, merging, splitting, preparing, and storing volumes of fluid. The fluid control structures can be used to implement a variety of sample introduction, preparation, processing, and storage techniques.

  15. Micromagnetic-microfluidic blood cleansing device.

    Science.gov (United States)

    Yung, Chong Wing; Fiering, Jason; Mueller, Andrew J; Ingber, Donald E

    2009-05-07

    Sepsis is a lethal disease caused by a systemic microbial infection that spreads via the bloodstream to overwhelm the body's defenses. Current therapeutic approaches are often suboptimal, in part, because they do not fully eliminate the pathogen, and hence the source of deadly toxins. Here we describe an extracorporeal blood cleansing device to selectively remove pathogens from contaminated blood and thereby enhance the patient's response to antibiotic therapy. Immunomagnetic microbeads were modified to create magnetic opsonins that were used to cleanse flowing human whole blood of Candida albicans fungi, a leading cause of sepsis-related deaths. The micromagnetic-microfluidic blood cleansing device generates magnetic field gradients across vertically stacked channels to enable continuous and high throughput separation of fungi from flowing whole blood. A multiplexed version of the device containing four parallel channels achieved over 80% clearance of fungi from contaminated blood at a flow rate of 20 mL/h in a single pass, a rate 1000 times faster than a previously described prototype micromagnetic-microfluidic cell separation system. These results provide the first proof-of-principle that a multiplexed micromagnetic-microfluidic separation system can be used to cleanse pathogens from flowing human blood at a rate and separation efficiency that is relevant for clinical applications.

  16. Microfluidic Control Using Colloidal Devices

    Science.gov (United States)

    Terray, Alex; Oakey, John; Marr, David W. M.

    2002-06-01

    By manipulating colloidal microspheres within customized channels, we have created micrometer-scale fluid pumps and particulate valves. We describe two positive-displacement designs, a gear and a peristaltic pump, both of which are about the size of a human red blood cell. Two colloidal valve designs are also demonstrated, one actuated and one passive, for the direction of cells or small particles. The use of colloids as both valves and pumps will allow device integration at a density far beyond what is currently achievable by other approaches and may provide a link between fluid manipulation at the macro- and nanoscale.

  17. A microfluidic multiplex proteomic immunoassay device for translational research

    OpenAIRE

    Cao, Jing; Seegmiller, Jesse; Hanson, Naomi Q; Zaun, Christopher; Li, Danni

    2015-01-01

    Objective Microfluidic technology has the potential to miniaturize and automate complex laboratory procedures. The objective of this study was to assess a microfluidic immunoassay device, Simple Plex, which simultaneously measured IL-1β, TNF-α, IL-6, and IL-10 in serum samples. This assessment is important to understanding the potentials of this microfluidic device as a valuable tool in translational research efforts. Methods We studied the operational characteristics of Simple Plex, and comp...

  18. A microfluidic device based on an evaporation-driven micropump

    NARCIS (Netherlands)

    Nie, C.; Frijns, A.J.H.; Mandamparambil, R.; Toonder, J.M.J. den

    2015-01-01

    In this paper we introduce a microfluidic device ultimately to be applied as a wearable sweat sensor. We show proof-of-principle of the microfluidic functions of the device, namely fluid collection and continuous fluid flow pumping. A filter-paper based layer, that eventually will form the interface

  19. A microfluidic device based on an evaporation-driven micropump

    NARCIS (Netherlands)

    Nie, C.; Frijns, A.J.H.; Mandamparambil, R.; Toonder, J.M.J. den

    2015-01-01

    In this paper we introduce a microfluidic device ultimately to be applied as a wearable sweat sensor. We show proof-of-principle of the microfluidic functions of the device, namely fluid collection and continuous fluid flow pumping. A filter-paper based layer, that eventually will form the interface

  20. Non-Linear Electrohydrodynamics in Microfluidic Devices

    Directory of Open Access Journals (Sweden)

    Jun Zeng

    2011-03-01

    Full Text Available Since the inception of microfluidics, the electric force has been exploited as one of the leading mechanisms for driving and controlling the movement of the operating fluid and the charged suspensions. Electric force has an intrinsic advantage in miniaturized devices. Because the electrodes are placed over a small distance, from sub-millimeter to a few microns, a very high electric field is easy to obtain. The electric force can be highly localized as its strength rapidly decays away from the peak. This makes the electric force an ideal candidate for precise spatial control. The geometry and placement of the electrodes can be used to design electric fields of varying distributions, which can be readily realized by Micro-Electro-Mechanical Systems (MEMS fabrication methods. In this paper, we examine several electrically driven liquid handling operations. The emphasis is given to non-linear electrohydrodynamic effects. We discuss the theoretical treatment and related numerical methods. Modeling and simulations are used to unveil the associated electrohydrodynamic phenomena. The modeling based investigation is interwoven with examples of microfluidic devices to illustrate the applications.

  1. Microfluidic PDMS on paper (POP) devices.

    Science.gov (United States)

    Shangguan, Jin-Wen; Liu, Yu; Pan, Jian-Bin; Xu, Bi-Yi; Xu, Jing-Juan; Chen, Hong-Yuan

    2016-12-20

    In this paper, we propose a generalized concept of microfluidic polydimethylsiloxane (PDMS) on paper (POP) devices, which combines well the merits of paper chips and PDMS chips. First, we optimized the conditions for accurate PDMS spatial patterning on paper, based on screen printing and a high temperature enabled superfast curing technique, which enables PDMS patterning to an accuracy of tens of microns in less than ten seconds. This, in turn, makes it available for seamless, reversible and reliable integration of the resulting paper layer with other PDMS channel structures. The integrated POP devices allow for both porous paper and smooth channels to be spatially defined on the devices, greatly extending the flexibility for designers to be able to construct powerful functional structures. To demonstrate the versatility of this design, a prototype POP device for the colorimetric analysis of liver function markers, serum protein, alkaline phosphatase (ALP) and aspartate aminotransferase (AST), was constructed. On this POP device, quantitative sample loading, mixing and multiplex analysis have all been realized.

  2. Probing cell mechanical properties with microfluidic devices

    Science.gov (United States)

    Rowat, Amy

    2012-02-01

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

  3. Fabrication of gravity-driven microfluidic device

    Science.gov (United States)

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

    2008-12-01

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

  4. Integration of Capacitive Micromachined Ultrasound Transducers to Microfluidic Devices

    KAUST Repository

    Viržonis, Darius

    2013-10-22

    The design and manufacturing flexibility of capacitive micromachined ultrasound transducers (CMUT) makes them attractive option for integration with microfluidic devices both for sensing and fluid manipulation. CMUT concept is introduced here by presentin

  5. A Microfluidic Device for Spatiotemporal Delivery of Stimuli to Cells

    Directory of Open Access Journals (Sweden)

    Zubaidah Ningsih

    2015-03-01

    Full Text Available Living cells encounter many stimuli from the immediate environment. Receptors recognize these environmental cues and transduce signals to produce cell responses. The frequency of a signal is now emerging as an important factor determining cell responses. As a componentry system in understanding temporal stimulation, microfluidic devices allow the observation of cell behaviour under dynamic stimulation and controllable environment. In this paper we describe the design, construction and characterization of a microfluidic device suitable for cell stimulation studies.

  6. Clear Castable Polyurethane Elastomer for Fabrication of Microfluidic Devices

    Science.gov (United States)

    Domansky, Karel; Leslie, Daniel C.; McKinney, James; Fraser, Jacob P.; Sliz, Josiah D.; Hamkins-Indik, Tiama; Hamilton, Geraldine A.; Bahinski, Anthony; Ingber, Donald E.

    2013-01-01

    Polydimethylsiloxane (PDMS) has numerous desirable properties for fabricating microfluidic devices, including optical transparency, flexibility, biocompatibility, and fabrication by casting; however, partitioning of small hydrophobic molecules into the bulk of PDMS hinders industrial acceptance of PDMS microfluidic devices for chemical processing and drug development applications. Here we describe an attractive alternative material that is similar to PDMS in terms of optical transparency, flexibility and castability, but that is also resistant to absorption of small hydrophobic molecules. PMID:23954953

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

    CERN Document Server

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

    2008-01-01

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

  8. Use of Vacuum Bagging for Fabricating Thermoplastic Microfluidic Devices

    Science.gov (United States)

    Cassano, Christopher L.; Simon, Andrew J.; Liu, Wei; Fredrickson, Carl; Fan, Z. Hugh

    2014-01-01

    In this work we present a novel thermal bonding method for thermoplastic microfluidic devices. This simple method employs a modified vacuum bagging technique, a concept borrowed from the aerospace industry, to produce conventional thick substrate microfluidic devices, as well as multi-layer film devices. The bonds produced using this method are superior to those obtained using conventional thermal bonding methods, including thermal lamination, and are capable of sustaining burst pressures in excess of 550 kPa. To illustrate the utility of this method, thick substrate devices were produced, as well as a six-layer film device that incorporated several complex features. PMID:25329244

  9. A microfluidic dialysis device for complex biological mixture SERS analysis

    KAUST Repository

    Perozziello, Gerardo

    2015-08-01

    In this paper, we present a microfluidic device fabricated with a simple and inexpensive process allowing rapid filtering of peptides from a complex mixture. The polymer microfluidic device can be used for sample preparation in biological applications. The device is fabricated by micromilling and solvent assisted bonding, in which a microdialysis membrane (cut-off of 12-14 kDa) is sandwiched in between an upper and a bottom microfluidic chamber. An external frame connects the microfluidic device to external tubes, microvalves and syringe pumps. Bonding strength and interface sealing are pneumatically tested. Microfluidic protocols are also described by using the presented device to filter a sample composed of specific peptides (MW 1553.73 Da, at a concentration of 1.0 ng/μl) derived from the BRCA1 protein, a tumor-suppressor molecule which plays a pivotal role in the development of breast cancer, and albumin (MW 66.5 kDa, at a concentration of 35 μg/μl), the most represented protein in human plasma. The filtered samples coming out from the microfluidic device were subsequently deposited on a SERS (surface enhanced Raman scattering) substrate for further analysis by Raman spectroscopy. By using this approach, we were able to sort the small peptides from the bigger and highly concentrated protein albumin and to detect them by using a label-free technique at a resolution down to 1.0 ng/μl.

  10. Real-time PCR in microfluidic devices

    Science.gov (United States)

    Becker, Holger; Hlawatsch, Nadine; Klemm, Richard; Moche, Christian; Hansen-Hagge, Thomas; Gärtner, Claudia

    2014-03-01

    A central method in a standard biochemical laboratory is represented by the polymerase chain reaction (PCR), therefore many attempts have been performed so far to implement this technique in lab-on-a-chip (LOC) devices. PCR is an ideal candidate for miniaturization because of a reduction of assay time and decreased costs for expensive bio-chemicals. In case of the "classical" PCR, detection is done by identification of DNA fragments electrophoretically separated in agarose gels. This method is meanwhile frequently replaced by the so-called Real-Time-PCR because here the exponential increase of amplificates can be observed directly by measurement of DNA interacting fluorescent dyes. Two main methods for on-chip PCRs are available: traditional "batch" PCR in chambers on a chip using thermal cycling, requiring about 30 minutes for a typical PCR protocol and continuous-flow PCR, where the liquid is guided over stationary temperature zones. In the latter case, the PCR protocol can be as fast as 5 minutes. In the presented work, a proof of concept is demonstrated for a real-time-detection of PCR products in microfluidic systems.

  11. A microfluidic device with groove patterns for studying cellular behavior.

    Science.gov (United States)

    Chung, Bong Geun; Manbachi, Amir; Khademhosseini, Ali

    2007-01-01

    We describe a microfluidic device with microgrooved patterns for studying cellular behavior. This microfluidic platform consists of a top fluidic channel and a bottom microgrooved substrate. To fabricate the microgrooved channels, a top poly(dimethylsiloxane) (PDMS) mold containing the impression of the microfluidic channels was aligned and bonded to a microgrooved substrate. Using this device, mouse fibroblast cells were immobilized and patterned within microgrooved substrates (25, 50, 75, and 100 microm wide). To study apoptosis in a microfluidic device, media containing hydrogen peroxide, Annexin V, and propidium iodide was perfused into the fluidic channel for 2 hours. We found that cells exposed to the oxidative stress became apoptotic. These apoptotic cells were confirmed by Annexin V that bound to phosphatidylserine at the outer leaflet of the plasma membrane during the apoptosis process. Using this microfluidic device with microgrooved patterns, the apoptosis process was observed in real-time and analyzed by using an inverted microscope containing an incubation chamber (37 degrees C, 5% CO(2)). Therefore, this microfluidic device incorporated with microgrooved substrates could be useful for studying the cellular behavior and performing high-throughput drug screening.

  12. A gradient-generating microfluidic device for cell biology.

    Science.gov (United States)

    Chung, Bong Geun; Manbachi, Amir; Saadi, Wajeeh; Lin, Francis; Jeon, Noo Li; Khademhosseini, Ali

    2007-01-01

    The fabrication and operation of a gradient-generating microfluidic device for studying cellular behavior is described. A microfluidic platform is an enabling experimental tool, because it can precisely manipulate fluid flows, enable high-throughput experiments, and generate stable soluble concentration gradients. Compared to conventional gradient generators, poly(dimethylsiloxane) (PDMS)-based microfluidic devices can generate stable concentration gradients of growth factors with well-defined profiles. Here, we developed simple gradient-generating microfluidic devices with three separate inlets. Three microchannels combined into one microchannel to generate concentration gradients. The stability and shape of growth factor gradients were confirmed by fluorescein isothyiocyanate (FITC)-dextran with a molecular weight similar to epidermal growth factor (EGF). Using this microfluidic device, we demonstrated that fibroblasts exposed to concentration gradients of EGF migrated toward higher concentrations. The directional orientation of cell migration and motility of migrating cells were quantitatively assessed by cell tracking analysis. Thus, this gradient-generating microfluidic device might be useful for studying and analyzing the behavior of migrating cells.

  13. Micro-scale and microfluidic devices for neurobiology.

    Science.gov (United States)

    Taylor, Anne M; Jeon, Noo Li

    2010-10-01

    The precise spatial and temporal control afforded by microfluidic devices make them uniquely suited as experimental tools for cellular neuroscience. Micro-structures have been developed to direct the placement of cells and small organisms within a device. Microfluidics can precisely define pharmacological microenvironments, mimicking conditions found in vivo with the advantage of defined parameters which are usually difficult to control and manipulate in vivo. These devices are compatible with high-resolution microscopy, are simple to assemble, and are reproducible. In this review we will focus on microfluidic devices that have recently been developed for small, whole organisms such as C. elegans and dissociated cultured neurons. These devices have improved control over the placement of cells or organisms and allowed unprecedented experimental access, enabling novel investigations in neurobiology.

  14. Paper based microfluidic devices for environmental diagnostics

    CSIR Research Space (South Africa)

    Govindasamy, K

    2012-09-01

    Full Text Available such as elevated temperatures and mechanical stresses. Paper based microfluidic chips are patterned with micron sized hydrophobic barriers which penetrate the paper?s cross section. These barriers guide the capillary movement of fluids through the cellulose... visual or electrochemical signal, indicating whether the analyte is present in the sample. Although based on a similar operational principal as lateral flow technologies (such as home pregnancy tests), paper based microfluidics seeks to offer a more...

  15. A Laminar Flow-Based Microfluidic Tesla Pump via Lithography Enabled 3D Printing.

    Science.gov (United States)

    Habhab, Mohammed-Baker; Ismail, Tania; Lo, Joe Fujiou

    2016-11-23

    Tesla turbine and its applications in power generation and fluid flow were demonstrated by Nicholas Tesla in 1913. However, its real-world implementations were limited by the difficulty to maintain laminar flow between rotor disks, transient efficiencies during rotor acceleration, and the lack of other applications that fully utilize the continuous flow outputs. All of the aforementioned limits of Tesla turbines can be addressed by scaling to the microfluidic flow regime. Demonstrated here is a microscale Tesla pump designed and fabricated using a Digital Light Processing (DLP) based 3D printer with 43 µm lateral and 30 µm thickness resolutions. The miniaturized pump is characterized by low Reynolds number of 1000 and a flow rate of up to 12.6 mL/min at 1200 rpm, unloaded. It is capable of driving a mixer network to generate microfluidic gradient. The continuous, laminar flow from Tesla turbines is well-suited to the needs of flow-sensitive microfluidics, where the integrated pump will enable numerous compact lab-on-a-chip applications.

  16. A Laminar Flow-Based Microfluidic Tesla Pump via Lithography Enabled 3D Printing

    Directory of Open Access Journals (Sweden)

    Mohammed-Baker Habhab

    2016-11-01

    Full Text Available Tesla turbine and its applications in power generation and fluid flow were demonstrated by Nicholas Tesla in 1913. However, its real-world implementations were limited by the difficulty to maintain laminar flow between rotor disks, transient efficiencies during rotor acceleration, and the lack of other applications that fully utilize the continuous flow outputs. All of the aforementioned limits of Tesla turbines can be addressed by scaling to the microfluidic flow regime. Demonstrated here is a microscale Tesla pump designed and fabricated using a Digital Light Processing (DLP based 3D printer with 43 µm lateral and 30 µm thickness resolutions. The miniaturized pump is characterized by low Reynolds number of 1000 and a flow rate of up to 12.6 mL/min at 1200 rpm, unloaded. It is capable of driving a mixer network to generate microfluidic gradient. The continuous, laminar flow from Tesla turbines is well-suited to the needs of flow-sensitive microfluidics, where the integrated pump will enable numerous compact lab-on-a-chip applications.

  17. A Laminar Flow-Based Microfluidic Tesla Pump via Lithography Enabled 3D Printing

    Science.gov (United States)

    Habhab, Mohammed-Baker; Ismail, Tania; Lo, Joe Fujiou

    2016-01-01

    Tesla turbine and its applications in power generation and fluid flow were demonstrated by Nicholas Tesla in 1913. However, its real-world implementations were limited by the difficulty to maintain laminar flow between rotor disks, transient efficiencies during rotor acceleration, and the lack of other applications that fully utilize the continuous flow outputs. All of the aforementioned limits of Tesla turbines can be addressed by scaling to the microfluidic flow regime. Demonstrated here is a microscale Tesla pump designed and fabricated using a Digital Light Processing (DLP) based 3D printer with 43 µm lateral and 30 µm thickness resolutions. The miniaturized pump is characterized by low Reynolds number of 1000 and a flow rate of up to 12.6 mL/min at 1200 rpm, unloaded. It is capable of driving a mixer network to generate microfluidic gradient. The continuous, laminar flow from Tesla turbines is well-suited to the needs of flow-sensitive microfluidics, where the integrated pump will enable numerous compact lab-on-a-chip applications. PMID:27886051

  18. Electroporation of cells in microfluidic devices: a review

    NARCIS (Netherlands)

    Fox, M.B.; Esveld, D.C.; Valero, A.; Luttge, R.; Mastwijk, H.C.; Bartels, P.V.; Berg, van den A.; Boom, R.M.

    2006-01-01

    In recent years, several publications on microfluidic devices have focused on the process of electroporation, which results in the poration of the biological cell membrane. The devices involved are designed for cell analysis, transfection or pasteurization. The high electric field strengths needed a

  19. Direct digital manufacturing of autonomous centrifugal microfluidic device

    Science.gov (United States)

    Ukita, Yoshiaki; Takamura, Yuzuru; Utsumi, Yuichi

    2016-06-01

    This paper presents strategies that attempt to solve two key problems facing the commercialization of microfluidics: cost reduction in microfluidic chip manufacturing and microfluidic device driver development. To reduce the cost of microfluidic chip manufacturing, we propose to use of three-dimensional (3D) printers for direct digital manufacturing (DDM). An evaluation of 3D micro-scale structure printing using several 3D printers is reported, and some of the technical issues to be addressed in the future are suggested. To evaluate micro-scale printing, three types of 3D printers, with the ability to print structures on the scale of several hundred meters, were selected by first screening six 3D printers. Line and space patterns with line widths of 100-500 µm and an aspect ratio of one were printed and evaluated. The estimated critical dimension was around 200 µm. The manufacturing of a monolithic microfluidic chip with embedded channels was also demonstrated. Monolithic microfluidic chips with embedded microchannels having 500 × 500 and 250 × 250 µm2 cross sections and 2-20 mm lengths were printed, and the fidelity of the channel shape, residual supporting material, and flow of liquid water were evaluated. The liquid flow evaluation showed that liquid water could flow through all of the microchannels with the 500 × 500 µm2 cross section, whereas this was not possible through some of the channels with the 250 × 250 µm2 cross section because of the residual resin or supporting material. To reduce the device-driver cost, we propose to use of the centrifugal microfluidic concept. An autonomous microfluidic device that could implement sequential flow control under a steadily rotating condition was printed. Four-step flow injection under a steadily rotating condition at 1500 rpm was successfully demonstrated without any external triggering such as changing the rotational speed.

  20. An easy-to-use microfluidic interconnection system to create quick and reversibly interfaced simple microfluidic devices

    DEFF Research Database (Denmark)

    Pfreundt, Andrea; Andersen, Karsten Brandt; Dimaki, Maria;

    2015-01-01

    The presented microfluidic interconnection system provides an alternative for the individual interfacing of simple microfluidic devices fabricated in polymers such as polymethylmethacrylate, polycarbonate and cyclic olefin polymer. A modification of the device inlet enables the direct attachment...... pressures above 250 psi and therefore supports applications with high flow rates or highly viscous fluids. The ease of incorporation, configuration, fabrication and use make this interconnection system ideal for the rapid prototyping of simple microfluidic devices or other integrated systems that require...

  1. Waste-to-energy conversion from a microfluidic device

    Science.gov (United States)

    López-González, B.; Jiménez-Valdés, R. J.; Moreno-Zuria, A.; Cuevas-Muñiz, F. M.; Ledesma-García, J.; García-Cordero, J. L.; Arriaga, L. G.

    2017-08-01

    This work reports the successful harvesting of energy from waste produced in a microfluidic device using a fuel cell. A miniaturized glucose air-breathing microfluidic fuel cell (ABμFFC) was designed, fabricated and tested with three different configurations according to their electrode nature: inorganic, hybrid and biofuel cell. Each ABμFFC was characterized using an ideal medium, with sterile cell culture medium, and with waste produced on a microfluidic device. The inorganic-ABμFFC exhibited the highest performance compared to the rest of the configurations. As a proof-of-concept, cancer cells were cultured on a microfluidic device and the consumed cell culture media (glucose concentration energy source without further treatment, into the inorganic-ABμFFC. The fuel cell generated a maximum total power of 5.2 μW, which is enough energy to power low-consumption microelectronic chips. This application demonstrates that the waste produced by microfluidic applications could be potentially scavenged to produce electrical energy. It also opens the possibility to develop truly energy self-sufficient portable devices.

  2. Recent microfluidic devices for studying gamete and embryo biomechanics.

    Science.gov (United States)

    Lai, David; Takayama, Shuichi; Smith, Gary D

    2015-06-25

    The technical challenges of biomechanic research such as single cell analysis at a high monetary cost, labor, and time for just a small number of measurements is a good match to the strengths of microfluidic devices. New scientific discoveries in the fertilization and embryo development process, of which biomechanics is a major subset of interest, is crucial to fuel the continual improvement of clinical practice in assisted reproduction. The following review will highlight some recent microfluidic devices tailored for gamete and embryo biomechanics where biomimicry arises as a major theme of microfluidic device design and function, and the application of fundamental biomechanic principles are used to improve outcomes of cryopreservation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Three-Dimensional Printing Based Hybrid Manufacturing of Microfluidic Devices.

    Science.gov (United States)

    Alapan, Yunus; Hasan, Muhammad Noman; Shen, Richang; Gurkan, Umut A

    2015-05-01

    Microfluidic platforms offer revolutionary and practical solutions to challenging problems in biology and medicine. Even though traditional micro/nanofabrication technologies expedited the emergence of the microfluidics field, recent advances in advanced additive manufacturing hold significant potential for single-step, stand-alone microfluidic device fabrication. One such technology, which holds a significant promise for next generation microsystem fabrication is three-dimensional (3D) printing. Presently, building 3D printed stand-alone microfluidic devices with fully embedded microchannels for applications in biology and medicine has the following challenges: (i) limitations in achievable design complexity, (ii) need for a wider variety of transparent materials, (iii) limited z-resolution, (iv) absence of extremely smooth surface finish, and (v) limitations in precision fabrication of hollow and void sections with extremely high surface area to volume ratio. We developed a new way to fabricate stand-alone microfluidic devices with integrated manifolds and embedded microchannels by utilizing a 3D printing and laser micromachined lamination based hybrid manufacturing approach. In this new fabrication method, we exploit the minimized fabrication steps enabled by 3D printing, and reduced assembly complexities facilitated by laser micromachined lamination method. The new hybrid fabrication method enables key features for advanced microfluidic system architecture: (i) increased design complexity in 3D, (ii) improved control over microflow behavior in all three directions and in multiple layers, (iii) transverse multilayer flow and precisely integrated flow distribution, and (iv) enhanced transparency for high resolution imaging and analysis. Hybrid manufacturing approaches hold great potential in advancing microfluidic device fabrication in terms of standardization, fast production, and user-independent manufacturing.

  4. Control and automation of multilayered integrated microfluidic device fabrication.

    Science.gov (United States)

    Kipper, Sarit; Frolov, Ludmila; Guy, Ortal; Pellach, Michal; Glick, Yair; Malichi, Asaf; Knisbacher, Binyamin A; Barbiro-Michaely, Efrat; Avrahami, Dorit; Yavets-Chen, Yehuda; Levanon, Erez Y; Gerber, Doron

    2017-01-31

    Integrated microfluidics is a sophisticated three-dimensional (multi layer) solution for high complexity serial or parallel processes. Fabrication of integrated microfluidic devices requires soft lithography and the stacking of thin-patterned PDMS layers. Precise layer alignment and bonding is crucial. There are no previously reported standards for alignment of the layers, which is mostly performed using uncontrolled processes with very low alignment success. As a result, integrated microfluidics is mostly used in academia rather than in the many potential industrial applications. We have designed and manufactured a semiautomatic Microfluidic Device Assembly System (μDAS) for full device production. μDAS comprises an electrooptic mechanical system consisting of four main parts: optical system, smart media holder (for PDMS), a micropositioning xyzθ system and a macropositioning XY mechanism. The use of the μDAS yielded valuable information regarding PDMS as the material for device fabrication, revealed previously unidentified errors, and enabled optimization of a robust fabrication process. In addition, we have demonstrated the utilization of the μDAS technology for fabrication of a complex 3 layered device with over 12 000 micromechanical valves and an array of 64 × 64 DNA spots on a glass substrate with high yield and high accuracy. We increased fabrication yield from 25% to about 85% with an average layer alignment error of just ∼4 μm. It also increased our protein expression yields from 80% to over 90%, allowing us to investigate more proteins per experiment. The μDAS has great potential to become a valuable tool for both advancing integrated microfluidics in academia and producing and applying microfluidic devices in the industry.

  5. High content screening in microfluidic devices

    Science.gov (United States)

    Cheong, Raymond; Paliwal, Saurabh; Levchenko, Andre

    2011-01-01

    Importance of the field Miniaturization is key to advancing the state-of-the-art in high content screening (HCS), in order to enable dramatic cost savings through reduced usage of expensive biochemical reagents and to enable large-scale screening on primary cells. Microfluidic technology offers the potential to enable HCS to be performed with an unprecedented degree of miniaturization. Areas covered in this review This perspective highlights a real-world example from the authors’ work of HCS assays implemented in a highly miniaturized microfluidic format. Advantages of this technology are discussed, including cost savings, high throughput screening on primary cells, improved accuracy, the ability to study complex time-varying stimuli, and ease of automation, integration, and scaling. What the reader will gain The reader will understand the capabilities of a new microfluidics-based platform for HCS, and the advantages it provides over conventional plate-based HCS. Take home message Microfluidics technology will drive significant advancements and broader usage and applicability of HCS in drug discovery. PMID:21852997

  6. Using Adhesive Patterning to Construct 3D Paper Microfluidic Devices.

    Science.gov (United States)

    Kalish, Brent; Tsutsui, Hideaki

    2016-04-01

    We demonstrate the use of patterned aerosol adhesives to construct both planar and nonplanar 3D paper microfluidic devices. By spraying an aerosol adhesive through a metal stencil, the overall amount of adhesive used in assembling paper microfluidic devices can be significantly reduced. We show on a simple 4-layer planar paper microfluidic device that the optimal adhesive application technique and device construction style depends heavily on desired performance characteristics. By moderately increasing the overall area of a device, it is possible to dramatically decrease the wicking time and increase device success rates while also reducing the amount of adhesive required to keep the device together. Such adhesive application also causes the adhesive to form semi-permanent bonds instead of permanent bonds between paper layers, enabling single-use devices to be non-destructively disassembled after use. Nonplanar 3D origami devices also benefit from the semi-permanent bonds during folding, as it reduces the likelihood that unrelated faces may accidently stick together. Like planar devices, nonplanar structures see reduced wicking times with patterned adhesive application vs uniformly applied adhesive.

  7. A microfluidic device to sort capsules by deformability

    CERN Document Server

    Zhu, L; Mitra, Dhrubaditya; Brandt, Luca

    2014-01-01

    Guided by extensive numerical simulations, we propose a microfluidic device that can sort elastic capsules by their deformability. The device consists of a duct embedded with a semi-cylindrical obstacle, and a diffuser which further enhances the sorting capability. We demonstrate that the device can operate reasonably well under changes in the initial position of the the capsule. The efficiency of the device remains essentially unaltered under small changes of the obstacle shape (from semi-circular to semi-elliptic cross-section). Confinement along the direction perpendicular to the plane of the device increases its efficiency. This work is the first numerical study of cell sorting by a realistic microfluidic device.

  8. Exploiting droplet formation in microfluidic devices to create functional particles

    Science.gov (United States)

    Nowak, Emilia; Simmons, Mark

    2014-11-01

    Microfluidic devices offer excellent capabilities for the formation of microstructured particles which have functional attributes e.g. in controlled delivery of pharmaceuticals, enhanced nutrition and flavours in food. In this work, a microfluidic device is employed to form microstructured particles in two steps: (i) by formation of single/double emulsions and (ii) solidification of the droplet by either gelation or solvent evaporation. Both may impart non-Newtonian properties to the component phases. The influence of phase flow rates (capillary number), surfactant type/concentration and the rheology of the component phases upon the particle formation and hydrodynamic behaviour are described. EPSRC Programme Grant, MEMPHIS, EP/K0039761/1.

  9. A Microfluidic Flow-switching Device Powered by Vorticella Stalk

    Science.gov (United States)

    Nagai, M.; Tanizaki, K.; Hayasaka, Y.; Kawashima, T.; Shibata, T.

    2013-04-01

    Bioactuators are an attractive alternative for mechanical components of MEMS devices. We propose a flow-switching device active to calcium ion based on bioactuator of Vorticella. We develop a fundamental procedure for immobilization of Vorticella in a microfluidic chamber and control of contraction and extension of stalks. Cells were trapped in microfluidic chambers and allowed to adhere. After treatment of cells, stalks were contracted and extended by injecting solutions. Flow speed changed during the motion. Our developed method presents a strategy for application of bioactuator.

  10. Fabrication of polyimide based microfluidic channels for biosensor devices

    Science.gov (United States)

    Zulfiqar, Azeem; Pfreundt, Andrea; Svendsen, Winnie Edith; Dimaki, Maria

    2015-03-01

    The ever-increasing complexity of the fabrication process of Point-of-care (POC) devices, due to high demand of functional versatility, compact size and ease-of-use, emphasizes the need of multifunctional materials that can be used to simplify this process. Polymers, currently in use for the fabrication of the often needed microfluidic channels, have limitations in terms of their physicochemical properties. Therefore, the use of a multipurpose biocompatible material with better resistance to the chemical, thermal and electrical environment, along with capability of forming closed channel microfluidics is inevitable. This paper demonstrates a novel technique of fabricating microfluidic devices using polyimide (PI) which fulfills the aforementioned properties criteria. A fabrication process to pattern microfluidic channels, using partially cured PI, has been developed by using a dry etching method. The etching parameters are optimized and compared to those used for fully cured PI. Moreover, the formation of closed microfluidic channel on wafer level by bonding two partially cured PI layers or a partially cured PI to glass with high bond strength has been demonstrated. The reproducibility in uniformity of PI is also compared to the most commonly used SU8 polymer, which is a near UV sensitive epoxy resin. The potential applications of PI processing are POC and biosensor devices integrated with microelectronics.

  11. Microcontact printing-based fabrication of digital microfluidic devices.

    Science.gov (United States)

    Watson, Michael W L; Abdelgawad, Mohamed; Ye, George; Yonson, Neal; Trottier, Justin; Wheeler, Aaron R

    2006-11-15

    Digital microfluidics is a fluid manipulation technique in which discrete droplets are actuated on patterned arrays of electrodes. Although there is great enthusiasm for the application of this technique to chemical and biological assays, development has been hindered by the requirement of clean room fabrication facilities. Here, we present a new fabrication scheme, relying on microcontact printing (microCP), an inexpensive technique that does not require clean room facilities. In microCP, an elastomeric poly(dimethylsiloxane) stamp is used to deposit patterns of self-assembled monolayers onto a substrate. We report three different microCP-based fabrication techniques: (1) selective etching of gold-on-glass substrates; (2) direct printing of a suspension of palladium colloids; and (3) indirect trapping of gold colloids from suspension. In method 1, etched gold electrodes are used for droplet actuation; in methods 2 and 3, colloid patterns are used to seed electroless deposition of copper. We demonstrate, for the first time, that digital microfluidic devices can be formed by microCP and are capable of the full range of digital microfluidics operations: dispensing, merging, motion, and splitting. Devices formed by the most robust of the new techniques were comparable in performance to devices formed by conventional methods, at a fraction of the fabrication time. These new techniques for digital microfluidics device fabrication have the potential to facilitate expansion of this technology to any research group, even those without access to conventional microfabrication tools and facilities.

  12. Microwave Induced Ethanol Bath Bonding for PMMA Microfluidic Device

    Institute of Scientific and Technical Information of China (English)

    Cuicui Zhuang

    2016-01-01

    High bonding strength, low deformation and convenient procedure are all very important aspects in the microfluidic device fabrication process. In this paper, an improved microwave induced bonding technology is proposed to fabricate microfluidic device based on methyl methacrylate (PMMA). This method employs pure ethanol as the bonding assisted solvent. The ethanol not only acts as the microwave absorbing material, but also works as the organic solvent in bath. The presented research work has shown that the bonding process can be completed in less than 45 s. Furthermore, the convenient bonding only applies microwave oven, beakers and binder clips. Then, we discuss effects of microwave power, bonding time on bonding strength and deformation of microstructures on PMMA microfluidic device. Finally, a 4 layers micro⁃mixer has been fabricated using the proposed bonding technique which includes 15 trapezoid micro⁃channels, 9 T⁃type mix units and an X⁃type mix unit. Experimental results show that the proposed bonding method have some advantages compared with several traditional bonding technologies, such as hot pressing bonding, ultrasonic bonding and solvent assisted bonding methods in respect of bonding strength, deformation and bonding process. The presented work would be helpful for low coat mass production of multilayer polymer microfluidic devices in lab.

  13. Microfluidic devices and methods including porous polymer monoliths

    Science.gov (United States)

    Hatch, Anson V; Sommer, Gregory J; Singh, Anup K; Wang, Ying-Chih; Abhyankar, Vinay V

    2014-04-22

    Microfluidic devices and methods including porous polymer monoliths are described. Polymerization techniques may be used to generate porous polymer monoliths having pores defined by a liquid component of a fluid mixture. The fluid mixture may contain iniferters and the resulting porous polymer monolith may include surfaces terminated with iniferter species. Capture molecules may then be grafted to the monolith pores.

  14. A Sensitive Chemotaxis Assay Using a Novel Microfluidic Device

    Directory of Open Access Journals (Sweden)

    Chen Zhang

    2013-01-01

    Full Text Available Existing chemotaxis assays do not generate stable chemotactic gradients and thus—over time—functionally measure only nonspecific random motion (chemokinesis. In comparison, microfluidic technology has the capacity to generate a tightly controlled microenvironment that can be stably maintained for extended periods of time and is, therefore, amenable to adaptation for assaying chemotaxis. We describe here a novel microfluidic device for sensitive assay of cellular migration and show its application for evaluating the chemotaxis of smooth muscle cells in a chemokine gradient.

  15. Surface micromachined PDMS microfluidic devices fabricated using a sacrificial photoresist

    Science.gov (United States)

    Ganapathy Subramani, Balasubramanian; Selvaganapathy, Ponnambalam Ravi

    2009-01-01

    PDMS is a widely used material for construction of microfluidic devices. The traditional PDMS microfabrication process, although versatile, cannot be used to form microfluidic devices with embedded tall topological features, such as thick-film electrodes and porous reactor beds. This paper presents an elegant surface micromachining process for microfluidic devices that allows complete leak-proof sealing and a conformal contact of the PDMS with tall pre-existing topographical features and demonstrates this approach by embedding 6 µm thick Ag/AgCl (high capacity 1680 µA s) electrodes inside the microchannels. In this process, thin spin-cast films of the PDMS are used as the structural material and a photoresist is used as the sacrificial material. A crucial parameter, namely adhesion of the spun-cast structural layer to the substrate, was characterized for different pre-polymer ratios using a standard tensile test, and a 1:3 (curing agent:base) combination was found to be the best with a maximum adhesion strength of 7.2 MPa. The elastic property of the PDMS allowed extremely fast release times of ~1 min of the fabricated microchannels. The versatility of this process was demonstrated by the fabrication of a pneumatic microvalve with multi-layered microchannel geometry. The valve closure occurred at 6.37 kPa. Preliminary results of this paper have been presented at the Canadian Workshop on MEMS and Microfluidics, Montréal, Canada, August 2007.

  16. Microfluidic device fabrication by thermoplastic hot-embossing.

    Science.gov (United States)

    Yang, Shuang; Devoe, Don L

    2013-01-01

    Due to their low cost compatibility with replication-based fabrication methods, thermoplastics represent an exceptionally attractive family of materials for the fabrication of lab-on-a-chip platforms. A diverse range of thermoplastic materials suitable for microfluidic fabrication is available, offering a wide selection of mechanical and chemical properties that can be leveraged and further tailored for specific applications. While high-throughput embossing methods such as reel-to-reel processing of thermoplastics is an attractive method for industrial microfluidic chip production, the use of single chip hot embossing is a cost-effective technique for realizing high-quality microfluidic devices during the prototyping stage. Here we describe methods for the replication of microscale features in two thermoplastics, polymethylmethacrylate (PMMA) and polycarbonate (PC), using hot embossing from a silicon template fabricated by deep reactive-ion etching.

  17. A microfluidic multiplex proteomic immunoassay device for translational research.

    Science.gov (United States)

    Cao, Jing; Seegmiller, Jesse; Hanson, Naomi Q; Zaun, Christopher; Li, Danni

    2015-01-01

    Microfluidic technology has the potential to miniaturize and automate complex laboratory procedures. The objective of this study was to assess a microfluidic immunoassay device, Simple Plex, which simultaneously measured IL-1β, TNF-α, IL-6, and IL-10 in serum samples. This assessment is important to understanding the potentials of this microfluidic device as a valuable tool in translational research efforts. We studied the operational characteristics of Simple Plex, and compared to other immunoassay systems including bead-based (i.e., Bio-Plex(®) from Bio-Rad) and planar micro-spot based (i.e., Multi-Array from Meso Scale Discovery) multiplex assays. We determined imprecisions for each of the Simple Plex assays and evaluated the ability of Simple Plex to detect IL-1β, TNF-α, IL-6, and IL-10 in serum samples. Simple Plex assays required 25 µL serum, and 1.5 h to run 16 samples per cartridge per instrument. Assay imprecisions, evaluated by measurement of 6 replicates in duplicate from a serum pool using three different cartridges, were less than 10 % for all 4 cytokine protein biomarkers, comparable to the imprecisions of traditional ELISAs. The Simple Plex assays were able to detect 32, 95, 97, and 100 % [i.e., percentages of the results within the respective analytical measurement ranges (AMRs)] of IL-1β, TNF-α, IL-6, and IL-10, respectively, in 66 serum samples. Simple Plex is a microfluidic multiplex immunoassay device that offers miniaturized, and automated analysis of protein biomarkers. Microfluidic devices such as Simple Plex represent a promising platform to be used in translational research to measure protein biomarkers in real clinical samples.

  18. A Comprehensive Microfluidics Device Construction and Characterization Module for the Advanced Undergraduate Analytical Chemistry Laboratory

    Science.gov (United States)

    Piunno, Paul A. E.; Zetina, Adrian; Chu, Norman; Tavares, Anthony J.; Noor, M. Omair; Petryayeva, Eleonora; Uddayasankar, Uvaraj; Veglio, Andrew

    2014-01-01

    An advanced analytical chemistry undergraduate laboratory module on microfluidics that spans 4 weeks (4 h per week) is presented. The laboratory module focuses on comprehensive experiential learning of microfluidic device fabrication and the core characteristics of microfluidic devices as they pertain to fluid flow and the manipulation of samples.…

  19. Paper-based inkjet-printed microfluidic analytical devices.

    Science.gov (United States)

    Yamada, Kentaro; Henares, Terence G; Suzuki, Koji; Citterio, Daniel

    2015-04-27

    Rapid, precise, and reproducible deposition of a broad variety of functional materials, including analytical assay reagents and biomolecules, has made inkjet printing an effective tool for the fabrication of microanalytical devices. A ubiquitous office device as simple as a standard desktop printer with its multiple ink cartridges can be used for this purpose. This Review discusses the combination of inkjet printing technology with paper as a printing substrate for the fabrication of microfluidic paper-based analytical devices (μPADs), which have developed into a fast-growing new field in analytical chemistry. After introducing the fundamentals of μPADs and inkjet printing, it touches on topics such as the microfluidic patterning of paper, tailored arrangement of materials, and functionalities achievable exclusively by the inkjet deposition of analytical assay components, before concluding with an outlook on future perspectives.

  20. Integration of isothermal amplification methods in microfluidic devices: Recent advances.

    Science.gov (United States)

    Giuffrida, Maria Chiara; Spoto, Giuseppe

    2017-04-15

    The integration of nucleic acids detection assays in microfluidic devices represents a highly promising approach for the development of convenient, cheap and efficient diagnostic tools for clinical, food safety and environmental monitoring applications. Such tools are expected to operate at the point-of-care and in resource-limited settings. The amplification of the target nucleic acid sequence represents a key step for the development of sensitive detection protocols. The integration in microfluidic devices of the most popular technology for nucleic acids amplifications, polymerase chain reaction (PCR), is significantly limited by the thermal cycling needed to obtain the target sequence amplification. This review provides an overview of recent advances in integration of isothermal amplification methods in microfluidic devices. Isothermal methods, that operate at constant temperature, have emerged as promising alternative to PCR and greatly simplify the implementation of amplification methods in point-of-care diagnostic devices and devices to be used in resource-limited settings. Possibilities offered by isothermal methods for digital droplet amplification are discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Ultrafast microfluidic mixer and freeze-quenching device.

    Science.gov (United States)

    Lin, Yu; Gerfen, Gary J; Rousseau, Denis L; Yeh, Syun-Ru

    2003-10-15

    The freeze-quenching technique is extremely useful for trapping meta-stable intermediates populated during fast chemical or biochemical reactions. The application of this technique, however, is limited by the long mixing time of conventional solution mixers and the slow freezing time of cryogenic fluids. To overcome these problems, we have designed and tested a novel microfluidic silicon mixer equipped with a new freeze-quenching device, with which reactions can be followed down to 50 micros. In the microfluidic silicon mixer, seven 10-microm-diameter vertical pillars are arranged perpendicular to the flow direction and in a staggered fashion in the 450-pL mixing chamber to enhance turbulent mixing. The mixed-solution jet, with a cross section of 10 microm x 100 microm, exits from the microfluidic silicon mixer with a linear flow velocity of 20 m/s. It instantaneously freezes on one of two rotating copper wheels maintained at 77 K and is subsequently ground into an ultrafine powder. The ultrafine frozen powder exhibits excellent spectral quality and high packing factor and can be readily transferred between spectroscopic observation cells. The microfluidic mixer was tested by the reaction between azide and myoglobin at pH 5.0. It was found that complete mixing was achieved within the mixing dead time of the mixer (20 micros), and the first observable point for this coupled device was determined to be 50 micros, which is approximately 2 orders of magnitude faster than commercially available instruments.

  2. A microfluidic device with a diffusion barrier

    DEFF Research Database (Denmark)

    2014-01-01

    The invention provides a microfiuidic device for macromoiecuie amplification by sequential addition of liquid reagents. The device of the invention comprises a chip forming a plurality of reaction chambers each extending between an inlet and an outlet, each inlet being in fluid communication with...

  3. Microwave Dielectric Heating of Drops in Microfluidic Devices

    CERN Document Server

    Issadore, David; Brown, Keith A; Sandberg, Lori; Weitz, David; Westervelt, Robert M

    2009-01-01

    We present a technique to locally and rapidly heat water drops in microfluidic devices with microwave dielectric heating. Water absorbs microwave power more efficiently than polymers, glass, and oils due to its permanent molecular dipole moment that has a large dielectric loss at GHz frequencies. The relevant heat capacity of the system is a single thermally isolated picoliter drop of water and this enables very fast thermal cycling. We demonstrate microwave dielectric heating in a microfluidic device that integrates a flow-focusing drop maker, drop splitters, and metal electrodes to locally deliver microwave power from an inexpensive, commercially available 3.0 GHz source and amplifier. The temperature of the drops is measured by observing the temperature dependent fluorescence intensity of cadmium selenide nanocrystals suspended in the water drops. We demonstrate characteristic heating times as short as 15 ms to steady-state temperatures as large as 30 degrees C above the base temperature of the microfluidi...

  4. Femtosecond fabricated photomasks for fabrication of microfluidic devices.

    Science.gov (United States)

    Day, Daniel; Gu, Min

    2006-10-30

    This paper describes the direct write laser fabrication of a photolithography mask for prototyping of microfluidic devices in polydimethylsiloxane. An amplified femtosecond pulse laser is used to selectively remove the aluminium metal layer from the poly(methyl methacrylate) photomask substrate. The use of a femtosecond pulse laser to selectively etch a metal layer has several advantages over other conventional methods for binary photomask fabrication, namely rapid prototyping of microfluidic devices using soft lightography. Control of the energy density and defocus position of the focusing objective lens results in the etching of features with widths ranging from 2 microm to 35 microm when using an objective lens with numerical aperture of 0.25.

  5. Fluoropolymer surface coatings to control droplets in microfluidic devices.

    Science.gov (United States)

    Riche, Carson T; Zhang, Chuchu; Gupta, Malancha; Malmstadt, Noah

    2014-06-07

    We have demonstrated the application of low surface energy fluoropolymer coatings onto poly(dimethylsiloxane) (PDMS) microfluidic devices for droplet formation and extraction-induced merger of droplets. Initiated chemical vapor deposition (iCVD) was used to pattern fluoropolymer coatings within microchannels based on geometrical constraints. In a two-phase flow system, the range of accessible flow rates for droplet formation was greatly enhanced in the coated devices. The ability to controllably apply the coating only at the inlet facilitated a method for merging droplets. An organic spacer droplet was extracted from between a pair of aqueous droplets. The size of the organic droplet and the flow rate controlled the time to merge the aqueous droplets; the process of merging was independent of the droplet sizes. Extraction-induced droplet merging is a robust method for manipulating droplets that could be applied in translating multi-step reactions to microfluidic platforms.

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

    Science.gov (United States)

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

    2011-06-01

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

  7. Polymeric salt bridges for conducting electric current in microfluidic devices

    Science.gov (United States)

    Shepodd, Timothy J.; Tichenor, Mark S.; Artau, Alexander

    2009-11-17

    A "cast-in-place" monolithic microporous polymer salt bridge for conducting electrical current in microfluidic devices, and methods for manufacture thereof is disclosed. Polymeric salt bridges are formed in place in capillaries or microchannels. Formulations are prepared with monomer, suitable cross-linkers, solvent, and a thermal or radiation responsive initiator. The formulation is placed in a desired location and then suitable radiation such as UV light is used to polymerize the salt bridge within a desired structural location. Embodiments are provided wherein the polymeric salt bridges have sufficient porosity to allow ionic migration without bulk flow of solvents therethrough. The salt bridges form barriers that seal against fluid pressures in excess of 5000 pounds per square inch. The salt bridges can be formulated for carriage of suitable amperage at a desired voltage, and thus microfluidic devices using such salt bridges can be specifically constructed to meet selected analytical requirements.

  8. Acoustofluidics 14: Applications of acoustic streaming in microfluidic devices.

    Science.gov (United States)

    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.

  9. Buckling delamination induced microchannel: Flow regulation in microfluidic devices

    Science.gov (United States)

    Kang, Jingtian; Wang, Changguo; Xue, Zhiming; Liu, Mengxiong; Tan, Huifeng

    2016-09-01

    The buckling delamination induced microchannel is employed to regulate fluid flow as a microvalve which can be utilized in microfluidic devices. This microvalve consists of a soft substrate and a stiff thin film, between which there is a pre-set small imperfection. Two critical strain values, namely, on-off strain and failure strain, have been proposed to determine the working strain interval using analytical predictions. Within this interval, the cross-sectional area of the microchannel can be controlled and predicted by different compressive strains of the film/substrate system. The fluid flow rate within this microchannel can be then estimated by both analytical and numerical simulations and adjusted to satisfy different values by alternating the compressive strain. In addition, a demonstrative experiment has been taken to verify the feasibility of this approach. This flexible microvalve has potential in the application where the use of traditional rigid microvalves is improper in flexible microfluidic devices. The method and approach of this paper can provide a general guide for flow rate control in microfluidic devices.

  10. Microfluidic structures for LOC devices designed by laser lithography

    Science.gov (United States)

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

    2016-12-01

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

  11. A Versatile Microfluidic Device for Automating Synthetic Biology.

    Science.gov (United States)

    Shih, Steve C C; Goyal, Garima; Kim, Peter W; Koutsoubelis, Nicolas; Keasling, Jay D; Adams, Paul D; Hillson, Nathan J; Singh, Anup K

    2015-10-16

    New microbes are being engineered that contain the genetic circuitry, metabolic pathways, and other cellular functions required for a wide range of applications such as producing biofuels, biobased chemicals, and pharmaceuticals. Although currently available tools are useful in improving the synthetic biology process, further improvements in physical automation would help to lower the barrier of entry into this field. We present an innovative microfluidic platform for assembling DNA fragments with 10× lower volumes (compared to that of current microfluidic platforms) and with integrated region-specific temperature control and on-chip transformation. Integration of these steps minimizes the loss of reagents and products compared to that with conventional methods, which require multiple pipetting steps. For assembling DNA fragments, we implemented three commonly used DNA assembly protocols on our microfluidic device: Golden Gate assembly, Gibson assembly, and yeast assembly (i.e., TAR cloning, DNA Assembler). We demonstrate the utility of these methods by assembling two combinatorial libraries of 16 plasmids each. Each DNA plasmid is transformed into Escherichia coli or Saccharomyces cerevisiae using on-chip electroporation and further sequenced to verify the assembly. We anticipate that this platform will enable new research that can integrate this automated microfluidic platform to generate large combinatorial libraries of plasmids and will help to expedite the overall synthetic biology process.

  12. Micron-scale tunability in photonic devices using microfluidics

    Science.gov (United States)

    Monat, Christelle; Domachuk, Peter; Jaouen, Vincent; Grillet, Christian; Littler, Ian; Croning-Golomb, Mark; Eggleton, Benjamin J.; Mutzenich, Simon; Mahmud, Tanveer; Rosengarten, Gary; Mitchell, Arnan

    2006-08-01

    Optofluidics offers new functionalities that can be useful for a large range of applications. What microfluidics can bring to microphotonics is the ability to tune and reconfigure ultra-compact optical devices. This flexibility is essentially provided by three characteristics of fluids that are scalable at the micron-scale: fluid mobility, large ranges of index modulation, and adaptable interfaces. Several examples of optofluidic devices are presented to illustrate the achievement of new functionalities onto (semi)planar and compact platforms. First, we report an ultra-compact and tunable interferometer that exploits a sharp and mobile air/water interface. We describe then a novel class of optically controlled switches and routers that rely on the actuation of optically trapped lens microspheres within fluid environment. A tunable optical switch device can alternatively be built from a transversely probed photonic crystal fiber infused with mobile fluids. The last reported optofluidic device relies on strong fluid/ light interaction to produce either a sensitive index sensor or a tunable optical filter. The common feature of these various devices is their significant flexibility. Higher degrees of functionality could be achieved in the future with fully integrated optofluidic platforms that associate complex microfluidic delivery and mixing schemes with microphotonic devices.

  13. Operation of Droplet-Microfluidic Devices with a Lab Centrifuge

    Directory of Open Access Journals (Sweden)

    Noorsher Ahmed

    2016-09-01

    Full Text Available Microfluidic devices are valuable for a variety of biotechnology applications, such as synthesizing biochemical libraries, screening enzymes, and analyzing single cells. However, normally, the devices are controlled using specialized pumps, which require expert knowledge to operate. Here, we demonstrate operation of poly(dimethylsiloxane devices without pumps. We build a scaffold that holds the device and reagents to be infused in a format that can be inserted into a 50 mL falcon tube and spun in a common lab centrifuge. By controlling the device design and centrifuge spin speed, we infuse the reagents at controlled flow rates. We demonstrate the encapsulation and culture of clonal colonies of red and green Escherichia coli in droplets seeded from single cells.

  14. Devices for the production and sorting of microfluidic droplets

    Science.gov (United States)

    Aubrecht, Donald; Heyman, John; Agresti, Jeremy; Köster, Sarah; Weitz, David

    2010-03-01

    Droplets produced in microfluidic devices are a great set of tools for studying large cell populations and permutations of reactions. Sample populations of 10^6 - 10^7 can be studied with relative ease, as encapsulation and screening rates in the kHz range are accessible. Previous droplet work has shown encapsulation of cells in droplets allows individual cells and their products to be studied. Advantages include correlation between detected products and initial drop contents, as well as minimized sample cross-contamination. Most microfluidic-based biological assays rely on fluorescent labeling of cells or use of cellular products to initiate a fluorescence-producing reaction. Detection of the fluorescence provides a trigger for sorting those cells or cell-containing droplets away from the general population. Though this allows some cellular processes to be studied, detection and quantification of all products, not just those expressed to the cell surface or those that catalyze reactions, would impact development of better therapeutics. We are currently working to adapt benchtop biological assays that label and detect cellular products for use in a droplet-based system. The work presented here details the chain of modular microfluidic devices we use to encapsulate, incubate, interrogate, and sort a population of droplets containing a model system.

  15. Magnetophoretic-based microfluidic device for DNA Concentration.

    Science.gov (United States)

    Shim, Sangjo; Shim, Jiwook; Taylor, William R; Kosari, Farhad; Vasmatzis, George; Ahlquist, David A; Bashir, Rashid

    2016-04-01

    Nucleic acids serve as biomarkers of disease and it is highly desirable to develop approaches to extract small number of such genomic extracts from human bodily fluids. Magnetic particles-based nucleic acid extraction is widely used for concentration of small amount of samples and is followed by DNA amplification in specific assays. However, approaches to integrate such magnetic particles based capture with micro and nanofluidic based assays are still lacking. In this report, we demonstrate a magnetophoretic-based approach for target-specific DNA extraction and concentration within a microfluidic device. This device features a large chamber for reducing flow velocity and an array of μ-magnets for enhancing magnetic flux density. With this strategy, the device is able to collect up to 95 % of the magnetic particles from the fluidic flow and to concentrate these magnetic particles in a collection region. Then an enzymatic reaction is used to detach the DNA from the magnetic particles within the microfluidic device, making the DNA available for subsequent analysis. Concentrations of over 1000-fold for 90 bp dsDNA molecules is demonstrated. This strategy can bridge the gap between detection of low concentration analytes from clinical samples and a range of micro and nanofluidic sensors and devices including nanopores, nano-cantilevers, and nanowires.

  16. Simulation of magnetic active polymers for versatile microfluidic devices

    CERN Document Server

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

    2013-01-01

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

  17. Electrostatic charging and control of droplets in microfluidic devices.

    Science.gov (United States)

    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.

  18. Enzymatic reactions in microfluidic devices: Michaelis-Menten kinetics.

    Science.gov (United States)

    Ristenpart, William D; Wan, Jiandi; Stone, Howard A

    2008-05-01

    Kinetic rate constants for enzymatic reactions are typically measured with a series of experiments at different substrate concentrations in a well-mixed container. Here we demonstrate a microfluidic technique for measuring Michaelis-Menten rate constants with only a single experiment. Enzyme and substrate are brought together in a coflow microfluidic device, and we establish analytically and numerically that the initial concentration of product scales with the distance x along the channel as x5/2. Measurements of the initial rate of product formation, combined with the quasi-steady rate of product formation further downstream, yield the rate constants. We corroborate the x5/2 scaling result experimentally using the bioluminescent reaction between ATP and luciferase/luciferin as a model system.

  19. Rapid, low-cost prototyping of centrifugal microfluidic devices for effective implementation of various microfluidic operations

    CSIR Research Space (South Africa)

    Hugo, S

    2013-10-01

    Full Text Available The work presented here details the implementation of a centrifugal microfluidic platform – the first of its kind in South Africa – as a foundation for the development of various microfluidic operations. Microfluidic systems enable the precise...

  20. Fabrication and Performance of a Photonic-Microfluidic Integrated Device

    Directory of Open Access Journals (Sweden)

    Benjamin R. Watts

    2012-02-01

    Full Text Available Fabrication and performance of a functional photonic-microfluidic flow cytometer is demonstrated. The devices are fabricated on a Pyrex substrate by photolithographically patterning the microchannels and optics in a SU-8 layer that is sealed via a poly(dimethylsiloxane (PDMS layer through a unique chemical bonding method. The resulting devices eliminate the free-space excitation optics through integration of microlenses onto the chip to mimic conventional cytometry excitation. Devices with beam waists of 6 μm and 12 μm in fluorescent detection and counting tests using 2.5 and 6 μm beads-show CVs of 9%–13% and 23% for the two devices, respectively. These results are within the expectations for a conventional cytometer (5%–15% and demonstrate the ability to integrate the photonic components for excitation onto the chip and the ability to maintain the level of reliable detection.

  1. Thermal loading in flow-through electroporation microfluidic devices.

    Science.gov (United States)

    del Rosal, Blanca; Sun, Chen; Loufakis, Despina Nelie; Lu, Chang; Jaque, Daniel

    2013-08-01

    Thermal loading effects in flow-through electroporation microfluidic devices have been systematically investigated by using dye-based ratiometric luminescence thermometry. Fluorescence measurements have revealed the crucial role played by both the applied electric field and flow rate on the induced temperature increments at the electroporation sections of the devices. It has been found that Joule heating could raise the intra-channel temperature up to cytotoxic levels (>45 °C) only when conditions of low flow rates and high applied voltages are applied. Nevertheless, when flow rates and electric fields are set to those used in real electroporation experiments we have found that local heating is not larger than a few degrees, i.e. temperature is kept within the safe range (electroporation devices from which the heat affected area can be elucidated. Experimental data have been found to be in excellent agreement with numerical simulations that have also revealed the presence of a non-homogeneous temperature distribution along the electroporation channel whose magnitude is critically dependent on both applied electric field and flow rate. Results included in this work will allow for full control over the electroporation conditions in flow-through microfluidic devices.

  2. Mail-order microfluidics: evaluation of stereolithography for the production of microfluidic devices.

    Science.gov (United States)

    Au, Anthony K; Lee, Wonjae; Folch, Albert

    2014-04-01

    The vast majority of microfluidic devices are developed in PDMS by molding ("soft lithography") because PDMS is an inexpensive material, has physicochemical properties that are well suited for biomedical and physical sciences applications, and design cycle lengths are generally adequate for prototype development. However, PDMS molding is tediously slow and thus cannot provide the high- or medium-volume production required for the commercialization of devices. While high-throughput plastic molding techniques (e.g. injection molding) exist, the exorbitant cost of the molds and/or the equipment can be a serious obstacle for device commercialization, especially for small startups. High-volume production is not required to reach niche markets such as clinical trials, biomedical research supplies, customized research equipment, and classroom projects. Crucially, both PDMS and plastic molding are layer-by-layer techniques where each layer is produced as a result of physicochemical processes not specified in the initial photomask(s) and where the final device requires assembly by bonding, all resulting in a cost that is very hard to predict at the start of the project. By contrast, stereolithography (SL) is an automated fabrication technique that allows for the production of quasi-arbitrary 3D shapes in a single polymeric material at medium-volume throughputs (ranging from a single part to hundreds of parts). Importantly, SL devices can be designed between several groups using CAD tools, conveniently ordered by mail, and their cost precisely predicted via a web interface. Here we evaluate the resolution of an SL mail-order service and the main causes of resolution loss; the optical clarity of the devices and how to address the lack of clarity for imaging in the channels; and the future role that SL could play in the commercialization of microfluidic devices.

  3. Microfluidic device with dual mechanical cues for cell migration investigation.

    Science.gov (United States)

    Tsai, Chin-Hsiung; Kuo, Po-Ling

    2013-01-01

    Cell migration plays an important role in numerous physiological and pathological conditions, such as angiogenesis, wound healing and cancer metastasis. Understanding the fundamental mechanisms of cell migration is crucial to develop strategies for disease treatment and regenerative medicine. Several biomechanical cues have been well studied about their effects on guiding cell migration. However, the effects of dual or multiple cues on cell migration are barely addressed. In this work, we developed a microfluidic-based device to study the combinatory effects of osmotic and stiffness gradient on cell migration. Computer simulation and experimental validation showed that the device was capable of providing stable osmotic and stiffness gradient to cultured cells at the same time. Preliminary results suggest that our device has a valuable potential in studying cell migration in complex conditions which better recapitulate the complex environmental conditions in vivo.

  4. Droplet Velocity in an Electrowetting on Dielectric Digital Microfluidic Device

    Directory of Open Access Journals (Sweden)

    Mun Mun Nahar

    2016-04-01

    Full Text Available In many electrowetting on dielectric (EWOD based microfluidics devices, droplet actuation speed is a crucial performance-controlling parameter. Our present study aims to characterize and study droplet speed in a typical EWOD device. First, a practical droplet speed measurement method has been methodically demonstrated and some related velocity terms have been introduced. Next, influence of electrode shape on droplet speed has been studied and a new design to enhance droplet speed has been proposed and experimentally demonstrated. Instead of using square shaped electrodes, rectangular electrodes with smaller widths are used to actuate droplets. Additionally, different schemes of activating electrodes are studied and compared for the same applied voltage. The experiments show that a particular scheme of activating the array of rectangular electrodes enhances the droplet speed up to 100% in comparison to the droplet speed in a conventional device with square shaped electrodes.

  5. Imaging diffusion in a microfluidic device by third harmonic microscopy

    Science.gov (United States)

    Petzold, Uwe; Büchel, Andreas; Hardt, Steffen; Halfmann, Thomas

    2012-09-01

    We monitor and characterize near-surface diffusion of miscible, transparent liquids in a microfluidic device by third harmonic microscopy. The technique enables observations even of transparent or index-matched media without perturbation of the sample. In particular, we image concentrations of ethanol diffusing in water and estimate the diffusion coefficient from the third harmonic images. We obtain a diffusion coefficient D = (460 ± 30) μm2/s, which is consistent with theoretical predictions. The investigations clearly demonstrate the potential of harmonic microscopy also under the challenging conditions of transparent fluids.

  6. Wireless induction heating in a microfluidic device for cell lysis.

    Science.gov (United States)

    Baek, Seung-ki; Min, Junghong; Park, Jung-Hwan

    2010-04-07

    A wireless induction heating system in a microfluidic device was devised for cell lysis to extract DNA and RNA from Escherichia coli. The thermal responses of nickel, iron and copper heating units were studied by applying an alternating magnetic field as a function of geometry of unit, strength of magnetic field, and kind of metal. Heating units were prepared by cutting metal film using a fiber laser, and the units were integrated into a microchannel system using a soft lithographic process. Variation and distribution of temperature on the surface of the heating units was observed using a thermographic camera and temperature labels. The amount of protein released from E. coli by thermal lysis was determined by protein concentration measurement. Hemoglobin released from red blood cells was observed using colorimetric intensity measurement. Extracted DNA was quantified by real-time polymerase chain reaction, and the profile was compared with that of a positive control of ultrasonically disrupted E. coli. The stability of RNA extracted by induction heating was quantified by the measurement of 23S/16S rRNA ratio and comparison with that by normal RNA extraction kit as a gold standard. A solid-shaped nickel structure was selected as the induction heating element in the microfluidic device because of the relatively small influence of geometries and faster thermal response.The amount of protein extracted from E. coli and hemoglobin released from red blood cells by induction heating of the nickel unit in the microfluidic device was proportional to the strength of the applied magnetic field. The lysis of E. coli by induction heating was as effective as lysis of DNA by the ultrasonication method because the threshold cycle values of the sample were compatible with those of the positive control as measured by ultrasonication. Thermal lysis of E. coli by induction heating represents a reasonable alternative to a commercial RNA extraction method as shown by the comparative

  7. Pressure-driven microfluidic perfusion culture device for integrated dose-response assays.

    Science.gov (United States)

    Hattori, Koji; Sugiura, Shinji; Kanamori, Toshiyuki

    2013-12-01

    Cell-based assays are widely used in the various stages of drug discovery. Advances in microfluidic systems over the past two decades have enabled them to become a powerful tool for cell-based assays to achieve both reliability and high throughput. The interface between the micro-world and macro-world is important in industrial assay processes. Therefore, microfluidic cell-based assays using pressure-driven liquid handling are an ideal platform for integrated assays. The aim of this article is to review recent advancements in microfluidic cell-based assays focusing on a pressure-driven perfusion culture device. Here, we review the development of microfluidic cell-based assay devices and discuss the techniques involved in designing a microfluidic network, device fabrication, liquid and cell manipulation, and detection schemes for pressure-driven perfusion culture devices. Finally, we describe recent progress in semiautomatic and reliable pressure-driven microfluidic cell-based assays.

  8. Thermoplastic elastomers for microfluidics: towards a high-throughput fabrication method of multilayered microfluidic devices.

    Science.gov (United States)

    Roy, Emmanuel; Galas, Jean-Christophe; Veres, Teodor

    2011-09-21

    Multilayer soft lithography of polydimethylsiloxane (PDMS) is a well-known method for the fabrication of complex fluidic functions. With advantages and drawbacks, this technique allows fabrication of valves, pumps and micro-mixers. However, the process is inadequate for industrial applications. Here, we report a rapid prototyping technique for the fabrication of multilayer microfluidic devices, using a different and promising class of polymers. Using styrenic thermoplastic elastomers (TPE), we demonstrate a rapid technique for the fabrication and assembly of pneumatically driven valves in a multilayer microfluidic device made completely from thermoplastics. This material solution is transparent, biocompatible and as flexible as PDMS, and has high throughput thermoforming processing characteristics. We established a proof of principle for valving and mixing with three different grades of TPE using an SU-8 master mold. Specific viscoelastic properties of each grade allow us to report enhanced bonding capabilities from room temperature bonding to free pressure thermally assisted bonding. In terms of microfabrication, beyond classically embossing means, we demonstrate a high-throughput thermoforming method, where TPE molding experiments have been carried out without applied pressure and vacuum assistance within an overall cycle time of 180 s. The quality of the obtained thermoplastic systems show robust behavior and an opening/closing frequency of 5 Hz.

  9. Novel microfluidic devices for Raman spectroscopy and optical trapping

    Science.gov (United States)

    Ottevaere, Heidi; Liu, Qing; de Coster, Diane; Van Erps, Jürgen; Vervaeke, Michael; Thienpont, Hugo

    2016-09-01

    Traditionally, Raman spectroscopy is done in a specialized lab, with considerable requirements in terms of equipment, time and manual sampling of substances of interest. We present the modeling, the design and the fabrication process of a microfluidic device incorporation Raman spectroscopy, from which one enables confocal Raman measurements on-chip. The latter is fabricated using ultra precision diamond tooling and is tested in a proof-of-concept setup, by for example measuring Raman spectra of urea solutions with various concentrations. If one wants to analyze single cells instead of a sample solution, precautions need to be taken. Since Raman scattering is a weak process, the molecular fingerprint of flowing particles would be hard to measure. One method is to stably position the cell under test in the detection area during acquisition of the Raman scattering such that the acquisition time can be increased. Positioning of cells can be done through optical trapping and leads to an enhanced signal-to-noise ratio and thus a more reliable cell identification. Like Raman spectroscopy, optical trapping can also be miniaturized. We present the modeling, design process and fabrication of a mass-manufacturable polymer microfluidic device for dual fiber optical trapping using two counterpropagating singlemode beams. 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 characterize the trapping capabilities of the hot embossed chip.

  10. Chemical and physical processes for integrated temperature control in microfluidic devices

    NARCIS (Netherlands)

    Guijt, Rosanne M.; Dodge, Arash; Van Dedem, Gijs W. K.; De Rooij, Nico F.; Verpoorte, Elisabeth

    2003-01-01

    Microfluidic devices are a promising new tool for studying and optimizing (bio)chemical reactions and analyses. Many (bio)chemical reactions require accurate temperature control, such as for example thermocycling for PCR. Here, a new integrated temperature control system for microfluidic devices is

  11. Integrated on-chip mass spectrometry reaction monitoring in microfluidic devices containing porous polymer monolithic columns.

    Science.gov (United States)

    Dietze, C; Schulze, S; Ohla, S; Gilmore, K; Seeberger, P H; Belder, D

    2016-09-21

    Chip-based microfluidics enable the seamless integration of different functions into single devices. Here, we present microfluidic chips containing porous polymer monolithic columns as a means to facilitate chemical transformations as well as both downstream chromatographic separation and mass spectrometric analysis. Rapid liquid phase lithography prototyping creates the multifunctional device economically.

  12. Suspension flow in microfluidic devices - a review of experimental techniques focussing on concentration and velocity gradients

    NARCIS (Netherlands)

    Dinther, van A.M.C.; Schroën, C.G.P.H.; Vergeldt, F.; Sman, van der R.G.M.; Boom, R.M.

    2012-01-01

    Microfluidic devices are an emerging technology for processing suspensions in e.g. medical applications, pharmaceutics and food. Compared to larger scales, particles will be more influenced by migration in microfluidic devices, and this may even be used to facilitate segregation and separation. In o

  13. Chemical and physical processes for integrated temperature control in microfluidic devices

    NARCIS (Netherlands)

    Guijt, Rosanne M.; Dodge, Arash; Van Dedem, Gijs W. K.; De Rooij, Nico F.; Verpoorte, Elisabeth

    2003-01-01

    Microfluidic devices are a promising new tool for studying and optimizing (bio)chemical reactions and analyses. Many (bio)chemical reactions require accurate temperature control, such as for example thermocycling for PCR. Here, a new integrated temperature control system for microfluidic devices is

  14. Single vegetal cell handling and fixing in a microfluidic device

    Science.gov (United States)

    Denoual, Matthieu J.; Koh, Aoki; Mita-Tixier, Agnes; Fujita, Hiroyuki

    2003-04-01

    The basic advantage of the microfluidic systems is that they enable reducing consumption of biological material and chemicals. But another major advantage of the microfluidic systems, not widely explored so far, is that with feature sizes reduced toward the size of cells, one can easily handle and fix a single cell. The interest of single cell handling and fixing appears when one wants to study biochemical exchanges between single cells or internal biochemical reactions inside an isolated cell. This work uses the shape of the microfluidc device to control the migration and placement of single vegetal cells. Three-dimensional micro-molding and poly-dimethylsiloxane (PDMS) patterning techniques have been used to realize device prototypes. Double-height micro-molds are made of thick negative photoresist (SU8) Experiments have been undergone to optimize fluid rate flow and cell concentration regarding to right cell placement percentage. The PDMS prototypes systems confirm the good operation of the design to migrate cells, place and fix them. The placement rate, even if it is enough for statistical biochemical experiments, will be improved by the use of new material. New material will allow to get rid of air bubbles due to PDMS long-term hydrophobicity that render up to 25% settlement places unserviceable.

  15. A microfluidic device for performing pressure-driven separations.

    Science.gov (United States)

    Dutta, Debashis; Ramsey, J Michael

    2011-09-21

    Microchannels in microfluidic devices are frequently chemically modified to introduce specific functional elements or operational modalities. In this work, we describe a miniaturized hydraulic pump created by coating selective channels in a glass microfluidic manifold with a polyelectrolyte multilayer (PEM) that alters the surface charge of the substrate. Pressure-driven flow is generated due to a mismatch in the electroosmotic flow (EOF) rates induced upon the application of an electric field to a tee channel junction that has one arm coated with a positively charged PEM and the other arm left uncoated in its native state. In this design, the channels that generate the hydraulic pressure are interconnected via the third arm of the tee to a field-free analysis channel for performing pressure-driven separations. We have also shown that modifications in the cross-sectional area of the channels in the pumping unit can enhance the hydrodynamic flow through the separation section of the manifold. The integrated device has been demonstrated by separating Coumarin dyes in the field-free analysis channel using open-channel liquid chromatography under pressure-driven flow conditions. This journal is © The Royal Society of Chemistry 2011

  16. Femtosecond Laser Micromachining Photonic and Microfluidic Devices in Transparent Materials

    CERN Document Server

    Cerullo, Giulio; Ramponi, Roberta

    2012-01-01

    Femtosecond laser micromachining of transparent material is a powerful and versatile technology. In fact, it can be applied to several materials. It is a maskless technology that allows rapid device prototyping, has intrinsic three-dimensional capabilities and can produce both photonic and microfluidic devices. For these reasons it is ideally suited for the fabrication of complex microsystems with unprecedented functionalities. The book is mainly focused on micromachining of transparent materials which, due to the nonlinear absorption mechanism of ultrashort pulses, allows unique three-dimensional capabilities and can be exploited for the fabrication of complex microsystems with unprecedented functionalities.This book presents an overview of the state of the art of this rapidly emerging topic with contributions from leading experts in the field, ranging from principles of nonlinear material modification to fabrication techniques and applications to photonics and optofluidics.

  17. Femtosecond laser fabrication of microfluidic channels for organic photonic devices.

    Science.gov (United States)

    Chaitanya Vishnubhatla, Krishna; Clark, Jenny; Lanzani, Guglielmo; Ramponi, Roberta; Osellame, Roberto; Virgili, Tersilla

    2009-11-01

    We report on innovative application of microchannels with access holes fabricated by femtosecond laser irradiation followed by chemical etching. This technique allows us to demonstrate a novel approach to the achievement of organic photonic devices in which the properties of a conjugated polymer in solution are exploited in a microfluidic configuration to produce an easy-to-integrate photonic device. Filling the microchannel with a diluted polyfluorene solution, we exploit the unique properties of isolated polymeric chains such as ultrafast gain switching (switching response time of 150 fs) with a 100% on-off ratio. In addition, by dispersing nanoparticles in the polymeric solution we are able to achieve random lasing in the microchannel.

  18. The electrochemical detection of droplets in microfluidic devices.

    Science.gov (United States)

    Liu, Shujuan; Gu, Yunfeng; Le Roux, Rudolph B; Matthews, Sinéad M; Bratton, Daniel; Yunus, Kamran; Fisher, Adrian C; Huck, Wilhelm T S

    2008-11-01

    This paper presents a new electrochemical method for the detection and characterisation of aqueous droplets in an organic carrier fluid (1,2-dichloroethane) formed in flow-focusing microfluidic devices. The devices consist of a conventional flow-focusing channel 250 microm wide and 250 microm deep cast out of poly(dimethylsiloxane) (PDMS) which is sealed onto a glass substrate containing a set of microelectrodes 100 microm long. Chronoamperometric analysis of a suitable electrolyte contained in the organic phase is presented for characterising the droplet frequency and size. This chronoamperometric method is then extended to a dual working electrode approach in order to determine the velocity of the droplet. Good agreement between experimental measurements and theory was observed.

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

    Science.gov (United States)

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

    2011-01-21

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

  20. Recent applications of AC electrokinetics in biomolecular analysis on microfluidic devices.

    Science.gov (United States)

    Sasaki, Naoki

    2012-01-01

    AC electrokinetics is a generic term that refers to an induced motion of particles and fluids under nonuniform AC electric fields. The AC electric fields are formed by application of AC voltages to microelectrodes, which can be easily integrated into microfluidic devices by standard microfabrication techniques. Moreover, the magnitude of the motion is large enough to control the mass transfer on the devices. These advantages are attractive for biomolecular analysis on the microfluidic devices, in which the characteristics of small space and microfluidics have been mainly employed. In this review, I describe recent applications of AC electrokinetics in biomolecular analysis on microfluidic devices. The applications include fluid pumping and mixing by AC electrokinetic flow, and manipulation of biomolecules such as DNA and proteins by various AC electrokinetic techniques. Future prospects for highly functional biomolecular analysis on microfluidic devices with the aid of AC electrokinetics are also discussed.

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

    DEFF Research Database (Denmark)

    Perozziello, Gerardo; Candeloro, Patrizio; De Grazia, Antonio

    2016-01-01

    In this work a Raman flow cytometer is presented. It consists of a microfluidic device that takes advantages of the basic principles of Raman spectroscopy and flow cytometry. The microfluidic device integrates calibrated microfluidic channels-where the cells can flow one-by-one -, allowing single...... cell Raman analysis. The microfluidic channel integrates plasmonic nanodimers in a fluidic trapping region. In this way it is possible to perform Enhanced Raman Spectroscopy on single cell. These allow a label-free analysis, providing information about the biochemical content of membrane and cytoplasm...

  2. Optimized fabrication protocols of microfluidic devices for X-ray analysis

    KAUST Repository

    Catalano, Rossella

    2014-07-01

    Microfluidics combined with X-ray scattering techniques allows probing conformational changes or assembly processes of biological materials. Our aim was to develop a highly X-ray transparent microfluidic cell for detecting small variations of X-ray scattering involved in such processes. We describe the fabrication of a polyimide microfluidic device based on a simple, reliable and inexpensive lamination process. The implemented microstructured features result in windows with optimized X-ray transmission. The microfluidic device was characterized by X-ray microbeam scattering at the ID13 beamline of the European Synchrotron Radiation Facility. © 2014 Elsevier B.V. All rights reserved.

  3. Microfluidic vias enable nested bioarrays and autoregulatory devices in Newtonian fluids.

    Science.gov (United States)

    Kartalov, Emil P; Walker, Christopher; Taylor, Clive R; Anderson, W French; Scherer, Axel

    2006-08-15

    We report on a fundamental technological advance for multilayer polydimethylsiloxane (PDMS) microfluidics. Vertical passages (vias), connecting channels located in different layers, are fabricated monolithically, in parallel, by simple and easy means. The resulting 3D connectivity greatly expands the potential complexity of microfluidic architecture. We apply the vias to printing nested bioarrays and building autoregulatory devices. A current source is demonstrated, while a diode and a rectifier are derived; all are building blocks for analog circuitry in Newtonian fluids. We also describe microfluidic septa and their applications. Vias lay the foundation for a new generation of microfluidic devices.

  4. Three-dimensional paper microfluidic devices assembled using the principles of origami.

    Science.gov (United States)

    Liu, Hong; Crooks, Richard M

    2011-11-01

    We report a method, based on the principles of origami (paper folding), for fabricating three-dimensional (3-D) paper microfluidic devices. The entire 3-D device is fabricated on a single sheet of flat paper in a single photolithographic step. It is assembled by simply folding the paper by hand. Following analysis, the device can be unfolded to reveal each layer. The applicability of the device to chemical analysis is demonstrated by colorimetric and fluorescence assays using multilayer microfluidic networks.

  5. Droplet Formation via Solvent Shifting in a Microfluidic Device

    CERN Document Server

    Hajian, Ramin

    2014-01-01

    Solvent shifting is a process in which a non-solvent is added to a solvent/solute mixture and extracts the solvent. The solvent and the non-solvent are miscible. Because of solution supersaturation a portion of the solute transforms to droplets. In this paper, based on this process, we present an investigation on droplet formation and their radial motion in a microfluidic device in which a jet is injected in a co-flowing liquid stream. Thanks to the laminar flow, the microfluidic setup enables studying diffusion mass transfer in radial direction and obtaining well-defined concentration distributions. Such profiles together with Ternary Phase Diagram (TPD) give detailed information about the conditions for droplet formation condition as well as their radial migration in the channel. The ternary system is composed of ethanol (solvent), de-ionized water (non-solvent) and divinyle benzene (solute). We employ analytical/numerical solutions of the diffusion equation to obtain concentration profiles of the component...

  6. AC Electrokinetic Cell Separation on a Microfluidic Device

    Science.gov (United States)

    Gagnon, Zachary; Chang, Hsueh-Chia

    2009-03-01

    Rapid cell separation and collection is demonstrated through the integration of electrokinetic pumps, dielectrophoretic (DEP) traps and field driven valves into a well designed microfluidic channel loop. We present the ground-up design and analysis of this fully functional microfluidic device for the rapid separation and collection of live and dead yeast cells and malaria red blood cells (RBCs) at low concentrations. DEP cell sorting and concentration schemes are based on the exploitation of cell specific DEP crossover frequencies (cof's). A rigorous DEP study of yeast and RBCs is presented and used to determine optimal conditions for cell separation. By utilizing a glutaraldehyde crosslinking cell fixation reaction that is sensitive to cell membrane protein concentration, we demonstrate the ability to further amplify these differences between healthy and unhealthy cells as well as stabilize their DEP cof's. Pumping is achieved with a new type of electrokinetic flow, AC electrothermal electro-osmosis (ETEO) and is shown to scale inversely with the field induced debye length and drive fluid velocities in excess of 6 mm/sec. The well characterized electrokinetic phenomena are integrated into a microchannel loop with a specifically designed electrode field penetration length for low concentration cell separation and concentration.

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

    Directory of Open Access Journals (Sweden)

    Christina Swanson

    2015-09-01

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

  8. Microfluidic baker's transformation device for three-dimensional rapid mixing.

    Science.gov (United States)

    Yasui, Takao; Omoto, Yusuke; Osato, Keiko; Kaji, Noritada; Suzuki, Norikazu; Naito, Toyohiro; Watanabe, Masaki; Okamoto, Yukihiro; Tokeshi, Manabu; Shamoto, Eiji; Baba, Yoshinobu

    2011-10-01

    We developed a new passive-type micromixer based on the baker's transformation and realized a fast mixing of a protein solution, which has lower diffusion constant. The baker's transformation is an ideal mixing method, but there is no report on the microfluidic baker's transformation (MBT), since it is required to fabricate the complicated three-dimensional (3D) structure to realize the MBT device. In this note, we successfully fabricate the MBT device by using precision diamond cutting of an oxygen-free copper substrate for the mould fabrication and PDMS replication. The MBT device with 10.4 mm mixing length enables us to achieve complete mixing of a FITC solution (D = 2.6 × 10(-10) m(2) s(-1)) within 51 ms and an IgG solution (D = 4.6 × 10(-11) m(2) s(-1)) within 306 ms. Its mixing speed is 70-fold higher for a FITC solution and 900-fold higher for an IgG solution than the mixing speed by the microchannel without MBT structures. The Péclet number to attain complete mixing in the MBT device is estimated to be 6.9 × 10(4).

  9. System-Level Modeling and Synthesis Techniques for Flow-Based Microfluidic Very Large Scale Integration Biochips

    DEFF Research Database (Denmark)

    Minhass, Wajid Hassan

    high densities, e.g., 1 million valves per cm2. By combining these valves, more complex units such as mixers, switches, multiplexers can be built up and the technology is therefore referred to as microfluidic Very Large Scale Integration (mVLSI). The manufacturing technology for the mVLSI biochips has...

  10. Using Microfluidic Device to Study Rheological Properties of Heavy Oil

    CERN Document Server

    Keshmiri, Kiarash; Tchoukov, Plamen; Huang, Haibo; Nazemifard, Neda

    2016-01-01

    In this study, capillary-driven flow of different pure liquids and diluted bitumen samples were studied using microfluidic channel (width of 30 um and depth of 9 um). Capillary filling kinetics of liquids as a function of time were evaluated and compared with theoretical predictions. For pure liquids including water, toluene, hexane, and methanol experimental results agreed well with theoretical predictions. However, for bitumen samples, as concentration of bitumen increased the deviation between theoretical and experimental results became larger. The higher deviation for high concentrations (i.e. above 30%) can be due to the difference between dynamic contact angle and bulk contact angle. Microchannels are suitable experimental devices to study the flow of heavy oil and bitumen in porous structure such as those of reservoirs.

  11. Origins of periodic and chaotic dynamics in microfluidic loop devices

    CERN Document Server

    Maddala, Jeevan; Rengaswamy, Raghunathan

    2012-01-01

    Droplets moving in a microfluidic loop device exhibit both periodic and chaotic behaviors based on the inlet droplet spacing. We propose that the periodic behavior is an outcome of a dispersed phase conservation principle. This conservation principle translates into a droplet spacing conservation equation. Additionally, we define a simple technique to identify periodicity in experimental systems with input scatter. Aperiodic behavior is observed in the transition regions between different periodic behaviors. We propose that the cause for aperiodicity is the synchronization of timing between the droplets entering and leaving the system. We derive an analytical expression to estimate the occurrence of these transition regions as a function of system parameters. We provide experimental, simulation and analytical results to validate the proposed theory.

  12. Laser induced fluorescence photobleaching anemometer for microfluidic devices.

    Science.gov (United States)

    Wang, G R

    2005-04-01

    We have developed a novel, non-intrusive fluid velocity measurement method based on photobleaching of a fluorescent dye for microfluidic devices. The residence time of the fluorescent dye in a laser beam depends on the flow velocity and approximately corresponds to the decaying time of the photobleaching of the dye in the laser beam. The residence time is inversely proportional to the flow velocity. The fluorescence intensity increases with the flow velocity due to the decrease of the residence time. A calibration curve between fluorescence intensity and known flow velocity should be obtained first. The calibration relationship is then used to calculate the flow velocity directly from the measured fluorescence intensity signal. The new method can measure the velocity very quickly and is easy to use. It is demonstrated for both pressure driven flow and electroosmotic flow.

  13. 3D Printed Paper-Based Microfluidic Analytical Devices

    Directory of Open Access Journals (Sweden)

    Yong He

    2016-06-01

    Full Text Available As a pump-free and lightweight analytical tool, paper-based microfluidic analytical devices (μPADs attract more and more interest. If the flow speed of μPAD can be programmed, the analytical sequences could be designed and they will be more popular. This reports presents a novel μPAD, driven by the capillary force of cellulose powder, printed by a desktop three-dimensional (3D printer, which has some promising features, such as easy fabrication and programmable flow speed. First, a suitable size-scale substrate with open microchannels on its surface is printed. Next, the surface of the substrate is covered with a thin layer of polydimethylsiloxane (PDMS to seal the micro gap caused by 3D printing. Then, the microchannels are filled with a mixture of cellulose powder and deionized water in an appropriate proportion. After drying in an oven at 60 °C for 30 min, it is ready for use. As the different channel depths can be easily printed, which can be used to achieve the programmable capillary flow speed of cellulose powder in the microchannels. A series of microfluidic analytical experiments, including quantitative analysis of nitrite ion and fabrication of T-sensor were used to demonstrate its capability. As the desktop 3D printer (D3DP is very cheap and accessible, this device can be rapidly printed at the test field with a low cost and has a promising potential in the point-of-care (POC system or as a lightweight platform for analytical chemistry.

  14. A microfluidic cell culture device with integrated microelectrodes for barrier studies

    DEFF Research Database (Denmark)

    Tan, Hsih-Yin; Dufva, Martin; Kutter, Jörg P.

    We present an eight cell culture microfluidic device fabricated using thiol-ene ‘click’ chemistry with embedded microelectrodes for evaluating barrier properties of human intestinal epithelial cells. The capability of the microelectrodes for trans-epithelial electrical resistance (TEER) measureme......We present an eight cell culture microfluidic device fabricated using thiol-ene ‘click’ chemistry with embedded microelectrodes for evaluating barrier properties of human intestinal epithelial cells. The capability of the microelectrodes for trans-epithelial electrical resistance (TEER......) measurements was demonstrated by using confluent human colorectal epithelial cells (Caco-2) and rat fibroblast (CT 26) cells cultured in the microfluidic device....

  15. Simple and inexpensive microfluidic devices for the generation of monodisperse multiple emulsions

    KAUST Repository

    Li, Erqiang

    2013-12-16

    Droplet-based microfluidic devices have become a preferred versatile platform for various fields in physics, chemistry and biology. Polydimethylsiloxane soft lithography, the mainstay for fabricating microfluidic devices, usually requires the usage of expensive apparatus and a complex manufacturing procedure. Here, we report the design and fabrication of simple and inexpensive microfluidic devices based on microscope glass slides and pulled glass capillaries, for generating monodisperse multiple emulsions. The advantages of our method lie in a simple manufacturing procedure, inexpensive processing equipment and flexibility in the surface modification of the designed microfluidic devices. Different types of devices have been designed and tested and the experimental results demonstrated their robustness for preparing monodisperse single, double, triple and multi-component emulsions. © 2014 IOP Publishing Ltd.

  16. Microwave sensing and heating of individual droplets in microfluidic devices.

    Science.gov (United States)

    Boybay, Muhammed S; Jiao, Austin; Glawdel, Tomasz; Ren, Carolyn L

    2013-10-07

    Droplet-based microfluidics is an emerging high-throughput screening technology finding applications in a variety of areas such as life science research, drug discovery and material synthesis. In this paper we present a cost-effective, scalable microwave system that can be integrated with microfluidic devices enabling remote, simultaneous sensing and heating of individual nanoliter-sized droplets generated in microchannels. The key component of this microwave system is an electrically small resonator that is able to distinguish between materials with different electrical properties (i.e. permittivity, conductivity). The change in these properties causes a shift in the operating frequency of the resonator, which can be used for sensing purposes. Alternatively, if microwave power is delivered to the sensing region at the frequency associated with a particular material (i.e. droplet), then only this material receives the power while passing the resonator leaving the surrounding materials (i.e. carrier fluid and chip material) unaffected. Therefore this method allows sensing and heating of individual droplets to be inherently synchronized, eliminating the need for external triggers. We confirmed the performance of the sensor by applying it to differentiate between various dairy fluids, identify salt solutions and detect water droplets with different glycerol concentrations. We experimentally verified that this system can increase the droplet temperature from room temperature by 42 °C within 5.62 ms with an input power of 27 dBm. Finally we employed this system to thermally initiate the formation of hydrogel particles out of the droplets that are being heated by this system.

  17. Acoustofluidics: theory and simulation of radiation forces at ultrasound resonances in microfluidic devices

    DEFF Research Database (Denmark)

    Barnkob, Rune; Bruus, Henrik

    2009-01-01

    Theoretical analysis is combined with numerical simulations to optimize designs and functionalities of acoustofluidic devices, i.e. microfluidic devices in which ultrasound waves are used to anipulate biological particles. The resonance frequencies and corresponding modes of the acoustic fields...... the largest possible acoustic powers are obtained in the microfluidic system, the time-averaged acoustic radiation force on single particles is determined. Schemes for in situ calibration of this force are presented and discussed....

  18. Fabrication of polystyrene microfluidic devices using a pulsed CO2 laser system

    KAUST Repository

    Li, Huawei

    2013-10-10

    In this article, we described a simple and rapid method for fabrication of droplet microfluidic devices on polystyrene substrate using a CO2 laser system. The effects of the laser power and the cutting speed on the depth, width and aspect ratio of the microchannels fabricated on polystyrene were investigated. The polystyrene microfluidic channels were encapsulated using a hot press bonding technique. The experimental results showed that both discrete droplets and laminar flows could be obtained in the device.

  19. Using a microfluidic device for high-content analysis of cell signaling.

    Science.gov (United States)

    Cheong, Raymond; Wang, Chiaochun Joanne; Levchenko, Andre

    2009-06-16

    Quantitative analysis and understanding of signaling networks require measurements of the location and activities of key proteins over time, at the level of single cells, in response to various perturbations. Microfluidic devices enable such analyses to be conducted in a high-throughput and in a highly controlled manner. We describe in detail how to design and use a microfluidic device to perform such information-rich experiments.

  20. Bacterial Response to Antibiotic Gradients in a Porous Microfluidic Device

    Science.gov (United States)

    Deng, J.; Shechtman, L. A.; Sanford, R. A.; Dong, Y.; Werth, C. J.; Fouke, B. W.

    2015-12-01

    Microorganisms in nature have evolved survival strategies to cope with a wide variety of environmental stresses, including gradients in temperature, pH, substrate availability and aqueous chemistry. Microfluidic devices provide a consistently reliable real-time means to quantitatively measure, control and reproduce the dynamic nature of these stresses. As an example, accelerated adaptation from genetic mutations have been observed in E. coli as it responds to gradients of Ciprofloxacin (Zhang et. al. 2011). However, the mechanisms by which bacteria respond to antibiotic gradients, as well as the effect of changes in how the stressor is applied, have not been systematically studied. In this study, newly designed and fabricated microfluidic devices with porous media have been utilized to determine the chemical stress fields that enhance adaptation and thus to test how E. coli bacterial communities adapt to antibiotic stresses. By applying antibiotic and nutrient into inlet channels adjacent to either side of the porous media inoculated with E. coli, a gradient of antibiotic was formed. Hydrogel barriers were selectively photo-polymerized in between of the inlet channels and the porous media to prevent any undesired convection. Hence, chemical solute can only be transported by diffusion, creating a reproducible antibiotic gradient over the porous media. The bacteria were also constrained by the hydrogel boundary barriers from escaping the porous media. Preliminary results suggest that E. coli moves freely with respect to Ciprofloxacin concentrations. In addition, and unexpectedly, the E. coli colonies exhibit a concentric pulsed growth front radiating away from the point of inoculation within the micromodel ecosystem and pulse over the porous media containing antibiotic. The bacteria at the growth front grow into long filaments (up to 100μm) while the bacteria in the inner concentric area are normal size. We hypothesize that the frontier bacteria, which are first

  1. Optofluidic Temperature and Pressure Measurements with Fiber Bragg Gratings Embedded in Microfluidic Devices

    CERN Document Server

    Cooksey, Gregory A

    2016-01-01

    The integration of photonic sensors into microfluidic devices provides opportunities for dynamic measurement of chemical and physical properties of fluids in very small volumes. We previously reported on the use of commercially available Fiber Bragg Gratings (FBGs) and on-chip silicon waveguides for temperature sensing. In this report, we demonstrate the integration of FBGs into easy-to-fabricate microfluidic devices and report on their sensitivity for temperature and pressure measurement in microliter volumes. These sensors present new routes to measurement in microfluidic applications such as small-volume calorimetry and microflow metrology.

  2. Ionic current devices-Recent progress in the merging of electronic, microfluidic, and biomimetic structures.

    Science.gov (United States)

    Koo, Hyung-Jun; Velev, Orlin D

    2013-05-09

    We review the recent progress in the emerging area of devices and circuits operating on the basis of ionic currents. These devices operate at the intersection of electrochemistry, electronics, and microfluidics, and their potential applications are inspired by essential biological processes such as neural transmission. Ionic current rectification has been demonstrated in diode-like devices containing electrolyte solutions, hydrogel, or hydrated nanofilms. More complex functions have been realized in ionic current based transistors, solar cells, and switching memory devices. Microfluidic channels and networks-an intrinsic component of the ionic devices-could play the role of wires and circuits in conventional electronics.

  3. Microfluidic device for cell capture and impedance measurement.

    Science.gov (United States)

    Jang, Ling-Sheng; Wang, Min-How

    2007-10-01

    This work presents a microfluidic device to capture physically single cells within microstructures inside a channel and to measure the impedance of a single HeLa cell (human cervical epithelioid carcinoma) using impedance spectroscopy. The device includes a glass substrate with electrodes and a PDMS channel with micro pillars. The commercial software CFD-ACE+ is used to study the flow of the microstructures in the channel. According to simulation results, the probability of cell capture by three micro pillars is about 10%. An equivalent circuit model of the device is established and fits closely to the experimental results. The circuit can be modeled electrically as cell impedance in parallel with dielectric capacitance and in series with a pair of electrode resistors. The system is operated at low frequency between 1 and 100 kHz. In this study, experiments show that the HeLa cell is successfully captured by the micro pillars and its impedance is measured by impedance spectroscopy. The magnitude of the HeLa cell impedance declines at all operation voltages with frequency because the HeLa cell is capacitive. Additionally, increasing the operation voltage reduces the magnitude of the HeLa cell because a strong electric field may promote the exchange of ions between the cytoplasm and the isotonic solution. Below an operating voltage of 0.9 V, the system impedance response is characteristic of a parallel circuit at under 30 kHz and of a series circuit at between 30 and 100 kHz. The phase of the HeLa cell impedance is characteristic of a series circuit when the operation voltage exceeds 0.8 V because the cell impedance becomes significant.

  4. A new UV-curing elastomeric substrate for rapid prototyping of microfluidic devices

    Science.gov (United States)

    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.

  5. Split and flow: reconfigurable capillary connection for digital microfluidic devices.

    Science.gov (United States)

    Lapierre, Florian; Harnois, Maxime; Coffinier, Yannick; Boukherroub, Rabah; Thomy, Vincent

    2014-09-21

    Supplying liquid to droplet-based microfluidic microsystems remains a delicate task facing the problems of coupling continuous to digital or macro- to microfluidic systems. Here, we take advantage of superhydrophobic microgrids to address this problem. Insertion of a capillary tube inside a microgrid aperture leads to a simple and reconfigurable droplet generation setup.

  6. Burn injury reduces neutrophil directional migration speed in microfluidic devices.

    Directory of Open Access Journals (Sweden)

    Kathryn L Butler

    Full Text Available Thermal injury triggers a fulminant inflammatory cascade that heralds shock, end-organ failure, and ultimately sepsis and death. Emerging evidence points to a critical role for the innate immune system, and several studies had documented concurrent impairment in neutrophil chemotaxis with these post-burn inflammatory changes. While a few studies suggest that a link between neutrophil motility and patient mortality might exist, so far, cumbersome assays have prohibited exploration of the prognostic and diagnostic significance of chemotaxis after burn injury. To address this need, we developed a microfluidic device that is simple to operate and allows for precise and robust measurements of chemotaxis speed and persistence characteristics at single-cell resolution. Using this assay, we established a reference set of migration speed values for neutrophils from healthy subjects. Comparisons with samples from burn patients revealed impaired directional migration speed starting as early as 24 hours after burn injury, reaching a minimum at 72-120 hours, correlated to the size of the burn injury and potentially serving as an early indicator for concurrent infections. Further characterization of neutrophil chemotaxis using this new assay may have important diagnostic implications not only for burn patients but also for patients afflicted by other diseases that compromise neutrophil functions.

  7. Mechanism governing separation in microfluidic pinched flow fractionation devices

    CERN Document Server

    Risbud, Sumedh R

    2014-01-01

    We present a computational investigation of the mechanism governing size-based particle separation in microfluidic pinched flow fractionation. We study the behavior of particles moving through a pinching gap (i.e., a constriction in the aperture of a channel) in the Stokes regime as a function of particle size. The constriction aperture is created by a plane wall and spherical obstacle, and emulates the pinching segment in pinched flow fractionation devices. The simulation results show that the distance of closest approach between the particle and obstacle surfaces (along a trajectory) decreases with increasing particle size. We then use the distance of closest approach to investigate the effect of short-range repulsive non-hydrodynamic interactions (e.g., solid-solid contact). We define a critical trajectory as the one in which the minimum particle-obstacle separation is equal to the range of the non-hydrodynamic interactions. The results further show that the initial offset of the critical trajectory (defin...

  8. A hybrid microfluidic-vacuum device for direct interfacing with conventional cell culture methods.

    Science.gov (United States)

    Chung, Bong Geun; Park, Jeong Won; Hu, Jia Sheng; Huang, Carlos; Monuki, Edwin S; Jeon, Noo Li

    2007-09-20

    Microfluidics is an enabling technology with a number of advantages over traditional tissue culture methods when precise control of cellular microenvironment is required. However, there are a number of practical and technical limitations that impede wider implementation in routine biomedical research. Specialized equipment and protocols required for fabrication and setting up microfluidic experiments present hurdles for routine use by most biology laboratories. We have developed and validated a novel microfluidic device that can directly interface with conventional tissue culture methods to generate and maintain controlled soluble environments in a Petri dish. It incorporates separate sets of fluidic channels and vacuum networks on a single device that allows reversible application of microfluidic gradients onto wet cell culture surfaces. Stable, precise concentration gradients of soluble factors were generated using simple microfluidic channels that were attached to a perfusion system. We successfully demonstrated real-time optical live/dead cell imaging of neural stem cells exposed to a hydrogen peroxide gradient and chemotaxis of metastatic breast cancer cells in a growth factor gradient. This paper describes the design and application of a versatile microfluidic device that can directly interface with conventional cell culture methods. This platform provides a simple yet versatile tool for incorporating the advantages of a microfluidic approach to biological assays without changing established tissue culture protocols.

  9. A hybrid microfluidic-vacuum device for direct interfacing with conventional cell culture methods

    Directory of Open Access Journals (Sweden)

    Monuki Edwin S

    2007-09-01

    Full Text Available Abstract Background Microfluidics is an enabling technology with a number of advantages over traditional tissue culture methods when precise control of cellular microenvironment is required. However, there are a number of practical and technical limitations that impede wider implementation in routine biomedical research. Specialized equipment and protocols required for fabrication and setting up microfluidic experiments present hurdles for routine use by most biology laboratories. Results We have developed and validated a novel microfluidic device that can directly interface with conventional tissue culture methods to generate and maintain controlled soluble environments in a Petri dish. It incorporates separate sets of fluidic channels and vacuum networks on a single device that allows reversible application of microfluidic gradients onto wet cell culture surfaces. Stable, precise concentration gradients of soluble factors were generated using simple microfluidic channels that were attached to a perfusion system. We successfully demonstrated real-time optical live/dead cell imaging of neural stem cells exposed to a hydrogen peroxide gradient and chemotaxis of metastatic breast cancer cells in a growth factor gradient. Conclusion This paper describes the design and application of a versatile microfluidic device that can directly interface with conventional cell culture methods. This platform provides a simple yet versatile tool for incorporating the advantages of a microfluidic approach to biological assays without changing established tissue culture protocols.

  10. Fabrication, Metrology, and Transport Characteristics of Single Polymeric Nanopores in Three-Dimensional Hybrid Microfluidic/Nanofluidic Devices

    Science.gov (United States)

    King, Travis L.

    2009-01-01

    The incorporation of nanofluidic elements between microfluidic channels to form hybrid microfluidic/nanofluidic architectures allows the extension of microfluidic systems into the third dimension, thus removing the constraints imposed by planarity. Measuring and understanding the behavior of these devices creates new analytical challenges due to…

  11. Nanoscale surface modifications to control capillary flow characteristics in PMMA microfluidic devices

    Directory of Open Access Journals (Sweden)

    Mukhopadhyay Subhadeep

    2011-01-01

    Full Text Available Abstract Polymethylmethacrylate (PMMA microfluidic devices have been fabricated using a hot embossing technique to incorporate micro-pillar features on the bottom wall of the device which when combined with either a plasma treatment or the coating of a diamond-like carbon (DLC film presents a range of surface modification profiles. Experimental results presented in detail the surface modifications in the form of distinct changes in the static water contact angle across a range from 44.3 to 81.2 when compared to pristine PMMA surfaces. Additionally, capillary flow of water (dyed to aid visualization through the microfluidic devices was recorded and analyzed to provide comparison data between filling time of a microfluidic chamber and surface modification characteristics, including the effects of surface energy and surface roughness on the microfluidic flow. We have experimentally demonstrated that fluid flow and thus filling time for the microfluidic device was significantly faster for the device with surface modifications that resulted in a lower static contact angle, and also that the incorporation of micro-pillars into a fluidic device increases the filling time when compared to comparative devices.

  12. An investigation of paper based microfluidic devices for size based separation and extraction applications.

    Science.gov (United States)

    Zhong, Z W; Wu, R G; Wang, Z P; Tan, H L

    2015-09-01

    Conventional microfluidic devices are typically complex and expensive. The devices require the use of pneumatic control systems or highly precise pumps to control the flow in the devices. This work investigates an alternative method using paper based microfluidic devices to replace conventional microfluidic devices. Size based separation and extraction experiments conducted were able to separate free dye from a mixed protein and dye solution. Experimental results showed that pure fluorescein isothiocyanate could be separated from a solution of mixed fluorescein isothiocyanate and fluorescein isothiocyanate labeled bovine serum albumin. The analysis readings obtained from a spectrophotometer clearly show that the extracted tartrazine sample did not contain any amount of Blue-BSA, because its absorbance value was 0.000 measured at a wavelength of 590nm, which correlated to Blue-BSA. These demonstrate that paper based microfluidic devices, which are inexpensive and easy to implement, can potentially replace their conventional counterparts by the use of simple geometry designs and the capillary action. These findings will potentially help in future developments of paper based microfluidic devices.

  13. Microfluidic Devices for Behavioral Analysis, Microscopy, and Neuronal Imaging in Caenorhabditis elegans.

    Science.gov (United States)

    Lagoy, Ross C; Albrecht, Dirk R

    2015-01-01

    Microfluidic devices offer several advantages for C. elegans research, particularly for presenting precise physical and chemical environments, immobilizing animals during imaging, quantifying behavior, and automating screens. However, challenges to their widespread adoption in the field include increased complexity over conventional methods, operational problems (such as clogging, leaks, and bubbles), difficulty in obtaining or fabricating devices, and the need to characterize biological results obtained from new assay formats. Here we describe the preparation and operation of simple, reusable microfluidic devices for quantifying behavioral responses to chemical patterns, and single-use devices to arrange animals for time-lapse microscopy and to measure neuronal activity. We focus on details that eliminate or reduce the frustrations commonly experienced by new users of microfluidic devices.

  14. Low-cost rapid prototyping of flexible plastic paper based microfluidic devices

    KAUST Repository

    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.

  15. A guiding light: spectroscopy on digital microfluidic devices using in-plane optical fibre waveguides.

    Science.gov (United States)

    Choi, Kihwan; Mudrik, Jared M; Wheeler, Aaron R

    2015-09-01

    We present a novel method for in-plane digital microfluidic spectroscopy. In this technique, a custom manifold (.stl file available online as ESM) aligns optical fibres with a digital microfluidic device, allowing optical measurements to be made in the plane of the device. Because of the greater width vs thickness of a droplet on-device, the in-plane alignment of this technique allows it to outperform the sensitivity of vertical absorbance measurements on digital microfluidic (DMF) devices by ∼14×. The new system also has greater calibration sensitivity for thymol blue measurements than the popular NanoDrop system by ∼2.5×. The improvements in absorbance sensitivity result from increased path length, as well as from additional effects likely caused by liquid lensing, in which the presence of a water droplet between optical fibres increases fibre-to-fibre transmission of light by ∼2× through refraction and internal reflection. For interrogation of dilute samples, stretching of droplets using digital microfluidic electrodes and adjustment of fibre-to-fibre gap width allows absorbance path length to be changed on-demand. We anticipate this new digital microfluidic optical fibre absorbance and fluorescence measurement system will be useful for a wide variety of analytical applications involving microvolume samples with digital microfluidics.

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

    Directory of Open Access Journals (Sweden)

    Kerstin Ramser

    2012-07-01

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

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

    KAUST Repository

    Perozziello, Gerardo

    2015-12-11

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

  18. Hydrogel microfluidic co-culture device for photothermal therapy and cancer migration.

    Science.gov (United States)

    Lee, Jong Min; Seo, Hye In; Bae, Jun Hyuk; Chung, Bong Geun

    2017-02-07

    We developed the photo-crosslinkable hydrogel microfluidic co-culture device to study photothermal therapy and cancer cell migration. To culture MCF7 human breast carcinoma cells and metastatic U87MG human glioblastoma in the microfluidic device, we used 10 w/v% gelatin methacrylate (GelMA) hydrogels as a semi-permeable physical barrier. We demonstrated the effect of gold nanorod on photothermal therapy of cancer cells in the microfluidic co-culture device. Interestingly, we observed that metastatic U87MG human glioblastoma largely migrated toward vascular endothelial growth factor (VEGF)-treated GelMA hydrogel-embedding microchannels. The main advantage of this hydrogel microfluidic co-culture device is to simultaneously analyze the physiological migration behaviors of two cancer cells with different physiochemical motilities and study gold nanorod-mediated photothermal therapy effect. Therefore, this hydrogel microfluidic co-culture device could be a potentially powerful tool for photothermal therapy and cancer cell migration applications. This article is protected by copyright. All rights reserved.

  19. Integration of a Novel Microfluidic Device with Silicon Light Emitting Diode-Antifuse and Photodetector

    NARCIS (Netherlands)

    LeMinh, P.; Holleman, J.; Berenschot, J.W.; Tas, N.R.; Berg, van den A.

    2002-01-01

    Light emitting diode antifuse has been integrated into a microfluidic device that is realized with extended standard CMOS technological steps. The device comprises of a microchannel sandwiched between a photodiode detector and a nanometer-scale diode antifuse light emitter. In this chapter, the devi

  20. Monolithic Integration of a Novel Microfluidic Device with Silicon Light Emitting Diode-Antifuse and Photodetector

    NARCIS (Netherlands)

    LeMinh, P.; Holleman, J.; Berenschot, J.W.; Tas, N.R.; Berg, van den A.

    2002-01-01

    Light emitting diode antifuse has been integrated into a microfluidic device that is realized with extended standard CMOS technological steps. The device comprises of a microchannel sandwiched between a photodiode detector and a nanometer-scale diode antifuse light emitter. Within this contribution,

  1. Diagnostics for the developing world: microfluidic paper-based analytical devices.

    Science.gov (United States)

    Martinez, Andres W; Phillips, Scott T; Whitesides, George M; Carrilho, Emanuel

    2010-01-01

    Microfluidic paper-based analytical devices (microPADs) are a new class of point-of-care diagnostic devices that are inexpensive, easy to use, and designed specifically for use in developing countries. (To listen to a podcast about this feature, please go to the Analytical Chemistry multimedia page at pubs.acs.org/page/ancham/audio/index.html.).

  2. Cost Effective Paper-Based Colorimetric Microfluidic Devices and Mobile Phone Camera Readers for the Classroom

    Science.gov (United States)

    Koesdjojo, Myra T.; Pengpumkiat, Sumate; Wu, Yuanyuan; Boonloed, Anukul; Huynh, Daniel; Remcho, Thomas P.; Remcho, Vincent T.

    2015-01-01

    We have developed a simple and direct method to fabricate paper-based microfluidic devices that can be used for a wide range of colorimetric assay applications. With these devices, assays can be performed within minutes to allow for quantitative colorimetric analysis by use of a widely accessible iPhone camera and an RGB color reader application…

  3. Fabricating process of hollow out-of-plane Ni microneedle arrays and properties of the integrated microfluidic device

    Science.gov (United States)

    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.

  4. Microfabrication of plastic-PDMS microfluidic devices using polyimide release layer and selective adhesive bonding

    Science.gov (United States)

    Wang, Shuyu; Yu, Shifeng; Lu, Ming; Zuo, Lei

    2017-05-01

    In this paper, we present an improved method to bond poly(dimethylsiloxane) (PDMS) with polyimide (PI) to develop flexible substrate microfluidic devices. The PI film was separately fabricated on a silicon wafer by spin coating followed by thermal treatment to avoid surface unevenness of the flexible substrate. In this way, we could also integrate flexible substrate into standard micro-electromechanical systems (MEMS) fabrication. Meanwhile, the adhesive epoxy was selectively transferred to the PDMS microfluidic device by a stamp-and-stick method to avoid epoxy clogging the microfluidic channels. To spread out the epoxy evenly on the transferring substrate, we used superhydrophilic vanadium oxide film coated glass as the transferring substrate. After the bonding process, the flexible substrate could easily be peeled off from the rigid substrate. Contact angle measurement was used to characterize the hydrophicity of the vanadium oxide film. X-ray photoelectron spectroscopy analysis was conducted to study the surface of the epoxy. We further evaluated the bonding quality by peeling tests, which showed a maximum bonding strength of 100 kPa. By injecting with black ink, the plastic microfluidic device was confirmed to be well bonded with no leakage for a day under 1 atm. This proposed versatile method could bond the microfluidic device and plastic substrate together and be applied in the fabrication of some biosensors and lab-on-a-chip systems.

  5. A review on recent developments for biomolecule separation at analytical scale using microfluidic devices.

    Science.gov (United States)

    Tetala, Kishore K R; Vijayalakshmi, M A

    2016-02-04

    Microfluidic devices with their inherent advantages like the ability to handle 10(-9) to 10(-18) L volume, multiplexing of microchannels, rapid analysis and on-chip detection are proving to be efficient systems in various fields of life sciences. This review highlights articles published since 2010 that reports the use of microfluidic devices to separate biomolecules (DNA, RNA and proteins) using chromatography principles (size, charge, hydrophobicity and affinity) along with microchip capillary electrophoresis, isotachophoresis etc. A detailed overview of stationary phase materials and the approaches to incorporate them within the microchannels of microchips is provided as well as a brief overview of chemical methods to immobilize ligand(s). Furthermore, we review research articles that deal with microfluidic devices as analytical tools for biomolecule (DNA, RNA and protein) separation.

  6. Theory and experiment on resonant frequencies of liquid-air interfaces trapped in microfluidic devices.

    Science.gov (United States)

    Chindam, Chandraprakash; Nama, Nitesh; Ian Lapsley, Michael; Costanzo, Francesco; Jun Huang, Tony

    2013-11-21

    Bubble-based microfluidic devices have been proven to be useful for many biological and chemical studies. These bubble-based microdevices are particularly useful when operated at the trapped bubbles' resonance frequencies. In this work, we present an analytical expression that can be used to predict the resonant frequency of a bubble trapped over an arbitrary shape. Also, the effect of viscosity on the dispersion characteristics of trapped bubbles is determined. A good agreement between experimental data and theoretical results is observed for resonant frequency of bubbles trapped over different-sized rectangular-shaped structures, indicating that our expression can be valuable in determining optimized operational parameters for many bubble-based microfluidic devices. Furthermore, we provide a close estimate for the harmonics and a method to determine the dispersion characteristics of a bubble trapped over circular shapes. Finally, we present a new method to predict fluid properties in microfluidic devices and complement the explanation of acoustic microstreaming.

  7. Latex immunoagglutination assay for bovine viral diarrhea virus utilizing forward light scattering in a microfluidic device

    Science.gov (United States)

    Heinze, Brian C.; Song, Jae-Young; Han, Jin-Hee; Yoon, Jeong-Yeol

    2008-02-01

    We have investigated the utilization of particle agglutination assays using forward light scattering measurements in a microfluidic device towards detecting viral particles. The model viral target was bovine viral diarrhea virus (BVDV). Highly carboxylated polystyrene microspheres (510 nm) were coated with anti-BVDV monoclonal antibodies. This solution was in turn used to detect live modified BVDV. This assay was first performed in a two well slide for proof of concept and then in a simple y-channel microfluidic device with optical fibers arranged in a close proximity setup. Particle immunoagglutination was detected through static light scattering measurements taken at 45° to incident light. In the microfluidic device, modified live BVDV was detected with a detection limit of 0.5 TCID 50 mL -1.

  8. Tunable Microfluidic Devices for Hydrodynamic Fractionation of Cells and Beads: A Review

    Directory of Open Access Journals (Sweden)

    Jafar Alvankarian

    2015-11-01

    Full Text Available The adjustable microfluidic devices that have been developed for hydrodynamic-based fractionation of beads and cells are important for fast performance tunability through interaction of mechanical properties of particles in fluid flow and mechanically flexible microstructures. In this review, the research works reported on fabrication and testing of the tunable elastomeric microfluidic devices for applications such as separation, filtration, isolation, and trapping of single or bulk of microbeads or cells are discussed. Such microfluidic systems for rapid performance alteration are classified in two groups of bulk deformation of microdevices using external mechanical forces, and local deformation of microstructures using flexible membrane by pneumatic pressure. The main advantage of membrane-based tunable systems has been addressed to be the high capability of integration with other microdevice components. The stretchable devices based on bulk deformation of microstructures have in common advantage of simplicity in design and fabrication process.

  9. Stimulus-active polymer actuators for next-generation microfluidic devices

    Science.gov (United States)

    Hilber, Wolfgang

    2016-08-01

    Microfluidic devices have not yet evolved into commercial off-the-shelf products. Although highly integrated microfluidic structures, also known as lab-on-a-chip (LOC) and micrototal-analysis-system (µTAS) devices, have consistently been predicted to revolutionize biomedical assays and chemical synthesis, they have not entered the market as expected. Studies have identified a lack of standardization and integration as the main obstacles to commercial breakthrough. Soft microfluidics, the utilization of a broad spectrum of soft materials (i.e., polymers) for realization of microfluidic components, will make a significant contribution to the proclaimed growth of the LOC market. Recent advances in polymer science developing novel stimulus-active soft-matter materials may further increase the popularity and spreading of soft microfluidics. Stimulus-active polymers and composite materials change shape or exert mechanical force on surrounding fluids in response to electric, magnetic, light, thermal, or water/solvent stimuli. Specifically devised actuators based on these materials may have the potential to facilitate integration significantly and hence increase the operational advantage for the end-user while retaining cost-effectiveness and ease of fabrication. This review gives an overview of available actuation concepts that are based on functional polymers and points out promising concepts and trends that may have the potential to promote the commercial success of microfluidics.

  10. Printable microfluidic systems using pressure sensitive adhesive material for biosensing devices.

    Science.gov (United States)

    Wang, Xin; Nilsson, David; Norberg, Petronella

    2013-09-01

    In biosensors with a fluid analyte, the integration of a microfluidic system, which guides the analyte into the sensing area, is critical. Quicker and economical ways to build up microfluidic systems will make point of care diagnostics viable. Printing is a low-cost technology that is increasingly used in emerging organic and flexible electronics and biosensors. In this paper, we present printed fluidic systems on flexible substrates made with pressure sensitive adhesive materials. Printable pressure sensitive adhesive materials have been used for making microfluidic systems. Flexible substrates have been used, and two types of adhesive materials, one thermally dried and another UV curable, have been tested. Top sealing layer was laminated directly on top of the printed microfluidic structure. Flow tests were done with deionized water. Flow tests with deionized water show that both adhesive materials are suitable for capillary flow driven fluidic devices. Flow test using water as dielectric material was also done successfully on a printed electrolyte gated organic field effect transistor with an integrated microfluidic system. Due to its ease of process and low cost, printed microfluidic system is believed to find more applications in biosensing devices. This article is part of a Special Issue entitled Organic Bioelectronics-Novel Applications in Biomedicine. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Monolayer-functionalized microfluidics devices for optical sensing of acidity

    NARCIS (Netherlands)

    Mela, P.; Onclin, S.; Goedbloed, M.H.; Levi, S.; Garcia-Parajo, M.F.; Hulst, van N.F.; Ravoo, B.J.; Reinhoudt, D.N.; Berg, van den A.

    2005-01-01

    This paper describes the integration of opto-chemosensors in microfluidics networks. Our technique exploits the internal surface of the network as a platform to build a sensing system by coating the surface with a self-assembled monolayer and subsequently binding a fluorescent sensing molecule to th

  12. A microfluidic device with fluorimetric detection for intracellular components analysis

    DEFF Research Database (Denmark)

    Kwapiszewski, Radosław; Skolimowski, Maciej; Ziółkowska, Karina

    2011-01-01

    An integrated microfluidic system that coupled lysis of two cell lines: L929 fibroblasts and A549 epithelial cells, with fluorescence-based enzyme assay was developed to determine β-glucocerebrosidase activity. The microdevice fabricated in poly(dimethylsiloxane) consists of three main parts: a c...

  13. Fabrication of a Paper-Based Microfluidic Device to Readily Determine Nitrite Ion Concentration by Simple Colorimetric Assay

    Science.gov (United States)

    Wang, Bo; Lin, Zhiqiang; Wang, Min

    2015-01-01

    Paper-based microfluidic devices (µPAD) are a burgeoning platform of microfluidic analysis technology. The method described herein is for use in undergraduate and high school chemistry laboratories. A simple and convenient µPAD was fabricated by easy patterning of filter paper using a permanent marker pen. The usefulness of the device was…

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

    Science.gov (United States)

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

    2012-05-07

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

  15. Solvent-resistant photocurable liquid fluoropolymers for microfluidic device fabrication [corrected].

    Science.gov (United States)

    Rolland, Jason P; Van Dam, R Michael; Schorzman, Derek A; Quake, Stephen R; DeSimone, Joseph M

    2004-03-01

    We report the first fabrication of a solvent-compatible microfluidic device based on photocurable "Liquid Teflon" materials. The materials are highly fluorinated functionalized perfluoropolyethers (PFPEs) that have liquidlike viscosities that can be cured into tough, highly durable elastomers that exhibit the remarkable chemical resistance of fluoropolymers such as Teflon. Poly(dimethylsiloxane) (PDMS) elastomers have rapidly become the material of choice for many recent microfluidic device applications. Despite the advantages of PDMS in relation to microfluidics technology, the material suffers from a serious drawback in that it swells in most organic solvents. The swelling of PDMS-based devices in organic solvents greatly disrupts the micrometer-sized features and makes it impossible for fluids to flow inside the channels. Our approach to this problem has been to replace PDMS with photocurable perfluoropolyethers. Device fabrication and valve actuation were accomplished using established procedures for PDMS devices. The additional advantage of photocuring allows fabrication time to be decreased from several hours to a matter of minutes. The PFPE-based device exhibited mechanical properties similar to those of Sylgard 184 before and after curing as well as remarkable resistance to organic solvents. This work has the potential to expand the field of microfluidics to many novel applications.

  16. An inkjet-printed microfluidic device for liquid-liquid extraction.

    Science.gov (United States)

    Watanabe, Masashi

    2011-04-01

    A microfluidic device for liquid-liquid extraction was quickly produced using an office inkjet printer. An advantage of this method is that normal end users, who are not familiar with microfabrication, can produce their original microfluidic devices by themselves. In this method, the printer draws a line on a hydrophobic and oil repellent surface using hydrophilic ink. This line directs a fluid, such as water or xylene, to form a microchannel along the printed line. Using such channels, liquid-liquid extraction was successfully performed under concurrent and countercurrent flow conditions.

  17. Microfluidic Device to Quantify the Behavior of Therapeutic Bacteria in Three-Dimensional Tumor Tissue

    Science.gov (United States)

    Brackett, Emily L.; Swofford, Charles A.; Forbes, Neil S.

    2016-01-01

    Summary Microfluidic devices enable precise quantification of the interactions between anticancer bacteria and tumor tissue. Direct observation of bacterial movement and gene expression in tissue is not possible with either monolayers of cells or tumor-bearing mice. Quantification of these interactions is necessary to understand the inherent mechanisms of bacterial targeting and to develop modified organisms with enhanced therapeutic properties. Here we describe the procedures for designing, printing and assembling microfluidic tumor-on-a-chip devices. We also describe the procedures for inserting three- dimensional tumor-cell masses, exposing to bacteria, and analyzing the resultant images. PMID:26846800

  18. The effects of heat treatment on microfluidic devices fabricated in silica glass by femtosecond lasers

    Institute of Scientific and Technical Information of China (English)

    Li Yan; Qu Shi-Liang

    2012-01-01

    We fabricated complex microfluidic devices in silica glass by water-assisted femtosecond laser ablation and sub-sequent heat treatment.The experimental results show that after heat treatment,the diameter of the microchannels is significantly reduced and the internal surface roughness is improved.The diameters of the fabricated microchannels can be modulated by changing the annealing temperature and the annealing time.During annealing,the temperature affects the diameter and shape of the protrusions in microfluidic devices very strongly,and these changes are mainly caused by uniform expansion and the action of surface tension.

  19. Microfluidic-optical integrated CMOS compatible devices for label-free biochemical sensing

    Science.gov (United States)

    Blanco, F. J.; Agirregabiria, M.; Berganzo, J.; Mayora, K.; Elizalde, J.; Calle, A.; Dominguez, C.; Lechuga, L. M.

    2006-05-01

    The fabrication, characterization and packaging of novel microfluidic-optical integrated biosensors for label-free biochemical detection is presented in this paper. The integrated device consists of a three-dimensional embedded microchannel network fabricated using enhanced CMOS compatible SU-8 multilevel polymer technology on top of a wafer containing Mach-Zehnder Interferometer (MZI) nanophotonic biosensor devices. PMMA housing provides connection to the macro-world and ensures robust leakage-free flow operation of the devices. This macro-microfluidic module can operate at pressure drops up to 1000 kPa. Fluid flow experiments have been performed in order to demonstrate the robustness of our microfluidic devices. The devices have been designed to operate under continuous flow. Steady-state flow rates ranging from 1 to 100 µl min-1 at pressure drops ranging from 10 to 500 kPa were measured in the laminar flow regime. Experimental results are in good agreement with laminar flow theory. The first interferometric sensing measurements are presented in order to demonstrate the functionality of these novel integrated devices for lab-on-a-chip and label-free biosensing applications. A bulk refractive index detection limit of 3.8 × 10-6 was obtained, close to the minimum detected up to now by label-free biosensor devices without microfluidic integration. As far as we know, this is the first time that a label-free biosensor device is integrated within a microfluidic network using a wafer-level CMOS compatible process technology.

  20. Fluid Flow Shear Stress Stimulation on a Multiplex Microfluidic Device for Rat Bone Marrow Stromal Cell Differentiation Enhancement

    Directory of Open Access Journals (Sweden)

    Chia-Wen Tsao

    2015-12-01

    Full Text Available Microfluidic devices provide low sample consumption, high throughput, high integration, and good environment controllability advantages. An alternative to conventional bioreactors, microfluidic devices are a simple and effective platform for stem cell investigations. In this study, we describe the design of a microfluidic device as a chemical and mechanical shear stress bioreactor to stimulate rat bone marrow stromal cells (rBMSCs into neuronal cells. 1-methyl-3-isobutylxanthine (IBMX was used as a chemical reagent to induce rBMSCs differentiation into neurons. Furthermore, the shear stress applied to rBMSCs was generated by laminar microflow in the microchannel. Four parallel microfluidic chambers were designed to provide a multiplex culture platform, and both the microfluidic chamber-to-chamber, as well as microfluidic device-to-device, culture stability were evaluated. Our research shows that rBMSCs were uniformly cultured in the microfluidic device and differentiated into neuronal cells with IBMX induction. A three-fold increase in the neuronal cell differentiation ratio was noted when rBMSCs were subjected to both IBMX and fluid flow shear stress stimulation. Here, we propose a microfluidic device which is capable of providing chemical and physical stimulation, and could accelerate neuronal cell differentiation from bone marrow stromal cells.

  1. Micromilling: a method for ultra-rapid prototyping of plastic microfluidic devices.

    Science.gov (United States)

    Guckenberger, David J; de Groot, Theodorus E; Wan, Alwin M D; Beebe, David J; Young, Edmond W K

    2015-06-07

    This tutorial review offers protocols, tips, insight, and considerations for practitioners interested in using micromilling to create microfluidic devices. The objective is to provide a potential user with information to guide them on whether micromilling would fill a specific need within their overall fabrication strategy. Comparisons are made between micromilling and other common fabrication methods for plastics in terms of technical capabilities and cost. The main discussion focuses on "how-to" aspects of micromilling, to enable a user to select proper equipment and tools, and obtain usable microfluidic parts with minimal start-up time and effort. The supplementary information provides more extensive discussion on CNC mill setup, alignment, and programming. We aim to reach an audience with minimal prior experience in milling, but with strong interests in fabrication of microfluidic devices.

  2. Microfluidic Device for Controllable Chemical Release via Field-Actuated Membrane Incorporating Nanoparticles

    KAUST Repository

    Wang, Xiang

    2013-01-01

    We report a robust magnetic-membrane-based microfluidic platform for controllable chemical release. The magnetic membrane was prepared by mixing polydimethylsiloxane (PDMS) and carbonyl-iron nanoparticles together to obtain a flexible thin film. With combined, simultaneous regulation of magnetic stimulus and mechanical pumping, the desired chemical release rate can easily be realized. For example, the dose release experimental data was well fitted by a mathematical sigmoidal model, exhibiting a typical dose-response relationship, which shows promise in providing significant guidance for on-demand drug delivery. To test the platform’s feasibility, our microfluidic device was employed in an experiment involving Escherichia coli culture under controlled antibiotic ciprofloxacin exposure, and the expected outcomes were successfully obtained. Our experimental results indicate that such a microfluidic device, with high accuracy and easy manipulation properties, can legitimately be characterized as active chemical release system.

  3. Flash μ-fluidics: a rapid prototyping method for fabricating microfluidic devices

    KAUST Repository

    Buttner, Ulrich

    2016-08-01

    Microfluidics has advanced in terms of design and structures; however, fabrication methods are time-consuming or expensive relative to facility costs and equipment needed. This work demonstrates a fast and economically viable 2D/3D maskless digital light-projection method based on a stereolithography process. Unlike other fabrication methods, one exposure step is used to form the whole device. Flash microfluidics is achieved by incorporating bonding and channel fabrication of complex structures in just 2.5 s to 4 s and by fabricating channel heights between 25 μm and 150 μm with photopolymer resin. The features of this fabrication technique, such as time and cost saving and easy fabrication, are used to build devices that are mostly needed in microfluidic/lab-on-chip systems. Due to the fast production method and low initial setup costs, the process could be used for point of care applications. © 2016 The Royal Society of Chemistry.

  4. Microfluidic Device for Controllable Chemical Release via Field-Actuated Membrane Incorporating Nanoparticles

    Directory of Open Access Journals (Sweden)

    Xiang Wang

    2013-01-01

    Full Text Available We report a robust magnetic-membrane-based microfluidic platform for controllable chemical release. The magnetic membrane was prepared by mixing polydimethylsiloxane (PDMS and carbonyl-iron nanoparticles together to obtain a flexible thin film. With combined, simultaneous regulation of magnetic stimulus and mechanical pumping, the desired chemical release rate can easily be realized. For example, the dose release experimental data was well fitted by a mathematical sigmoidal model, exhibiting a typical dose-response relationship, which shows promise in providing significant guidance for on-demand drug delivery. To test the platform’s feasibility, our microfluidic device was employed in an experiment involving Escherichia coli culture under controlled antibiotic ciprofloxacin exposure, and the expected outcomes were successfully obtained. Our experimental results indicate that such a microfluidic device, with high accuracy and easy manipulation properties, can legitimately be characterized as active chemical release system.

  5. UV-nanoimprint lithography as a tool to develop flexible microfluidic devices for electrochemical detection.

    Science.gov (United States)

    Chen, Juhong; Zhou, Yiliang; Wang, Danhui; He, Fei; Rotello, Vincent M; Carter, Kenneth R; Watkins, James J; Nugen, Sam R

    2015-07-21

    Research in microfluidic biosensors has led to dramatic improvements in sensitivities. Very few examples of these devices have been commercially successful, keeping this methodology out of the hands of potential users. In this study, we developed a method to fabricate a flexible microfluidic device containing electrowetting valves and electrochemical transduction. The device was designed to be amenable to a roll-to-roll manufacturing system, allowing a low manufacturing cost. Microchannels with high fidelity were structured on a PET film using UV-NanoImprint Lithography (UV-NIL). The electrodes were inkjet-printed and photonically sintered on second flexible PET film. The film containing electrodes was bonded directly to the channel-containing layer to form sealed fluidic device. Actuation of the multivalve system with food dye in PBS buffer was performed to demonstrate automated fluid delivery. The device was then used to detect Salmonella in a liquid sample.

  6. Continuous flow synthesis of nanoparticles using ceramic microfluidic devices.

    Science.gov (United States)

    Gómez-de Pedro, S; Puyol, M; Alonso-Chamarro, J

    2010-10-15

    A microfluidic system based on the low-temperature co-fired ceramics technology (LTCC) is proposed to reproducibly carry out a simple one-phase synthesis and functionalization of monodispersed gold nanoparticles. It takes advantage of the LTCC technology, offering a fast prototyping without the need to use sophisticated facilities, reducing significantly the cost and production time of microfluidic systems. Some other interesting advantages of the ceramic materials compared to glass, silicon or polymers are their versatility and chemical resistivity. The technology enables the construction of multilayered systems, which can integrate other mechanical, electronic and fluidic components in a single substrate. This approach allows rapid, easy, low cost and automated synthesis of the gold colloidal, thus it becomes a useful approach in the progression from laboratory scale to pilot-line scale processes, which is currently demanded.

  7. Microfluidics & nanotechnology: Towards fully integrated analytical devices for the detection of cancer biomarkers

    KAUST Repository

    Perozziello, Gerardo

    2014-01-01

    In this paper, we describe an innovative modular microfluidic platform allowing filtering, concentration and analysis of peptides from a complex mixture. The platform is composed of a microfluidic filtering device and a superhydrophobic surface integrating surface enhanced Raman scattering (SERS) sensors. The microfluidic device was used to filter specific peptides (MW 1553.73 D) derived from the BRCA1 protein, a tumor-suppressor molecule which plays a pivotal role in the development of breast cancers, from albumin (66.5 KD), the most represented protein in human plasma. The filtering process consisted of driving the complex mixture through a porous membrane having a cut-off of 12-14 kD by hydrodynamic flow. The filtered samples coming out of the microfluidic device were subsequently deposited on a superhydrophobic surface formed by micro pillars on top of which nanograins were fabricated. The nanograins coupled to a Raman spectroscopy instrument acted as a SERS sensor and allowed analysis of the filtered sample on top of the surface once it evaporated. By using the presented platform, we demonstrate being able to sort small peptides from bigger proteins and to detect them by using a label-free technique at a resolution down to 0.1 ng μL-1. The combination of microfluidics and nanotechnology to develop the presented microfluidic platform may give rise to a new generation of biosensors capable of detecting low concentration samples from complex mixtures without the need for any sample pretreatment or labelling. The developed devices could have future applications in the field of early diagnosis of severe illnesses, e.g. early cancer detection. This journal is

  8. Manufacturing and testing flexible microfluidic devices with optical and electrical detection mechanisms

    NARCIS (Netherlands)

    Ivan, M.G.; Vivet, F.; Meinders, E.R.

    2010-01-01

    Flexible microfluidic devices made of poly(dimethylsiloxane) (PDMS) were manufactured by soft lithography, and tested in detection of ionic species using optical absorption spectroscopy and electrical measurements. PDMS was chosen due to its flexibility and ease of surface modification by exposure

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

    Science.gov (United States)

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

    2014-01-01

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

  10. A Supramolecular Sensing Platform for Phosphate Anions and an Anthrax Biomarker in a Microfluidic Device

    NARCIS (Netherlands)

    Eker, Bilge; Yilmaz, Mahmut Deniz; Schlautmann, Stefan; Gardeniers, Johannes G.E.; Huskens, Jurriaan

    2011-01-01

    A supramolecular platform based on self-assembled monolayers (SAMs) has been implemented in a microfluidic device. The system has been applied for the sensing of two different analyte types: biologically relevant phosphate anions and aromatic carboxylic acids, which are important for anthrax detecti

  11. A serial sample loading system: interfacing multiwell plates with microfluidic devices.

    Science.gov (United States)

    Rane, Tushar D; Zec, Helena C; Wang, Tza-Huei

    2012-10-01

    There is an increasing demand for novel high-throughput screening (HTS) technologies in the pharmaceutical and biotechnological industries. The robotic sample-handling techniques currently used in these industries, although fast, are still limited to operating in multiwell plates with the sample volumes per reaction in the microliter regime. Digital microfluidics offers an alternative for reduction in sample volume consumption for HTS but lacks a reliable technique for transporting a large number of samples to the microfluidic device. In this report, we develop a technique for serial delivery of sample arrays to a microfluidic device from multiwell plates, through a single sample inlet. Under this approach, a serial array of sample plugs, separated by an immiscible carrier fluid, is loaded into a capillary and delivered to a microfluidic device. Similar approaches have been attempted in the past, however, either with a slower sample loading device such as a syringe pump or vacuum-based sample loading with limited driving pressure. We demonstrated the application of our positive-pressure-based serial sample loading (SSL) system to load a series of sample plugs into a capillary. The adaptability of the SSL system to generate sample plugs with a variety of volumes in a predictable manner was also demonstrated.

  12. A Supramolecular Sensing Platform for Phosphate Anions and an Anthrax Biomarker in a Microfluidic Device

    NARCIS (Netherlands)

    Eker, B.; Yilmaz, M.D.; Schlautmann, Stefan; Gardeniers, Johannes G.E.; Huskens, Jurriaan

    2011-01-01

    A supramolecular platform based on self-assembled monolayers (SAMs) has been implemented in a microfluidic device. The system has been applied for the sensing of two different analyte types: biologically relevant phosphate anions and aromatic carboxylic acids, which are important for anthrax detecti

  13. Student-Fabricated Microfluidic Devices as Flow Reactors for Organic and Inorganic Synthesis

    Science.gov (United States)

    Feng, Z. Vivian; Edelman, Kate R.; Swanson, Benjamin P.

    2015-01-01

    Flow synthesis in microfluidic devices has been rapidly adapted in the pharmaceutical industry and in many research laboratories. Yet, the cost of commercial flow reactors is a major factor limiting the dissemination of this technology in the undergraduate curriculum. Here, we present a laboratory activity where students design and fabricate…

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  15. Characterization of microfluidic components for low-cost point-of-care devices

    CSIR Research Space (South Africa)

    Hugo, S

    2013-10-01

    Full Text Available This paper presents the characterization of microfluidic components for the realization of low-cost point-of-care diagnostic devices, with focus on full blood count applications. Increasing emphasis is being placed on low-cost point...

  16. Manufacturing and testing flexible microfluidic devices with optical and electrical detection mechanisms

    NARCIS (Netherlands)

    Ivan, M.G.; Vivet, F.; Meinders, E.R.

    2010-01-01

    Flexible microfluidic devices made of poly(dimethylsiloxane) (PDMS) were manufactured by soft lithography, and tested in detection of ionic species using optical absorption spectroscopy and electrical measurements. PDMS was chosen due to its flexibility and ease of surface modification by exposure t

  17. Student-Fabricated Microfluidic Devices as Flow Reactors for Organic and Inorganic Synthesis

    Science.gov (United States)

    Feng, Z. Vivian; Edelman, Kate R.; Swanson, Benjamin P.

    2015-01-01

    Flow synthesis in microfluidic devices has been rapidly adapted in the pharmaceutical industry and in many research laboratories. Yet, the cost of commercial flow reactors is a major factor limiting the dissemination of this technology in the undergraduate curriculum. Here, we present a laboratory activity where students design and fabricate…

  18. Integrated Microfluidic Devices for Automated Microarray-Based Gene Expression and Genotyping Analysis

    Science.gov (United States)

    Liu, Robin H.; Lodes, Mike; Fuji, H. Sho; Danley, David; McShea, Andrew

    Microarray assays typically involve multistage sample processing and fluidic handling, which are generally labor-intensive and time-consuming. Automation of these processes would improve robustness, reduce run-to-run and operator-to-operator variation, and reduce costs. In this chapter, a fully integrated and self-contained microfluidic biochip device that has been developed to automate the fluidic handling steps for microarray-based gene expression or genotyping analysis is presented. The device consists of a semiconductor-based CustomArray® chip with 12,000 features and a microfluidic cartridge. The CustomArray was manufactured using a semiconductor-based in situ synthesis technology. The micro-fluidic cartridge consists of microfluidic pumps, mixers, valves, fluid channels, and reagent storage chambers. Microarray hybridization and subsequent fluidic handling and reactions (including a number of washing and labeling steps) were performed in this fully automated and miniature device before fluorescent image scanning of the microarray chip. Electrochemical micropumps were integrated in the cartridge to provide pumping of liquid solutions. A micromixing technique based on gas bubbling generated by electrochemical micropumps was developed. Low-cost check valves were implemented in the cartridge to prevent cross-talk of the stored reagents. Gene expression study of the human leukemia cell line (K562) and genotyping detection and sequencing of influenza A subtypes have been demonstrated using this integrated biochip platform. For gene expression assays, the microfluidic CustomArray device detected sample RNAs with a concentration as low as 0.375 pM. Detection was quantitative over more than three orders of magnitude. Experiment also showed that chip-to-chip variability was low indicating that the integrated microfluidic devices eliminate manual fluidic handling steps that can be a significant source of variability in genomic analysis. The genotyping results showed

  19. Biomedical microfluidic devices by using low-cost fabrication techniques: A review.

    Science.gov (United States)

    Faustino, Vera; Catarino, Susana O; Lima, Rui; Minas, Graça

    2016-07-26

    One of the most popular methods to fabricate biomedical microfluidic devices is by using a soft-lithography technique. However, the fabrication of the moulds to produce microfluidic devices, such as SU-8 moulds, usually requires a cleanroom environment that can be quite costly. Therefore, many efforts have been made to develop low-cost alternatives for the fabrication of microstructures, avoiding the use of cleanroom facilities. Recently, low-cost techniques without cleanroom facilities that feature aspect ratios more than 20, for fabricating those SU-8 moulds have been gaining popularity among biomedical research community. In those techniques, Ultraviolet (UV) exposure equipment, commonly used in the Printed Circuit Board (PCB) industry, replaces the more expensive and less available Mask Aligner that has been used in the last 15 years for SU-8 patterning. Alternatively, non-lithographic low-cost techniques, due to their ability for large-scale production, have increased the interest of the industrial and research community to develop simple, rapid and low-cost microfluidic structures. These alternative techniques include Print and Peel methods (PAP), laserjet, solid ink, cutting plotters or micromilling, that use equipment available in almost all laboratories and offices. An example is the xurography technique that uses a cutting plotter machine and adhesive vinyl films to generate the master moulds to fabricate microfluidic channels. In this review, we present a selection of the most recent lithographic and non-lithographic low-cost techniques to fabricate microfluidic structures, focused on the features and limitations of each technique. Only microfabrication methods that do not require the use of cleanrooms are considered. Additionally, potential applications of these microfluidic devices in biomedical engineering are presented with some illustrative examples.

  20. Computationally Informed Design of a Multi-Axial Actuated Microfluidic Chip Device.

    Science.gov (United States)

    Gizzi, Alessio; Giannitelli, Sara Maria; Trombetta, Marcella; Cherubini, Christian; Filippi, Simonetta; De Ninno, Adele; Businaro, Luca; Gerardino, Annamaria; Rainer, Alberto

    2017-07-14

    This paper describes the computationally informed design and experimental validation of a microfluidic chip device with multi-axial stretching capabilities. The device, based on PDMS soft-lithography, consisted of a thin porous membrane, mounted between two fluidic compartments, and tensioned via a set of vacuum-driven actuators. A finite element analysis solver implementing a set of different nonlinear elastic and hyperelastic material models was used to drive the design and optimization of chip geometry and to investigate the resulting deformation patterns under multi-axial loading. Computational results were cross-validated by experimental testing of prototypal devices featuring the in silico optimized geometry. The proposed methodology represents a suite of computationally handy simulation tools that might find application in the design and in silico mechanical characterization of a wide range of stretchable microfluidic devices.

  1. Single cell analysis of yeast replicative aging using a new generation of microfluidic device.

    Directory of Open Access Journals (Sweden)

    Yi Zhang

    Full Text Available A major limitation to yeast aging study has been the inability to track mother cells and observe molecular markers during the aging process. The traditional lifespan assay relies on manual micro-manipulation to remove daughter cells from the mother, which is laborious, time consuming, and does not allow long term tracking with high resolution microscopy. Recently, we have developed a microfluidic system capable of retaining mother cells in the microfluidic chambers while removing daughter cells automatically, making it possible to observe fluorescent reporters in single cells throughout their lifespan. Here we report the development of a new generation of microfluidic device that overcomes several limitations of the previous system, making it easier to fabricate and operate, and allowing functions not possible with the previous design. The basic unit of the device consists of microfluidic channels with pensile columns that can physically trap the mother cells while allowing the removal of daughter cells automatically by the flow of the fresh media. The whole microfluidic device contains multiple independent units operating in parallel, allowing simultaneous analysis of multiple strains. Using this system, we have reproduced the lifespan curves for the known long and short-lived mutants, demonstrating the power of the device for automated lifespan measurement. Following fluorescent reporters in single mother cells throughout their lifespan, we discovered a surprising change of expression of the translation elongation factor TEF2 during aging, suggesting altered translational control in aged mother cells. Utilizing the capability of the new device to trap mother-daughter pairs, we analyzed mother-daughter inheritance and found age dependent asymmetric partitioning of a general stress response reporter between mother and daughter cells.

  2. Hot Roller Embossing for the Creation of Microfluidic Devices

    CERN Document Server

    Ng, Sum Huan

    2008-01-01

    We report on the hot roller embossing of polymer sheets for the creation of microfluidic structures. Measurements conducted on 100 $\\mu$m features showed that the lateral dimensions could be replicated to within 2% tolerance, while over 85% of mould depth was embossed. Feature sizes down to 50 $\\mu$m and feature depths up to 30 $\\mu$m had been achieved. At lower temperatures, asymmetric pile up of polymer material outside embossed regions was observed with higher pile up occurring on the trailing side of the embossed regions.

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

    Science.gov (United States)

    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.

  4. A portable and power-free microfluidic device for rapid and sensitive lead (Pb2+) detection.

    Science.gov (United States)

    Fan, Chunhui; He, Shijiang; Liu, Gang; Wang, Lianhui; Song, Shiping

    2012-01-01

    A portable and power-free microfluidic device was designed for rapid and sensitive detection of lead (Pb(2+)). 11-mercaptoundecanoic acid (MUA)-functionalized gold nanoparticles (MUA-AuNPs) aggregated in the presence of Pb(2+) for the chelation mechanism. When we performed this analysis on a polydimethylsiloxane (PDMS) microfluidic chip, the aggregations deposited onto the surface of chip and formed dark lines along the laminar flows in the zigzag microchannels. This visual result can be observed by the naked eye through a microscope or just a drop of water as a magnifier. Ten μM Pb(2+) was successfully detected.

  5. SU-8 as Hydrophobic and Dielectric Thin Film in Electrowetting-on-Dielectric Based Microfluidics Device

    OpenAIRE

    Vijay Kumar; N. N. Sharma

    2012-01-01

    Electrowetting-on-dielectric (EWOD) based droplet actuation in microfluidic chip is designed and fabricated. EWOD is used as on-chip micro-pumping scheme for moving fluid digitally in Lab-on-a-chip devices. For enabling this scheme, stacked deposition of thin dielectric and hydrophobic layer in that order between microchannel and electrodes is done. The present paper investigates the potential use of SU-8 as hydrophobic layer in conjunction of acting as dielectric in the device. The objective...

  6. Photoinitiated grafting of porous polymer monoliths and thermoplastic polymers for microfluidic devices

    Science.gov (United States)

    Frechet, Jean M. J.; Svec, Frantisek; Rohr, Thomas

    2008-10-07

    A microfluidic device preferably made of a thermoplastic polymer that includes a channel or a multiplicity of channels whose surfaces are modified by photografting. The device further includes a porous polymer monolith prepared via UV initiated polymerization within the channel, and functionalization of the pore surface of the monolith using photografting. Processes for making such surface modifications of thermoplastic polymers and porous polymer monoliths are set forth.

  7. Demonstration of an integrated electroactive polymer actuator on a microfluidic electrophoresis device.

    Science.gov (United States)

    Price, Alexander K; Anderson, Kristen M; Culbertson, Christopher T

    2009-07-21

    The construction of microfluidic devices from siloxane-based polymers is widely reported in the current literature. While the use of these materials is primarily due to their rapid and facile fabrication, low cost and robustness, they also have the ability to function as smart materials. This feature, however, has not been commonly exploited in conjunction with their fluid-handling capabilities. Siloxanes are considered smart materials because their shapes can be modified in the presence of an electric field. The energy in the electric field can be transduced into mechanical energy and directly coupled with a microfabricated channel network in order to affect or initiate the movement of fluids. Here, we present a novel microfluidic device into which an electroactive polymer (EAP) actuation unit is integrated. The EAP actuation unit features a microfluidic channel placed above a patterned electrode. The patterned electrode is insulated from the channel by an EAP layer that is composed of PDMS. When a potential is applied across the EAP layer, it changes shape, which also changes the volume of the microfluidic channel above it. With this proof-of-concept device we demonstrated the ability to inject plugs of sample on a standard electrophoresis cross chip solely by changing the magnitude of the electric field between the channel and the electrode. Using an EAP actuation unit, the size of the injection plugs can be varied as a function of the electric field, the active area of the EAP actuation unit and the softness of the EAP.

  8. Generation of emulsion droplets and micro-bubbles in microfluidic devices

    KAUST Repository

    Zhang, Jiaming

    2016-04-01

    Droplet-based microfluidic devices have become a preferred versatile platform for various fields in physics, chemistry and biology to manipulate small amounts of liquid samples. In addition to microdroplets, microbubbles are also needed for various pro- cesses in the food, healthcare and cosmetic industries. Polydimethylsiloxane (PDMS) soft lithography, the mainstay for fabricating microfluidic devices, usually requires the usage of expensive apparatus and a complex manufacturing procedure. In ad- dition, current methods have the limited capabilities for fabrication of microfluidic devices within three dimensional (3D) structures. Novel methods for fabrication of droplet-based microfluidic devices for the generation microdroplets and microbubbles are therefore of great interest in current research. In this thesis, we have developed several simple, rapid and low-cost methods for fabrication of microfluidic devices, especially for generation of microdroplets and mi- crobubbles. We first report an inexpensive full-glass microfluidic devices with as- sembly of glass capillaries, for generating monodisperse multiple emulsions. Different types of devices have been designed and tested and the experimental results demon- strated the robust capability of preparing monodisperse single, double, triple and multi-component emulsions. Second, we propose a similar full-glass device for generation of microbubbles, but with assembly of a much smaller nozzle of a glass capillary. Highly monodisperse microbubbles with diameter range from 3.5 to 60 microns have been successfully produced, at rates up to 40 kHz. A simple scaling law based on the capillary number and liquid-to-gas flow rate ratio, successfully predicts the bubble size. Recently, the emergent 3D printing technology provides an attractive fabrication technique, due to its simplicity and low cost. A handful of studies have already demonstrated droplet production through 3D-printed microfluidic devices. However, two

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

    OpenAIRE

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

    2001-01-01

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

  10. HistoFlex--a microfluidic device providing uniform flow conditions enabling highly sensitive, reproducible and quantitative in situ hybridizations.

    Science.gov (United States)

    Søe, Martin Jensen; Okkels, Fridolin; Sabourin, David; Alberti, Massimo; Holmstrøm, Kim; Dufva, Martin

    2011-11-21

    A microfluidic device (the HistoFlex) designed to perform and monitor molecular biological assays under dynamic flow conditions on microscope slide-substrates, with special emphasis on analyzing histological tissue sections, is presented. Microscope slides were reversibly sealed onto a cast polydimethylsiloxane (PDMS) insert, patterned with distribution channels and reaction chambers. Topology optimization was used to design reaction chambers with uniform flow conditions. The HistoFlex provided uniform hybridization conditions, across the reaction chamber, as determined by hybridization to microscope slides of spotted DNA microarrays when applying probe concentrations generally used in in situ hybridization (ISH) assays. The HistoFlex's novel ability in online monitoring of an in situ hybridization assay was demonstrated using direct fluorescent detection of hybridization to 18S rRNA. Tissue sections were not visually damaged during assaying, which enabled adapting a complete ISH assay for detection of microRNAs (miRNA). The effects of flow based incubations on hybridization, antibody incubation and Tyramide Signal Amplification (TSA) steps were investigated upon adapting the ISH assay for performing in the HistoFlex. The hybridization step was significantly enhanced using flow based incubations due to improved hybridization efficiency. The HistoFlex device enabled a fast miRNA ISH assay (3 hours) which provided higher hybridization signal intensity compared to using conventional techniques (5 h 40 min). We further demonstrate that the improved hybridization efficiency using the HistoFlex permits more complex assays e.g. those comprising sequential hybridization and detection of two miRNAs to be performed with significantly increased sensitivity. The HistoFlex provides a new histological analysis platform that will allow multiple and sequential assays to be performed under their individual optimum assay conditions. Images can subsequently be recorded either in

  11. A simple method of fabricating mask-free microfluidic devices for biological analysis.

    KAUST Repository

    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.

  12. Novel developments in mobile sensing based on the integration of microfluidic devices and smartphones.

    Science.gov (United States)

    Yang, Ke; Peretz-Soroka, Hagit; Liu, Yong; Lin, Francis

    2016-03-21

    Portable electronic devices and wireless communication systems enable a broad range of applications such as environmental and food safety monitoring, personalized medicine and healthcare management. Particularly, hybrid smartphone and microfluidic devices provide an integrated solution for the new generation of mobile sensing applications. Such mobile sensing based on microfluidic devices (broadly defined) and smartphones (MS(2)) offers a mobile laboratory for performing a wide range of bio-chemical detection and analysis functions such as water and food quality analysis, routine health tests and disease diagnosis. MS(2) offers significant advantages over traditional platforms in terms of test speed and control, low cost, mobility, ease-of-operation and data management. These improvements put MS(2) in a promising position in the fields of interdisciplinary basic and applied research. In particular, MS(2) enables applications to remote in-field testing, homecare, and healthcare in low-resource areas. The marriage of smartphones and microfluidic devices offers a powerful on-chip operating platform to enable various bio-chemical tests, remote sensing, data analysis and management in a mobile fashion. The implications of such integration are beyond telecommunication and microfluidic-related research and technology development. In this review, we will first provide the general background of microfluidic-based sensing, smartphone-based sensing, and their integration. Then, we will focus on several key application areas of MS(2) by systematically reviewing the important literature in each area. We will conclude by discussing our perspectives on the opportunities, issues and future directions of this emerging novel field.

  13. Real-time Functional Analysis of Inertial Microfluidic Devices via Spectral Domain Optical Coherence Tomography

    Science.gov (United States)

    Dong, Biqin; Chen, Siyu; Zhou, Fan; Chan, Christina H. Y.; Yi, Ji; Zhang, Hao F.; Sun, Cheng

    2016-09-01

    We report the application of spectral-domain optical coherence tomography (SD-OCT) technology that enables real-time functional analysis of sorting microparticles and cells in an inertial microfluidic device. We demonstrated high-speed, high-resolution acquisition of cross-sectional images at a frame rate of 350 Hz, with a lateral resolution of 3 μm and an axial resolution of 1 μm within the microfluidic channel filled with water. We analyzed the temporal sequence of cross-sectional SD-OCT images to determine the position and diameter of microspheres in a spiral microfluidic channel under various flow rates. We used microspheres with known diameters to validate the sub-micrometer precision of the particle size analysis based on a scattering model of spherical microparticles. An additional investigation of sorting live HT-29 cells in the spiral microfluidic channel indicated that the distribution of cells within in the microchannel has a close correspondence with the cells’ size distribution. The label-free real-time imaging and analysis of microscale particles in flow offers robustness for practical applications with live cells and allows us to better understand the mechanisms of particle separations in microfluidic sorting systems.

  14. Magnetic optical sensor particles: a flexible analytical tool for microfluidic devices.

    Science.gov (United States)

    Ungerböck, Birgit; Fellinger, Siegfried; Sulzer, Philipp; Abel, Tobias; Mayr, Torsten

    2014-05-21

    In this study we evaluate magnetic optical sensor particles (MOSePs) with incorporated sensing functionalities regarding their applicability in microfluidic devices. MOSePs can be separated from the surrounding solution to form in situ sensor spots within microfluidic channels, while read-out is accomplished outside the chip. These magnetic sensor spots exhibit benefits of sensor layers (high brightness and convenient usage) combined with the advantages of dispersed sensor particles (ease of integration). The accumulation characteristics of MOSePs with different diameters were investigated as well as the in situ sensor spot stability at varying flow rates. Magnetic sensor spots were stable at flow rates specific to microfluidic applications. Furthermore, MOSePs were optimized regarding fiber optic and imaging read-out systems, and different referencing schemes were critically discussed on the example of oxygen sensors. While the fiber optic sensing system delivered precise and accurate results for measurement in microfluidic channels, limitations due to analyte consumption were found for microscopic oxygen imaging. A compensation strategy is provided, which utilizes simple pre-conditioning by exposure to light. Finally, new application possibilities were addressed, being enabled by the use of MOSePs. They can be used for microscopic oxygen imaging in any chip with optically transparent covers, can serve as flexible sensor spots to monitor enzymatic activity or can be applied to form fixed sensor spots inside microfluidic structures, which would be inaccessible to integration of sensor layers.

  15. A microfluidic device for studying cell signaling with multiple inputs and adjustable amplitudes and frequencies

    Science.gov (United States)

    Ningsih, Zubaidah; Chon, James W. M.; Clayton, Andrew H. A.

    2013-12-01

    Cell function is largely controlled by an intricate web of macromolecular interactions called signaling networks. It is known that the type and the intensity (concentration) of stimulus affect cell behavior. However, the temporal aspect of the stimulus is not yet fully understood. Moreover, the process of distinguishing between two stimuli by a cell is still not clear. A microfluidic device enables the delivery of a precise and exact stimulus to the cell due to the laminar flow established inside its micro-channel. The slow stream delivers a constant stimulus which is adjustable according to the experiment set up. Moreover, with controllable inputs, microfluidic facilitates the stimuli delivery according to a certain pattern with adjustable amplitude, frequency and phase. Several designs of PDMS microfluidic device has been produced in this project via photolithography and soft lithography processes. To characterize the microfluidic performance, two experiments has been conducted. First, by comparing the fluorescence intensity and the lifetime of fluorescein in the present of KI, mixing extent between two inputs was observed using Frequency Lifetime Imaging Microscopy (FLIM). Furthermore, the input-output relationship of fluorescein concentration delivered was also drawn to characterize the amplitude, frequency and phase of the inputs. Second experiment involved the cell culturing inside microfluidic. Using NG108-15 cells, proliferation and differentiation were observed based on the cell number and cell physiological changes. Our results demonstrate that hurdle design gives 86% mixing of fluorescein and buffer. Relationship between inputoutput fluorescein concentrations delivered has also been demonstrated and cells were successfully cultured inside the microfluidic.

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

    Science.gov (United States)

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

    2016-08-01

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

  17. Rapid fabrication of microfluidic PDMS devices from reusable PDMS molds using laser ablation

    Science.gov (United States)

    Isiksacan, Ziya; Tahsin Guler, M.; Aydogdu, Berkan; Bilican, Ismail; Elbuken, Caglar

    2016-03-01

    The conventional fabrication methods for microfluidic devices require cleanroom processes that are costly and time-consuming. We present a novel, facile, and low-cost method for rapid fabrication of polydimethylsiloxane (PDMS) molds and devices. The method consists of three main fabrication steps: female mold (FM), male mold (MM), and chip fabrication. We use a CO2 laser cutter to pattern a thin, spin-coated PDMS layer for FM fabrication. We then obtain reusable PDMS MM from the FM using PDMS/PDMS casting. Finally, a second casting step is used to replicate PDMS devices from the MM. Demolding of one PDMS layer from another is carried out without any potentially hazardous chemical surface treatment. We have successfully demonstrated that this novel method allows fabrication of microfluidic molds and devices with precise dimensions (thickness, width, length) using a single material, PDMS, which is very common across microfluidic laboratories. The whole process, from idea to device testing, can be completed in 1.5 h in a standard laboratory.

  18. Comparison of Pectin Hydrogel Collection Methods in Microfluidic Device

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chaeyeon; Park, Ki-Su; Kang, Sung-Min; Kim, Jongmin; Song, YoungShin; Lee, Chang-Soo [Chungnam National University, Daejeon (Korea, Republic of)

    2015-12-15

    This study investigated the effect of different collection methods on physical properties of pectin hydrogels in microfluidic synthetic approach. The pectin hydrogels were simply produced by the incorporation of calcium ions dissolved in continuous mineral oil. Then, different collection methods, pipetting, tubing, and settling, for harvesting pectin hydrogels were applied. The settling method showed most uniform and monodispersed hydrogels. In the case of settling, a coefficient of variation was 3.46 which was lower than pipetting method (18.60) and tubing method (14.76). Under the settling method, we could control the size of hydrogels, ranging from 30 μm to 180 μm, by simple manipulation of the viscosity of pectin and volumetric flow rate of dispersed and continuous phase. Finally, according to the characteristics of simple encapsulation of biological materials, we envision that the pectin hydrogels can be applied to drug delivery, food, and biocompatible materials.

  19. Towards time-resolved serial crystallography in a microfluidic device.

    Science.gov (United States)

    Pawate, Ashtamurthy S; Šrajer, Vukica; Schieferstein, Jeremy; Guha, Sudipto; Henning, Robert; Kosheleva, Irina; Schmidt, Marius; Ren, Zhong; Kenis, Paul J A; Perry, Sarah L

    2015-07-01

    Serial methods for crystallography have the potential to enable dynamic structural studies of protein targets that have been resistant to single-crystal strategies. The use of serial data-collection strategies can circumvent challenges associated with radiation damage and repeated reaction initiation. This work utilizes a microfluidic crystallization platform for the serial time-resolved Laue diffraction analysis of macroscopic crystals of photoactive yellow protein (PYP). Reaction initiation was achieved via pulsed laser illumination, and the resultant electron-density difference maps clearly depict the expected pR(1)/pR(E46Q) and pR(2)/pR(CW) states at 10 µs and the pB1 intermediate at 1 ms. The strategies presented here have tremendous potential for extension to chemical triggering methods for reaction initiation and for extension to dynamic, multivariable analyses.

  20. Comparison of Chip Inlet Geometry in Microfluidic Devices for Cell Studies

    Directory of Open Access Journals (Sweden)

    Yung-Shin Sun

    2016-06-01

    Full Text Available Micro-fabricated devices integrated with fluidic components provide an in vitro platform for cell studies best mimicking the in vivo micro-environment. These devices are capable of creating precise and controllable surroundings of pH value, temperature, salt concentration, and other physical or chemical stimuli. Various cell studies such as chemotaxis and electrotaxis can be performed by using such devices. Moreover, microfluidic chips are designed and fabricated for applications in cell separations such as circulating tumor cell (CTC chips. Usually, there are two most commonly used inlets in connecting the microfluidic chip to sample/reagent loading tubes: the vertical (top-loading inlet and the parallel (in-line inlet. Designing this macro-to-micro interface is believed to play an important role in device performance. In this study, by using the commercial COMSOL Multiphysics software, we compared the cell capture behavior in microfluidic devices with different inlet types and sample flow velocities. Three different inlets were constructed: the vertical inlet, the parallel inlet, and the vertically parallel inlet. We investigated the velocity field, the flow streamline, the cell capture rate, and the laminar shear stress in these inlets. It was concluded that the inlet should be designed depending on the experimental purpose, i.e., one wants to maximize or minimize cell capture. Also, although increasing the flow velocity could reduce cell sedimentation, too high shear stresses are thought harmful to cells. Our findings indicate that the inlet design and flow velocity are crucial and should be well considered in fabricating microfluidic devices for cell studies.

  1. An electric stimulation system for electrokinetic particle manipulation in microfluidic devices

    Science.gov (United States)

    Lopez-de la Fuente, M. S.; Moncada-Hernandez, H.; Perez-Gonzalez, V. H.; Lapizco-Encinas, B. H.; Martinez-Chapa, S. O.

    2013-03-01

    Microfluidic devices have grown significantly in the number of applications. Microfabrication techniques have evolved considerably; however, electric stimulation systems for microdevices have not advanced at the same pace. Electric stimulation of micro-fluidic devices is an important element in particle manipulation research. A flexible stimulation instrument is desired to perform configurable, repeatable, automated, and reliable experiments by allowing users to select the stimulation parameters. The instrument presented here is a configurable and programmable stimulation system for electrokinetic-driven microfluidic devices; it consists of a processor, a memory system, and a user interface to deliver several types of waveforms and stimulation patterns. It has been designed to be a flexible, highly configurable, low power instrument capable of delivering sine, triangle, and sawtooth waveforms with one single frequency or two superimposed frequencies ranging from 0.01 Hz to 40 kHz, and an output voltage of up to 30 Vpp. A specific stimulation pattern can be delivered over a single time period or as a sequence of different signals for different time periods. This stimulation system can be applied as a research tool where manipulation of particles suspended in liquid media is involved, such as biology, medicine, environment, embryology, and genetics. This system has the potential to lead to new schemes for laboratory procedures by allowing application specific and user defined electric stimulation. The development of this device is a step towards portable and programmable instrumentation for electric stimulation on electrokinetic-based microfluidic devices, which are meant to be integrated with lab-on-a-chip devices.

  2. In search of low cost biological analysis: Wax or acrylic glue bonded paper microfluidic devices

    KAUST Repository

    Kodzius, Rimantas

    2011-01-22

    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 from the standpoint of adsorption. Most of the materials did not inhibit the DNA, whereas they did show noticeable interaction with the DNA polymerase. This work provides a simple low cost fabrication method for creating microfluidic devices for biological analysis. Example assays were undertaken and the biocompatibility of our technology was studied, both of which demonstrated the utility of our approach.

  3. Surface modification of droplet polymeric microfluidic devices for the stable and continuous generation of aqueous droplets.

    Science.gov (United States)

    Subramanian, Balamurugan; Kim, Namwon; Lee, Wonbae; Spivak, David A; Nikitopoulos, Dimitris E; McCarley, Robin L; Soper, Steven A

    2011-06-21

    Droplet microfluidics performed in poly(methyl methacrylate) (PMMA) microfluidic devices resulted in significant wall wetting by water droplets formed in a liquid-liquid segmented flow when using a hydrophobic carrier fluid such as perfluorotripropylamine (FC-3283). This wall wetting led to water droplets with nonuniform sizes that were often trapped on the wall surfaces, leading to unstable and poorly controlled liquid-liquid segmented flow. To circumvent this problem, we developed a two-step procedure to hydrophobically modify the surfaces of PMMA and other thermoplastic materials commonly used to make microfluidic devices. The surface-modification route involved the introduction of hydroxyl groups by oxygen plasma treatment of the polymer surface followed by a solution-phase reaction with heptadecafluoro-1,1,2,2-tetrahydrodecyl trichlorosilane dissolved in fluorocarbon solvent FC-3283. This procedure was found to be useful for the modification of PMMA and other thermoplastic surfaces, including polycyclic olefin copolymer (COC) and polycarbonate (PC). Angle-resolved X-ray photoelectron spectroscopy indicated that the fluorination of these polymers took place with high surface selectivity. This procedure was used to modify the surface of a PMMA droplet microfluidic device (DMFD) and was shown to be useful in reducing the wetting problem during the generation of aqueous droplets in a perfluorotripropylamine (FC-3283) carrier fluid and could generate stable segmented flows for hours of operation. In the case of PMMA DMFD, oxygen plasma treatment was carried out after the PMMA cover plate was thermally fusion bonded to the PMMA microfluidic chip. Because the appended chemistry to the channel wall created a hydrophobic surface, it will accommodate the use of other carrier fluids that are hydrophobic as well, such as hexadecane or mineral oils.

  4. Bright conjugated polymer nanoparticles containing a biodegradable shell produced at high yields and with tuneable optical properties by a scalable microfluidic device.

    Science.gov (United States)

    Abelha, T F; Phillips, T W; Bannock, J H; Nightingale, A M; Dreiss, C A; Kemal, E; Urbano, L; deMello, J C; Green, M; Dailey, L A

    2017-02-02

    This study compares the performance of a microfluidic technique and a conventional bulk method to manufacture conjugated polymer nanoparticles (CPNs) embedded within a biodegradable poly(ethylene glycol) methyl ether-block-poly(lactide-co-glycolide) (PEG5K-PLGA55K) matrix. The influence of PEG5K-PLGA55K and conjugated polymers cyano-substituted poly(p-phenylene vinylene) (CN-PPV) and poly(9,9-dioctylfluorene-2,1,3-benzothiadiazole) (F8BT) on the physicochemical properties of the CPNs was also evaluated. Both techniques enabled CPN production with high end product yields (∼70-95%). However, while the bulk technique (solvent displacement) under optimal conditions generated small nanoparticles (∼70-100 nm) with similar optical properties (quantum yields ∼35%), the microfluidic approach produced larger CPNs (140-260 nm) with significantly superior quantum yields (49-55%) and tailored emission spectra. CPNs containing CN-PPV showed smaller size distributions and tuneable emission spectra compared to F8BT systems prepared under the same conditions. The presence of PEG5K-PLGA55K did not affect the size or optical properties of the CPNs and provided a neutral net electric charge as is often required for biomedical applications. The microfluidics flow-based device was successfully used for the continuous preparation of CPNs over a 24 hour period. On the basis of the results presented here, it can be concluded that the microfluidic device used in this study can be used to optimize the production of bright CPNs with tailored properties with good reproducibility.

  5. High-throughput microfluidic device for single cell analysis using multiple integrated soft lithographic pumps.

    Science.gov (United States)

    Patabadige, Damith E W; Mickleburgh, Tom; Ferris, Lorin; Brummer, Gage; Culbertson, Anne H; Culbertson, Christopher T

    2016-05-01

    The ability to accurately control fluid transport in microfluidic devices is key for developing high-throughput methods for single cell analysis. Making small, reproducible changes to flow rates, however, to optimize lysis and injection using pumps external to the microfluidic device are challenging and time-consuming. To improve the throughput and increase the number of cells analyzed, we have integrated previously reported micropumps into a microfluidic device that can increase the cell analysis rate to ∼1000 cells/h and operate for over an hour continuously. In order to increase the flow rates sufficiently to handle cells at a higher throughput, three sets of pumps were multiplexed. These pumps are simple, low-cost, durable, easy to fabricate, and biocompatible. They provide precise control of the flow rate up to 9.2 nL/s. These devices were used to automatically transport, lyse, and electrophoretically separate T-Lymphocyte cells loaded with Oregon green and 6-carboxyfluorescein. Peak overlap statistics predicted the number of fully resolved single-cell electropherograms seen. In addition, there was no change in the average fluorescent dye peak areas indicating that the cells remained intact and the dyes did not leak out of the cells over the 1 h analysis time. The cell lysate peak area distribution followed that expected of an asynchronous steady-state population of immortalized cells.

  6. Surface treatment of flow channels in microfluidic devices fabricated by stereolithography.

    Science.gov (United States)

    Ohtani, Kanako; Tsuchiya, Masaki; Sugiyama, Hitomi; Katakura, Toru; Hayakawa, Masatoshi; Kanai, Toshimitsu

    2014-01-01

    A microfluidic device with three-dimensional flow channels was fabricated by stereolithography, and hydrophilic surface treatment of the flow channel was performed by coating the wall of the channel with a silica layer. After the treatment, the device produced monodisperse oil-in-water (O/W) emulsions. The silica layer on the channel surface was then coated with a fluorinated silane coupling agent to make it hydrophobic, thus enabling the treated device to produce monodisperse inverted water-in-oil (W/O) emulsions.

  7. Integrated microfluidic device for single-cell trapping and spectroscopy

    KAUST Repository

    Liberale, Carlo

    2013-02-13

    Optofluidic microsystems are key components towards lab-on-a-chip devices for manipulation and analysis of biological specimens. In particular, the integration of optical tweezers (OT) in these devices allows stable sample trapping, while making available mechanical, chemical and spectroscopic analyses.

  8. Non-contact reflectometric readout of disposable microfluidic devices by near infra-red low-coherence interferometry

    OpenAIRE

    2016-01-01

    We are here demonstrating the functionality of infra-red low-coherence reflectometry for the spot optical readout of solution concentrations in commercially available microfluidic devices. Disposable polymeric microfluidic devices composed by 100-µm-deep channels were connected to an external fluidic path that allowed flow-through of water-glucose solutions at different concentrations. Measurements were performed with near-infrared low-power sources, namely a tungsten lamp and a Superluminesc...

  9. Rapid screening of phenylketonuria using a CD microfluidic device.

    Science.gov (United States)

    Chen, Bin; Zhou, Xiaomian; Li, Chunyu; Wang, Qiuping; Liu, Dayu; Lin, Bingcheng

    2011-04-08

    We herein present a compact disc (CD) microfluidic chip based hybridization assay for phenylketonuria (PKU) screening. This CD chip is composed of a polydimethylsiloxane (PDMS) top layer containing 12 DNA hybridization microchannels, and a glass bottom layer with hydrogel pad conjugated DNA oligonucleotides. Reciprocating flow was generated on the CD chip through a simple rotation-pause operation to facilitate rapid DNA hybridization. When rotated the CD chip, the sample solution was driven into the hybridization channel by centrifugal force. When stopped the CD chip, the sample plug was pulled backward through the channel by capillary force. The hybridization assay was firstly validated with control samples and was then used to analyze 30 clinical samples from pregnant women with suspected PKU fetus. The on-chip DNA hybridization was completed in 15 min with a sample consumption as low as 1.5μL, and the limit-of-detection (LOD) of DNA template was 0.7ng/μL. Among the 30 samples tested, V245V mutation was identified in 4 cases while R243Q mutation was detected in one case. Results of the hybridization assay were confirmed by DNA sequencing. This CD-chip based hybridization assay features short analysis time, simple operation and low cost, thus has the potential to serve as the tool for PKU screening.

  10. Study of the Chemotactic Response of Multicellular Spheroids in a Microfluidic Device

    Science.gov (United States)

    Ayuso, Jose M.; Basheer, Haneen A.; Monge, Rosa; Sánchez-Álvarez, Pablo; Doblaré, Manuel; Shnyder, Steven D.; Vinader, Victoria; Afarinkia, Kamyar

    2015-01-01

    We report the first application of a microfluidic device to observe chemotactic migration in multicellular spheroids. A microfluidic device was designed comprising a central microchamber and two lateral channels through which reagents can be introduced. Multicellular spheroids were embedded in collagen and introduced to the microchamber. A gradient of fetal bovine serum (FBS) was established across the central chamber by addition of growth media containing serum into one of the lateral channels. We observe that spheroids of oral squamous carcinoma cells OSC–19 invade collectively in the direction of the gradient of FBS. This invasion is more directional and aggressive than that observed for individual cells in the same experimental setup. In contrast to spheroids of OSC–19, U87-MG multicellular spheroids migrate as individual cells. A study of the exposure of spheroids to the chemoattractant shows that the rate of diffusion into the spheroid is slow and thus, the chemoattractant wave engulfs the spheroid before diffusing through it. PMID:26444904

  11. A microfluidic device for the study of the orientational dynamics of microrods

    CERN Document Server

    Mishra, Y N; John, O A; Andersson, P; Mehlig, B; Hanstorp, D

    2012-01-01

    We describe a microfluidic device for studying the orientational dynamics of microrods. The device enables us to experimentally investigate the tumbling of microrods immersed in the shear flow in a microfluidic channel with a depth of 400 mu and a width of 2.5 mm. The orientational dynamics was recorded using a 20 X microscopic objective and a CCD camera. The microrods were produced by shearing microdroplets of photocurable epoxy resin. We show different examples of empirically observed tumbling. On the one hand we find that short stretches of the experimentally determined time series are well described by fits to solutions of Jeffery's approximate equation of motion [Jeffery, Proc. R. Soc. London. 102 (1922), 161-179]. On the other hand we find that the empirically observed trajectories drift between different solutions of Jeffery's equation. We discuss possible causes of this orbit drift.

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

    Directory of Open Access Journals (Sweden)

    Ana Rubina Perestrelo

    2015-12-01

    Full Text Available Recent advances in biomedical technologies are mostly related to the convergence of biology with microengineering. For instance, microfluidic devices are now commonly found in most research centers, clinics and hospitals, contributing to more accurate studies and therapies as powerful tools for drug delivery, monitoring of specific analytes, and medical diagnostics. Most remarkably, integration of cellularized constructs within microengineered platforms has enabled the recapitulation of the physiological and pathological conditions of complex tissues and organs. The so-called “organ-on-a-chip” technology, which represents a new avenue in the field of advanced in vitro models, with the potential to revolutionize current approaches to drug screening and toxicology studies. This review aims to highlight recent advances of microfluidic-based devices towards a body-on-a-chip concept, exploring their technology and broad applications in the biomedical field.

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

    Science.gov (United States)

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

    2015-12-10

    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.

  14. Fabrication of Embedded Microvalve on PMMA Microfluidic Devices through Surface Functionalization

    CERN Document Server

    Toh, A G G; Ng, S H

    2008-01-01

    The integration of a PDMS membrane within orthogonally placed PMMA microfluidic channels enables the pneumatic actuation of valves within bonded PMMA-PDMS-PMMA multilayer devices. Here, surface functionalization of PMMA substrates via acid catalyzed hydrolysis and air plasma corona treatment were investigated as possible techniques to permanently bond PMMA microfluidic channels to PDMS surfaces. FTIR and water contact angle analysis of functionalized PMMA substrates showed that air plasma corona treatment was most effective in inducing PMMA hydrophilicity. Subsequent fluidic tests showed that air plasma modified and bonded PMMA multilayer devices could withstand fluid pressure at an operational flow rate of 9 mircoliters/min. The pneumatic actuation of the embedded PDMS membrane was observed through optical microscopy and an electrical resistance based technique. PDMS membrane actuation occurred at pneumatic pressures of as low as 10kPa and complete valving occurred at 14kPa for 100 micrometers x 100 micromet...

  15. Topology optimization of flexible micro-fluidic devices

    DEFF Research Database (Denmark)

    Kreissl, Sebastian; Pingen, Georg; Evgrafov, Anton;

    2010-01-01

    A multi-objective topology optimization formulation for the design of dynamically tunable fluidic devices is presented. The flow is manipulated via external and internal mechanical actuation, leading to elastic deformations of flow channels. The design objectives characterize the performance...

  16. A Portable and Power-Free Microfluidic Device for Rapid and Sensitive Lead (Pb2+) Detection

    OpenAIRE

    Lianhui Wang; Shiping Song; Gang Liu; Shijiang He; Chunhui Fan

    2012-01-01

    A portable and power-free microfluidic device was designed for rapid and sensitive detection of lead (Pb2+). 11-mercaptoundecanoic acid (MUA)-functionalized gold nanoparticles (MUA-AuNPs) aggregated in the presence of Pb2+ for the chelation mechanism. When we performed this analysis on a polydimethylsiloxane (PDMS) microfluidic chip, the aggregations deposited onto the surface of chip and formed dark lines along the laminar flows in the zigzag micr...

  17. Utilization of microfluidic V-junction device to prepare surface itraconazole adsorbed nanospheres.

    OpenAIRE

    Kucuk, I.; Ahmad, Z.; Edirisinghe, M.; Orlu-Gul, M.

    2014-01-01

    Itraconazole is widely used as an anti-fungal drug to treat infections. However its poor aqueous solubility results in low bioavailability. The aim of the present study was to improve the drug release profile by preparing surface itraconazole adsorbed polymethylsilsesquioxane (PMSQ) nanospheres using a V-junction microfluidic (VJM) device. In order to generate nanospheres with rough surface, the process flow rate of Perfluorohexane (PFH) was set between 50 and 300 μl min(-1) while the flow ra...

  18. Measurements of Elastic Moduli of Silicone Gel Substrates with a Microfluidic Device

    OpenAIRE

    Edgar Gutierrez; Alex Groisman

    2011-01-01

    Thin layers of gels with mechanical properties mimicking animal tissues are widely used to study the rigidity sensing of adherent animal cells and to measure forces applied by cells to their substrate with traction force microscopy. The gels are usually based on polyacrylamide and their elastic modulus is measured with an atomic force microscope (AFM). Here we present a simple microfluidic device that generates high shear stresses in a laminar flow above a gel-coated substrate and apply the d...

  19. Concurrent Connection of Embryonic Chick Heart Using a Microfluidic Device for Organ-Explant-Chip

    OpenAIRE

    Owaki, Hirofumi; Masuda, Taisuke; Kawahara, Tomohiro; Miyasaka, Kota; Ogura, Toshihiko; Arai, Fumihito

    2013-01-01

    We propose a concurrent microvascular connection method called suction-induced vascular fixation (SVF) method for the achievement of Organ-Explant-Chip which is a biologically-designed simulator having biological materials such as cells, tissues, and organs. The advantages of proposed method with using a microfluidic device are as follows: (1) operation of flexible objects (blood vessels), (2) alignment the blood vessels concurrently, and (3) reduction of the DOFs of the blood vessels. From t...

  20. Hydrodynamic Flow Confinement Technology in Microfluidic Perfusion Devices

    Directory of Open Access Journals (Sweden)

    Aldo Jesorka

    2012-05-01

    Full Text Available Hydrodynamically confined flow device technology is a young research area with high practical application potential in surface processing, assay development, and in various areas of single cell research. Several variants have been developed, and most recently, theoretical and conceptual studies, as well as fully developed automated systems, were presented. In this article we review concepts, fabrication strategies, and application areas of hydrodynamically confined flow (HCF devices.

  1. Development of a real-world direct interface for integrated DNA extraction and amplification in a microfluidic device.

    Science.gov (United States)

    Shaw, Kirsty J; Joyce, Domino A; Docker, Peter T; Dyer, Charlotte E; Greenway, Gillian M; Greenman, John; Haswell, Stephen J

    2011-02-07

    Integrated DNA extraction and amplification have been carried out in a microfluidic device using electro-osmotic pumping (EOP) for fluidic control. All the necessary reagents for performing both DNA extraction and polymerase chain reaction (PCR) amplification were pre-loaded into the microfluidic device following encapsulation in agarose gel. Buccal cells were collected using OmniSwabs [Whatman™, UK] and manually added to a chaotropic binding/lysis solution pre-loaded into the microfluidic device. The released DNA was then adsorbed onto a silica monolith contained within the DNA extraction chamber and the microfluidic device sealed using polymer electrodes. The washing and elution steps for DNA extraction were carried out using EOP, resulting in transfer of the eluted DNA into the PCR chamber. Thermal cycling, achieved using a Peltier element, resulted in amplification of the Amelogenin locus as confirmed using conventional capillary gel electrophoresis. It was demonstrated that the PCR reagents could be stored in the microfluidic device for at least 8 weeks at 4 °C with no significant loss of activity. Such methodology lends itself to the production of 'ready-to-use' microfluidic devices containing all the necessary reagents for sample processing, with many obvious applications in forensics and clinical medicine.

  2. Fabrication of microfluidic devices: improvement of surface quality of CO2 laser machined poly(methylmethacrylate) polymer

    Science.gov (United States)

    Mohammed, Mazher I.; Nazrul Hisham Zainal Alam, Muhd; Kouzani, Abbas; Gibson, Ian

    2017-01-01

    Laser engraving has considerable potential for the rapid and cost effective manufacturing of polymeric microfluidic devices. However, fabricated devices are hindered by relatively large surface roughness in the engraved areas, which can perturb smooth fluidic flow and can damage sensitive biological components. This effect is exacerbated when engraving at depths beyond the laser focal range, limiting the production of large aspect ratio devices such as microbioreactors. This work aims to overcome such manufacturing limitations and to realise more reproducible and defect free microfluidic channels and structures. We present a strategy of multiple engraving passes alongside solvent polymer reflow for shallow depth (500 µm) features. To examine the proposed methodologies, capillary action and bioreactor microfluidic devices were fabricated and evaluated. Results indicate that the multiple engraving technique could reproduce engraved microfluidic channels to depths between 50-470 µm, both rapidly (6-8 min) and with low average surface roughness (1.5-2.5 µm). The layer cutting approach was effective at manufacturing microfluidic devices with depths  <500 µm, rapidly (<1 min) and with low surface roughness. Ultimately, the proposed methodology is highly beneficial for the rapid development of polymer-based microfluidic devices.

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

    Science.gov (United States)

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

    2015-10-20

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

  4. A microfluidic device integrating plasmonic nanodevices for Raman spectroscopy analysis on trapped single living cells

    KAUST Repository

    Perozziello, Gerardo

    2013-11-01

    In this work we developed a microfluidic device integrating nanoplasmonic devices combined with fluidic trapping regions. The microfuidic traps allow to capture single cells in areas where plasmonic sensors are placed. In this way it is possible to perform Enhanced Raman analysis on the cell membranes. Moreover, by changing direction of the flux it is possible to change the orientation of the cell in the trap, so that it is possible to analyze different points of the membrane of the same cell. We shows an innovative procedure to fabricate and assembly the microfluidic device which combine photolithography, focused ion beam machining, and hybrid bonding between a polymer substrate and lid of Calcium fluoride. This procedure is compatible with the fabrication of the plasmonic sensors in close proximity of the microfluidic traps. Moreover, the use of Calcium fluoride as lid allows full compatibility with Raman measurements producing negligible Raman background signal and avoids Raman artifacts. Finally, we performed Raman analysis on cells to monitor their oxidative stress under particular non physiological conditions. © 2013 Elsevier B.V. All rights reserved.

  5. Optical fiber loops and helices: tools for integrated photonic device characterization and microfluidic trapping

    Science.gov (United States)

    Ren, Yundong; Zhang, Rui; Ti, Chaoyang; Liu, Yuxiang

    2016-09-01

    Tapered optical fibers can deliver guided light into and carry light out of micro/nanoscale systems with low loss and high spatial resolution, which makes them ideal tools in integrated photonics and microfluidics. Special geometries of tapered fibers are desired for probing monolithic devices in plane as well as optical manipulation of micro particles in fluids. However, for many specially shaped tapered fibers, it remains a challenge to fabricate them in a straightforward, controllable, and repeatable way. In this work, we fabricated and characterized two special geometries of tapered optical fibers, namely fiber loops and helices, that could be switched between one and the other. The fiber loops in this work are distinct from previous ones in terms of their superior mechanical stability and high optical quality factors in air, thanks to a post-annealing process. We experimentally measured an intrinsic optical quality factor of 32,500 and a finesse of 137 from a fiber loop. A fiber helix was used to characterize a monolithic cavity optomechanical device. Moreover, a microfluidic "roller coaster" was demonstrated, where microscale particles in water were optically trapped and transported by a fiber helix. Tapered fiber loops and helices can find various applications ranging from on-the-fly characterization of integrated photonic devices to particle manipulation and sorting in microfluidics.

  6. Analysis of Electric Fields inside Microchannels and Single Cell Electrical Lysis with a Microfluidic Device

    Directory of Open Access Journals (Sweden)

    Tofy Mussivand

    2013-06-01

    Full Text Available Analysis of electric fields generated inside the microchannels of a microfluidic device for electrical lysis of biological cells along with experimental verification are presented. Electrical lysis is the complete disintegration of cell membranes, due to a critical level of electric fields applied for a critical duration on a biological cell. Generating an electric field inside a microchannel of a microfluidic device has many advantages, including the efficient utilization of energy and low-current requirement. An ideal microchannel model was compared with a practical microchannel model using a finite element analysis tool that suggests that the overestimation error can be over 10%, from 2.5 mm or smaller, in the length of a microchannel. Two analytical forms are proposed to reduce this overestimation error. Experimental results showed that the high electric field is confined only inside the microchannel that is in agreement with the simulation results. Single cell electrical lysis was conducted with a fabricated microfluidic device. An average of 800 V for seven seconds across an 8 mm-long microchannel with the dimension of 100 μm × 20 μm was required for lysis, with electric fields exceeding 100 kV/m and consuming 300 mW.

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

    Science.gov (United States)

    Xiang, Nan; Ni, Zhonghua

    2015-12-01

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

  8. Mapping the Salinity Gradient in a Microfluidic Device with Schlieren Imaging

    Directory of Open Access Journals (Sweden)

    Chen-li Sun

    2015-05-01

    Full Text Available This work presents the use of the schlieren imaging to quantify the salinity gradients in a microfluidic device. By partially blocking the back focal plane of the objective lens, the schlieren microscope produces an image with patterns that correspond to spatial derivative of refractive index in the specimen. Since salinity variation leads to change in refractive index, the fluid mixing of an aqueous salt solution of a known concentration and water in a T-microchannel is used to establish the relation between salinity gradients and grayscale readouts. This relation is then employed to map the salinity gradients in the target microfluidic device from the grayscale readouts of the corresponding micro-schlieren image. For saline solution with salinity close to that of the seawater, the grayscale readouts vary linearly with the salinity gradient, and the regression line is independent of the flow condition and the salinity of the injected solution. It is shown that the schlieren technique is well suited to quantify the salinity gradients in microfluidic devices, for it provides a spatially resolved, non-invasive, full-field measurement.

  9. An integrated microfluidic device in marine microalgae culture for toxicity screening application.

    Science.gov (United States)

    Zheng, Guoxia; Wang, Yunhua; Wang, Zumin; Zhong, Weiliang; Wang, Hu; Li, Yajie

    2013-07-15

    Algal assay using marine microalgae has emerged as an important method to evaluate the toxicity of chemicals, which is currently undertaken using conventional culture and additional detection of physiological cellular endpoints. While effective, this approach can be labor-intensive and thus could benefit from a more streamlined, integrated approach. Microfluidics offers a way to accomplish this goal. Here, we demonstrate a microfluidic device which consists of a concentration gradient generator (CGG), diffusible culturing module and power-free valve system. It allows the processes of chemical liquid dilution and diffusion, micro-scale microalgal culture (in batch or chemostatic conditions), cell stimulation and on-lined screening to be integrated into a single device. Using the device, marine microalgae were successfully cultured and stressed on-chip. The simple assay provides multi-biological response measurements of cell division rate, autofluorescence and esterase activity. This work showed promising in developing a microfluidic platform for toxicity screening based on marine microalgal culture. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Enzyme incorporated microfluidic device for in-situ glucose detection in water-in-air microdroplets.

    Science.gov (United States)

    Piao, Yunxian; Han, Dong Ju; Azad, Mohammad Reza; Park, Minsu; Seo, Tae Seok

    2015-03-15

    Droplet generating microfluidic systems can provide miniaturized bioanalytical tools by using the homogenous and high-throughput droplets as nanoreactors. In this study, we demonstrated a sensitive and in-situ glucose monitoring system using water-in-air droplets in an enzyme incorporated microfluidic device. A thin film structure of a glucose oxidase (GOx) enzyme immobilized hydrogel was constructed in the middle of the microfluidic channel, and nanoliter scaled water-in-air droplets which contain a glucose sample, horseradish peroxidase (HRP), and an Amplex Red substrate were generated by flow focusing of water phase with air. Once the droplets passed through the enzyme trapped hydrogel, the droplets temporarily halted and a GOx mediated catalytic reaction with glucose proceeded, resulting in producing fluorescent resorufin products in the droplets. With optimized conditions such as the thickness of a hydrogel film and the size and flowing rate of droplets, fluorescence intensities of the released droplets linearly increased in proportional to the glucose concentration up to 3mM, and the limit of detection was calculated as 6.64µM. A spiked glucose in a real urine sample was also successfully analyzed, and the functionality of the proposed enzyme immobilized microfluidic chip was maintained for at least two weeks without loss of enzymatic activity and detection sensitivity. Thus, our methodology suggests a novel droplet based glucose sensing chip which can monitor glucose in a real-time and high-throughput manner.

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

    DEFF Research Database (Denmark)

    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...... communicate what is happening around us. Following the advances of all these communication devices as well as those in microfabrication and nanofabrication and the emergence of new materials, technologies such as lab-on-a-chip (LOC) and micro total analysis systems (microTAS) were also boosted, albeit...... at a slower pace. LOC and microTAS applications have principally been utilized in the biomedical, food and environmental fields. But lately they have also found their place in the synthesis of new chemical compounds and the fabrication of nanostructures. It has become obvious that the LOC and micro...

  12. Fabrication of polyimide based microfluidic channels for biosensor devices

    DEFF Research Database (Denmark)

    Zulfiqar, Azeem; Pfreundt, Andrea; Svendsen, Winnie Edith

    2015-01-01

    The ever-increasing complexity of the fabrication process of Point-of-care (POC) devices, due to high demand of functional versatility, compact size and ease-of-use, emphasizes the need of multifunctional materials that can be used to simplify this process. Polymers, currently in use for the fabr...... in uniformity of PI is also compared to the most commonly used SU8 polymer, which is a near UV sensitive epoxy resin. The potential applications of PI processing are POC and biosensor devices integrated with microelectronics....

  13. Passive micro-assembly of modular, hot embossed, polymer microfluidic devices using exact constraint design

    Science.gov (United States)

    You, Byoung Hee; Chen, Pin-Chuan; Park, Daniel S.; Park, Sunggook; Nikitopoulos, Dimitris E.; Soper, Steven A.; Murphy, Michael C.

    2009-12-01

    Low-cost microfluidic platforms have the potential to change accepted practices in many fields, including biology and medicine, in the near future. Micro-assembly of molded polymer microfluidic devices is one approach to cost-effective mass production of modular, microfluidic instruments. Polymer, passive alignment structures were used to precisely assemble molded polymer components to prevent infinitesimal motions and minimize the misalignment between assembled components and devices. The motion and constraint of the assemblies were analyzed using screw theory to identify combinations of passive alignment structures that would provide exact constraint of all degrees of freedom of the two mating parts without over-constraint. One option identified by kinematic analysis was a set of three v-groove and hemisphere-tipped pin joints, which are well known from precision engineering and suitable for microfabrication. To validate the passive alignment scheme, brass mold inserts containing alignment structures were micro-milled and used to hot emboss components in polycarbonate (PC). Dimensional and location variations of prototype alignment structures were measured to quantify the difference between the as-designed and actual dimensions and the locations of the alignment structures. The dimensional variation was 0.2-3% less than the designed dimensions and the location variation was 0.7% less. The alignment accuracy of an assembly was characterized by measuring the mismatch and vertical variation between molded alignment standards embossed on each pair of mating plates. With molded, polymer alignment structures the mean mismatch and mean vertical variation were as low as 13 ± 3 µm in the lateral plane along the x- and y-axes and -6 ± 15 µm with respect to the nominal value of 107 µm. This micro-assembly technology is applicable to the integration of all microsystems including the interconnection of microfluidic devices, the assembly of hybrid microsystems and the

  14. Design and Fabrication a Microfluidic Device for Fetal Cells Dielectrophoretic Properties Characterization

    Energy Technology Data Exchange (ETDEWEB)

    Xu Guolin [Institute of Bioengineering and Nanotechnologies, 31 Biopolis, Way, The Nanos, hashmark 04-01, Singapore 138669 (Singapore); Chan, M B [Nanyang Technological University, Singapore. 16 Nanyang Drive, Singapore 637722 (Singapore); Yang, Charles [Nanyang Technological University, Singapore. 16 Nanyang Drive, Singapore 637722 (Singapore); Sukumar, P [National University Hospital, Singapore. 10 Medical Drive, Singapore 117597 (Singapore); Choolani, M [National University Hospital, Singapore. 10 Medical Drive, Singapore 117597 (Singapore); Ying, Jackie Y [Institute of Bioengineering and Nanotechnologies, 31 Biopolis, Way, The Nanos, hashmark 04-01, Singapore 138669 (Singapore)

    2006-04-01

    The present work presents a microfluidic device with interdigitated microelectrode and microchannel for fetal nucleated red blood cell dielectrophoresis properties characterization using crossover frequency method. To obtain the electric field and its gradient along the microchannel, simulation study was done by using MAXWELL{sup TM} software. Results show maximum electric field and gradient are obtained near the electrode edge and they are affected by electrode width and the electrode gap. The crossover frequency should be obtained by keeping the cell moving near the electrode edge. The device has been successfully used in fetal cell characterization with better than 1KHz frequency repeatability, which is about 2% of the measured crossover frequency.

  15. Two-ply channels for faster wicking in paper-based microfluidic devices.

    Science.gov (United States)

    Camplisson, Conor K; Schilling, Kevin M; Pedrotti, William L; Stone, Howard A; Martinez, Andres W

    2015-12-01

    This article describes the development of porous two-ply channels for paper-based microfluidic devices that wick fluids significantly faster than conventional, porous, single-ply channels. The two-ply channels were made by stacking two single-ply channels on top of each other and were fabricated entirely out of paper, wax and toner using two commercially available printers, a convection oven and a thermal laminator. The wicking in paper-based channels was studied and modeled using a modified Lucas-Washburn equation to account for the effect of evaporation, and a paper-based titration device incorporating two-ply channels was demonstrated.

  16. Microfluidic devices for stem-cell cultivation, differentiation and toxicity testing

    Science.gov (United States)

    Becker, Holger; Hansen-Hagge, Thomas; Kurtz, Andreas; Mrowka, Ralf; Wölfl, Stefan; Gärtner, Claudia

    2017-02-01

    The development of new drugs is time-consuming, extremely expensive and often promising drug candidates fail in late stages of the development process due to the lack of suitable tools to either predict toxicological effects or to test drug candidates in physiologically relevant environments prior to clinical tests. We therefore try to develop diagnostic multiorgan microfluidic chips based on patient specific induced pluripotent stem cell (iPS) technology to explore liver dependent toxic effects of drugs on individual human tissues such as liver or kidney cells. Based initially on standardized microfluidic modules for cell culture, we have developed integrated microfluidic devices which contain different chambers for cell/tissue cultivation. The devices are manufactured using injection molding of thermoplastic polymers such as polystyrene or cyclo-olefin polymer. In the project, suitable surface modification methods of the used materials had to be explored. We have been able to successfully demonstrate the seeding, cultivation and further differentiation of modified iPS, as shown by the use of differentiation markers, thus providing a suitable platform for toxicity testing and potential tissue-tissue interactions.

  17. Combining Electro-Osmotic Flow and FTA® Paper for DNA Analysis on Microfluidic Devices

    Directory of Open Access Journals (Sweden)

    Ryan Wimbles

    2016-07-01

    Full Text Available FTA® paper can be used to protect a variety of biological samples prior to analysis, facilitating ease-of-transport to laboratories or long-term archive storage. The use of FTA® paper as a solid phase eradicates the need to elute the nucleic acids from the matrix prior to DNA amplification, enabling both DNA purification and polymerase chain reaction (PCR-based DNA amplification to be performed in a single chamber on the microfluidic device. A disc of FTA® paper, containing a biological sample, was placed within the microfluidic device on top of wax-encapsulated DNA amplification reagents. The disc containing the biological sample was then cleaned up using Tris-EDTA (TE buffer, which was passed over the disc, via electro-osmotic flow, in order to remove any potential inhibitors of downstream processes. DNA amplification was successfully performed (from buccal cells, whole blood and semen using a Peltier thermal cycling system, whereupon the stored PCR reagents were released during the initial denaturing step due to the wax barrier melting between the FTA® disc and PCR reagents. Such a system offers advantages in terms of a simple sample introduction interface and the ability to process archived samples in an integrated microfluidic environment with minimal risk of contamination.

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

    Science.gov (United States)

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

    2014-11-04

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

  19. Investigating the fluid dynamics of rapid processes within microfluidic devices using bright-field microscopy.

    Science.gov (United States)

    Pirbodaghi, Tohid; Vigolo, Daniele; Akbari, Samin; deMello, Andrew

    2015-05-07

    The widespread application of microfluidic devices in the biological and chemical sciences requires the implementation of complex designs and geometries, which in turn leads to atypical fluid dynamic phenomena. Accordingly, a complete understanding of fluid dynamics in such systems is key in the facile engineering of novel and efficient analytical tools. Herein, we present an accurate approach for studying the fluid dynamics of rapid processes within microfluidic devices using bright-field microscopy with white light illumination and a standard high-speed camera. Specifically, we combine Ghost Particle Velocimetry and the detection of moving objects in automated video surveillance to track submicron size tracing particles via cross correlation between the speckle patterns of successive images. The efficacy of the presented technique is demonstrated by measuring the flow field over a square pillar (80 μm × 80 μm) in a 200 μm wide microchannel at high volumetric flow rates. Experimental results are in excellent agreement with those obtained via computational fluid dynamics simulations. The method is subsequently used to study the dynamics of droplet generation at a flow focusing microfluidic geometry. A unique feature of the presented technique is the ability to perform velocimetry analysis of high-speed phenomena, which is not possible using micron-resolution particle image velocimetry (μPIV) approaches based on confocal or fluorescence microscopy.

  20. SU-8 as Hydrophobic and Dielectric Thin Film in Electrowetting-on-Dielectric Based Microfluidics Device

    Directory of Open Access Journals (Sweden)

    Vijay Kumar

    2012-01-01

    Full Text Available Electrowetting-on-dielectric (EWOD based droplet actuation in microfluidic chip is designed and fabricated. EWOD is used as on-chip micro-pumping scheme for moving fluid digitally in Lab-on-a-chip devices. For enabling this scheme, stacked deposition of thin dielectric and hydrophobic layer in that order between microchannel and electrodes is done. The present paper investigates the potential use of SU-8 as hydrophobic layer in conjunction of acting as dielectric in the device. The objective for the investigation is to lower the cost and a thin simplification in fabrication process of EWOD-based devices. We have done design and optimization of dimensions of electrode array including gap between arrays for EWOD micropump. Design and optimization are carried out in CoventorWare. The designing is followed by fabrication of device and analysis for droplet motion. The fabrication of the device includes array of electrodes over the silicon surface and embedding them in hydrophobic SU-8 layer. Water droplet movement in the order of microliter of spherical shape is demonstrated. It has been shown that an SU-8 microchannel in the current design allows microfluidic flow at tens of voltages comparable with costlier and more complicated to fabricate designs reported in the literature.

  1. Microfluidic device based on a micro-hydrocyclone for particle-liquid separation.

    Science.gov (United States)

    Bhardwaj, P; Bagdi, P; Sen, A K

    2011-12-07

    This paper presents theoretical analysis, design, simulation, fabrication and test of a microfluidic device ('Micro-hydrocyclone') for separation of micron and submicron size solid particles from liquid in a particle liquid mixture. A theoretical analysis of the micro-hydrocyclone is performed to understand the physics and develop suitable design models. The structure of the proposed device is designed based on the Bradley model, as it offers lower cut-size thus making it suitable for microfluidics applications. The operational parameters are derived from the dimensional group model. The particle separation process inside the micro-hydrocyclone is simulated by solving fluid flows using Navier-Stokes equations and particle dynamics using a Lagrangian approach in a Eulerian fluid. The influence of inlet velocity and density on separation efficiency is investigated. The device is fabricated with SU-8 photoresist on a PMMA substrate using a combination of photolithography and micro-milling. Experiments are performed to demonstrate particle-liquid separation using polystyrene microbeads suspended in PBS as the feed sample. The influence of inlet velocity and particle size on particle separation efficiency is measured and compared with that obtained from simulations and a good match was found. The proposed device can be easily integrated with micro-environments thus it is suitable for lab-on-chip and microsystems development. The device may have applications in chemical analysis, materials research, point-of-care, blood sample preparation and other biomedical applications.

  2. SAW-grade SiO2 for advanced microfluidic devices

    Science.gov (United States)

    Winkler, Andreas; Menzel, Siegfried; Schmidt, Hagen

    2009-05-01

    Acoustoelectronic devices based on surface acoustic wave (SAW) technology are primarily used in radio frequency filters, delay lines, duplexers, amplifiers and RFID tags. Thereby, SAW's are excited at the surface of piezoelectric materials (e.g. Quartz, LiTaO3, LiNbO3) by an RF signal applied via interdigital transducers (IDTs)1. Novel SAW applications that emerged recently in the field of microfluidics such as the handling of minimum quantities of fluids or gases2,3 require a fluid compatible design approach, high power durability and long lifetime of the devices. However, conventional SAW devices with finger electrodes arranged on top of the chip surface experience acoustomigration damage4,5 at high power input and/or higher operating temperature leading to failure of the device. Additionally, inappropriate material systems or chip surface topography can limit their performance in microfluidic application. To overcome these limitations the electrodes can be buried in an acoustically suited ("SAW-grade") functional layer which moreover should be adjustable to the specific biotechnological task. Depending on the properties of this layer, it can suppress the acoustomigration impact6 and improve the power durability of the device. Also, a reduction of the thermally-induced frequency shift is possible7. The present paper describes a novel SAW based chip technology approach using a modular concept. Here, the electrodes are buried in surface polished SAW-grade SiO2 fabricated by means of reactive RF magnetron sputtering from a SiO2- target. This approach will be demonstrated for two different metallization systems based on Al or Cu thin films on 128° YX-LiNbO3 substrates. We also show the application of the SiO2-layer with respect to compensation of thermallyinduced frequency shift and bio /chemical surface modification. Investigations were carried out using atomic force microscopy, laser-pulse acoustic measurement, glow-discharge optical emission spectroscopy

  3. Single cell array impedance analysis in a microfluidic device

    Science.gov (United States)

    Altinagac, Emre; Taskin, Selen; Kizil, Huseyin

    2016-10-01

    Impedance analysis of single cells is presented in this paper. Following the separation of a target cell type by dielectrophoresis in our previous work, this paper focuses on capturing the cells as a single array and performing impedance analysis to point out the signature difference between each cell type. Lab-on-a-chip devices having a titanium interdigitated electrode layer on a glass substrate and a PDMS microchannel are fabricated to capture each cell in a single form and perform impedance analysis. HCT116 (homosapiens colon colorectal carcin) and HEK293 (human embryonic kidney) cells are used in our experiments.

  4. Microfluidic devices for analysis of spatial orientation behaviors in semi-restrained Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Kathryn E McCormick

    Full Text Available This article describes the fabrication and use of microfluidic devices for investigating spatial orientation behaviors in nematode worms (Caenorhabditis elegans. Until now, spatial orientation has been studied in freely moving nematodes in which the frequency and nature of encounters with the gradient are uncontrolled experimental variables. In the new devices, the nematode is held in place by a restraint that aligns the longitudinal axis of the body with the border between two laminar fluid streams, leaving the animal's head and tail free to move. The content of the fluid streams can be manipulated to deliver step gradients in space or time. We demonstrate the utility of the device by identifying previously uncharacterized aspects of the behavioral mechanisms underlying chemotaxis, osmotic avoidance, and thermotaxis in this organism. The new devices are readily adaptable to behavioral and imaging studies involving fluid borne stimuli in a wide range of sensory modalities.

  5. USING OXYGEN-CONSUMING THERMOSET PLASTICS TO GENERATE HYPOXIC CONDITIONS IN MICROFLUIDIC DEVICES FOR POTENTIAL CELL CULTURE APPLICATIONS

    DEFF Research Database (Denmark)

    Sticker, Drago; Rothbauer, Mario; Ehgartner, Josef

    2017-01-01

    The precise control of the oxygen concentration in a cellular environment allows the study of cells under physiologically relevant conditions. This work reports on a novel method for the generation of reduced dissolved oxygen concentrations in microfluidic chambers for cell- and organ......-on-chip applications. Using a thermoset polymeric material (OSTEMERTM), which effectively scavenges dissolved oxygen (DO), microfluidic devices have been fabricated where oxygen was rapidly depleted from the microfluidic chamber. It is shown that hypoxic and anaerobic conditions can be generated through the inherent...

  6. Fast production of microfluidic devices by CO2 laser engraving of wax-coated glass slides.

    Science.gov (United States)

    da Costa, Eric T; Santos, Mauro F S; Jiao, Hong; do Lago, Claudimir L; Gutz, Ivano G R; Garcia, Carlos D

    2016-07-01

    Glass is one of the most convenient materials for the development of microfluidic devices. However, most fabrication protocols require long processing times and expensive facilities. As a convenient alternative, polymeric materials have been extensively used due their lower cost and versatility. Although CO2 laser ablation has been used for fast prototyping on polymeric materials, it cannot be applied to glass devices because the local heating causes thermal stress and results in extensive cracking. A few papers have shown the ablation of channels or thin holes (used as reservoirs) on glass but the process is still far away from yielding functional glass microfluidic devices. To address these shortcomings, this communication describes a simple method to engrave glass-based capillary electrophoresis devices using standard (1 mm-thick) microscope glass slides. The process uses a sacrificial layer of wax as heat sink and enables the development of both channels (with semicircular shape) and pass-through reservoirs. Although microscope images showed some small cracks around the channels (that became irrelevant after sealing the engraved glass layer to PDMS) the proposed strategy is a leap forward in the application of the technology to glass. In order to demonstrate the capabilities of the approach, the separation of dopamine, catechol and uric acid was accomplished in less than 100 s.

  7. A cell sorting and trapping microfluidic device with an interdigital channel

    Science.gov (United States)

    Tu, Jing; Qiao, Yi; Xu, Minghua; Li, Junji; Liang, Fupeng; Duan, Mengqin; Ju, An; Lu, Zuhong

    2016-12-01

    The growing interest in cell sorting and trapping is driving the demand for high performance technologies. Using labeling techniques or external forces, cells can be identified by a series of methods. However, all of these methods require complicated systems with expensive devices. Based on inherent differences in cellular morphology, cells can be sorted by specific structures in microfluidic devices. The weir filter is a basic and efficient cell sorting and trapping structure. However, in some existing weir devices, because of cell deformability and high flow velocity in gaps, trapped cells may become stuck or even pass through the gaps. Here, we designed and fabricated a microfluidic device with interdigital channels for cell sorting and trapping. The chip consisted of a sheet of silicone elastomer polydimethylsiloxane and a sheet of glass. A square-wave-like weir was designed in the middle of the channel, comprising the interdigital channels. The square-wave pattern extended the weir length by three times with the channel width remaining constant. Compared with a straight weir, this structure exhibited a notably higher trapping capacity. Interdigital channels provided more space to slow down the rate of the pressure decrease, which prevented the cells from becoming stuck in the gaps. Sorting a mixture K562 and blood cells to trap cells demonstrated the efficiency of the chip with the interdigital channel to sort and trap large and less deformable cells. With stable and efficient cell sorting and trapping abilities, the chip with an interdigital channel may be widely applied in scientific research fields.

  8. An integrated hybrid microfluidic device for oviposition-based chemical screening of adult Drosophila melanogaster.

    Science.gov (United States)

    Leung, Jacob C K; Hilliker, Arthur J; Rezai, Pouya

    2016-02-21

    Chemical screening using Drosophila melanogaster (the fruit fly) is vital in drug discovery, agricultural, and toxicological applications. Oviposition (egg laying) on chemically-doped agar plates is an important read-out metric used to quantitatively assess the biological fitness and behavioral responses of Drosophila. Current oviposition-based chemical screening studies are inaccurate, labor-intensive, time-consuming, and inflexible due to the manual chemical doping of agar. In this paper, we have developed a novel hybrid agar-polydimethylsiloxane (PDMS) microfluidic device for single- and multi-concentration chemical dosing and on-chip oviposition screening of free-flying adult stage Drosophila. To achieve this, we have devised a novel technique to integrate agar with PDMS channels using ice as a sacrificial layer. Subsequently, we have conducted single-chemical toxicity and multiple choice chemical preference assays on adult Drosophila melanogaster using zinc and acetic acid at various concentrations. Our device has enabled us to 1) demonstrate that Drosophila is capable of sensing the concentration of different chemicals on a PDMS-agar microfluidic device, which plays significant roles in determining oviposition site selection and 2) investigate whether oviposition preference differs between single- and multi-concentration chemical environments. This device may be used to study fundamental and applied biological questions in Drosophila and other egg laying insects. It can also be extended in design to develop sophisticated and dynamic chemical dosing and high-throughput screening platforms in the future that are not easily achievable with the existing oviposition screening techniques.

  9. Single-cell cloning and expansion of human induced pluripotent stem cells by a microfluidic culture device.

    Science.gov (United States)

    Matsumura, Taku; Tatsumi, Kazuya; Noda, Yuichiro; Nakanishi, Naoyuki; Okonogi, Atsuhito; Hirano, Kunio; Li, Liu; Osumi, Takashi; Tada, Takashi; Kotera, Hidetoshi

    2014-10-10

    The microenvironment of cells, which includes basement proteins, shear stress, and extracellular stimuli, should be taken into consideration when examining physiological cell behavior. Although microfluidic devices allow cellular responses to be analyzed with ease at the single-cell level, few have been designed to recover cells. We herein demonstrated that a newly developed microfluidic device helped to improve culture conditions and establish a clonality-validated human pluripotent stem cell line after tracing its growth at the single-cell level. The device will be a helpful tool for capturing various cell types in the human body that have not yet been established in vitro.

  10. Fractionation by shape in deterministic lateral displacement microfluidic devices

    CERN Document Server

    Jiang, Mingliang; Drazer, German

    2014-01-01

    We investigate the migration of particles of different geometrical shapes and sizes in a scaled-up model of a gravity-driven deterministic lateral displacement (g-DLD) device. Specifically, particles move through a square array of cylindrical posts as they settle under the action of gravity. We performed experiments that cover a broad range of orientations of the driving force (gravity) with respect to the columns (or rows) in the square array of posts. We observe that as the forcing angle increases particles initially locked to move parallel to the columns in the array begin to move across the columns of obstacles and migrate at angles different from zero. We measure the probability that a particle would move across a column of obstacles, and define the critical angle {\\theta}c as the forcing angle at which this probability is 1/2. We show that critical angle depends both on particle size and shape, thus enabling both size- and shape-based separations. Finally, we show that using the diameter of the inscribe...

  11. Long-Term Growth of Moss in Microfluidic Devices Enables Subcellular Studies in Development.

    Science.gov (United States)

    Bascom, Carlisle S; Wu, Shu-Zon; Nelson, Katherine; Oakey, John; Bezanilla, Magdalena

    2016-09-01

    Key developmental processes that occur on the subcellular and cellular level or occur in occluded tissues are difficult to access, let alone image and analyze. Recently, culturing living samples within polydimethylsiloxane (PDMS) microfluidic devices has facilitated the study of hard-to-reach developmental events. Here, we show that an early diverging land plant, Physcomitrella patens, can be continuously cultured within PDMS microfluidic chambers. Because the PDMS chambers are bonded to a coverslip, it is possible to image P. patens development at high resolution over long time periods. Using PDMS chambers, we report that wild-type protonemal tissue grows at the same rate as previously reported for growth on solid medium. Using long-term imaging, we highlight key developmental events, demonstrate compatibility with high-resolution confocal microscopy, and obtain growth rates for a slow-growing mutant. By coupling the powerful genetic tools available to P. patens with long-term growth and imaging provided by PDMS microfluidic chambers, we demonstrate the capability to study cellular and subcellular developmental events in plants directly and in real time.

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

    Science.gov (United States)

    Durant, Eden; Higgins, Adam; Sharp, Kendra

    2014-11-01

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

  13. Microfluidic electrochemical device and process for chemical imaging and electrochemical analysis at the electrode-liquid interface in-situ

    Science.gov (United States)

    Yu, Xiao-Ying; Liu, Bingwen; Yang, Li; Zhu, Zihua; Marshall, Matthew J.

    2016-03-01

    A microfluidic electrochemical device and process are detailed that provide chemical imaging and electrochemical analysis under vacuum at the surface of the electrode-sample or electrode-liquid interface in-situ. The electrochemical device allows investigation of various surface layers including diffuse layers at selected depths populated with, e.g., adsorbed molecules in which chemical transformation in electrolyte solutions occurs.

  14. Flexible microfluidic device for mechanical property characterization of soft viscoelastic solids such as bacterial biofilms.

    Science.gov (United States)

    Hohne, Danial N; Younger, John G; Solomon, Michael J

    2009-07-01

    We introduce a flexible microfluidic device to characterize the mechanical properties of soft viscoelastic solids such as bacterial biofilms. In the device, stress is imposed on a test specimen by the application of a fixed pressure to a thin, flexible poly(dimethyl siloxane) (PDMS) membrane that is in contact with the specimen. The stress is applied by pressurizing a microfabricated air channel located above the test area. The strain resulting from the applied stress is quantified by measuring the membrane deflection with a confocal laser scanning microscope. The deflection is governed by the viscoelastic properties of the PDMS membrane and of the test specimen. The relative contributions of the membrane and test material to the measured deformation are quantified by comparing a finite element analysis with an independent (control) measurement of the PDMS membrane mechanical properties. The flexible microfluidic rheometer was used to characterize both the steady-state elastic modulus and the transient strain recoil of two soft materials: gellan gums and bacterial biofilms. The measured linear elastic moduli and viscoelastic relaxation times of gellan gum solutions were in good agreement with the results of conventional mechanical rheometry. The linear Young's moduli of biofilms of Staphylococcus epidermidis and Klebsiella pneumoniae, which could not be measured using conventional methods, were found to be 3.2 and 1.1 kPa, respectively, and the relaxation time of the S. epidermidis biofilm was 13.8 s. Additionally, strain hardening was observed in all the biofilms studied. Finally, design parameters and detection limits of the method show that the device is capable of characterizing soft viscoelastic solids with elastic moduli in the range of 102-105 Pa. The flexible microfluidic rheometer addresses the need for mechanical property characterization of soft viscoelastic solids common in fields such as biomaterials, food, and consumer products. It requires only 200 p

  15. Isothermal circular-strand-displacement polymerization of DNA and microRNA in digital microfluidic devices.

    Science.gov (United States)

    Giuffrida, Maria Chiara; Zanoli, Laura Maria; D'Agata, Roberta; Finotti, Alessia; Gambari, Roberto; Spoto, Giuseppe

    2015-02-01

    Nucleic-acid amplification is a crucial step in nucleic-acid-sequence-detection assays. The use of digital microfluidic devices to miniaturize amplification techniques reduces the required sample volume and the analysis time and offers new possibilities for process automation and integration in a single device. The recently introduced droplet polymerase-chain-reaction (PCR) amplification methods require repeated cycles of two or three temperature-dependent steps during the amplification of the nucleic-acid target sequence. In contrast, low-temperature isothermal-amplification methods have no need for thermal cycling, thus requiring simplified microfluidic-device features. Here, the combined use of digital microfluidics and molecular-beacon (MB)-assisted isothermal circular-strand-displacement polymerization (ICSDP) to detect microRNA-210 sequences is described. MicroRNA-210 has been described as the most consistently and predominantly upregulated hypoxia-inducible factor. The nmol L(-1)-pmol L(-1) detection capabilities of the method were first tested by targeting single-stranded DNA sequences from the genetically modified Roundup Ready soybean. The ability of the droplet-ICSDP method to discriminate between full-matched, single-mismatched, and unrelated sequences was also investigated. The detection of a range of nmol L(-1)-pmol L(-1) microRNA-210 solutions compartmentalized in nanoliter-sized droplets was performed, establishing the ability of the method to detect as little as 10(-18) mol of microRNA target sequences compartmentalized in 20 nL droplets. The suitability of the method for biological samples was tested by detecting microRNA-210 from transfected K562 cells.

  16. Investigating Nonalcoholic Fatty Liver Disease in a Liver-on-a-Chip Microfluidic Device

    Science.gov (United States)

    Simonelli, Maria Chiara; Giannitelli, Sara Maria; Businaro, Luca; Trombetta, Marcella; Rainer, Alberto

    2016-01-01

    Background and Aim Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease worldwide, ranging from simple steatosis to nonalcoholic steatohepatitis, which may progress to cirrhosis, eventually leading to hepatocellular carcinoma (HCC). HCC ranks as the third highest cause of cancer-related death globally, requiring an early diagnosis of NAFLD as a potential risk factor. However, the molecular mechanisms underlying NAFLD are still under investigation. So far, many in vitro studies on NAFLD have been hampered by the limitations of 2D culture systems, in which cells rapidly lose tissue-specific functions. The present liver-on-a-chip approach aims at filling the gap between conventional in vitro models, often scarcely predictive of in vivo conditions, and animal models, potentially biased by their xenogeneic nature. Methods HepG2 cells were cultured into a microfluidically perfused device under free fatty acid (FFA) supplementation, namely palmitic and oleic acid, for 24h and 48h. The device mimicked the endothelial-parenchymal interface of a liver sinusoid, allowing the diffusion of nutrients and removal of waste products similar to the hepatic microvasculature. Assessment of intracellular lipid accumulation, cell viability/cytotoxicity and oxidative stress due to the FFA overload, was performed by high-content analysis methodologies using fluorescence-based functional probes. Results The chip enables gradual and lower intracellular lipid accumulation, higher hepatic cell viability and minimal oxidative stress in microfluidic dynamic vs. 2D static cultures, thus mimicking the chronic condition of steatosis observed in vivo more closely. Conclusions Overall, the liver-on-a-chip system provides a suitable culture microenvironment, representing a more reliable model compared to 2D cultures for investigating NAFLD pathogenesis. Hence, our system is amongst the first in vitro models of human NAFLD developed within a microfluidic device in a sinusoid

  17. Investigating Nonalcoholic Fatty Liver Disease in a Liver-on-a-Chip Microfluidic Device.

    Directory of Open Access Journals (Sweden)

    Manuele Gori

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is a chronic liver disease worldwide, ranging from simple steatosis to nonalcoholic steatohepatitis, which may progress to cirrhosis, eventually leading to hepatocellular carcinoma (HCC. HCC ranks as the third highest cause of cancer-related death globally, requiring an early diagnosis of NAFLD as a potential risk factor. However, the molecular mechanisms underlying NAFLD are still under investigation. So far, many in vitro studies on NAFLD have been hampered by the limitations of 2D culture systems, in which cells rapidly lose tissue-specific functions. The present liver-on-a-chip approach aims at filling the gap between conventional in vitro models, often scarcely predictive of in vivo conditions, and animal models, potentially biased by their xenogeneic nature.HepG2 cells were cultured into a microfluidically perfused device under free fatty acid (FFA supplementation, namely palmitic and oleic acid, for 24h and 48h. The device mimicked the endothelial-parenchymal interface of a liver sinusoid, allowing the diffusion of nutrients and removal of waste products similar to the hepatic microvasculature. Assessment of intracellular lipid accumulation, cell viability/cytotoxicity and oxidative stress due to the FFA overload, was performed by high-content analysis methodologies using fluorescence-based functional probes.The chip enables gradual and lower intracellular lipid accumulation, higher hepatic cell viability and minimal oxidative stress in microfluidic dynamic vs. 2D static cultures, thus mimicking the chronic condition of steatosis observed in vivo more closely.Overall, the liver-on-a-chip system provides a suitable culture microenvironment, representing a more reliable model compared to 2D cultures for investigating NAFLD pathogenesis. Hence, our system is amongst the first in vitro models of human NAFLD developed within a microfluidic device in a sinusoid-like fashion, endowing a more permissive

  18. Integration of Multiple Components in Polystyrene-based Microfluidic Devices Part 1: Fabrication and Characterization

    Science.gov (United States)

    Johnson, Alicia S.; Anderson, Kari B.; Halpin, Stephen T.; Kirkpatrick, Douglas C.; Spence, Dana M.; Martin, R. Scott

    2012-01-01

    In Part I of a two-part series, we describe a simple, and inexpensive approach to fabricate polystyrene devices that is based upon melting polystyrene (from either a Petri dish or powder form) against PDMS molds or around electrode materials. The ability to incorporate microchannels in polystyrene and integrate the resulting device with standard laboratory equipment such as an optical plate reader for analyte readout and micropipettors for fluid propulsion is first described. A simple approach for sample and reagent delivery to the device channels using a standard, multi-channel micropipette and a PDMS-based injection block is detailed. Integration of the microfluidic device with these off-chip functions (sample delivery and readout) enables high throughput screens and analyses. An approach to fabricate polystyrene-based devices with embedded electrodes is also demonstrated, thereby enabling the integration of microchip electrophoresis with electrochemical detection through the use of a palladium electrode (for a decoupler) and carbon-fiber bundle (for detection). The device was sealed against a PDMS-based microchannel and used for the electrophoretic separation and amperometric detection of dopamine, epinephrine, catechol, and 3,4-dihydroxyphenylacetic acid. Finally, these devices were compared against PDMS-based microchips in terms of their optical transparency and absorption of an anti-platelet drug, clopidogrel. Part I of this series lays the foundation for Part II, where these devices were utilized for various on-chip cellular analysis. PMID:23120747

  19. Simulation of Droplet Dynamics and Mixing in Microfluidic Devices Using a VOF-Based Method

    Directory of Open Access Journals (Sweden)

    Anurag CHANDORKAR

    2009-10-01

    Full Text Available This paper demonstrates that the Volume of Fluid (TruVOF® method in FLOW-3D® general purpose CFD software is an effective tool for studying droplet dynamics and mixing in microfluidic devices. The first example studied is a T-junction where flow patterns for both droplet generation and passive mixing are analyzed. The second example studied is a co-flowing device where the formation and breakup of bubbles is simulated. The effect of viscosity on bubble formation is also analyzed. For a T-junction the bubble size is corroborated with experimental data. Both the bubble size and frequency are studied and corroborated with experimental data for a co-flowing device. The third example studied is the electrowetting phenomenon observed in a small water droplet resting on a dielectric material. The steady-state contact angle is plotted against the voltage applied. The results are compared with both the Young-Lippmann curve and experimental results.

  20. Polyimide microfluidic devices with integrated nanoporous filtration areas manufactured by micromachining and ion track technology

    Science.gov (United States)

    Metz, S.; Trautmann, C.; Bertsch, A.; Renaud, Ph

    2004-03-01

    This paper reports on polyimide microfluidic devices fabricated by photolithography and a layer transfer lamination technology. The microchannels are sealed by laminating an uncured polyimide film on a partially cured layer and subsequent imidization. Selected areas of the microchannels were irradiated with heavy ions of several hundred MeV and the generated ion tracks are chemically etched to submicron pores of high aspect ratio. The ion beam parameters and the track etching conditions define density, length, diameter and shape of the pores. Membrane permeability and separation performance is demonstrated in cross-flow filtration experiments. The devices can be used for selective delivery or probing of fluids to biological tissue, e.g. drug delivery or microdialysis. For chip-based devices the filters can be used as a sample pre-treatment unit for filtration or concentration of particles or molecules.

  1. Microfluidic device to study cell transmigration under physiological shear stress conditions

    DEFF Research Database (Denmark)

    Kwasny, Dorota; Kiilerich-Pedersen, Katrine; Moresco, Jacob Lange

    2011-01-01

    the membrane under flow conditions. The 3D environment of migrating cells is imitated by injecting cell adhesion proteins to coat the membrane in the device. We tested the developed device with Jurkat cells migration towards medium supplemented with serum, and with chemokine induced lymphocytes migration......The development of new drug therapies relies on studies of cell transmigration in in vitro systems. Migration has traditionally been studied using two methods, the Boyden chamber and a shear flow chamber assay. Though, commonly applied in cell transmigration studies, they are far from imitating...... a natural migration process. Here we describe a novel in vitro cell transmigration microfluidic assay, which mimicks physiological shear flow conditions in blood vessels. The device was designed to incorporate the principles of both the Boyden chamber and the shear flow chamber assay, i.e. migration through...

  2. Rapid Fabrication of Electrophoretic Microfluidic Devices from Polyester, Adhesives and Gold Leaf

    Directory of Open Access Journals (Sweden)

    Christopher Birch

    2017-01-01

    Full Text Available In the last decade, the microfluidic community has witnessed an evolution in fabrication methodologies that deviate from using conventional glass and polymer-based materials. A leading example within this group is the print, cut and laminate (PCL approach, which entails the laser cutting of microfluidic architecture into ink toner-laden polyester sheets, followed by the lamination of these layers for device assembly. Recent success when applying this method to human genetic fingerprinting has highlighted that it is now ripe for the refinements necessary to render it amenable to mass-manufacture. In this communication, we detail those modifications by identifying and implementing a suitable heat-sensitive adhesive (HSA material to equip the devices with the durability and resilience required for commercialization and fieldwork. Importantly, this augmentation is achieved without sacrificing any of the characteristics which make the PCL approach attractive for prototyping. Exemplary HSA-devices performed DNA extraction, amplification and separation which, when combined, constitute the complete sequence necessary for human profiling and other DNA-based analyses.

  3. Quantitative Study of Cell Invasion Process under Extracellular Stimulation of Cytokine in a Microfluidic Device

    Science.gov (United States)

    Lei, Kin Fong; Tseng, Hsueh-Peng; Lee, Chia-Yi; Tsang, Ngan-Ming

    2016-05-01

    Cell invasion is the first step of cancer metastasis that is the primary cause of death for cancer patients and defined as cell movement through extracellular matrix (ECM). Investigation of the correlation between cell invasive and extracellular stimulation is critical for the inhabitation of metastatic dissemination. Conventional cell invasion assay is based on Boyden chamber assay, which has a number of limitations. In this work, a microfluidic device incorporating with impedance measurement technique was developed for quantitative investigation of cell invasion process. The device consisted of 2 reservoirs connecting with a microchannel filled with hydrogel. Malignant cells invaded along the microchannel and impedance measurement was concurrently conducted by measuring across electrodes located at the bottom of the microchannel. Therefore, cell invasion process could be monitored in real-time and non-invasive manner. Also, cell invasion rate was then calculated to study the correlation between cell invasion and extracellular stimulation, i.e., IL-6 cytokine. Results showed that cell invasion rate was directly proportional to the IL-6 concentration. The microfluidic device provides a reliable and convenient platform for cell-based assays to facilitate more quantitative assessments in cancer research.

  4. Isothermal Amplification Methods for the Detection of Nucleic Acids in Microfluidic Devices

    Directory of Open Access Journals (Sweden)

    Giuseppe Spoto

    2012-12-01

    Full Text Available Diagnostic tools for biomolecular detection need to fulfill specific requirements in terms of sensitivity, selectivity and high-throughput in order to widen their applicability and to minimize the cost of the assay. The nucleic acid amplification is a key step in DNA detection assays. It contributes to improving the assay sensitivity by enabling the detection of a limited number of target molecules. The use of microfluidic devices to miniaturize amplification protocols reduces the required sample volume and the analysis times and offers new possibilities for the process automation and integration in one single device. The vast majority of miniaturized systems for nucleic acid analysis exploit the polymerase chain reaction (PCR amplification method, which requires repeated cycles of three or two temperature-dependent steps during the amplification of the nucleic acid target sequence. In contrast, low temperature isothermal amplification methods have no need for thermal cycling thus requiring simplified microfluidic device features. Here, the use of miniaturized analysis systems using isothermal amplification reactions for the nucleic acid amplification will be discussed.

  5. Immobilization Techniques and Integrated Signal Enhancement for POC Nanocolor Microfluidic Devices

    Directory of Open Access Journals (Sweden)

    Marlies Schlauf

    2015-01-01

    Full Text Available Resonance enhanced absorption (REA nanocolor microfluidic devices are new promising bioassay platforms, which employ nanoparticle- (NP- protein conjugates for the immunodetection of medically relevant markers in biologic samples such as blood, urine, and saliva. The core component of a REA test device is a PET chip coated with aluminum and SiO2 thin layers, onto which biorecognitive molecules are immobilized. Upon addition of a sample containing the analyte of interest, a NP-protein-analyte complex is formed in the test device that is captured on the REA chip, for example, via streptavidin-biotin interaction. Thereby, a colored symbol is generated, which allows optical readout. Silver enhancement of the bound nanoparticles may be used to increase the sensitivity of the assay. Herein, we demonstrate that adsorptive immobilization via a cationic polymeric interlayer is a competitive and fast technique for the binding of the capture protein streptavidin onto planar SiO2 surfaces such as REA biochips. Moreover, we report the development of a silver enhancement technology that operates even in the presence of high chloride concentrations as may be encountered in biologic samples. The silver enhancement reagents may be integrated into the microfluidic assay platform to be released upon sample addition. Hereby, a highly sensitive one-step assay can be realized.

  6. Electrical Impedance Spectroscopy for Detection of Cells in Suspensions Using Microfluidic Device with Integrated Microneedles

    Directory of Open Access Journals (Sweden)

    Muhammad Asraf Mansor

    2017-02-01

    Full Text Available In this study, we introduce novel method of flow cytometry for cell detection based on impedance measurements. The state of the art method for impedance flow cytometry detection utilizes an embedded electrode in the microfluidic to perform measurement of electrical impedance of the presence of cells at the sensing area. Nonetheless, this method requires an expensive and complicated electrode fabrication process. Furthermore, reuse of the fabricated electrode also requires an intensive and tedious cleaning process. Due to that, we present a microfluidic device with integrated microneedles. The two microneedles are placed at the half height of the microchannel for cell detection and electrical measurement. A commercially-available Tungsten needle was utilized for the microneedles. The microneedles are easily removed from the disposable PDMS (Polydimethylsiloxane microchannel and can be reused with a simple cleaning process, such as washing by ultrasonic cleaning. Although this device was low cost, it preserves the core functionality of the sensor, which is capable of detecting passing cells at the sensing area. Therefore, this device is suitable for low-cost medical and food safety screening and testing process in developing countries.

  7. Online coupling of digital microfluidic devices with mass spectrometry detection using an eductor with electrospray ionization.

    Science.gov (United States)

    Baker, Christopher A; Roper, Michael G

    2012-03-20

    MS detection coupled with digital microfluidic (DMF) devices has most commonly been demonstrated in an offline manner using matrix assisted laser desorption ionization. In this work, an eductor is demonstrated which facilitated online coupling of DMF with electrospray ionization MS detection. The eductor consisted of a transfer capillary, a standard ESI needle, and a tapered gas nozzle. As a pulse of N(2) was applied to the nozzle, a pressure differential was induced at the outlet of the ESI needle that pulled droplets from the DMF, past the ESI needle, and into the flow of gas exiting the nozzle, allowing detection by MS. Operating position, ionization potential, and N(2) pressure were optimized, with the optimum ionization potential and N(2) pressure found to be 3206 V and 80 psi, respectively. Online MS detection was demonstrated from both open and closed DMF devices using 2.5 μL and 630 nL aqueous droplets, respectively. Relative quantitation by DMF-MS was demonstrated by mixing droplets of caffeine with droplets of theophylline on an open DMF device and comparing the peak area ratio obtained to an on-chip generated calibration curve. This eductor-based method for transferring droplets has the potential for rapid, versatile, and high-throughput microfluidic analyses.

  8. Three-dimensional paper-based microfluidic device for assays of protein and glucose in urine.

    Science.gov (United States)

    Sechi, Deidre; Greer, Brady; Johnson, Jesse; Hashemi, Nastaran

    2013-11-19

    The first step in curing a disease is being able to detect the disease effectively. Paper-based microfluidic devices are biodegradable and can make diagnosing diseases cost-effective and easy in almost all environments. We created a three-dimesnional (3D) paper device using wax printing fabrication technique and basic principles of origami. This design allows for a versatile fabrication technique over previously reported patterning of SU-8 photoresist on chromatography paper by employing a readily available wax printer. The design also utilizes multiple colorimetric assays that can accommodate one or more analytes including urine, blood, and saliva. In this case to demonstrate the functionality of the 3D paper-based microfluidic system, a urinalysis of protein and glucose assays is conducted. The amounts of glucose and protein introduced to the device are found to be proportional to the color change of each assay. This color change was quantified by use of Adobe Photoshop. Urine samples from participants with no pre-existing health conditions and one person with diabetes were collected and compared against synthetic urine samples with predetermined glucose and protein levels. Utilizing this method, we were able to confirm that both protein and glucose levels were in fact within healthy ranges for healthy participants. For the participant with diabetes, glucose was found to be above the healthy range while the protein level was in the healthy range.

  9. Performing chemical reactions in virtual capillary of surface tension-confined microfluidic devices

    Indian Academy of Sciences (India)

    Angshuman Nag; Biswa Ranjan Panda; Arun Chattopadhyay

    2005-10-01

    In this paper we report a new method of fabrication of surface tension-confined microfluidic devices on glass. We have also successfully carried out some well-known chemical reactions in these fluidic channels to demonstrate the usefulness of these wall-less microchannels. The confined flow path of liquid was achieved on the basis of extreme differences in hydrophobic and hydrophilic characters of the surface. The flow paths were fabricated by making parallel lines using permanent marker pen ink or other polymer on glass surfaces. Two mirror image patterned glass plates were then sandwiched one on top of the other, separated by a thin gap - created using a spacer. The aqueous liquid moves between the surfaces by capillary forces, confined to the hydrophilic areas without wetting the hydrophobic lines, achieving liquid confinement without physical side-walls. We have shown that the microfluidic devices designed in such a way can be very useful due to their simplicity and low fabrication cost. More importantly, we have also demonstrated that the minimum requirement of such a working device is a hydrophilic line surrounded by hydrophobic environment, two walls of which are constituted of air and the rest is made of a hydrophobic surface.

  10. A Microfluidic Love-Wave Biosensing Device for PSA Detection Based on an Aptamer Beacon Probe.

    Science.gov (United States)

    Zhang, Feng; Li, Shuangming; Cao, Kang; Wang, Pengjuan; Su, Yan; Zhu, Xinhua; Wan, Ying

    2015-06-11

    A label-free and selective aptamer beacon-based Love-wave biosensing device was developed for prostate specific antigen (PSA) detection. The device consists of the following parts: LiTaO3 substrate with SiO2 film as wave guide layer, two set of inter-digital transducers (IDT), gold film for immobilization of the biorecongniton layer and a polydimethylsiloxane (PDMS) microfluidic channels. DNA aptamer, or "artificial antibody", was used as the specific biorecognition probe for PSA capture. Some nucleotides were added to the 3'-end of the aptamer to form a duplex with the 3'-end, turning the aptamer into an aptamer-beacon. Taking advantage of the selective target-induced assembly changes arising from the "aptamer beacon", highly selective and specific detection of PSA was achieved. Furthermore, PDMS microfluidic channels were designed and fabricated to realize automated quantitative sample injection. After optimization of the experimental conditions, the established device showed good performance for PSA detection between 10 ng/mL to 1 μg/mL, with a detection limit of 10 ng/mL. The proposed sensor might be a promising alternative for point of care diagnostics.

  11. A Microfluidic Love-Wave Biosensing Device for PSA Detection Based on an Aptamer Beacon Probe

    Directory of Open Access Journals (Sweden)

    Feng Zhang

    2015-06-01

    Full Text Available A label-free and selective aptamer beacon-based Love-wave biosensing device was developed for prostate specific antigen (PSA detection. The device consists of the following parts: LiTaO3 substrate with SiO2 film as wave guide layer, two set of inter-digital transducers (IDT, gold film for immobilization of the biorecongniton layer and a polydimethylsiloxane (PDMS microfluidic channels. DNA aptamer, or “artificial antibody”, was used as the specific biorecognition probe for PSA capture. Some nucleotides were added to the 3'-end of the aptamer to form a duplex with the 3'-end, turning the aptamer into an aptamer-beacon. Taking advantage of the selective target-induced assembly changes arising from the “aptamer beacon”, highly selective and specific detection of PSA was achieved. Furthermore, PDMS microfluidic channels were designed and fabricated to realize automated quantitative sample injection. After optimization of the experimental conditions, the established device showed good performance for PSA detection between 10 ng/mL to 1 μg/mL, with a detection limit of 10 ng/mL. The proposed sensor might be a promising alternative for point of care diagnostics.

  12. A microfluidic device for simple and rapid evaluation of multidrug efflux pump inhibitors

    Directory of Open Access Journals (Sweden)

    Ryota eIino

    2012-02-01

    Full Text Available Recently, multidrug resistant pathogens have disseminated widely owing essentially to their increased multidrug efflux pump activity. Presently, there is a scarcity of new antibacterial agents, and hence, inhibitors of multidrug efflux pumps belonging to the resistance-nodulation-cell division (RND family appear useful in the treatment of infections by multidrug-resistant pathogens. Moreover, recent progress in microfabrication technologies has expanded the application of nano/micro-devices to the field of human healthcare, such as the detection of infections and diagnosis of diseases. We developed a microfluidic channel device for a simple and rapid evaluation of bacterial drug efflux activity. By combining the microfluidic device with a fluorogenic compound, fluorescein-di-β-D-galactopyranoside, which is hydrolyzed to a fluorescent dye in the cytoplasm of Escherichia coli, we successfully evaluated the effects of inhibitors on the RND-type multidrug efflux pumps MexAB-OprM and MexXY-OprM from Pseudomonas aeruginosa in E. coli. Our new method successfully detected the MexB-specific inhibitory effect of D13-9001 and revealed an unexpected membrane-permeabilizing effect of Phe-Arg-β-naphthylamide, which has long been used as an inhibitor.

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

  14. A Disposable Microfluidic Device with a Screen Printed Electrode for Mimicking Phase II Metabolism

    Directory of Open Access Journals (Sweden)

    Rafaela Vasiliadou

    2016-09-01

    Full Text Available Human metabolism is investigated using several in vitro methods. However, the current methodologies are often expensive, tedious and complicated. Over the last decade, the combination of electrochemistry (EC with mass spectrometry (MS has a simpler and a cheaper alternative to mimic the human metabolism. This paper describes the development of a disposable microfluidic device with a screen-printed electrode (SPE for monitoring phase II GSH reactions. The proposed chip has the potential to be used as a primary screening tool, thus complementing the current in vitro methods.

  15. High-stringency screening of target-binding partners using a microfluidic device

    Energy Technology Data Exchange (ETDEWEB)

    Soh, Hyongsok; Lou, Xinhui; Lagally, Eric

    2015-12-01

    The invention provides a method of screening a library of candidate agents by contacting the library with a target in a reaction mixture under a condition of high stringency, wherein the target includes a tag that responds to a controllable force applied to the tag, and passing the members of the library through a microfluidic device in a manner that exposes the library members to the controllable force, thereby displacing members of the library that are bound to the target relative to their unbound counterparts. Kits and systems for use with the methods of the invention are also provided.

  16. Development of microfluidic cell culture devices towards an in vitro human intestinal barrier model

    DEFF Research Database (Denmark)

    Tan, Hsih-Yin

    folds that closely resembled the intestinal villi and formation of a tight barrier. Furthermore, the microelectrodes embedded in the microchip also allow real-time monitoring of the barrier integrity by means of measuring the trans-epithelial electrical resistance. Demonstrations of transport studies...... using different compounds on the in vitro human intestinal model in the microfluidic device showed comparable results with static cultures. In addition, a normal commensal intestinal bacteria, Escherichia coli (E. coli) was successfully co-cultured on the luminal surface of the cultured epithelium...

  17. Microfluidic electronics.

    Science.gov (United States)

    Cheng, Shi; Wu, Zhigang

    2012-08-21

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

  18. Biologically Inspired Electronic, Photovoltaic and Microfluidic Devices Based on Aqueous Soft Matter

    Science.gov (United States)

    Koo, Hyung Jun

    Hydrogels are a water-based soft material where three dimensional networks of hydrophilic polymer retain large amounts of water. We developed hydrogel based devices with new functionalities inspired by materials, structures and processes in nature. The advantages, such as softness, biocompatibility and high ionic conductivity, could enable hydrogels to be novel materials for biomimetic devices operated by ionic current. Moreover, microfluidic patterns are easily embedded in moldable hydrogels and allow for unique convective/diffusive transport mechanism in porous gel to be used for uniform delivery of reagent solution. We first developed and characterized a device with unidirectional ionic current flow across a SiO2/Gel junction, which showed highly efficient rectification of the ionic current by non-linear conductivity of SiO2 films. Addition of polyelectrolytes and salt to the gel layer significantly improved the performance of the new diode device because of the enhanced gel conductance. A soft matter based diode composed of hydrogel and liquid metal (eutectic gallium indium, EGaIn) was also presented. The ability to control the thickness, and thus resistivity, of an insulating oxide skin on the metal enables the current rectification. The effect of ionic conductivity and pH on the formation of the insulating oxide was investigated in a simple model system with liquid metal/electrolyte solution or hydrogel/Pt interfaces. Finally, we present a diode composed entirely of soft materials by replacing the platinum electrode with a second liquid metal electrode. A new type of hydrogel-based photovoltaic systems (HGPVs) was constructed. Two photosensitive ionized molecules embedded in aqueous gel served as photoactive species. The HGPVs showed performance comparable with or higher than those of some other biomimetic or ionic photovoltaic systems reported recently. We suggest a provisional mechanism of the device operation, based on a synergetic effect of the two dye

  19. Flow control using audio tones in resonant microfluidic networks: towards cell-phone controlled lab-on-a-chip devices.

    Science.gov (United States)

    Phillips, Reid H; Jain, Rahil; Browning, Yoni; Shah, Rachana; Kauffman, Peter; Dinh, Doan; Lutz, Barry R

    2016-08-16

    Fluid control remains a challenge in development of portable lab-on-a-chip devices. Here, we show that microfluidic networks driven by single-frequency audio tones create resonant oscillating flow that is predicted by equivalent electrical circuit models. We fabricated microfluidic devices with fluidic resistors (R), inductors (L), and capacitors (C) to create RLC networks with band-pass resonance in the audible frequency range available on portable audio devices. Microfluidic devices were fabricated from laser-cut adhesive plastic, and a "buzzer" was glued to a diaphragm (capacitor) to integrate the actuator on the device. The AC flowrate magnitude was measured by imaging oscillation of bead tracers to allow direct comparison to the RLC circuit model across the frequency range. We present a systematic build-up from single-channel systems to multi-channel (3-channel) networks, and show that RLC circuit models predict complex frequency-dependent interactions within multi-channel networks. Finally, we show that adding flow rectifying valves to the network creates pumps that can be driven by amplified and non-amplified audio tones from common audio devices (iPod and iPhone). This work shows that RLC circuit models predict resonant flow responses in multi-channel fluidic networks as a step towards microfluidic devices controlled by audio tones.

  20. Fast pesticide detection inside microfluidic device with integrated optical pH, oxygen sensors and algal fluorescence.

    Science.gov (United States)

    Tahirbegi, Islam Bogachan; Ehgartner, Josef; Sulzer, Philipp; Zieger, Silvia; Kasjanow, Alice; Paradiso, Mirco; Strobl, Martin; Bouwes, Dominique; Mayr, Torsten

    2017-02-15

    The necessities of developing fast, portable, cheap and easy to handle pesticide detection platforms are getting attention of scientific and industrial communities. Although there are some approaches to develop microchip based pesticide detection platforms, there is no compact microfluidic device for the complementary, fast, cheap, reusable and reliable analysis of different pesticides. In this work, a microfluidic device is developed for in-situ analysis of pesticide concentration detected via metabolism/photosynthesis of Chlamydomonas reinhardtii algal cells (algae) in tap water. Algae are grown in glass based microfluidic chip, which contains integrated optical pH and oxygen sensors in a portable system for on-site detection. In addition, intrinsic algal fluorescence is detected to analyze the pesticide concentration in parallel to pH and oxygen sensors with integrated fluorescence detectors. The response of the algae under the effect of different concentrations of pesticides is evaluated and complementary inhibition effects depending on the pesticide concentration are demonstrated. The three different sensors allow the determination of various pesticide concentrations in the nanomolar concentration range. The miniaturized system provides the fast quantification of pesticides in less than 10min and enables the study of toxic effects of different pesticides on Chlamydomonas reinhardtii green algae. Consequently, the microfluidic device described here provides fast and complementary detection of different pesticides with algae in a novel glass based microfluidic device with integrated optical pH, oxygen sensors and algal fluorescence. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Development of a Mechatronic Syringe Pump to Control Fluid Flow in a Microfluidic Device Based on Polyimide Film

    Science.gov (United States)

    Sek Tee, Kian; Sharil Saripan, Muhammad; Yap, Hiung Yin; Fhong Soon, Chin

    2017-08-01

    With the advancement in microfluidic technology, fluid flow control for syringe pump is always essential. In this paper, a mechatronic syringe pump will be developed and customized to control the fluid flow in a poly-dimethylsiloxane (PDMS) microfluidic device based on a polyimide laminating film. The syringe pump is designed to drive fluid with flow rates of 100 and 1000 μl/min which intended to drive continuous fluid in a polyimide based microfluidic device. The electronic system consists of an Arduino microcontroller board and a uni-polar stepper motor. In the system, the uni-polar stepper motor was coupled to a linear slider attached to the plunger of a syringe pump. As the motor rotates, the plunger pumps the liquid out of the syringe. The accuracy of the fluid flow rate was determined by adjusting the number of micro-step/revolution to drive the stepper motor to infuse fluid into the microfluidic device. With the precise control of the electronic system, the syringe pump could accurately inject fluid volume at 100 and 1000 μl/min into a microfluidic device.

  2. Microfluidic Biopsy Trapping Device for the Real-Time Monitoring of Tumor Microenvironment.

    Science.gov (United States)

    Holton, Angela Babetski; Sinatra, Francy L; Kreahling, Jenny; Conway, Amy J; Landis, David A; Altiok, Soner

    2017-01-01

    The tumor microenvironment is composed of cellular and stromal components such as tumor cells, mesenchymal cells, immune cells, cancer associated fibroblasts and the supporting extracellular matrix. The tumor microenvironment provides crucial support for growth and progression of tumor cells and affects tumor response to therapeutic interventions. To better understand tumor biology and to develop effective cancer therapeutic agents it is important to develop preclinical platforms that can faithfully recapitulate the tumor microenvironment and the complex interaction between the tumor and its surrounding stromal elements. Drug studies performed in vitro with conventional two-dimensional cancer cell line models do not optimally represent clinical drug response as they lack true tumor heterogeneity and are often performed in static culture conditions lacking stromal tumor components that significantly influence the metabolic activity and proliferation of cells. Recent microfluidic approaches aim to overcome such obstacles with the use of cell lines derived in artificial three-dimensional supportive gels or micro-chambers. However, absence of a true tumor microenvironment and full interstitial flow, leads to less than optimal evaluation of tumor response to drug treatment. Here we report a continuous perfusion microfluidic device coupled with microscopy and image analysis for the assessment of drug effects on intact fresh tumor tissue. We have demonstrated that fine needle aspirate biopsies obtained from patient-derived xenograft models of adenocarcinoma of the lung can successfully be analyzed for their response to ex vivo drug treatment within this biopsy trapping microfluidic device, wherein a protein kinase C inhibitor, staurosporine, was used to assess tumor cell death as a proof of principle. This approach has the potential to study tumor tissue within its intact microenvironment to better understand tumor response to drug treatments and eventually to choose the

  3. Out-of-focus effects on microscale schlieren measurements of mass transport in a microfluidic device

    Science.gov (United States)

    Chen, Shao-Tuan; Sun, Chen-li

    2016-08-01

    The microscale schlieren technique provides a means for a non-invasive, full-field measurement for mixing microfluidics with excellent sensitivity and resolution. Nevertheless, an out-of-focus effect due to microscopic optics may lead to undesirable errors in quantifying the gradient information at high degrees of magnification. If the channel in the microfluidic device under study is too deep, light deflection caused by inhomogeneity located far from the focal plane may contributes little to the intensity change on the image plane. To address this issue, we propose the use of a weighting function that approximates a Gaussian profile with an optical-system-dependable width. We assume that the resultant intensity change is proportional to a weighted sum of the gradient across the channel depth and acquire micro-schlieren images of fluid mixing in a T-junction microchannel at various positions along the optical axis. For each objective, the width of the weighting function is then determined iteratively by curve fitting the ratio of changes in grayscale readouts for out-of-focus and focus micro-schlieren images. The standard deviation in the Gaussian distribution facilitates the quantification of the out-of-focus effect. In addition, we measure the sensitivities of a microscale schlieren system equipped with different objectives and compare the values to the model. Despite its better resolution, we find that an objective with higher magnification suffers from a more severe out-of-focus effect and a loss of sensitivity. Equations are proposed for estimations of the standard deviation and the sensitivity of microscale schlieren measurements. The outcome will facilitate the selection of proper microchannel depths for various microscale schlieren systems or vice versa, thus improving the precision of micro-schlieren measurements in microfluidic devices.

  4. Integration of Multiple Components in Polystyrene-based Microfluidic Devices Part 2: Cellular Analysis

    Science.gov (United States)

    Anderson, Kari B.; Halpin, Stephen T.; Johnson, Alicia S.; Martin, R. Scott; Spence, Dana M.

    2012-01-01

    In Part II of this series describing the use of polystyrene (PS) devices for microfluidic-based cellular assays, various cellular types and detection strategies are employed to determine three fundamental assays often associated with cells. Specifically, using either integrated electrochemical sensing or optical measurements with a standard multi-well plate reader, cellular uptake, production, or release of important cellular analytes are determined on a PS-based device. One experiment involved the fluorescence measurement of nitric oxide (NO) produced within an endothelial cell line following stimulation with ATP. The result was a four-fold increase in NO production (as compared to a control), with this receptor-based mechanism of NO production verifying the maintenance of cell receptors following immobilization onto the PS substrate. The ability to monitor cellular uptake was also demonstrated by optical determination of Ca2+ into endothelial cells following stimulation with the Ca2+ ionophore A20317. The result was a significant increase (42%) in the calcium uptake in the presence of the ionophore, as compared to a control (17%) (p < 0.05). Finally, the release of catecholamines from a dopaminergic cell line (PC 12 cells) was electrochemically monitored, with the electrodes being embedded into the PS-based device. The PC 12 cells had better adherence on the PS devices, as compared to use of PDMS. Potassium-stimulation resulted in the release of 114 ± 11 µM catecholamines, a significant increase (p < 0.05) over the release from cells that had been exposed to an inhibitor (reserpine, 20 ± 2 µM of catecholamines). The ability to successfully measure multiple analytes, generated in different means from various cells under investigation, suggests that PS may be a useful material for microfluidic device fabrication, especially considering the enhanced cell adhesion to PS, its enhanced rigidity/amenability to automation, and its ability to enable a wider range of

  5. A Simple Paper-Based Microfluidic Device for the Determination of the Total Amino Acid Content in a Tea Leaf Extract

    Science.gov (United States)

    Cai, Longfei; Wu, Yunying; Xu, Chunxiu; Chen, Zefeng

    2013-01-01

    An experiment was developed to demonstrate a microfluidic device in the analytical chemistry (instrumental analysis) laboratory. Students made the paper-based microfluidic device with a wax pen and a piece of filter paper and used it to determine the total quantity of amino acids in a green tea leaf

  6. Design Optimization and Evaluation of a Bioluminescence Detection Part on a Microfluidic Device for in situ ATP Quantification

    Science.gov (United States)

    Aoki, Yusuke; Fukuba, Tatsuhiro; Yamamoto, Takatoki; Fujii, Teruo

    An integrated in situ analyzer for microbial ATP (IISA-ATP) has been developed with a microfluidic device as its core component to realize a compact and fully integrated system. In the system, a bioluminescence (luciferin—luciferase) reaction is conducted for ATP quantification. The microfluidic device has a coil-shaped microchannel for highly sensitive photo intensity measurement. In this paper, the concept of the IISA-ATP and optimization of the microchannel design to enhance sensitivity are presented. As a result of the optimization, linear correlation of the luminescence intensity with the ATP concentration in the range of 2 to 2 × 104 pM was achieved.

  7. A polystyrene-based microfluidic device with three-dimensional interconnected microporous walls for perfusion cell culture

    Science.gov (United States)

    Chan, Chung Yu; Goral, Vasiliy N.; DeRosa, Michael E.; Huang, Tony Jun

    2014-01-01

    In this article, we present a simple, rapid prototyped polystyrene-based microfluidic device with three-dimensional (3D) interconnected microporous walls for long term perfusion cell culture. Patterned 3D interconnected microporous structures were created by a chemical treatment together with a protective mask and the native hydrophobic nature of the microporous structures were selectively made hydrophilic using oxygen plasma treatment together with a protective mask. Using this polystyrene-based cell culture microfluidic device, we successfully demonstrated the support of four days perfusion cell culture of hepatocytes (C3A cells). PMID:25379110

  8. A portable microfluidic fluorescence spectrometer device for {gamma}-H2AX-based biological dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Pope, I.A.; Barber, P.R. [Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom); Horn, S.; Ainsbury, E. [Health Protection Agency Centre for Radiation, Chemical and Environmental Hazards, Chilton, Didcot OX11 0RQ, Oxon (United Kingdom); Rothkamm, K., E-mail: kai.rothkamm@hpa.org.uk [Health Protection Agency Centre for Radiation, Chemical and Environmental Hazards, Chilton, Didcot OX11 0RQ, Oxon (United Kingdom); Vojnovic, B. [Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom)

    2011-09-15

    Following a radiological incident the rapid identification of those individuals exposed to critically high radiation doses is important for initial triage and medical treatment. It has been previously demonstrated that scoring of radiation-induced foci of the phosphorylated histone {gamma}-H2AX, which form at the sites of DNA double-strand breaks, may be used to determine radiation exposure levels from blood samples. Although faster than the 'gold standard' dicentric assay, foci scoring is still impractical in a field situation where large numbers of people may need to be screened. To deal with such a situation, an inexpensive portable device with high throughput capacity is desirable. Here we describe a portable microfluidic fluorescence spectrometer device which passes a suspension of {gamma}-H2AX immunofluorescence-stained lymphocytes through a focused 488 nm laser beam in a microfluidic chamber and records emission spectra over the range 495-725 nm. The recorded emission spectra are spectrally unmixed into their constituent parts from which radiation exposure levels are determined. Proof of principle is demonstrated using cultured lymphoblastoid cells, exposed to X-ray doses between 0 and 8 Gy. With the current prototype setup it takes approximately 6 min to acquire and analyse 10,000 spectra. Further effort is required to fully develop this approach into a portable triage tool that could be used to help classify people into appropriate treatment categories based on radiation exposure levels.

  9. Pressure driven digital logic in PDMS based microfluidic devices fabricated by multilayer soft lithography.

    Science.gov (United States)

    Devaraju, Naga Sai Gopi K; Unger, Marc A

    2012-11-21

    Advances in microfluidics now allow an unprecedented level of parallelization and integration of biochemical reactions. However, one challenge still faced by the field has been the complexity and cost of the control hardware: one external pressure signal has been required for each independently actuated set of valves on chip. Using a simple post-modification to the multilayer soft lithography fabrication process, we present a new implementation of digital fluidic logic fully analogous to electronic logic with significant performance advances over the previous implementations. We demonstrate a novel normally closed static gain valve capable of modulating pressure signals in a fashion analogous to an electronic transistor. We utilize these valves to build complex fluidic logic circuits capable of arbitrary control of flows by processing binary input signals (pressure (1) and atmosphere (0)). We demonstrate logic gates and devices including NOT, NAND and NOR gates, bi-stable flip-flops, gated flip-flops (latches), oscillators, self-driven peristaltic pumps, delay flip-flops, and a 12-bit shift register built using static gain valves. This fluidic logic shows cascade-ability, feedback, programmability, bi-stability, and autonomous control capability. This implementation of fluidic logic yields significantly smaller devices, higher clock rates, simple designs, easy fabrication, and integration into MSL microfluidics.

  10. In vivo fast equilibrium microextraction by stable and biocompatible nanofiber membrane sandwiched in microfluidic device.

    Science.gov (United States)

    Wu, Qian; Wu, Dapeng; Guan, Yafeng

    2013-12-03

    In vivo analysis poses higher requirements about the biocompatibility, selectivity and speed of analytical method. In this study, an in vivo fast equilibrium microextraction method was developed with a biocompatible core-sheath electrospun nanofiber membrane sandwiched within a microfluidic unit. The polystyrene/collagen core-sheath nanofiber membrane was coaxially electrospun and strengthened with in situ glutaraldehyde cross-linking. This membrane not only kept high mass transfer rate, large extraction capacity and biomatrix resistance as our previously proposed membrane (Anal. Chem. 2013, 85 (12), 5924-5932), but also got much better mechanical strength and stability in water. The microfluidic device was designed to sandwich the membrane, and the blood in vivo can be introduced into it and get contact with the membrane repetitively. With this membrane and device, a 2-min equilibrium in vivo extraction method was established, validated in a simulated blood circulation system, and was used to monitor the pharmacokinetic profiles of desipramine in rabbits. The free and total concentration of desipramine in vivo was monitored with 10-min interval almost without rabbit blood consumed. The results met well with those of in vitro extraction, and a correlation factor of 0.99 was obtained.

  11. Paper-based microfluidic devices for electrochemical immunofiltration analysis of human chorionic gonadotropin.

    Science.gov (United States)

    Cao, Liangli; Fang, Cheng; Zeng, Ruosheng; Zhao, Xiongjie; Jiang, Yuren; Chen, Zhencheng

    2017-02-02

    An electrochemical immunofiltration analysis was introduced into microfluidic paper-based analytical devices (μPADs) for the first time, which was based on photolithography and screen-printing technology. The hydrophilic test zones of the aldehyde-functionalized screen-printed electrodes (SPEs) were biofunctionalized with capture antibodies (Ab1). A sensitive immune detection method was developed by using primary signal antibody functionalized gold nanoparticles (GNPs/Ab2) and alkaline phosphatase conjugated secondary antibody (ALP-IgG). Differential pulse voltammetry (DPV) was performed to detect the electrochemical response. The microfluidic paper-based electrochemical immunosensor (μ-PEI) was optimized and characterized for the detection of human chorionic gonadotropin (HCG), a model analyte, in a linear range from 1.0mIUmL(-1) to 100.0 IU mL(-1) with a detection limit of 0.36mIUmL(-1). Additionally, the proposed μ-PEI was used to test HCG in real human serum and obtained satisfactory results. The disposable, efficient, sensitive and low-cost μ-PEI has exhibited great potential for the development of point-of-care testing (POCT) devices that can be applicated in healthcare monitoring.

  12. Electrowetting-induced drop generation and control in a microfluidic flow-focusing device

    Science.gov (United States)

    Malloggi, Florent; Vanapalli, Siva A.; Gu, Hao; van den Ende, Dirk; Mugele, Frieder

    2007-11-01

    Recent upsurge in droplet-based microfluidic research is fueled by the potential application of drops as well-controlled environments for biochemical reactions, single cell analysis and fluid logical devices. Commonly pressure driven flows are used to create droplets continuously either in a flow-focusing or in T-junction geometry. While this approach provides high throughput capability, it is neither amenable to detailed on-demand generation of individual drops nor to dynamic control of surface wettability, which can dramatically affect the dynamics of two-phase microflows. Alternatively, electrowetting (EW)-on-dielectric is used to digitally manipulate drops. The EW provides exquisite control over individual drops and surface wettability. However, current implementations have low throughput and cannot readily be integrated with existing channel-based technologies. Here, we adopt a unified approach to create a soft microfluidic platform that harvests the power of both methods and offers the capability to address their limitations. We achieve this integration by incorporating EW into a flow-focusing device and demonstrate EW-controlled drop formation. We identify experimentally the range of voltages and driving pressures that yields EW-induced droplet generation. A theoretical description based on the balance of external pressures and voltage-controlled capillary pressures quantitatively accounts for the observations. Moreover we show that the smaller the geometric scales the more efficient the electrowetting control of drop generation.

  13. Investigation of injection molding of orthogonal fluidic connector for microfluidic devices

    Directory of Open Access Journals (Sweden)

    Zheng Xu

    2017-02-01

    Full Text Available Orthogonal fluidic connections are essential for developing multilayered microfluidic devices. At present, most orthogonal connectors are realized by a horizontal channel and a vertical channel in different plates. Therefore, some extra alignment and adhesion processes for precise plate assembly are required. In this paper, the method of injection molding is proposed to make a one-body-type orthogonal connector in a single plastic plate. The connector was composed of a cantilevered tube and the other in the substrate. An injection mold was developed in which a side core-pulling mechanism and an ejection mechanism of push-pipes were combined to form the mold for an orthogonal connector. Both the type and the location of gate were optimized for the mold. The results showed that the fan gate in the middle position of the plate was the most suitable in term of both defect control and practicability. The effect of melt temperature was numerically investigated and then verified experimentally. With the optimized parameters, the relative length and the relative wall thickness of a cantilevered tube in the plastic part can reach 98.89% and 99.80%, respectively. Furthermore, using the plastic part as a cover plate, a three-layer plastic microfluidic device was conveniently fabricated for electrochemical detection.

  14. Fabrication and validation of a multi-channel type microfluidic chip for electrokinetic streaming potential devices.

    Science.gov (United States)

    Chun, Myung-Suk; Shim, Min Suk; Choi, Nak Won

    2006-02-01

    To elaborate on the applicability of the electrokinetic micro power generation, we designed and fabricated the silicon-glass as well as the PDMS-glass microfluidic chips with the unique features of a multi-channel. Besides miniaturizing the device, the key advantage of our microfluidic chip utilization lies in the reduction in water flow rate. Both a distributor and a collector taking the tapered duct geometry are positioned aiming the uniform distribution of water flow into all individual channels of the chip, in which several hundreds of single microchannels are assembled in parallel. A proper methodology is developed accompanying the deep reactive ion etching as well as the anodic bonding, and optimum process conditions necessary for hard and soft micromachining are presented. It has been shown experimentally and theoretically that the silicon-based microchannel leads to increasing streaming potential and higher external current compared to those of the PDMS-based one. A proper comparison between experimental results and theoretical computations allows justification of the validity of our novel devices. It is useful to recognize that a material inducing a higher magnitude of zeta potential has an advantage for obtaining higher power density under the same external resistance.

  15. Characterization of Microfluidic Devices by Measurements with μ-PIV and CLSM

    Science.gov (United States)

    Schlter, Michael; Hoffmann, Marko; Rbiger, Norbert

    Microfluidic devices are successfully in use for several applications in chemical engineering and biotechnology. Nevertheless, there is still no breakthrough for microprocess engineering because of a huge lack in understanding of the mechanisms on microscales for momentum transfer, hydrodynamics and mass transfer. Some important questions concern the design of a junction to reach acceptable mixing qualities with minimum pressure drop and narrow residence time distribution even under laminar flow conditions. The micro-particle image velocimetry (μ-PIV) in conjunction with confocal laser scanning microscopy (CLSM) have been used for the characterization of momentum and mass transfer at the Institute of Environmental Process Engineering to evaluate microfluidic devices. The calculation of three-dimensional flow and concentration fields is possible with two-dimensional measurement data for common stationary cases. Streamlines out of velocity gradients and isosurfaces out of fields of the same concentration are providing a helpful impression of the performance of microdevices based on highly reliable measurement data. A quantitative analysis of the velocity and concentration fields allows the calculation of residence-time distribution and mixing quality, which enables the adjustment of microreactor geometries for the demands of chemical, and biochemical reactions.

  16. Reagent-loaded cartridges for valveless and automated fluid delivery in microfluidic devices.

    Science.gov (United States)

    Linder, Vincent; Sia, Samuel K; Whitesides, George M

    2005-01-01

    An important problem in the life sciences and in health care is simple and rapid detection of biomarkers. Although microfluidic devices are potentially useful in addressing this problem, current techniques for automating fluid delivery--which include valves and electroosmosis--require sophisticated microfabrication of the chip, bulky instrumentation, or both. In this paper, we describe a simple and reliable technique for storing and delivering a sequence of reagents to a microfluidic device. The technique is low-cost, requires minimal user intervention, and can be performed in resource-poor settings (e.g., outside of a laboratory) in the absence of electricity and computer-controlled equipment. In this method, cartridges made of commercially available tubing are filled by sequentially injecting plugs of reagents separated by air spacers. The air spacers prevent the reagents from mixing with each other during cartridge preparation, storage, and usage. As an example, we used this "plug-in cartridge" technology to complete a solid-phase immunoassay in a microchannel in 2 min with low-nanomolar sensitivity and demonstrate the diagnosis of HIV in 13 min.

  17. Microfluidic biosensing device for controlled trapping and detection of magnetic microparticles

    KAUST Repository

    Giouroudi, Ioanna

    2013-05-01

    A magnetic microfluidic device is proposed to transport and trap magnetic microparticles (MPs) to a sensing area. Once the MPs are concentrated in the vicinity of the sensing area, a spin valve type giant magnetoresistance (GMR) sensor is used to detect their presence. The device is used for the detection of biological targets once they are labeled with functionalized MPs. Manipulation of the MPs is achieved by employing a microstructure which consists of planar ringshaped conducting microloops. These microloops are designed to produce high magnetic field gradients which are directly proportional to the force applied to manipulate the MPs. Upon sequential application of current, starting from the outermost loop, MPs are directed to move from the outermost to the innermost loop. The speed with which the MPs move towards the sensing area is controlled by the speed with which current is switched between the loops. On top of the microstructure, a microfluidic channel is fabricated using a standard photolithography technique and a dry film resist layer (Ordyl SY355). Experimental results showed that MPs of different diameters were successfully trapped at the sensing area and detected by the GMR sensor located directly under the innermost square loop. © 2013 IEEE.

  18. Investigation of injection molding of orthogonal fluidic connector for microfluidic devices

    Science.gov (United States)

    Xu, Zheng; Cao, Dong; Zhao, Wei; Song, Man-cang; Liu, Jun-shan

    2017-02-01

    Orthogonal fluidic connections are essential for developing multilayered microfluidic devices. At present, most orthogonal connectors are realized by a horizontal channel and a vertical channel in different plates. Therefore, some extra alignment and adhesion processes for precise plate assembly are required. In this paper, the method of injection molding is proposed to make a one-body-type orthogonal connector in a single plastic plate. The connector was composed of a cantilevered tube and the other in the substrate. An injection mold was developed in which a side core-pulling mechanism and an ejection mechanism of push-pipes were combined to form the mold for an orthogonal connector. Both the type and the location of gate were optimized for the mold. The results showed that the fan gate in the middle position of the plate was the most suitable in term of both defect control and practicability. The effect of melt temperature was numerically investigated and then verified experimentally. With the optimized parameters, the relative length and the relative wall thickness of a cantilevered tube in the plastic part can reach 98.89% and 99.80%, respectively. Furthermore, using the plastic part as a cover plate, a three-layer plastic microfluidic device was conveniently fabricated for electrochemical detection.

  19. Modulating chemotaxis of lung cancer cells by using electric fields in a microfluidic device.

    Science.gov (United States)

    Kao, Yu-Chiu; Hsieh, Meng-Hua; Liu, Chung-Chun; Pan, Huei-Jyuan; Liao, Wei-Yu; Cheng, Ji-Yen; Kuo, Po-Ling; Lee, Chau-Hwang

    2014-03-01

    We employed direct-current electric fields (dcEFs) to modulate the chemotaxis of lung cancer cells in a microfluidic cell culture device that incorporates both stable concentration gradients and dcEFs. We found that the chemotaxis induced by a 0.5 μM/mm concentration gradient of epidermal growth factor can be nearly compensated by a 360 mV/mm dcEF. When the effect of chemical stimulation was balanced by the electrical drive, the cells migrated randomly, and the path lengths were largely reduced. We also demonstrated electrically modulated chemotaxis of two types of lung cancer cells with opposite directions of electrotaxis in this device.

  20. Electrokinetically-driven deterministic lateral displacement for particle separation in microfluidic devices

    CERN Document Server

    Hanasoge, Srinivas; Diez, Javier F; Drazer, German

    2014-01-01

    An electrokinetically-driven deterministic lateral displacement (e-DLD) device is proposed for the continuous, two-dimensional fractionation of suspensions in microfluidic platforms. The suspended species are driven through an array of regularly spaced cylindrical posts by applying an electric field across the device. We explore the entire range of orientations of the driving field with respect to the array of obstacles and show that, at specific forcing-angles, particles of different size migrate in different directions, thus enabling continuous, two-dimensional separation. We discuss a number of features observed in the kinetics of the particles, including directional locking and sharp transitions between migration angles upon variations in the direction of the force, that are advantageous for high-resolution two-dimensional separation. A simple model based on individual particle-obstacle interactions accurately describes the migration angle of the particles depending on the orientation of the driving field...

  1. A High Power-Density Mediator-Free Microfluidic Biophotovoltaic Device for Cyanobacterial Cells

    CERN Document Server

    Bombelli, Paolo; Herling, Therese W; Howe, Christopher J; Knowles, Tuomas P J

    2014-01-01

    Biophotovoltaics has emerged as a promising technology for generating renewable energy since it relies on living organisms as inexpensive, self-repairing and readily available catalysts to produce electricity from an abundant resource - sunlight. The efficiency of biophotovoltaic cells, however, has remained significantly lower than that achievable through synthetic materials. Here, we devise a platform to harness the large power densities afforded by miniaturised geometries. To this effect, we have developed a soft-lithography approach for the fabrication of microfluidic biophotovoltaic devices that do not require membranes or mediators. Synechocystis sp. PCC 6803 cells were injected and allowed to settle on the anode, permitting the physical proximity between cells and electrode required for mediator-free operation. We demonstrate power densities of above 100 mW/m2 for a chlorophyll concentration of 100 {\\mu}M under white light, a high value for biophotovoltaic devices without extrinsic supply of additional...

  2. A cell sorting and trapping microfluidic device with an interdigital channel

    Directory of Open Access Journals (Sweden)

    Jing Tu

    2016-12-01

    Full Text Available The growing interest in cell sorting and trapping is driving the demand for high performance technologies. Using labeling techniques or external forces, cells can be identified by a series of methods. However, all of these methods require complicated systems with expensive devices. Based on inherent differences in cellular morphology, cells can be sorted by specific structures in microfluidic devices. The weir filter is a basic and efficient cell sorting and trapping structure. However, in some existing weir devices, because of cell deformability and high flow velocity in gaps, trapped cells may become stuck or even pass through the gaps. Here, we designed and fabricated a microfluidic device with interdigital channels for cell sorting and trapping. The chip consisted of a sheet of silicone elastomer polydimethylsiloxane and a sheet of glass. A square-wave-like weir was designed in the middle of the channel, comprising the interdigital channels. The square-wave pattern extended the weir length by three times with the channel width remaining constant. Compared with a straight weir, this structure exhibited a notably higher trapping capacity. Interdigital channels provided more space to slow down the rate of the pressure decrease, which prevented the cells from becoming stuck in the gaps. Sorting a mixture K562 and blood cells to trap cells demonstrated the efficiency of the chip with the interdigital channel to sort and trap large and less deformable cells. With stable and efficient cell sorting and trapping abilities, the chip with an interdigital channel may be widely applied in scientific research fields.

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

    KAUST Repository

    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

  4. Single-pipetting microfluidic assay device for rapid detection of Salmonella from poultry package.

    Science.gov (United States)

    Fronczek, Christopher F; You, David J; Yoon, Jeong-Yeol

    2013-02-15

    A direct, sensitive, near-real-time, handheld optical immunoassay device was developed to detect Salmonella typhimurium in the naturally occurring liquid from fresh poultry packages (hereafter "chicken matrix"), with just single pipetting of sample (i.e., no filtration, culturing and/or isolation, thus reducing the assay time and the error associated with them). Carboxylated, polystyrene microparticles were covalently conjugated with anti-Salmonella, and the immunoagglutination due to the presence of Salmonella was detected by reading the Mie scatter signals from the microfluidic channels using a handheld device. The presence of chicken matrix did not affect the light scatter signal, since the optical parameters (particle size d, wavelength of incident light λ and scatter angle θ) were optimized to minimize the effect of sample matrix (animal tissues and blood proteins, etc.). The sample was loaded into a microfluidic chip that was split into two channels, one pre-loaded with vacuum-dried, antibody-conjugated particles and the other with vacuum-dried, bovine serum albumin-conjugated particles. This eliminated the need for a separate negative control, effectively minimizing chip-to-chip and sample-to-sample variations. Particles and the sample were diffused in-channel through chemical agitation by Tween 80, also vacuum-dried within the microchannels. Sequential mixing of the sample to the reagents under a strict laminar flow condition synergistically improved the reproducibility and linearity of the assay. In addition, dried particles were shown to successfully detect lower Salmonella concentrations for up to 8 weeks. The handheld device contains simplified circuitry eliminating unnecessary adjustment stages, providing a stable signal, thus maximizing sensitivity. Total assay time was 10 min, and the detection limit 10 CFU mL(-1) was observed in all matrices, demonstrating the suitability of this device for field assays.

  5. Logic digital fluidic in miniaturized functional devices: Perspective to the next generation of microfluidic lab-on-chips.

    Science.gov (United States)

    Zhang, Qiongdi; Zhang, Ming; Djeghlaf, Lyas; Bataille, Jeanne; Gamby, Jean; Haghiri-Gosnet, Anne-Marie; Pallandre, Antoine

    2017-04-01

    Microfluidics has emerged following the quest for scale reduction inherent to micro- and nanotechnologies. By definition, microfluidics manipulates fluids in small channels with dimensions of tens to hundreds of micrometers. Recently, microfluidics has been greatly developed and its influence extends not only the domains of chemical synthesis, bioanalysis, and medical researches but also optics and information technology. In this review article, we will shortly discuss an enlightening analogy between electrons transport in electronics and fluids transport in microfluidic channels. This analogy helps to master transport and sorting. We will present some complex microfluidic devices showing that the analogy is going a long way off toward more complex components with impressive similarities between electronics and microfluidics. We will in particular explore the vast manifold of fluidic operations with passive and active fluidic components, respectively, as well as the associated mechanisms and corresponding applications. Finally, some relevant applications and an outlook will be cited and presented. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    KAUST Repository

    Tallerico, Marco

    2015-05-04

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

  8. Development of a paper-based carbon nanotube sensing microfluidic device for biological detection.

    Science.gov (United States)

    Yang, Shih-I; Lei, Kin Fong; Tsai, Shiao-Wen; Hsu, Hsiao-Ting

    2013-01-01

    Carbon nanotube (CNT) has been utilized for the biological detection due to its extremely sensitive to biological molecules. A paper-based CNT sensing microfluidic device has been developed for the detection of protein, i.e., biotin-avidin, binding. We have developed a fabrication method that allows controlled deposition of bundled CNTs with well-defined dimensions to form sensors on paper. Then, polydimethyl siloxane (PDMS) was used to pattern the hydrophobic boundary on paper to form the reaction sites. The proposed fabrication method is based on vacuum filtration process with a metal mask covering on a filter paper for the definition of the dimension of sensor. The length, width, and thickness of the CNT-based sensors are readily controlled by the metal mask and the weight of the CNT powder used during the filtration process, respectively. Homogeneous deposition of CNTs with well-defined dimensions can be achieved. The CNT-based sensor on paper has been demonstrated on the detection of the protein binding. Biotin was first immobilized on the CNT's sidewall and avidin suspended solution was applied to the site. The result of the biotin-avidin binding was measured by the resistance change of the sensor, which is a label-free detection method. It showed the CNT is sensitive to the biological molecules and the proposed paper-based CNT sensing device is a possible candidate for point-of-care biosensors. Thus, electrical bio-assays on paper-based microfluidics can be realized to develop low cost, sensitive, and specific diagnostic devices.

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

    DEFF Research Database (Denmark)

    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......-expert users and Point-Of-Care (POC) applications. It has been demonstrated that this device is capable of detecting and counting particles down to 1 μm at 100 particles per second. This device only depends on a single microfluidic channel. Hence, the device is easy to implement, or to use on its own....

  10. Electro-Deformation of Fused Cells in a Microfluidic Array Device

    Directory of Open Access Journals (Sweden)

    Yan Liu

    2016-11-01

    Full Text Available We present a new method of analyzing the deformability of fused cells in a microfluidic array device. Electrical stresses—generated by applying voltages (4–20 V across discrete co-planar microelectrodes along the side walls of a microfluidic channel—have been used to electro-deform fused and unfused stem cells. Under an electro-deformation force induced by applying an alternating current (AC signal, we observed significant electro-deformation phenomena. The experimental results show that the fused stem cells were stiffer than the unfused stem cells at a relatively low voltage (<16 V. However, at a relatively high voltage, the fused stem cells were more easily deformed than were the unfused stem cells. In addition, the electro-deformation process is modeled based on the Maxwell stress tensor and structural mechanics of cells. The theoretical results show that a positive correlation is found between the deformation of the cell and the applied voltage, which is consistent with the experimental results. Combined with a numerical analysis and experimental study, the results showed that the significant difference of the deformation ratio of the fused and unfused cells is not due to their size difference. This demonstrates that some other properties of cell membranes (such as the membrane structure were also changed in the electrofusion process, in addition to the size modification of that process.

  11. Mixing with herringbone-inspired microstructures: overcoming the diffusion limit in co-laminar microfluidic devices.

    Science.gov (United States)

    Marschewski, Julian; Jung, Stefan; Ruch, Patrick; Prasad, Nishant; Mazzotti, Sergio; Michel, Bruno; Poulikakos, Dimos

    2015-04-21

    Enhancing mixing is of uttermost importance in many laminar microfluidic devices, aiming at overcoming the severe performance limitation of species transport by diffusion alone. Here we focus on the significant category of microscale co-laminar flows encountered in membraneless redox flow cells for power delivery. The grand challenge is to achieve simultaneously convective mixing within each individual reactant, to thin the reaction depletion boundary layers, while maintaining separation of the co-flowing reactants, despite the absence of a membrane. The concept presented here achieves this goal with the help of optimized herringbone flow promoting microstructures with an integrated separation zone. Our electrochemical experiments using a model redox couple show that symmetric flow promoter designs exhibit laminar to turbulent flow behavior, the latter at elevated flow rates. This change in flow regime is accompanied by a significant change in scaling of the Sherwood number with respect to the Reynolds number from Sh ~ Re(0.29) to Sh ~ Re(0.58). The stabilized continuous laminar flow zone along the centerline of the channel allows operation in a co-laminar flow regime up to Re ~325 as we demonstrate by micro laser-induced fluorescence (μLIF) measurements. Micro particle image velocimetry (μPIV) proves the maintenance of a stratified flow along the centerline, mitigating reactant cross-over effectively. The present work paves the way toward improved performance in membraneless microfluidic flow cells for electrochemical energy conversion.

  12. Time lapse investigation of antibiotic susceptibility using a microfluidic linear gradient 3D culture device.

    Science.gov (United States)

    Hou, Zining; An, Yu; Hjort, Karin; Hjort, Klas; Sandegren, Linus; Wu, Zhigang

    2014-09-01

    This study reports a novel approach to quantitatively investigate the antibacterial effect of antibiotics on bacteria using a three-dimensional microfluidic culture device. In particular, our approach is suitable for studying the pharmacodynamics effects of antibiotics on bacterial cells temporally and with a continuous range of concentrations in a single experiment. The responses of bacterial cells to a linear concentration gradient of antibiotics were observed using time-lapse photography, by encapsulating bacterial cells in an agarose-based gel located in a commercially available microfluidics chamber. This approach generates dynamic information with high resolution, in a single operation, e.g., growth curves and antibiotic pharmacodynamics, in a well-controlled environment. No pre-labelling of the cells is needed and therefore any bacterial sample can be tested in this setup. It also provides static information comparable to that of standard techniques for measuring minimum inhibitory concentration (MIC). Five antibiotics with different mechanisms were analysed against wild-type Escherichia coli, Staphylococcus aureus and Salmonella Typhimurium. The entire process, including data analysis, took 2.5-4 h and from the same analysis, high-resolution growth curves were obtained. As a proof of principle, a pharmacodynamic model of streptomycin against Salmonella Typhimurium was built based on the maximal effect model, which agreed well with the experimental results. Our approach has the potential to be a simple and flexible solution to study responding behaviours of microbial cells under different selection pressures both temporally and in a range of concentrations.

  13. A Microfluidic Device with Integrated Sonication and Immunoprecipitation for Sensitive Epigenetic Assays.

    Science.gov (United States)

    Cao, Zhenning; Lu, Chang

    2016-02-01

    Epigenetic studies increasingly require analysis of a small number of cells that are of one specific type and derived from patients or animals. In this report, we demonstrate a simple microfluidic device that integrates sonication and immunoprecipitation (IP) for epigenetic assays, such as chromatin immunoprecipitation (ChIP) and methylated DNA immunoprecipitation (MeDIP). By incorporating an ultrasonic transducer with a microfluidic chamber, we implemented microscale sonication for both shearing chromatin/DNA and mixing/washing of IP beads. Such integration allowed highly sensitive tests starting with 100 cross-linked cells for ChIP or 500 pg of genomic DNA for MeDIP (compared to 10(6)-10(7) cells for ChIP and 1-10 μg of DNA for MeDIP in conventional assays). The entire on-chip process of sonication and IP took only 1 h. Our tool will be useful for highly sensitive epigenetic studies based on a small quantity of sample.

  14. Design and fabrication of microfluidic/microelectronic devices from nano particle based composites

    Science.gov (United States)

    Liu, Liyu

    In this thesis, two kinds of nanoparticle functional composite Giant Electrorheological(GER) fluid and polydimethylsiloxane (PDMS) conductive composites and their applications in micro scales are studied. GER fluid is synthesized with ˜50 nm polarizable solid particles and non-polarizable oil, whose apparent viscosity is continuously variable through applications of an electric field. We have successfully applied ER fluid as actuations in microfluidic chips. With soft lithography techniques, we developed various micro functional chips based on PDMS, including micro flexible platform, micro active mixer and micro pump, all of which have desirable performances. The PDMS conducting composites are synthesized by mixing nano to sub micro-sized conductive particles (silver/carbon black) with PDMS gel. Such composite materials exhibit good electrical conductivity and mechanical reliability, as well as desirable thermal characteristics. By employing this type of composite, we have developed some realistic micro-structural devices and explored their potential applications, including flexible bio-electrodes, micro-heaters and flexible displays, micro temperature indicators, etc. With these two composites and corresponding results, we succeeded in realizing a highly integrated microfluidic chip with the function of DNA amplification. The system has the advantages of small size with a high degree of integration, high PCR efficiency, digital control and simple fabrication at low cost and shows promise for a broad range of applications in chemical synthesis and biological sensing/analysis.

  15. Microfluidic devices for cell culture and handling in organ-on-a-chip applications

    Science.gov (United States)

    Becker, Holger; Schulz, Ingo; Mosig, Alexander; Jahn, Tobias; Gärtner, Claudia

    2014-03-01

    For many problems in system biology or pharmacology, in-vivo-like models of cell-cell interactions or organ functions are highly sought after. Conventional stationary cell culture in 2D plates quickly reaches its limitations with respect to an in-vivo like expression and function of individual cell types. Microfabrication technologies and microfluidics offer an attractive solution to these problems. The ability to generate flow as well as geometrical conditions for cell culture and manipulation close to the in-vivo situation allows for an improved design of experiments and the modeling of organ-like functionalities. Furthermore, reduced internal volumes lead to a reduction in reagent volumes necessary as well as an increased assay sensitivity. In this paper we present a range of microfluidic devices designed for the co-culturing of a variety of cells. The influence of substrate materials and surface chemistry on the cell morphology and viability for long-term cell culture has been investigated as well as strategies and medium supply for on-chip cell cultivation.

  16. Self-regenerating and hybrid irreversible/reversible PDMS microfluidic devices

    Science.gov (United States)

    Shiroma, Letícia S.; Piazzetta, Maria H. O.; Duarte-Junior, Gerson F.; Coltro, Wendell K. T.; Carrilho, Emanuel; Gobbi, Angelo L.; Lima, Renato S.

    2016-05-01

    This paper outlines a straightforward, fast, and low-cost method to fabricate polydimethylsiloxane (PDMS) chips. Termed sandwich bonding (SWB), this method requires only a laboratory oven. Initially, SWB relies on the reversible bonding of a coverslip over PDMS channels. The coverslip is smaller than the substrate, leaving a border around the substrate exposed. Subsequently, a liquid composed of PDMS monomers and a curing agent is poured onto the structure. Finally, the cover is cured. We focused on PDMS/glass chips because of their key advantages in microfluidics. Despite its simplicity, this method created high-performance microfluidic channels. Such structures featured self-regeneration after leakages and hybrid irreversible/reversible behavior. The reversible nature was achieved by removing the cover of PDMS with acetone. Thus, the PDMS substrate and glass coverslip could be detached for reuse. These abilities are essential in the stages of research and development. Additionally, SWB avoids the use of surface oxidation, half-cured PDMS as an adhesive, and surface chemical modification. As a consequence, SWB allows surface modifications before the bonding, a long time for alignment, the enclosure of sub-micron channels, and the prototyping of hybrid devices. Here, the technique was successfully applied to bond PDMS to Au and Al.

  17. In vitro development of donated frozen-thawed human embryos in a prototype static microfluidic device: a randomized controlled trial

    NARCIS (Netherlands)

    Kieslinger, Dorit C.; Hao, Zhenxia; Vergouw, Carlijn G.; Kostelijk, Elisabeth H.; Lambalk, Cornelis B.; Le Gac, Séverine

    2015-01-01

    Objective: To compare the development of human embryos in microfluidic devices with culture in standard microdrop dishes, both under static conditions. Design: Prospective randomized controlled trial. Setting: In vitro fertilization laboratory. Patient(s): One hundred eighteen donated frozen-t

  18. In search of low cost biological analysis: Wax or acrylic glue bonded paper microfluidic devices

    KAUST Repository

    Kodzius, Rimantas

    2011-11-04

    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 o

  19. Femtosecond laser fabrication for the integration of optical sensors in microfluidic lab-on-chip devices

    NARCIS (Netherlands)

    Osellame, R.; Martinez-Vazquez, R.; Dongre, C.; Dekker, R.; Hoekstra, H.J.W.M.; Ramponi, R.; Pollnau, M.; Cerullo, G.; Corkum, P.; Silvestri, de S.; Nelson, K.A.; Riedle, E.; Schoenlein, R.W.

    2009-01-01

    Femtosecond lasers enable the fabrication of both optical waveguides and buried microfluidic channels on a glass substrate. The waveguides are used to integrate optical detection in a commercial microfluidic lab-on-chip for capillary electrophoresis.

  20. Femtosecond laser fabrication for the integration of optical sensors in microfluidic lab-on-chip devices

    NARCIS (Netherlands)

    Osellame, R.; Martinez Vazquez, R.; Dongre, C.; Dekker, R.; Hoekstra, H.J.W.M.; Pollnau, M.; Ramponi, R.; Cerullo, G.

    2008-01-01

    Femtosecond lasers enable the fabrication of both optical waveguides and buried microfluidic channels on a glass substrate. The waveguides are used to integrate optical detection in a commercial microfluidic lab-on-chip for capillary electrophoresis

  1. Dynamics of Electrowetting Droplet Motion in Digital Microfluidics Systems: From Dynamic Saturation to Device Physics

    Directory of Open Access Journals (Sweden)

    Weiwei Cui

    2015-06-01

    Full Text Available A quantitative description of the dynamics of droplet motion has been a long-standing concern in electrowetting research. Although many static and dynamic models focusing on droplet motion induced by electrowetting-on-dielectric (EWOD already exist, some dynamic features do not fit these models well, especially the dynamic saturation phenomenon. In this paper, a dynamic saturation model of droplet motion on the single-plate EWOD device is presented. The phenomenon that droplet velocity is limited by a dynamic saturation effect is precisely predicted. Based on this model, the relationship between droplet motion and device physics is extensively discussed. The static saturation phenomenon is treated with a double-layer capacitance electric model, and it is demonstrated as one critical factor determining the dynamics of droplet motion. This work presents the relationship between dynamics of electrowetting induced droplet motion and device physics including device structure, surface material and interface electronics, which helps to better understand electrowetting induced droplet motions and physics of digital microfluidics systems.

  2. Production of Fluconazole-Loaded Polymeric Micelles Using Membrane and Microfluidic Dispersion Devices

    Directory of Open Access Journals (Sweden)

    Yu Lu

    2016-05-01

    Full Text Available Polymeric micelles with a controlled size in the range between 41 and 80 nm were prepared by injecting the organic phase through a microengineered nickel membrane or a tapered-end glass capillary into an aqueous phase. The organic phase was composed of 1 mg·mL−1 of PEG-b-PCL diblock copolymers with variable molecular weights, dissolved in tetrahydrofuran (THF or acetone. The pore size of the membrane was 20 μm and the aqueous/organic phase volumetric flow rate ratio ranged from 1.5 to 10. Block copolymers were successfully synthesized with Mn ranging from ~9700 to 16,000 g·mol−1 and polymeric micelles were successfully produced from both devices. Micelles produced from the membrane device were smaller than those produced from the microfluidic device, due to the much smaller pore size compared with the orifice size in a co-flow device. The micelles were found to be relatively stable in terms of their size with an initial decrease in size attributed to evaporation of residual solvent rather than their structural disintegration. Fluconazole was loaded into the cores of micelles by injecting the organic phase composed of 0.5–2.5 mg·mL−1 fluconazole and 1.5 mg·mL−1 copolymer. The size of the drug-loaded micelles was found to be significantly larger than the size of empty micelles.

  3. A Disposable Microfluidic Virus Concentration Device Based on Evaporation and Interfacial Tension

    Directory of Open Access Journals (Sweden)

    Catherine M. Klapperich

    2013-02-01

    Full Text Available We report a disposable and highly effective polymeric microfluidic viral sample concentration device capable of increasing the concentration of virus in a human nasopharyngeal specimen more than one order of magnitude in less than 30 min without the use of a centrifuge. The device is fabricated using 3D maskless xurography method using commercially available polymeric materials, which require no cleanroom operations. The disposable components can be fabricated and assembled in five minutes. The device can concentrate a few milliliters (mL of influenza virus in solution from tissue culture or clinical nasopharyngeal swab specimens, via reduction of the fluid volume, to tens of microliters (mL. The performance of the device was evaluated by nucleic acid extraction from the concentrated samples, followed by a real-time quantitative polymerase chain reaction (qRT-PCR. The viral RNA concentration in each sample was increased on average over 10-fold for both cultured and patient specimens compared to the starting samples, with recovery efficiencies above 60% for all input concentrations. Highly concentrated samples in small fluid volumes can increase the downstream process speed of on-chip nucleic acid extraction, and result in improvements in the sensitivity of many diagnostic platforms that interrogate small sample volumes.

  4. An integrated microfluidic device for rapid and high-sensitivity analysis of circulating tumor cells

    Science.gov (United States)

    Jiang, Jianing; Zhao, Hui; Shu, Weiliang; Tian, Jing; Huang, Yuqing; Song, Yongxin; Wang, Ruoyu; Li, Encheng; Slamon, Dennis; Hou, Dongmei; Du, Xiaohui; Zhang, Lichuan; Chen, Yan; Wang, Qi

    2017-01-01

    Recently there has been a more focus on the development of an efficient technique for detection of circulating tumor cells (CTCs), due to their significance in prognosis and therapy of metastatic cancer. However, it remains a challenge because of the low count of CTCs in the blood. Herein, a rapid and high-sensitivity approach for CTCs detection using an integrated microfluidic system, consisting of a deterministic lateral displacement (DLD) isolating structure, an automatic purifying device with CD45-labeled immunomagnetic beads and a capturing platform coated with rat-tail collagen was reported. We observed high capture rate of 90%, purity of about 50% and viability of more than 90% at the high throughput of 1 mL/min by capturing green fluorescent protein (GFP)-positive cells from blood. Further capturing of CTCs from metastatic cancers patients revealed a positive capture rate of 83.3%. Furthermore, our device was compared with CellSearch system via parallel analysis of 30 cancer patients, to find no significant difference between the capture efficiency of both methods. However, our device displayed advantage in terms of time, sample volume and cost for analysis. Thus, our integrated device with sterile environment and convenient use will be a promising platform for CTCs detection with potential clinical application. PMID:28198402

  5. Production of Fluconazole-Loaded Polymeric Micelles Using Membrane and Microfluidic Dispersion Devices

    Science.gov (United States)

    Lu, Yu; Chowdhury, Danial; Vladisavljević, Goran T.; Koutroumanis, Konstantinos; Georgiadou, Stella

    2016-01-01

    Polymeric micelles with a controlled size in the range between 41 and 80 nm were prepared by injecting the organic phase through a microengineered nickel membrane or a tapered-end glass capillary into an aqueous phase. The organic phase was composed of 1 mg·mL−1 of PEG-b-PCL diblock copolymers with variable molecular weights, dissolved in tetrahydrofuran (THF) or acetone. The pore size of the membrane was 20 μm and the aqueous/organic phase volumetric flow rate ratio ranged from 1.5 to 10. Block copolymers were successfully synthesized with Mn ranging from ~9700 to 16,000 g·mol−1 and polymeric micelles were successfully produced from both devices. Micelles produced from the membrane device were smaller than those produced from the microfluidic device, due to the much smaller pore size compared with the orifice size in a co-flow device. The micelles were found to be relatively stable in terms of their size with an initial decrease in size attributed to evaporation of residual solvent rather than their structural disintegration. Fluconazole was loaded into the cores of micelles by injecting the organic phase composed of 0.5–2.5 mg·mL−1 fluconazole and 1.5 mg·mL−1 copolymer. The size of the drug-loaded micelles was found to be significantly larger than the size of empty micelles. PMID:27231945

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

    Science.gov (United States)

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

    2012-02-01

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

  7. Constant pressure fluid infusion into rat neocortex from implantable microfluidic devices

    Science.gov (United States)

    Retterer, S. T.; Smith, K. L.; Bjornsson, C. S.; Turner, J. N.; Isaacson, M. S.; Shain, W.

    2008-12-01

    Implantable electrode arrays capable of recording and stimulating neural activity with high spatial and temporal resolution will provide a foundation for future brain computer interface technology. Currently, their clinical impact has been curtailed by a general lack of functional stability, which can be attributed to the acute and chronic reactive tissue responses to devices implanted in the brain. Control of the tissue environment surrounding implanted devices through local drug delivery could significantly alter both the acute and chronic reactive responses, and thus enhance device stability. Here, we characterize pressure-mediated release of test compounds into rat cortex using an implantable microfluidic platform. A fixed volume of fluorescent cell marker cocktail was delivered using constant pressure infusion at reservoir backpressures of 0, 5 and 10 psi. Affected tissue volumes were imaged and analyzed using epifluorescence and confocal microscropies and quantitative image analysis techniques. The addressable tissue volume for the 5 and 10 psi infusions, defined by fluorescent staining with Hoescht 33342 dye, was significantly larger than the tissue volume addressed by simple diffusion (0 psi) and the tissue volume exhibiting insertion-related cell damage (stained by propidium iodide). The results demonstrate the potential for using constant pressure infusion to address relevant tissue volumes with appropriate pharmacologies to alleviate reactive biological responses around inserted neuroprosthetic devices.

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

    Science.gov (United States)

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

    2015-12-01

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

  9. A Review on Microfluidic Paper-Based Analytical Devices for Glucose Detection

    Directory of Open Access Journals (Sweden)

    Shuopeng Liu

    2016-12-01

    Full Text Available Glucose, as an essential substance directly involved in metabolic processes, is closely related to the occurrence of various diseases such as glucose metabolism disorders and islet cell carcinoma. Therefore, it is crucial to develop sensitive, accurate, rapid, and cost effective methods for frequent and convenient detections of glucose. Microfluidic Paper-based Analytical Devices (μPADs not only satisfying the above requirements but also occupying the advantages of portability and minimal sample consumption, have exhibited great potential in the field of glucose detection. This article reviews and summarizes the most recent improvements in glucose detection in two aspects of colorimetric and electrochemical μPADs. The progressive techniques for fabricating channels on μPADs are also emphasized in this article. With the growth of diabetes and other glucose indication diseases in the underdeveloped and developing countries, low-cost and reliably commercial μPADs for glucose detection will be in unprecedentedly demand.

  10. Origin of periodic and chaotic dynamics due to drops moving in a microfluidic loop device.

    Science.gov (United States)

    Maddala, Jeevan; Vanapalli, Siva A; Rengaswamy, Raghunathan

    2014-02-01

    Droplets moving in a microfluidic loop device exhibit both periodic and chaotic behaviors based on the inlet droplet spacing. We observe that the periodic behavior is an outcome of carrier phase mass conservation principle, which translates into a droplet spacing quantization rule. This rule implies that the summation of exit spacing is equal to an integral multiple of inlet spacing. This principle also enables identification of periodicity in experimental systems with input scatter. We find that the origin of chaotic behavior is through intermittency, which arises when drops enter and leave the junctions at the same time. We derive an analytical expression to estimate the occurrence of these chaotic regions as a function of system parameters. We provide experimental, simulation, and analytical results to validate the origin of periodic and chaotic behavior.

  11. Evaluation of biofouling in stainless microfluidic channels for implantable multilayered dialysis device

    Science.gov (United States)

    Ota, Takashi; To, Naoya; Kanno, Yoshihiko; Miki, Norihisa

    2017-06-01

    An implantable artificial kidney can markedly improve the quality of life of renal disease patients. Our group has developed an implantable multilayered dialysis system consisting of microfluidic channels and dialysis membranes. Long-term evaluation is necessary for implant devices where biofouling is a critical factor, culminating in the deterioration of dialysis performance. Our previous work revealed that surface conditions, which depend on the manufacturing process, determine the amount of biofouling, and that electrolytic etching is the most suitable technique for forming a channel wall free of biofouling. In this study, we investigated the electrolytic etching conditions in detail. We conducted in vitro experiments for 7 d and evaluated the adhesion of biomaterials by scanning electron microscopy. The experiments revealed that a surface mirror-finished by electrolytic etching effectively prevents biofouling.

  12. Facile fabrication processes for hydrogel-based microfluidic devices made of natural biopolymers

    Science.gov (United States)

    Yajima, Yuya; Yamada, Masumi; Yamada, Emi; Iwase, Masaki; Seki, Minoru

    2014-01-01

    We present facile strategies for the fabrication of two types of microfluidic devices made of hydrogels using the natural biopolymers, alginate, and gelatin as substrates. The processes presented include the molding-based preparation of hydrogel plates and their chemical bonding. To prepare calcium-alginate hydrogel microdevices, we suppressed the volume shrinkage of the alginate solution during gelation using propylene glycol alginate in the precursor solution along with sodium alginate. In addition, a chemical bonding method was developed using a polyelectrolyte membrane of poly-L-lysine as the electrostatic glue. To prepare gelatin-based microdevices, we used microbial transglutaminase to bond hydrogel plates chemically and to cross-link and stabilize the hydrogel matrix. As an application, mammalian cells (fibroblasts and vascular endothelial cells) were cultivated on the microchannel surface to form three-dimensional capillary-embedding tissue models for biological research and tissue engineering. PMID:24803964

  13. Measurement of buried undercut structures in microfluidic devices by laser fluorescent confocal microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Li Shiguang; Liu Jing; Nguyen, Nam-Trung; Fang Zhongping; Yoon, Soon Fatt

    2009-11-20

    Measuring buried, undercut microstructures is a challenging task in metrology. These structures are usually characterized by measuring their cross sections after physically cutting the samples. This method is destructive and the obtained information is incomplete. The distortion due to cutting also affects the measurement accuracy. In this paper, we first apply the laser fluorescent confocal microscopy and intensity differentiation algorithm to obtain the complete three-dimensional profile of the buried, undercut structures in microfluidic devices, which are made by the soft lithography technique and bonded by the oxygen plasma method. The impact of material wettability and the refractive index (n) mismatch among the liquid, samples, cover layer, and objective on the measurement accuracy are experimentally investigated.

  14. Rapid, highly efficient extraction and purification of membrane proteins using a microfluidic continuous-flow based aqueous two-phase system.

    Science.gov (United States)

    Hu, Rui; Feng, Xiaojun; Chen, Pu; Fu, Meng; Chen, Hong; Guo, Lin; Liu, Bi-Feng

    2011-01-07

    Membrane proteins play essential roles in regulating various fundamental cellular functions. To investigate membrane proteins, extraction and purification are usually prerequisite steps. Here, we demonstrated a microfluidic aqueous PEG/detergent two-phase system for the purification of membrane proteins from crude cell extract, which replaced the conventional discontinuous agitation method with continuous extraction in laminar flows, resulting in significantly increased extraction speed and efficiency. To evaluate this system, different separation and detection methods were used to identify the purified proteins, such as capillary electrophoresis, SDS-PAGE and nano-HPLC-MS/MS. Swiss-Prot database with Mascot search engine was used to search for membrane proteins from random selected bands of SDS-PAGE. Results indicated that efficient purification of membrane proteins can be achieved within 5-7s and approximately 90% of the purified proteins were membrane proteins (the highest extraction efficiency reported up to date), including membrane-associated proteins and integral membrane proteins with multiple transmembrane domains. Compared to conventional approaches, this new method had advantages of greater specific surface area, minimal emulsification, reduced sample consumption and analysis time. We expect the developed method to be potentially useful in membrane protein purifications, facilitating the investigation of membrane proteomics.

  15. Isolation of Circulating Plasma Cells in Multiple Myeloma Using CD138 Antibody-Based Capture in a Microfluidic Device

    Science.gov (United States)

    Qasaimeh, Mohammad A.; Wu, Yichao C.; Bose, Suman; Menachery, Anoop; Talluri, Srikanth; Gonzalez, Gabriel; Fulciniti, Mariateresa; Karp, Jeffrey M.; Prabhala, Rao H.; Karnik, Rohit

    2017-04-01

    The necessity for bone marrow aspiration and the lack of highly sensitive assays to detect residual disease present challenges for effective management of multiple myeloma (MM), a plasma cell cancer. We show that a microfluidic cell capture based on CD138 antigen, which is highly expressed on plasma cells, permits quantitation of rare circulating plasma cells (CPCs) in blood and subsequent fluorescence-based assays. The microfluidic device is based on a herringbone channel design, and exhibits an estimated cell capture efficiency of ~40-70%, permitting detection of <10 CPCs/mL using 1-mL sample volumes, which is difficult using existing techniques. In bone marrow samples, the microfluidic-based plasma cell counts exhibited excellent correlation with flow cytometry analysis. In peripheral blood samples, the device detected a baseline of 2-5 CD138+ cells/mL in healthy donor blood, with significantly higher numbers in blood samples of MM patients in remission (20-24 CD138+ cells/mL), and yet higher numbers in MM patients exhibiting disease (45-184 CD138+ cells/mL). Analysis of CPCs isolated using the device was consistent with serum immunoglobulin assays that are commonly used in MM diagnostics. These results indicate the potential of CD138-based microfluidic CPC capture as a useful ‘liquid biopsy’ that may complement or partially replace bone marrow aspiration.

  16. A DFT Scheme for Pneumatic Control Logic in Flow-based Biochips

    OpenAIRE

    Potluri, Seetal; Pop, Paul; Madsen, Jan

    2016-01-01

    Microfluidic flow-based biochips help perform biochemistry at miniaturized scales, thus enabling cost, performance and other benefits. Although biochips are expected to replace biochemical labs, including point-of-care devices, the off-chip pressure actuators and pumps are bulky, thereby limiting them to laboratory environments. To address this issue, recent work has focused on reducing the number of off-chip pressure sources, using on-chip pneumatic control logic circuits fabricated using th...

  17. A microfluidic device for 2D to 3D and 3D to 3D cell navigation

    Science.gov (United States)

    Shamloo, Amir; Amirifar, Leyla

    2016-01-01

    Microfluidic devices have received wide attention and shown great potential in the field of tissue engineering and regenerative medicine. Investigating cell response to various stimulations is much more accurate and comprehensive with the aid of microfluidic devices. In this study, we introduced a microfluidic device by which the matrix density as a mechanical property and the concentration profile of a biochemical factor as a chemical property could be altered. Our microfluidic device has a cell tank and a cell culture chamber to mimic both 2D to 3D and 3D to 3D migration of three types of cells. Fluid shear stress is negligible on the cells and a stable concentration gradient can be obtained by diffusion. The device was designed by a numerical simulation so that the uniformity of the concentration gradients throughout the cell culture chamber was obtained. Adult neural cells were cultured within this device and they showed different branching and axonal navigation phenotypes within varying nerve growth factor (NGF) concentration profiles. Neural stem cells were also cultured within varying collagen matrix densities while exposed to NGF concentrations and they experienced 3D to 3D collective migration. By generating vascular endothelial growth factor concentration gradients, adult human dermal microvascular endothelial cells also migrated in a 2D to 3D manner and formed a stable lumen within a specific collagen matrix density. It was observed that a minimum absolute concentration and concentration gradient were required to stimulate migration of all types of the cells. This device has the advantage of changing multiple parameters simultaneously and is expected to have wide applicability in cell studies.

  18. Microfluidic device for a rapid immobilization of zebrafish larvae in environmental scanning electron microscopy.

    Science.gov (United States)

    Akagi, Jin; Zhu, Feng; Skommer, Joanna; Hall, Chris J; Crosier, Philip S; Cialkowski, Michal; Wlodkowic, Donald

    2015-03-01

    Small vertebrate model organisms have recently gained popularity as attractive experimental models that enhance our understanding of human tissue and organ development. Despite a large body of evidence using optical spectroscopy for the characterization of small model organism on chip-based devices, no attempts have been so far made to interface microfabricated technologies with environmental scanning electron microscopy (ESEM). Conventional scanning electron microscopy requires high vacuum environments and biological samples must be, therefore, submitted to many preparative procedures to dehydrate, fix, and subsequently stain the sample with gold-palladium deposition. This process is inherently low-throughput and can introduce many analytical artifacts. This work describes a proof-of-concept microfluidic chip-based system for immobilizing zebrafish larvae for ESEM imaging that is performed in a gaseous atmosphere, under low vacuum mode and without any need for sample staining protocols. The microfabricated technology provides a user-friendly and simple interface to perform ESEM imaging on zebrafish larvae. Presented lab-on-a-chip device was fabricated using a high-speed infrared laser micromachining in a biocompatible poly(methyl methacrylate) thermoplastic. It consisted of a reservoir with multiple semispherical microwells designed to hold the yolk of dechorionated zebrafish larvae. Immobilization of the larvae was achieved by a gentle suction generated during blotting of the medium. Trapping region allowed for multiple specimens to be conveniently positioned on the chip-based device within few minutes for ESEM imaging.

  19. Scattering detection using a photonic-microfluidic integrated device with on-chip collection capabilities.

    Science.gov (United States)

    Watts, Benjamin R; Zhang, Zhiyi; Xu, Chang Qing; Cao, Xudong; Lin, Min

    2014-02-01

    SU-8-based photonic-microfluidic integrated devices with on-chip beam shaping and collection capabilities were demonstrated in a scattering detection and counting application. Through the proper deployment of the tailored beam geometries via the on-chip excitation optics, excellent CV values were measured for 1, 2, and 5 μm blank beads, 16.4, 11.0, and 12.5%, respectively, coupled with a simple free-space optical detection scheme. The performance of these devices was found dependent on the combination of on-chip, lens-shaped beam geometry and bead size. While very low CVs were obtained when the combination was ideal, a nonideal combination could still result in acceptable CVs for flow cytometry; the reliability was confirmed via devices being able to resolve separate populations of 2.0 and 5.0 μm beads from their mixture with low CV values of 15.9 and 18.5%, respectively. On-chip collection using integrated on-chip optical waveguides was shown to be very reliable in comparison with a free-space collection scheme, yielding a coincident rate of 94.2%. A CV as low as 19.2% was obtained from the on-chip excitation and collection of 5 μm beads when the on-chip lens-shaped beam had a 6.0-μm beam waist.

  20. Fabrication techniques for microfluidic paper-based analytical devices and their applications for biological testing: A review.

    Science.gov (United States)

    Xia, Yanyan; Si, Jin; Li, Zhiyang

    2016-03-15

    Paper is increasingly recognized as a user-friendly and ubiquitous substrate for construction of microfluidic devices. Microfluidic paper-based analytical devices (μPADs) provide an alternative technology for development of affordable, portable, disposable and low-cost diagnostic tools for improving point of care testing (POCT) and disease screening in the developing world, especially in those countries with no- or low-infrastructure and limited trained medical and health professionals. We in this review present fabrication techniques for microfluidic devices and their respective applications for biological detection as reported to date. These include: (i) fabrication techniques: examples of devices fabricated by using two-dimensional (2D) and three-dimensional (3D) methods; (ii) detection application: biochemical, immunological and molecular detection by incorporating efficient detection methods such as, colorimetric detection, electrochemical detection, fluorescence detection, chemiluminescence (CL) detection, electrochemiluninescence (ECL) detection, photoelectrochemi (PEC) detection and so on. In addition, main advantages, disadvantages and future trends for the devices are also discussed in this review.

  1. Microfluidic Dye Lasers

    DEFF Research Database (Denmark)

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

    2006-01-01

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

  2. A continuous glucose monitoring device by graphene modified electrochemical sensor in microfluidic system.

    Science.gov (United States)

    Pu, Zhihua; Zou, Chongwei; Wang, Ridong; Lai, Xiaochen; Yu, Haixia; Xu, Kexin; Li, Dachao

    2016-01-01

    This paper presents a continuous glucose monitoring microsystem consisting of a three-electrode electrochemical sensor integrated into a microfluidic chip. The microfluidic chip, which was used to transdermally extract and collect subcutaneous interstitial fluid, was fabricated from five polydimethylsiloxane layers using micromolding techniques. The electrochemical sensor was integrated into the chip for continuous detection of glucose. Specifically, a single-layer graphene and gold nanoparticles (AuNPs) were decorated onto the working electrode (WE) of the sensor to construct a composite nanostructured surface and improve the resolution of the glucose measurements. Graphene was transferred onto the WE surface to improve the electroactive nature of the electrode to enable measurements of low levels of glucose. The AuNPs were directly electrodeposited onto the graphene layer to improve the electron transfer rate from the activity center of the enzyme to the electrode to enhance the sensitivity of the sensor. Glucose oxidase (GOx) was immobilized onto the composite nanostructured surface to specifically detect glucose. The factors required for AuNPs deposition and GOx immobilization were also investigated, and the optimized parameters were obtained. The experimental results displayed that the proposed sensor could precisely measure glucose in the linear range from 0 to 162 mg/dl with a detection limit of 1.44 mg/dl (S/N = 3). The proposed sensor exhibited the potential to detect hypoglycemia which is still a major challenge for continuous glucose monitoring in clinics. Unlike implantable glucose sensors, the wearable device enabled external continuous monitoring of glucose without interference from foreign body reaction and bioelectricity.

  3. Attenuated total reflection-Fourier transform infrared spectroscopic imaging of pharmaceuticals in microfluidic devices.

    Science.gov (United States)

    Ewing, Andrew V; Clarke, Graham S; Kazarian, Sergei G

    2016-03-01

    The poor aqueous solubility of many active pharmaceutical ingredients presents challenges for effective drug delivery. In this study, the combination of attenuated total reflection (ATR)-FTIR spectroscopic imaging with specifically designed polydimethylsiloxane microfluidic devices to study drug release from pharmaceutical formulations has been developed. First, the high-throughput analysis of the dissolution of micro-formulations studied under flowing conditions has been introduced using a model formulation of ibuprofen and polyethylene glycol. The behaviour and release of the drug was monitored in situ under different pH conditions. In contrast to the neutral solution, where both the drug and excipient dissolved at a similar rate, structural change from the molecularly dispersed to a crystalline form of ibuprofen was characterised in the obtained spectroscopic images and the corresponding ATR-FTIR spectra for the experiments carried out in the acidic medium. Further investigations into the behaviour of the drug after its release from formulations (i.e., dissolved drug) were also undertaken. Different solutions of sodium ibuprofen dissolved in a neutral medium were studied upon contact with acidic conditions. The phase transition from a dissolved species of sodium ibuprofen to the formation of solid crystalline ibuprofen was revealed in the microfluidic channels. This innovative approach could offer a promising platform for high-throughput analysis of a range of micro-formulations, which are of current interest due to the advent of 3D printed pharmaceutical and microparticulate delivery systems. Furthermore, the ability to study dissolved drug in solution under flowing conditions can be useful for the studies of the diffusion of drugs into tissues or live cells.

  4. Low-distortion, high-strength bonding of thermoplastic microfluidic devices employing case-II diffusion-mediated permeant activation.

    Science.gov (United States)

    Wallow, Thomas I; Morales, Alfredo M; Simmons, Blake A; Hunter, Marion C; Krafcik, Karen Lee; Domeier, Linda A; Sickafoose, Shane M; Patel, Kamlesh D; Gardea, Andy

    2007-12-01

    We demonstrate a new method for joining thermoplastic surfaces to produce microfluidic devices. The method takes advantage of the sharply defined permeation boundary of case-II diffusion to generate dimensionally controlled, activated bonding layers at the surfaces being joined. The technique is capable of producing bonds that exhibit cohesive failure, while preserving the fidelity of fine features in the bonding interface. This approach is uniquely suited to production of layered microfluidic structures, as it allows the bond-forming interface between plastic parts to be precisely manipulated at micrometre length scales. Distortions in microfluidic device channels are limited to the size scale of the permeant-swollen layer; 6 microm deep channels are routinely produced with no detectable cross-sectional distortions. Conventional thermal diffusion bonding of identical parts yields less strongly bonded microfluidic structures with increasingly severe dimensional compressions as bonding temperatures approach the thermoplastic glass-transition temperature: a preliminary rheological analysis is consistent with the observed compressions. The bond-enhancing procedure is easily integrated in standard process flows, uses inexpensive reagents, and requires no specialized equipment.

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

    Science.gov (United States)

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

    2014-10-21

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

  6. Rapid identification of ESKAPE bacterial strains using an autonomous microfluidic device.

    Directory of Open Access Journals (Sweden)

    Jack Y Ho

    Full Text Available This article describes Bacteria ID Chips ('BacChips': an inexpensive, portable, and autonomous microfluidic platform for identifying pathogenic strains of bacteria. BacChips consist of a set of microchambers and channels molded in the elastomeric polymer, poly(dimethylsiloxane (PDMS. Each microchamber is preloaded with mono-, di-, or trisaccharides and dried. Pressing the layer of PDMS into contact with a glass coverslip forms the device; the footprint of the device in this article is ∼6 cm(2. After assembly, BacChips are degased under large negative pressure and are stored in vacuum-sealed plastic bags. To use the device, the bag is opened, a sample containing bacteria is introduced at the inlet of the device, and the degased PDMS draws the sample into the central channel and chambers. After the liquid at the inlet is consumed, air is drawn into the BacChip via the inlet and provides a physical barrier that separates the liquid samples in adjacent microchambers. A pH indicator is admixed with the samples prior to their loading, enabling the metabolism of the dissolved saccharides in the microchambers to be visualized. Importantly, BacChips operate without external equipment or instruments. By visually detecting the growth of bacteria using ambient light after ∼4 h, we demonstrate that BacChips with ten microchambers containing different saccharides can reproducibly detect the ESKAPE panel of pathogens, including strains of: Enterococcus faecalis, Enteroccocus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter aerogenes, and Enterobacter cloacae. This article describes a BacChip for point-of-care detection of ESKAPE pathogens and a starting point for designing multiplexed assays that identify bacterial strains from clinical samples and simultaneously determine their susceptibility to antibiotics.

  7. Behavior of Caulobacter Crescentus Diagnosed Using a 3-Channel Microfluidic Device

    Science.gov (United States)

    Tang, Jay; Morse, Michael; Colin, Remy; Wilson, Laurence

    2015-03-01

    Many motile microorganisms are able to detect chemical gradients in their surroundings in order to bias their motion towards more favorable conditions. We study the biased motility of Caulobacter crescentus, a singly flagellated bacteria, which alternate between forward and backward swimming, driven by its flagella motor, which switches in rotation direction. We observe the swimming patterns of C. crescents in an oxygen gradient, which is established by flowing atmospheric air and pure nitrogen through a 3 parallel channel microfluidic device. In this setup, oxygen diffuses through the PDMS device and the bacterial medium, creating a linear gradient. Using low magnification, dark field microscopy, individual cells are tracked over a large field of view, with particular interest in the cells' motion relative to the oxygen gradient. Utilizing observable differences between backward and forward swimming motion, motor switching events can be identified. By analyzing these run time intervals between motor switches as a function of a cell's local oxygen level, we demonstrate that C. crescentus displays aerotacitc behavior by extending forward swimming run times while moving up an oxygen gradient, resulting in directed motility towards oxygen sources. Additionally, motor switching response is sensitive to both the steepness of the gradient experienced and background oxygen levels with cells exhibiting a logarithmic response to oxygen levels. Work funded by the United States National Science Foundation and by the Rowland Institute at Harvard University.

  8. Measurements of elastic moduli of silicone gel substrates with a microfluidic device.

    Science.gov (United States)

    Gutierrez, Edgar; Groisman, Alex

    2011-01-01

    Thin layers of gels with mechanical properties mimicking animal tissues are widely used to study the rigidity sensing of adherent animal cells and to measure forces applied by cells to their substrate with traction force microscopy. The gels are usually based on polyacrylamide and their elastic modulus is measured with an atomic force microscope (AFM). Here we present a simple microfluidic device that generates high shear stresses in a laminar flow above a gel-coated substrate and apply the device to gels with elastic moduli in a range from 0.4 to 300 kPa that are all prepared by mixing two components of a transparent commercial silicone Sylgard 184. The elastic modulus is measured by tracking beads on the gel surface under a wide-field fluorescence microscope without any other specialized equipment. The measurements have small and simple to estimate errors and their results are confirmed by conventional tensile tests. A master curve is obtained relating the mixing ratios of the two components of Sylgard 184 with the resulting elastic moduli of the gels. The rigidity of the silicone gels is less susceptible to effects from drying, swelling, and aging than polyacrylamide gels and can be easily coated with fluorescent tracer particles and with molecules promoting cellular adhesion. This work can lead to broader use of silicone gels in the cell biology laboratory and to improved repeatability and accuracy of cell traction force microscopy and rigidity sensing experiments.

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

    Science.gov (United States)

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

    2017-01-01

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

  10. Rapid ultraviolet monitoring of multiple psychotropic drugs with a renewable microfluidic device.

    Science.gov (United States)

    Sheng, Jin; Lei, Jianping; Ju, Huangxian; Song, Chaojin; Zhang, Daming

    2010-10-29

    A rapid method for sensitive ultraviolet detection of multiple psychotropic drugs in human plasma was developed on a low-cost and expediently fabricated hybrid microfluidic device. The device was composed of one fused-silica capillary with a sampling fracture, a poly(methyl methacrylate) board with four reservoirs, and a printed circuit board. At the optimal separation and detection conditions, the baseline separation of three kinds of psychotropic drugs including barbiturates (phenobarbital and barbital), benzodiazepines (nitrazepam, clonazepam, chlordiazepoxide, alprazolam and diazepam) and tricyclic antidepressant drugs (amitriptyline) was achieved within 200 s with separation efficiency up to 3.80 × 10(5) plates m(-1). The linear ranges for ultraviolet detection were from 2.0 to 1000.0 μg mL(-1) for chlordiazepoxide and 1.0 to 1000.0 μg mL(-1) for other seven drugs. Combining with solid-phase extraction, this novel protocol could successfully be used to screen naturally existing psychotropic drugs in a known human plasma sample. The minimum detectable concentration was down to 27 ng mL(-1) for phenobarbital spiked in plasma. This work provided a promising way to initially screen different psychotropic drugs with high resolution, rapid separation and low-cost.

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

    Science.gov (United States)

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

    2017-03-01

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

  12. Microfluidic devices for imaging neurological response of Drosophila melanogaster larva to auditory stimulus.

    Science.gov (United States)

    Ghaemi, Reza; Rezai, Pouya; Iyengar, Balaji G; Selvaganapathy, Ponnambalam Ravi

    2015-02-21

    Two microfluidic devices (pneumatic chip and FlexiChip) have been developed for immobilization and live-intact fluorescence functional imaging of Drosophila larva's Central Nervous System (CNS) in response to controlled acoustic stimulation. The pneumatic chip is suited for automated loading/unloading and potentially allows high throughput operation for studies with a large number of larvae while the FlexiChip provides a simple and quick manual option for animal loading and is suited for smaller studies. Both chips were capable of significantly reducing the endogenous CNS movement while still allowing the study of sound-stimulated CNS activities of Drosophila 3rd instar larvae using genetically encoded calcium indicator GCaMP5. Temporal effects of sound frequency (50-5000 Hz) and intensity (95-115 dB) on CNS activities were investigated and a peak neuronal response of 200 Hz was identified. Our lab-on-chip devices can not only aid further studies of Drosophila larva's auditory responses but can be also adopted for functional imaging of CNS activities in response to other sensory cues. Auditory stimuli and the corresponding response of the CNS can potentially be used as a tool to study the effect of chemicals on the neurophysiology of this model organism.

  13. Maskless fabrication of a microfluidic device with interdigitated electrodes on PCB using laser ablation

    Science.gov (United States)

    Contreras-Saenz, Michael; Hassard, Christian; Vargas-Chacon, Rafael; Gordillo, Jose Luis; Camacho-Leon, Sergio

    2016-03-01

    This paper reports the maskless fabrication of a microfluidic device with interdigitated electrodes (IDE) based on the technology of MicroElectroMechanical Systems on Printed Circuit Board (PCB-MEMS) and laser ablation. The device has flame retardant (FR)-4 resin as substrate, cooper (Cu) as active material and SU-8 polymer as structural material. By adjusting the laser parameters, Cu IDEs and SU-8 microchannels were successfully patterned onto the FR-4 substrate. The respective width, gap and overlap of the IDEs were 50 μm, 25 μm and 500 μm. The respective width, depth and length of the microchannels were 210 μm, 24.6 μm and 6.3 mm. The resolution and repeatability achieved in this approach, along with the low cost of the involved materials and techniques, enable an affordable micromachining platform with rapid fabrication-test cycle to develop active multiphysic microdevices with several applications in the fields of biosensing, cell culture, drug delivery, transport and sorting of molecules, among others.

  14. A Microfluidic Device for Continuous Sensing of Systemic Acute Toxicants in Drinking Water

    Directory of Open Access Journals (Sweden)

    Xinyan Zhao

    2013-12-01

    Full Text Available A bioluminescent-cell-based microfluidic device for sensing toxicants in drinking water was designed and fabricated. The system employed Vibrio fischeri cells as broad-spectrum sensors to monitor potential systemic cell toxicants in water, such as heavy metal ions and phenol. Specifically, the chip was designed for continuous detection. The chip design included two counter-flow micromixers, a T-junction droplet generator and six spiral microchannels. The cell suspension and water sample were introduced into the micromixers and dispersed into droplets in the air flow. This guaranteed sufficient oxygen supply for the cell sensors. Copper (Cu2+, zinc (Zn2+, potassium dichromate and 3,5-dichlorophenol were selected as typical toxicants to validate the sensing system. Preliminary tests verified that the system was an effective screening tool for acute toxicants although it could not recognize or quantify specific toxicants. A distinct non-linear relationship was observed between the zinc ion concentration and the Relative Luminescence Units (RLU obtained during testing. Thus, the concentration of simple toxic chemicals in water can be roughly estimated by this system. The proposed device shows great promise for an early warning system for water safety.

  15. Measurements of elastic moduli of silicone gel substrates with a microfluidic device.

    Directory of Open Access Journals (Sweden)

    Edgar Gutierrez

    Full Text Available Thin layers of gels with mechanical properties mimicking animal tissues are widely used to study the rigidity sensing of adherent animal cells and to measure forces applied by cells to their substrate with traction force microscopy. The gels are usually based on polyacrylamide and their elastic modulus is measured with an atomic force microscope (AFM. Here we present a simple microfluidic device that generates high shear stresses in a laminar flow above a gel-coated substrate and apply the device to gels with elastic moduli in a range from 0.4 to 300 kPa that are all prepared by mixing two components of a transparent commercial silicone Sylgard 184. The elastic modulus is measured by tracking beads on the gel surface under a wide-field fluorescence microscope without any other specialized equipment. The measurements have small and simple to estimate errors and their results are confirmed by conventional tensile tests. A master curve is obtained relating the mixing ratios of the two components of Sylgard 184 with the resulting elastic moduli of the gels. The rigidity of the silicone gels is less susceptible to effects from drying, swelling, and aging than polyacrylamide gels and can be easily coated with fluorescent tracer particles and with molecules promoting cellular adhesion. This work can lead to broader use of silicone gels in the cell biology laboratory and to improved repeatability and accuracy of cell traction force microscopy and rigidity sensing experiments.

  16. Inkjet patterned superhydrophobic paper for open-air surface microfluidic devices.

    Science.gov (United States)

    Elsharkawy, Mohamed; Schutzius, Thomas M; Megaridis, Constantine M

    2014-03-21

    We present a facile approach for the fabrication of low-cost surface biomicrofluidic devices on superhydrophobic paper created by drop-casting a fluoroacrylic copolymer onto microtextured paper. Wettability patterning is performed with a common household printer, which produces regions of varying wettability by simply controlling the intensity of ink deposited over prespecified domains. The procedure produces surfaces that are capable of selective droplet sliding and adhesion, when inclined. Using this methodology, we demonstrate the ability to tune the sliding angles of 10 μL water droplets in the range from 13° to 40° by printing lines of constant ink intensity and varied width from 0.1 mm to 2 mm. We also formulate a simple model to predict the onset of droplet sliding on printed lines of known width and wettability. Experiments demonstrate open-air surface microfluidic devices that are capable of pumpless transport, mixing and rapid droplet sampling (~0.6 μL at 50 Hz). Lastly, post treatment of printed areas with pH indicator solutions exemplifies the utility of these substrates in point-of-care diagnostics, which are needed at geographical locations where access to sophisticated testing equipment is limited or non-existent.

  17. Tetrazine-based chemistry for nitrite determination in a paper microfluidic device.

    Science.gov (United States)

    Ortiz-Gomez, Inmaculada; Ortega-Muñoz, Mariano; Salinas-Castillo, Alfonso; Álvarez-Bermejo, José Antonio; Ariza-Avidad, Maria; de Orbe-Payá, Ignacio; Santoyo-Gonzalez, Francisco; Capitan-Vallvey, Luis Fermin

    2016-11-01

    We present a new chemistry to determine nitrites implemented in a microfluidic paper-based analytical device (µPAD). The device is fabricated in cellulose paper with a sample reception area and three replicate detection areas with recognition chemistry immobilized by adsorption. The method involves the use of nitrite in an acid medium reaction to generate nitrous acid, which produces the oxidation of s-dihydrotetrazine: 1,2-dihydro-3,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)-1,2,4,5-tetrazine (DHBPTz), which change the detection zone from colorless to pink. We used a digital camera and smartphone for the quantitative analysis of nitrite with the color coordinate S of the HSV color space as the analytical parameter. Parameters such as concentration and volume of s-dihydrotetrazine, pH, sample volume and reaction time were studied. The detection limit for this method is 1.30µM nitrite. To estimate the selectivity of the method an interference study of common ions in water samples was performed. The procedure was applied to natural water and compared with reference procedures.

  18. Chitosan microgels obtained by on-chip crosslinking reaction employing a microfluidic device

    Science.gov (United States)

    Zamora-Mora, Vanessa; Velasco, Diego; Hernández, Rebeca; Mijangos, Carmen

    2014-12-01

    In the present work, we report on the preparation of microgels of chitosan crosslinked with sodium tripolyphosphate (TPP) employing the microfluidics technique (MF). To achieve this, several flow focusing geometries were designed and tested. As a first step, a two-inlet flow focusing geometry was employed to emulsify chitosan and the crosslinking reaction was carried out offchip. This procedure did not allow separating the resulting chitosan microgels due to an incomplete crosslinking reaction. A crosslinking reaction on-chip was studied as an alternative. A four-inlet flow focusing geometrywas designed in which three dispersed phases, chitosan 0.25% (w/v), TPP 0.05% (w/v) and acetic acid 1% (v/v) and an continuous phase mineral oil + Span 80 (3% w/v) were employed. The flow rates for the continuous phase were varied from 6.7 to 11.7 μL/min and chitosan microgels were successfully obtained with average diameters from 68 to 42 μm. The average size of the microgels outside the MF device decreased up to ~21% with respect to their size inside the MF device due to partial expulsion of water from the microgels when complete gelation occurred.

  19. A microfluidic dual-well device for high-throughput single-cell capture and culture.

    Science.gov (United States)

    Lin, Ching-Hui; Hsiao, Yi-Hsing; Chang, Hao-Chen; Yeh, Chuan-Feng; He, Cheng-Kun; Salm, Eric M; Chen, Chihchen; Chiu, Ing-Ming; Hsu, Chia-Hsien

    2015-07-21

    In vitro culture of single cells facilitates biological studies by deconvoluting complications from cell population heterogeneity. However, there is still a lack of simple yet high-throughput methods to perform single cell culture experiments. In this paper, we report the development and application of a microfluidic device with a dual-well (DW) design concept for high-yield single-cell loading (~77%) in large microwells (285 and 485 μm in diameter) which allowed for cell spreading, proliferation and differentiation. The increased single-cell loading yield is achieved by using sets of small microwells termed "capture-wells" and big microwells termed "culture-wells" according to their utilities for single-cell capture and culture, respectively. This novel device architecture allows the size of the "culture" microwells to be flexibly adjusted without affecting the single-cell loading efficiency making it useful for cell culture applications as demonstrated by our experiments of KT98 mouse neural stem cell differentiation, A549 and MDA-MB-435 cancer cell proliferation, and single-cell colony formation assay with A549 cells in this paper.

  20. Characterization of acoustic droplet formation in a microfluidic flow-focusing device.

    Science.gov (United States)

    Cheung, Yin Nee; Qiu, Huihe

    2011-12-01

    Local control of droplet formation with acoustic actuation in a microfluidic flow-focusing device is investigated, and the effects of acoustic voltage, frequency, flow-rate ratio, fluid viscosity, and flow vorticity are characterized. Acoustic actuation is provided to affect droplet breakup in the squeezing regime by imposing periodic oscillation to the fluid-fluid interface and, therefore, a periodic change in its curvature at the cross-junction of the device. Time reduction is observed for the three key stages of droplet breakup in the squeezing regime: dispersed phase flow-front advancement into the orifice, pressure buildup upstream and within the orifice together with liquid inflation downstream, and finally the thinning and pinch-off of the liquid thread. It is found that acoustic actuation has less of an effect on droplet size for the continuous phase with a higher viscosity due to the restrained interfacial vibration under a high shear stress environment. Periodic velocity flow fields within the dispersed phase at different phases of one oscillation cycle are calculated based on the results from phase-averaged microresolution-particle-image velocimetry (μPIV). The oscillation paths for the points of maximum vorticities of phase-averaged velocity components are traced, which reveals that the motion is mainly along the y direction.

  1. A miniature quantitative PCR device for directly monitoring a sample processing on a microfluidic rapid DNA system.

    Science.gov (United States)

    Hurth, Cedric; Yang, Jianing; Barrett, Matthew; Brooks, Carla; Nordquist, Alan; Smith, Stanley; Zenhausern, Frederic

    2014-12-01

    We report a microfluidic device and measurement method to perform real-time PCR (or qPCR) in a miniaturized configuration for on-chip implementation using reaction volumes of less than 20 μL. The qPCR bioreactor is designed as a module to be embedded in an automated sample-in/profile-out system for rapid DNA biometrics or human identification. The PCR mixture is excited with a 505 nm diode-pumped solid-state laser (DPSSL) and the fluorescence build-up is measured using optical fibers directly embedded to the sidewalls of the microfluidic qPCR bioreactor. We discuss manufacturing and operating parameters necessary to adjust the internal surface conditions and temperature profiles of the bioreactor and to optimize the yield and quality of the PCR reaction for the amplification of 62 bp hTERT intron fragments using the commercial Quantifiler® kit (Life Technologies, Carlsbad, CA) commonly accepted for genotyping analysis. We designed a microfluidic device suitable for continuously processing a specimen by efficiently mixing the reagents from the kit to a set volume of DNA template on chip. Our approach relies on a calibration curve for the specific device using control DNA. We successfully applied this method to determine the concentration of genomic DNA extracted from a buccal swab on separate microfluidic devices which are operated upstream the qPCR device and perform buccal swab lysis and buccal DNA extraction. A precise correlation between the amount determined on chip and that obtained using a commercial cycler is demonstrated.

  2. Tabu Search-based Synthesis of Digital Microfluidic Biochips with Dynamically Reconfigurable Non-rectangular Devices

    DEFF Research Database (Denmark)

    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 necessary functions for biochemical analysis. The "digital" microfluidic biochips are manipulating liquids not as a continuous flow, but as discrete droplets, and hence...... rectangular. In this paper, we present a Tabu Search metaheuristic for the synthesis of digital microfluidic biochips, which, starting from a biochemical application and a given biochip architecture, determines the allocation, resource binding, scheduling and placement of the operations in the application...

  3. A novel temperature control method for shortening thermal cycling time to achieve rapid polymerase chain reaction (PCR) in a disposable polymer microfluidic device

    DEFF Research Database (Denmark)

    Bu, Minqiang; R. Perch-Nielsen, Ivan; Sørensen, Karen Skotte

    We present a new temperature control method capable of effectively shortening the thermal cycling time of polymerase chain reaction (PCR) in a disposable polymer microfluidic device with external heater and temperature sensor. The method employs optimized temperature overshooting and undershooting...

  4. A microfluidic device providing continuous-flow polymerase chain reaction heating and cooling

    Science.gov (United States)

    Harandi, A.; Farquhar, T.

    2014-11-01

    The objective of this study is to describe a new type of microfluidic device that could be used to manipulate fluid temperature in many microfluidic applications. The key component is a composite material containing a thermally conductive phase placed in a purposeful manner to manipulate heat flow into and out of an embedded microchannel. In actual use, the device is able to vary temperature along a defined flow path with remarkable precision. As a demonstration of capability, a functional prototype was designed and fabricated using four layers of patterned copper laminated between alternating layers of polyimide and acrylic. The key fabrication steps included laser micromachining, acid etching, microchannel formation, and hot lamination. In order to achieve the desired temperature variations along the microchannel, an outer optimization loop and an inner finite element analysis loop were used to iteratively obtain a near-optimal copper pattern. With a minor loss of generality, admissible forms were restricted to comb-like patterns. For a given temperature profile, the pattern was found by refining a starting guess based on a deterministic rubric. Thermal response was measured using fine thermocouples placed at critical locations along the microchannel wall. At most of these points, the agreement between measured and predicted temperatures was within 1 °C, and temperature gradients as high as ±45 °C mm-1 (equivalent to ±90 °C s-1 at 2 μl min-1 flow rate) were obtained within the range of 59-91 °C. The particular profile chosen for case study makes it possible to perform five cycles of continuous-flow polymerase chain reaction (PCR) in less than 15 s, i.e. it entails five successive cycles of cooling from 91 to 59 °C, rapid reheating from 59 to 73 °C, slow reheating from 73 to 76 °C, and a final reheating from 73 to 91 °C, using a resistively heated source at 100 °C at and a thermoelectrically cooled sink at 5 °C.

  5. A passive-flow microfluidic device for imaging latent HIV activation dynamics in single T cells.

    Science.gov (United States)

    Ramji, Ramesh; Wong, Victor C; Chavali, Arvind K; Gearhart, Larisa M; Miller-Jensen, Kathryn

    2015-09-01

    Quantifying cell-to-cell variability in drug response dynamics is important when evaluating therapeutic efficacy. For example, optimizing latency reversing agents (LRAs) for use in a clinical "activate-and-kill" strategy to purge the latent HIV reservoir in patients requires minimizing heterogeneous viral activation dynamics. To evaluate how heterogeneity in latent HIV activation varies across a range of LRAs, we tracked drug-induced response dynamics in single cells via live-cell imaging using a latent HIV-GFP reporter virus in a clonal Jurkat T cell line. To enable these studies in suspension cells, we designed a simple method to capture an array of single Jurkat T cells using a passive-flow microfluidic device. Our device, which does not require external pumps or tubing, can trap hundreds of cells within minutes with a high retention rate over 12 hours of imaging. Using this device, we quantified heterogeneity in viral activation stimulated by transcription factor (TF) activators and histone deacetylase (HDAC) inhibitors. Generally, TF activators resulted in both faster onset of viral activation and faster rates of production, while HDAC inhibitors resulted in more uniform onset times, but more heterogeneous rates of production. Finally, we demonstrated that while onset time of viral gene expression and rate of viral production together predict total HIV activation, rate and onset time were not correlated within the same individual cell, suggesting that these features are regulated independently. Overall, our results reveal drug-specific patterns of noisy HIV activation dynamics not previously identified in static single-cell assays, which may require consideration for the most effective activate-and-kill regime.

  6. Utilization of microfluidic V-junction device to prepare surface itraconazole adsorbed nanospheres.

    Science.gov (United States)

    Kucuk, Israfil; Ahmad, Zeeshan; Edirisinghe, Mohan; Orlu-Gul, Mine

    2014-09-10

    Itraconazole is widely used as an anti-fungal drug to treat infections. However, its poor aqueous solubility results in low bioavailability. The aim of the present study was to improve the drug release profile by preparing surface itraconazole adsorbed polymethylsilsesquioxane (PMSQ) nanospheres using a V-junction microfluidic (VJM) device. In order to generate nanospheres with rough surface, the process flow rate of perfluorohexane (PFH) was set between 50 and 300 μl min(-1) while the flow rate of PMSQ and itraconazole solution were constant at 300 μl min(-1). Variations in the PFH flow rate enable the controlled size generation of nanospheres. PMSQ nanospheres adsorbing itraconazole were characterized by SEM, FTIR and Zetasizer. The release of itraconazole from PMSQ nanosphere surface was measured using UV spectroscopy. Nanosphere formulations with a range of sphere size (120, 320 and 800 nm diameter) were generated and drug release was studied. 120 nm itraconazole coated PMSQ nanospheres were found to present highest drug encapsulation efficiency and 13% drug loading in a more reproducible manner compared to 320 nm and 800 nm sized nanosphere formulations. Moreover, 120 nm itraconazole coated PMSQ nanospheres (encapsulation efficiency: 88%) showed higher encapsulation efficiency compared to 320 nm (encapsulation efficiency: 74%) and 800 nm (encapsulation efficiency: 62%) sized nanosphere formulations. The itraconazole coated PMSQ nanospheres were prepared continuously at the rate of 2.6 × 10(6) per minute via VJM device. Overall the VJM device enabled the preparation of monodisperse surface itraconazole adsorbed nanospheres with controlled in vitro drug release profile.

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

    Science.gov (United States)

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

    2012-01-21

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

  8. Understanding wax screen-printing: a novel patterning process for microfluidic cloth-based analytical devices.

    Science.gov (United States)

    Liu, Min; Zhang, Chunsun; Liu, Feifei

    2015-09-01

    In this work, we first introduce the fabrication of microfluidic cloth-based analytical devices (μCADs) using a wax screen-printing approach that is suitable for simple, inexpensive, rapid, low-energy-consumption and high-throughput preparation of cloth-based analytical devices. We have carried out a detailed study on the wax screen-printing of μCADs and have obtained some interesting results. Firstly, an analytical model is established for the spreading of molten wax in cloth. Secondly, a new wax screen-printing process has been proposed for fabricating μCADs, where the melting of wax into the cloth is much faster (∼5 s) and the heating temperature is much lower (75 °C). Thirdly, the experimental results show that the patterning effects of the proposed wax screen-printing method depend to a certain extent on types of screens, wax melting temperatures and melting time. Under optimized conditions, the minimum printing width of hydrophobic wax barrier and hydrophilic channel is 100 μm and 1.9 mm, respectively. Importantly, the developed analytical model is also well validated by these experiments. Fourthly, the μCADs fabricated by the presented wax screen-printing method are used to perform a proof-of-concept assay of glucose or protein in artificial urine with rapid high-throughput detection taking place on a 48-chamber cloth-based device and being performed by a visual readout. Overall, the developed cloth-based wax screen-printing and arrayed μCADs should provide a new research direction in the development of advanced sensor arrays for detection of a series of analytes relevant to many diverse applications.

  9. Rapid and low-cost fabrication of polystyrene-based molds for PDMS microfluidic devices using a CO2 laser

    KAUST Repository

    Li, Huawei

    2011-11-01

    In this article, we described a rapid and low-cost method to fabricate polystyrene molds for PDMS microfluidic devices using a CO2 laser system. It takes only several minutes to fabricate the polystyrene mold with bump pattern on top of it using a CO2 laser system. The bump pattern can be easily transferred to PDMS and fabricate microchannles as deep as 3μm on PDMS. © (2012) Trans Tech Publications, Switzerland.

  10. Microfluidic supercritical antisolvent continuous processing and direct spray-coating of poly(3-hexylthiophene) nanoparticles for OFET devices.

    Science.gov (United States)

    Couto, Ricardo; Chambon, Sylvain; Aymonier, Cyril; Mignard, Emmanuel; Pavageau, Bertrand; Erriguible, Arnaud; Marre, Samuel

    2015-01-21

    We report for the first time the use of a microfluidic supercritical antisolvent process (μSAS) to synthesize semiconducting polymer nanoparticles (NPs) of poly(3-hexylthiophene) (P3HT). Solvent-free P3HT NPs with average diameters as small as 36 ± 8 nm are obtained. They are continuously spray-coated on substrates to fabricate OFET devices, demonstrating hole mobility through the nanoparticle film equivalent to that of conventional spin-coated P3HT.

  11. Non-contact reflectometric readout of disposable microfluidic devices by near infra-red low-coherence interferometry

    Directory of Open Access Journals (Sweden)

    Giulia Rigamonti

    2016-11-01

    Full Text Available We are here demonstrating the functionality of infra-red low-coherence reflectometry for the spot optical readout of solution concentrations in commercially available microfluidic devices. Disposable polymeric microfluidic devices composed by 100-µm-deep channels were connected to an external fluidic path that allowed flow-through of water-glucose solutions at different concentrations. Measurements were performed with near-infrared low-power sources, namely a tungsten lamp and a Superluminescent Light Emitting Diode (SLED, allowing the read-out in a wavelength region of minimum invasiveness for biological fluids. The selected optical scheme based on an all-fiber Michelson configuration is well suited for non-contact, remote investigations of the fluids flowing in plastic microfluidic devices, with arbitrary layout and thickness. For the first time, using the SLED, we exploited the double round trip of light in the fluid channel for doubling the sensitivity with respect to the standard single pass set-up, previously demonstrated.

  12. A programmable and configurable multi-port System-on-Chip for stimulating electrokinetically-driven microfluidic devices.

    Science.gov (United States)

    Lopez, Martha Salome; Gerstlauer, Andreas; Avila, Alfonso; Martinez-Chapa, Sergio O

    2011-01-01

    Recent research has demonstrated the use of microfluidic devices and electro-kinetics in areas such as medicine, genetics, embryology, epidemiology and pollution analysis, where manipulation of particles suspended in liquid media is required. Micro-fabrication technology has made it possible to increase system complexity and functionality by allowing integration of different processing and analysis stages in a single chip. However, fully integrated and autonomous microfluidic systems supporting ad-hoc stimulation have yet to be developed. This paper presents a flexible, configurable and programmable stimulator for electro-kinetically driven microfluidic devices. The stimulator is a dedicated System-on-Chip (SoC) architecture that generates sine, triangle, and sawtooth signals within a frequency range of 1 Hz to 20 MHz, capable of delivering single, dual, and superimposed waveforms, in a user defined test sequence for a selected time period. The system is designed to be integrated into complete, autonomous Lab-on-Chip, portable or implantable devices. As such, it is expected to help significantly advance current and future research on particle manipulation.

  13. Drug testing and flow cytometry analysis on a large number of uniform sized tumor spheroids using a microfluidic device

    Science.gov (United States)

    Patra, Bishnubrata; Peng, Chien-Chung; Liao, Wei-Hao; Lee, Chau-Hwang; Tung, Yi-Chung

    2016-02-01

    Three-dimensional (3D) tumor spheroid possesses great potential as an in vitro model to improve predictive capacity for pre-clinical drug testing. In this paper, we combine advantages of flow cytometry and microfluidics to perform drug testing and analysis on a large number (5000) of uniform sized tumor spheroids. The spheroids are formed, cultured, and treated with drugs inside a microfluidic device. The spheroids can then be harvested from the device without tedious operation. Due to the ample cell numbers, the spheroids can be dissociated into single cells for flow cytometry analysis. Flow cytometry provides statistical information in single cell resolution that makes it feasible to better investigate drug functions on the cells in more in vivo-like 3D formation. In the experiments, human hepatocellular carcinoma cells (HepG2) are exploited to form tumor spheroids within the microfluidic device, and three anti-cancer drugs: Cisplatin, Resveratrol, and Tirapazamine (TPZ), and their combinations are tested on the tumor spheroids with two different sizes. The experimental results suggest the cell culture format (2D monolayer vs. 3D spheroid) and spheroid size play critical roles in drug responses, and also demonstrate the advantages of bridging the two techniques in pharmaceutical drug screening applications.

  14. Microfluidic devices for in vitro studies on liver drug metabolism and toxicity

    NARCIS (Netherlands)

    van Midwoud, Paul M.; Verpoorte, Elisabeth; Groothuis, Geny M. M.

    2011-01-01

    Microfluidic technologies enable the fabrication of advanced in vitro systems incorporating liver tissue or cells to perform metabolism and toxicity studies for drugs and other xenobiotics. The use of microfluidics provides the possibility to utilize a flow of medium, thereby creating a

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

    Science.gov (United States)

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

    2016-01-01

    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.

  16. A droplet routing technique for fault-tolerant digital microfluidic devices

    NARCIS (Netherlands)

    Zhang, X.; van Proosdij, Frits; Kerkhoff, Hans G.

    2008-01-01

    Abstract—Efficient droplet routing is one of the key approaches for realizing fault-tolerant microfluidic biochips. It requires that run-time diagnosis and fault recovery can be made possible in such systems. This paper describes a droplet routing technique for a fault-tolerant digital microfluidic

  17. A droplet routing technique for fault-tolerant digital microfluidic devices

    NARCIS (Netherlands)

    Zhang, Xiao; Proosdij, van Frits; Kerkhoff, Hans G.

    2008-01-01

    Abstract—Efficient droplet routing is one of the key approaches for realizing fault-tolerant microfluidic biochips. It requires that run-time diagnosis and fault recovery can be made possible in such systems. This paper describes a droplet routing technique for a fault-tolerant digital microfluidic

  18. Microfluidic conceived drug loaded Janus particles in side-by-side capillaries device.

    Science.gov (United States)

    Khan, Ikram Ullah; Serra, Christophe A; Anton, Nicolas; Li, Xiang; Akasov, Roman; Messaddeq, Nadia; Kraus, Isabelle; Vandamme, Thierry F

    2014-10-01

    A side-by-side capillaries microfluidic device was developed to fabricate drug loaded poly(acrylamide)/poly(methyl acrylate) Janus particles in the range of 59-240 μm by UV-assisted free radical polymerization. This system was characterized in terms of continuous and dispersed phases flow rates (Qc/Qd), monomer composition of the two compartments, surfactant nature and concentration, outlet tube diameter and UV intensity. These factors were adequately controlled to get different particle shapes ranging from core-shell to bi-compartmental particles. For the latter, a low surfactant concentration (0.75 wt.%) was necessary when the two dispersed phases were pumped at equal flow rate, while at high surfactant concentration, dispersed phases flow rates have to be changed. FTIR analysis suggested complete polymerization of monomers and cytotoxicity test showed these particles were biocompatible having LD 50 of 9 mg/mL. Both ketoprofen and sodium fluorescein were released in sustained release manner at pH 6.8 by following a diffusion type release mechanism. Drug release was faster for bigger particles and found to result from the irregular distribution of the two phases and indentation on bigger particles as revealed by SEM analysis. In comparison, sodium fluorescein release was slower which was attributed to low encapsulation but could be modified by decreasing crosslinker concentration.

  19. Investigation of the Effect of Plasma Polymerized Siloxane Coating for Enzyme Immobilization and Microfluidic Device Conception

    Directory of Open Access Journals (Sweden)

    Kalim Belhacene

    2016-12-01

    Full Text Available This paper describes the impact of a physical immobilization methodology, using plasma polymerized 1,1,3,3, tetramethyldisiloxane, on the catalytic performance of β-galactosidase from Aspergillus oryzae in a microfluidic device. The β-galactosidase was immobilized by a polymer coating grown by Plasma Enhanced Chemical Vapor Deposition (PEVCD. Combined with a microchannel patterned in the silicone, a microreactor was obtained with which the diffusion through the plasma polymerized layer and the hydrolysis of a synthetic substrate, the resorufin-β-d-galactopyranoside, were studied. A study of the efficiency of the immobilization procedure was investigated after several uses and kinetic parameters of immobilized β-galactosidase were calculated and compared with those of soluble enzyme. Simulation and a modelling approach were also initiated to understand phenomena that influenced enzyme behavior in the physical immobilization method. Thus, the catalytic performances of immobilized enzymes were directly influenced by immobilization conditions and particularly by the diffusion behavior and availability of substrate molecules in the enzyme microenvironment.

  20. Chelate titrations of Ca(2+) and Mg(2+) using microfluidic paper-based analytical devices.

    Science.gov (United States)

    Karita, Shingo; Kaneta, Takashi

    2016-06-14

    We developed microfluidic paper-based analytical devices (μPADs) for the chelate titrations of Ca(2+) and Mg(2+) in natural water. The μPAD consisted of ten reaction zones and ten detection zones connected through narrow channels to a sample zone located at the center. Buffer solutions with a pH of 10 or 13 were applied to all surfaces of the channels and zones. Different amounts of ethylenediaminetetraacetic acid (EDTA) were added to the reaction zones and a consistent amount of a metal indicator (Eriochrome Black T or Calcon) was added to the detection zones. The total concentrations of Ca(2+) and Mg(2+) (total hardness) in the water were measured using a μPAD containing a buffer solution with a pH of 10, whereas only Ca(2+) was titrated using a μPAD prepared with a potassium hydroxide solution with a pH of 13. The μPADs permitted the determination of Ca(2+) and Mg(2+) in mineral water, river water, and seawater samples within only a few minutes using only the naked eye-no need of instruments.

  1. A digital microfluidic device with integrated nanostructured microelectrodes for electrochemical immunoassays.

    Science.gov (United States)

    Rackus, Darius G; Dryden, Michael D M; Lamanna, Julian; Zaragoza, Alexandre; Lam, Brian; Kelley, Shana O; Wheeler, Aaron R

    2015-01-01

    Nanostructured microelectrodes (NMEs) are three-dimensional electrodes that have superb sensitivity for electroanalysis. Here we report the integration of NMEs with the versatile fluid-handling system digital microfluidics (DMF), for eventual application to distributed diagnostics outside of the laboratory. In the new methods reported here, indium tin oxide DMF top plates were modified to include Au NMEs as well as counter and pseudoreference electrodes. The new system was observed to outperform planar sensing electrodes of the type that are typically integrated with DMF. A rubella virus (RV) IgG immunoassay was developed to evaluate the diagnostic potential for the new system, relying on magnetic microparticles coated with RV particles and analysis by differential pulse voltammetry. The limit of detection of the assay (0.07 IU mL(-1)) was >100× below the World Health Organization defined cut-off for rubella immunity. The sensitivity of the integrated device and its small size suggest future utility for distributed diagnostics.

  2. Laser vibrometry characterisation of a microfluidic lab-on-a-chip device: a preliminary investigation

    Science.gov (United States)

    Fury, C.; Gélat, P. N.; Jones, P. H.; Memoli, G.

    2014-04-01

    Since their original inception as ultrasound contrast agents, potential applications of microbubbles have evolved to encompass molecular imaging and targeted drug delivery. As these areas develop, so does the need to understand the mechanisms behind the interaction of microbubbles both with biological tissue and with other microbubbles. There is therefore a metrological requirement to develop a controlled environment in which to study these processes. Presented here is the design and characterisation of such a system, which consists of a microfluidic chip, specifically developed for manipulating microbubbles using both optical and acoustic trapping. A laser vibrometer is used to observe the coupling of acoustic energy into the chip from a piezoelectric transducer bonded to the surface. Measurement of the velocity of surface waves on the chip is investigated as a potential method for inferring the nature of the acoustic fields excited within the liquid medium of the device. Comparison of measured surface wavelengths with wave types suggests the observation of anti-symmetric Lamb or Love-Kirchhoff waves. Further visual confirmation of the acoustic fields through bubble aggregation highlights differences between the model and experimental results in predicting the position of acoustic pressure nodes in relation to excitation frequency.

  3. A Supramolecular Sensing Platform for Phosphate Anions and an Anthrax Biomarker in a Microfluidic Device

    Directory of Open Access Journals (Sweden)

    Jurriaan Huskens

    2011-10-01

    Full Text Available A supramolecular platform based on self-assembled monolayers (SAMs has been implemented in a microfluidic device. The system has been applied for the sensing of two different analyte types: biologically relevant phosphate anions and aromatic carboxylic acids, which are important for anthrax detection. A Eu(III-EDTA complex was bound to β-cyclodextrin monolayers via orthogonal supramolecular host-guest interactions. The self-assembly of the Eu(III-EDTA conjugate and naphthalene β-diketone as an antenna resulted in the formation of a highly luminescent lanthanide complex on the microchannel surface. Detection of different phosphate anions and aromatic carboxylic acids was demonstrated by monitoring the decrease in red emission following displacement of the antenna by the analyte. Among these analytes, adenosine triphosphate (ATP and pyrophosphate, as well as dipicolinic acid (DPA which is a biomarker for anthrax, showed a strong response. Parallel fabrication of five sensing SAMs in a single multichannel chip was performed, as a first demonstration of phosphate and carboxylic acid screening in a multiplexed format that allows a general detection platform for both analyte systems in a single test run with µM and nM detection sensitivity for ATP and DPA, respectively.

  4. Flow injection based microfluidic device with carbon nanotube electrode for rapid salbutamol detection.

    Science.gov (United States)

    Karuwan, Chanpen; Wisitsoraat, Anurat; Maturos, Thitima; Phokharatkul, Disayut; Sappat, Assawapong; Jaruwongrungsee, Kata; Lomas, Tanom; Tuantranont, Adisorn

    2009-09-15

    A microfabicated flow injection device has been developed for in-channel electrochemical detection (ECD) of a beta-agonist, namely salbutamol. The microfluidic system consists of PDMS (polydimethylsiloxane) microchannel and electrochemical electrodes formed on glass substrate. The carbon nanotube (CNT) on gold layer as working electrode, silver as reference electrode and platinum as auxiliary electrode were deposited on a glass substrate. Silver, platinum, gold and stainless steel catalyst layers were coated by DC-sputtering. CNTs were then grown on the glass substance by thermal chemical vapor deposition (CVD) with gravity effect and water-assisted etching. 100-microm-deep and 500-microm-wide PDMS microchannels fabricated by SU-8 molding and casting were then bonded on glass substrate by oxygen plasma treatment. Flow injection and ECD of salbutamol was performed with the amperometric detection mode for in-channel detection of salbutamol. The influences of flow rate, injection volume, and detection potential on the response of current signal were optimized. Analytical characteristics, such as sensitivity, repeatability and dynamic range have been evaluated. Fast and highly sensitive detection of salbutamol have been achieved. Thus, the proposed combination of the efficient CNT electrode and miniaturized lab-on-a-chip is a powerful platform for beta-agonists detection.

  5. Determination of glucose and uric acid with bienzyme colorimetry on microfluidic paper-based analysis devices.

    Science.gov (United States)

    Chen, Xi; Chen, Jin; Wang, Fubin; Xiang, Xia; Luo, Ming; Ji, Xinghu; He, Zhike

    2012-05-15

    In this work, we first employ a drying method combining with the bienzyme colorimetric detection of glucose and uric acid on microfluidic paper-based analysis devices (μPADs). The channels of 3D μPADs are also designed by us to get better results. The color results are recorded by both Gel Documentation systems and a common camera. By using Gel Documentation systems, the limits of detection (LOD) of glucose and uric acid are 3.81 × 10(-5)M and 4.31 × 10(-5)M, respectively one order of magnitude lower than that of the reported methods on μPADs. By using a common camera, the limits of detection (LOD) of glucose and uric acid are 2.13 × 10(-4)M and 2.87 × 10(-4)M, respectively. Furthermore, the effects of detection conditions have been investigated and discussed comprehensively. Human serum samples are detected with satisfactory results, which are comparable with the clinical testing results. A low-cost, simple and rapid colorimetric method for the simultaneous detection of glucose and uric acid on the μPADs has been developed with enhanced sensitivity.

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

    Science.gov (United States)

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

    2015-08-01

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

  7. A microfluidic device for the continuous culture and analysis of Caenorhabditis elegans in a toxic aqueous environment

    Science.gov (United States)

    Jung, Jaehoon; Nakajima, Masahiro; Tajima, Hirotaka; Huang, Qiang; Fukuda, Toshio

    2013-08-01

    The nematode Caenorhabditis elegans (C. elegans) receives attention as a bioindicator, and the C. elegans condition has been recently analyzed using microfluidic devices equipped with an imaging system. To establish a method without an imaging system, we have proposed a novel microfluidic device with which to analyze the condition of C. elegans from the capacitance change using a pair of micro-electrodes. The device was designed to culture C. elegans, to expose C. elegans to an external stimulus, such as a chemical or toxicant, and to measure the capacitance change which indicates the condition of C. elegans. In this study, to demonstrate the capability of our device in a toxic aqueous environment, the device was applied to examine the effect of cadmium on C. elegans. Thirty L4 larval stage C. elegans were divided into three groups. One group was a control group and the other groups were exposed to cadmium solutions with concentrations of 5% and 10% LC50 for 24 h. The capacitance change and the body volume of C. elegans as a reference were measured four times and we confirmed the correlation between them. It shows that our device can analyze the condition of C. elegans without an imaging system.

  8. A diffusion based long-range and steady chemical gradient generator on a microfluidic device for studying bacterial chemotaxis

    Science.gov (United States)

    Murugesan, Nithya; Singha, Siddhartha; Panda, Tapobrata; Das, Sarit K.

    2016-03-01

    Studies on chemotaxis in microfluidics device have become a major area of research to generate physiologically similar environment in vitro. In this work, a novel micro-fluidic device has been developed to study chemo-taxis of cells in near physiological condition which can create controllable, steady and long-range chemical gradients using various chemo-effectors in a micro-channel. Hydrogels like agarose, collagen, etc, can be used in the device to maintain exclusive diffusive flux of various chemical species into the micro-channel under study. Variations of concentrations and flow rates of Texas Red dextran in the device revealed that an increase in the concentration of the dye in the feed from 6 to 18 μg ml-1, causes a steeper chemical gradient in the device, whereas the flow rate of the dye has practically no effect on the chemical gradient in the device. This observation confirms that a diffusion controlled chemical gradient is generated in the micro-channel. Chemo-taxis of E. coli cells were studied under the steady gradient of a chemo-attractant and a chemo-repellent separately in the same chemical gradient generator. For sorbitol and NiSO4·6H2O, the bacterial cells exhibit a steady distribution in the micro channel after 1 h and 30 min, respectively. From the distribution of bacterial population chemo-tactic strength of the chemo-effectors was estimated for E. coli. In a long microfluidic channel, migration behavior of bacterial cells under diffusion controlled chemical gradient showed chemotaxis, random movement, aggregation, and concentration dependent reverse chemotaxis.

  9. A microfluidic paper-based analytical device for rapid quantification of particulate chromium

    Energy Technology Data Exchange (ETDEWEB)

    Rattanarat, Poomrat [Electrochemistry and Optical Spectroscopy Research Unit (EOSRU), Department of Chemistry, Faculty of Science, Chulalongkorn University, Patumwan, Bangkok 10330 (Thailand); Dungchai, Wijitar [Department of Chemistry, Faculty of Science, King Mongkut' s University of Technology Thonburi, 91 Prachautid Road, Thungkru, Bangkok 10140 (Thailand); Cate, David M. [School of Biomedical Engineering, Colorado State University, Fort Collins, CO 80523 (United States); Siangproh, Weena [Department of Chemistry, Faculty of Science, Srinakharinwirot University, Sukhumvit 23, Wattana, Bangkok 10110 (Thailand); Volckens, John, E-mail: john.volckens@colostate.edu [Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523 (United States); Chailapakul, Orawon, E-mail: corawon@chula.ac.th [Electrochemistry and Optical Spectroscopy Research Unit (EOSRU), Department of Chemistry, Faculty of Science, Chulalongkorn University, Patumwan, Bangkok 10330 (Thailand); National Center of Excellence for Petroleum, Petrochemicals and Advanced Materials, Chulalongkorn University, Patumwan, Bangkok 10330 (Thailand); Henry, Charles S., E-mail: chuck.henry@colostate.edu [School of Biomedical Engineering, Colorado State University, Fort Collins, CO 80523 (United States); Department of Chemistry, Colorado State University, Fort Collins, CO 80523 (United States)

    2013-10-24

    Graphical abstract: -- Highlights: •Cr detection using a paper-based analytical device. •Analysis of total Cr levels in particulate matter was achieved. •Method for on-paper oxidation of Cr to Cr(VI) using Ce(IV) was established. -- Abstract: Occupational exposure to Cr is concerning because of its myriad of health effects. Assessing chromium exposure is also cost and resource intensive because the analysis typically uses sophisticated instrumental techniques like inductively coupled plasma-mass spectrometry (ICP-MS). Here, we report a novel, simple, inexpensive microfluidic paper-based analytical device (μPAD) for measuring total Cr in airborne particulate matter. In the μPAD, tetravalent cerium (Ce(IV)) was used in a pretreatment zone to oxidize all soluble Cr to Cr(VI). After elution to the detection zone, Cr(VI) reacts with 1,5-diphenylcarbazide (1,5-DPC) forming 1,5-diphenylcarbazone (DPCO) and Cr(III). The resulting Cr(III) forms a distinct purple colored complex with the DPCO. As proof-of-principle, particulate matter (PM) collected on a sample filter was analyzed with the μPAD to quantify the mass of total Cr. A log-linear working range (0.23–3.75 μg; r{sup 2} = 0.998) between Cr and color intensity was obtained with a detection limit of 0.12 μg. For validation, a certified reference containing multiple competing metals was analyzed. Quantitative agreement was obtained between known Cr levels in the sample and the Cr measured using the μPAD.

  10. Instrument for Real-Time Digital Nucleic Acid Amplification on Custom Microfluidic Devices.

    Science.gov (United States)

    Selck, David A; Ismagilov, Rustem F

    2016-01-01

    Nucleic acid amplification tests that are coupled with a digital readout enable the absolute quantification of single molecules, even at ultralow concentrations. Digital methods are robust, versatile and compatible with many amplification chemistries including isothermal amplification, making them particularly invaluable to assays that require sensitive detection, such as the quantification of viral load in occult infections or detection of sparse amounts of DNA from forensic samples. A number of microfluidic platforms are being developed for carrying out digital amplification. However, the mechanistic investigation and optimization of digital assays has been limited by the lack of real-time kinetic information about which factors affect the digital efficiency and analytical sensitivity of a reaction. Commercially available instruments that are capable of tracking digital reactions in real-time are restricted to only a small number of device types and sample-preparation strategies. Thus, most researchers who wish to develop, study, or optimize digital assays rely on the rate of the amplification reaction when performed in a bulk experiment, which is now recognized as an unreliable predictor of digital efficiency. To expand our ability to study how digital reactions proceed in real-time and enable us to optimize both the digital efficiency and analytical sensitivity of digital assays, we built a custom large-format digital real-time amplification instrument that can accommodate a wide variety of devices, amplification chemistries and sample-handling conditions. Herein, we validate this instrument, we provide detailed schematics that will enable others to build their own custom instruments, and we include a complete custom software suite to collect and analyze the data retrieved from the instrument. We believe assay optimizations enabled by this instrument will improve the current limits of nucleic acid detection and quantification, improving our fundamental

  11. Electrowetting-based microfluidic operations on rapid-manufactured devices for heat pipe applications

    Science.gov (United States)

    Hale, Renee S.; Bahadur, Vaibhav

    2017-07-01

    The heat transport capacity of traditional heat pipes is limited by the capillary pressure generated in the internal wick that pumps condensate to the evaporator. Recently, the authors conceptualized a novel heat pipe architecture, wherein wick-based pumping is replaced by electrowetting (EW)-based pumping of microliter droplets in the adiabatic section. An electrowetting heat pipe (EHP) can overcome the capillary limit to heat transport capacity and enable compact, planar, gravity-insensitive, and ultralow power consumption heat pipes that transport kiloWatt heat loads over extended distances. This work develops a novel technique for rapid, scalable fabrication of EW-based devices and studies critical microfluidic operations underlying the EHP, with the objective of predicting the key performance parameters of the EHP. Devices are fabricated on a printed circuit board (PCB) substrate with mechanically-milled electrodes, and a removable polyimide dielectric film. The first set of experiments uncovers the maximum channel gap (1 mm) for reliable EW-based pumping; this parameter determines the heat transport capacity of the EHP, which scales linearly with the channel gap. The second set of experiments uncovers the maximum channel gap (375 microns) at which EW voltages can successfully split droplets. This is an important consideration which ensures EHP operability in the event of unintentional droplet merging. The third set of experiments demonstrate and study EW-induced droplet generation from an open-to-air reservoir, which mimics the interface between the condenser and adiabatic sections of the EHP. The experimental findings predict that planar, water-based EHPs with a (10 cm by 4 mm) cross section can transport 1.6 kW over extended distances (>1 m), with a thermal resistance of 0.01 K W-1.

  12. Functional characterization of circulating tumor cells with a prostate-cancer-specific microfluidic device.

    Directory of Open Access Journals (Sweden)

    Brian J Kirby

    Full Text Available Cancer metastasis accounts for the majority of cancer-related deaths owing to poor response to anticancer therapies. Molecular understanding of metastasis-associated drug resistance remains elusive due to the scarcity of available tumor tissue. Isolation of circulating tumor cells (CTCs from the peripheral blood of patients has emerged as a valid alternative source of tumor tissue that can be subjected to molecular characterization. However, issues with low purity and sensitivity have impeded adoption to clinical practice. Here we report a novel method to capture and molecularly characterize CTCs isolated from castrate-resistant prostate cancer patients (CRPC receiving taxane chemotherapy. We have developed a geometrically enhanced differential immunocapture (GEDI microfluidic device that combines an anti-prostate specific membrane antigen (PSMA antibody with a 3D geometry that captures CTCs while minimizing nonspecific leukocyte adhesion. Enumeration of GEDI-captured CTCs (defined as intact, nucleated PSMA+/CD45- cells revealed a median of 54 cells per ml identified in CRPC patients versus 3 in healthy donors. Direct comparison with the commercially available CellSearch® revealed a 2-400 fold higher sensitivity achieved with the GEDI device. Confocal microscopy of patient-derived GEDI-captured CTCs identified the TMPRSS2:ERG fusion protein, while sequencing identified specific androgen receptor point mutation (T868A in blood samples spiked with only 50 PC C4-2 cells. On-chip treatment of patient-derived CTCs with docetaxel and paclitaxel allowed monitoring of drug-target engagement by means of microtubule bundling. CTCs isolated from docetaxel-resistant CRPC patients did not show any evidence of drug activity. These measurements constitute the first functional assays of drug-target engagement in living circulating tumor cells and therefore have the potential to enable longitudinal monitoring of target response and inform the development of new

  13. Optimization of Surface-Enhanced Raman Spectroscopy Conditions for Implementation into a Microfluidic Device for Drug Detection.

    Science.gov (United States)

    Kline, Neal D; Tripathi, Ashish; Mirsafavi, Rustin; Pardoe, Ian; Moskovits, Martin; Meinhart, Carl; Guicheteau, Jason A; Christesen, Steven D; Fountain, Augustus W

    2016-11-01

    A microfluidic device is being developed by University of California-Santa Barbara as part of a joint effort with the United States Army to develop a portable, rapid drug detection device. Surface-enhanced Raman spectroscopy (SERS) is used to provide a sensitive, selective detection technique within the microfluidic platform employing metallic nanoparticles as the SERS medium. Using several illicit drugs as analytes, the work presented here describes the efforts of the Edgewood Chemical Biological Center to optimize the microfluidic platform by investigating the role of nanoparticle material, nanoparticle size, excitation wavelength, and capping agents on the performance, and drug concentration detection limits achievable with Ag and Au nanoparticles that will ultimately be incorporated into the final design. This study is particularly important as it lays out a systematic comparison of limits of detection and potential interferences from working with several nanoparticle capping agents-such as tannate, citrate, and borate-which does not seem to have been done previously as the majority of studies only concentrate on citrate as the capping agent. Morphine, cocaine, and methamphetamine were chosen as test analytes for this study and were observed to have limits of detection (LOD) in the range of (1.5-4.7) × 10(-8) M (4.5-13 ng/mL), with the borate capping agent having the best performance.

  14. Dynamic pH mapping in microfluidic devices by integrating adaptive coatings based on polyaniline with colorimetric imaging techniques.

    Science.gov (United States)

    Florea, Larisa; Fay, Cormac; Lahiff, Emer; Phelan, Thomas; O'Connor, Noel E; Corcoran, Brian; Diamond, Dermot; Benito-Lopez, Fernando

    2013-03-21

    In this paper we present a microfluidic device that has integrated pH optical sensing capabilities based on polyaniline. The optical properties of polyaniline coatings change in response to the pH of the solution that is flushed inside the microchannel offering the possibility of monitoring pH in continuous flow over a wide pH range throughout the entire channel length. This work also features an innovative detection system for spatial localisation of chemical pH gradients along microfluidic channels through the use of a low cost optical device. Specifically, the use of a microfluidic channel coated with polyaniline is shown to respond colorimetrically to pH and that effect is detected by the detection system, even when pH gradients are induced within the channel. This study explores the capability of detecting this gradient by means of imaging techniques and the mapping of the camera's response to its corresponding pH after a successful calibration process. The provision of an inherently responsive channel means that changes in the pH of a sample moving through the system can be detected dynamically using digital imaging along the entire channel length in real time, without the need to add reagents to the sample. This approach is generic and can be applied to other chemically responsive coatings immobilised on microchannels.

  15. A microfluidic device with multi-valves system to enable several simultaneous exposure tests on Caenorhabditis elegans

    Science.gov (United States)

    Jung, Jaehoon; Nakajima, Masahiro; Masaru, Takeuchi; Huang, Qiang; Fukuda, Toshio

    2014-03-01

    In this paper, we report on a microfluidic device with a multi-valve system to conduct several exposure tests on Caenorhabditis elegans (C. elegans) simultaneously. It has pneumatic valves and no-moving-parts (NMP) valves. An NMP valve is incorporated with a chamber and enables the unidirectional movement of C. elegans in the chamber; once worms are loaded into the chamber, they cannot exit, regardless of the flow direction. To demonstrate the ability of the NMP valve to handle worms, we made a microfluidic device with three chambers. Each chamber was used to expose worms to Cd and Cu solutions, and K-medium. A pair of electrodes was installed in the device and the capacitance in-between the electrode was measured. When a C. elegans passed through the electrodes, the capacitance was changed. The capacitance change was proportional to the body volume of the worm, thus the body volume change by the heavy metal exposure was measured in the device. Thirty worms were divided into three groups and exposed to each solution. We confirmed that the different solutions induced differences in the capacitance changes for each group. These results indicate that our device is a viable method for simultaneously analyzing the effect of multiple stimuli on C. elegans.

  16. Continuous separation of multiple size microparticles using alternating current dielectrophoresis in microfluidic device with acupuncture needle electrodes

    Science.gov (United States)

    Tao, Ye; Ren, Yukun; Yan, Hui; Jiang, Hongyuan

    2016-03-01

    The need to continuously separate multiple microparticles is required for the recent development of lab-on-chip technology. Dielectrophoresis(DEP)-based separation device is extensively used in kinds of microfluidic applications. However, such conventional DEP-based device is relatively complicated and difficult for fabrication. A concise microfluidic device is presented for effective continuous separation of multiple size particle mixtures. A pair of acupuncture needle electrodes are creatively employed and embedded in a PDMS(poly-dimethylsiloxane) hurdle for generating non-uniform electric field thereby achieving a continuous DEP separation. The separation mechanism is that the incoming particle samples with different sizes experience different negative DEP(nDEP) forces and then they can be transported into different downstream outlets. The DEP characterizations of particles are calculated, and their trajectories are numerically predicted by considering the combined action of the incoming laminar flow and the nDEP force field for guiding the separation experiments. The device performance is verified by successfully separating a three-sized particle mixture, including polystyrene microspheres with diameters of 3 μm, 10 μm and 25 μm. The separation purity is below 70% when the flow rate ratio is less than 3.5 or more than 5.1, while the separation purity can be up to more than 90% when the flow rate ratio is between 3.5 and 5.1 and meanwhile ensure the voltage output falls in between 120 V and 150 V. Such simple DEP-based separation device has extensive applications in future microfluidic systems.

  17. Microfluidic electrochemical reactors

    Science.gov (United States)

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

    2011-03-22

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

  18. Zeta potential and electroosmotic mobility in microfluidic devices fabricated from hydrophobic polymers: 1. The origins of charge.

    Science.gov (United States)

    Tandon, Vishal; Bhagavatula, Sharath K; Nelson, Wyatt C; Kirby, Brian J

    2008-03-01

    This paper combines new experimental data for electrokinetic characterization of hydrophobic polymers with a detailed discussion of the putative origins of charge at water-hydrophobe interfaces. Complexities in determining the origin of charge are discussed in the context of design and modeling challenges for electrokinetic actuation in hydrophobic microfluidic devices with aqueous working fluids. Measurements of interfacial charge are complicated by slip and interfacial water structuring phenomena (see Part 2, this issue). Despite these complexities, it is shown that (i) several hydrophobic materials, such as Teflon and Zeonor, have predictable electrokinetic properties and (ii) electrokinetic data for hydrophobic microfluidic systems is most consistent with the postulate that hydroxyl ion adsorption is the origin of charge.

  19. Use of PLL-g-PEG in micro-fluidic devices for localizing selective and specific protein binding.

    Science.gov (United States)

    Marie, Rodolphe; Beech, Jason P; Vörös, Janos; Tegenfeldt, Jonas O; Höök, Fredrik

    2006-11-21

    By utilizing flow-controlled PLL-g-PEG and PLL-g-PEGbiotin modification of predefined regions of a poly(dimethylsiloxane) (PDMS) micro-fluidic device, with an intentionally chosen large (approximately 1 cm2) internal surface area, we report rapid (10 min), highly localized (6 x 10(-6) cm2), and specific surface-based protein capture from a sample volume (100 microL) containing a low amount of protein (160 attomol in pure buffer and 400 attomol in serum). The design criteria for this surface modification were achieved using QCM-D (quartz crystal microbalance with energy dissipation monitoring) of serum protein adsorption onto PLL-g-PEG-modified oxidized PDMS. Equally good, or almost as good, results were obtained for oxidized SU-8, Topas, and poly(methyl metacrylate) (PMMA), demonstrating the generic potential of PLL-g-PEG for surface modification in various micro-fluidic applications.

  20. Microfluidic sieve valves

    Science.gov (United States)

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

    2015-01-13

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

  1. Enhancement of acoustic streaming induced flow on a focused surface acoustic wave device: Implications for biosensing and microfluidics

    Science.gov (United States)

    Singh, Reetu; Sankaranarayanan, Subramanian K. R. S.; Bhethanabotla, Venkat R.

    2010-01-01

    the F-SAW device manifests itself as enhanced biofouling removal efficiency of F-SAW throughout the device delay path compared to the conventional device, thereby providing enhanced device sensitivity, selectivity, and reusability. Furthermore, contrary to the conventional SAW in which the smallest particle is removable near the input IDTs, the F-SAW device removes the smallest particle near the device focal point. The results of this work are shown to have significant implications in typical biosensing and microfluidic applications. In a broader context, the results of the present study demonstrate a technique of enhancing streaming induced flows, which is of great importance to contemporary problems involving microfluidic and sensing applications of piezoelectric devices.

  2. Electrical Impedance Spectroscopy for Detection of Cells in Suspensions Using Microfluidic Device with Integrated Microneedles

    National Research Council Canada - National Science Library

    Mansor, Muhammad; Takeuchi, Masaru; Nakajima, Masahiro; Hasegawa, Yasuhisa; Ahmad, Mohd

    2017-01-01

    .... The state of the art method for impedance flow cytometry detection utilizes an embedded electrode in the microfluidic to perform measurement of electrical impedance of the presence of cells at the sensing area...

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

    Science.gov (United States)

    Hu, Chunxiao; Dillon, James; Kearn, James; Murray, Caitriona; O'Connor, Vincent; Holden-Dye, Lindy; Morgan, Hywel

    2013-01-01

    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.

  4. Fabrication of continuous flow microfluidics device with 3D electrode structures for high throughput DEP applications using mechanical machining.

    Science.gov (United States)

    Zeinali, Soheila; Çetin, Barbaros; Oliaei, Samad Nadimi Bavil; Karpat, Yiğit

    2015-07-01

    Microfluidics is the combination of micro/nano fabrication techniques with fluid flow at microscale to pursue powerful techniques in controlling and manipulating chemical and biological processes. Sorting and separation of bio-particles are highly considered in diagnostics and biological analyses. Dielectrophoresis (DEP) has offered unique advantages for microfluidic devices. In DEP devices, asymmetric pair of planar electrodes could be employed to generate non-uniform electric fields. In DEP applications, facing 3D sidewall electrodes is considered to be one of the key solutions to increase device throughput due to the generated homogeneous electric fields along the height of microchannels. Despite the advantages, fabrication of 3D vertical electrodes requires a considerable challenge. In this study, two alternative fabrication techniques have been proposed for the fabrication of a microfluidic device with 3D sidewall electrodes. In the first method, both the mold and the electrodes are fabricated using high precision machining. In the second method, the mold with tilted sidewalls is fabricated using high precision machining and the electrodes are deposited on the sidewall using sputtering together with a shadow mask fabricated by electric discharge machining. Both fabrication processes are assessed as highly repeatable and robust. Moreover, the two methods are found to be complementary with respect to the channel height. Only the manipulation of particles with negative-DEP is demonstrated in the experiments, and the throughput values up to 105 particles / min is reached in a continuous flow. The experimental results are compared with the simulation results and the limitations on the fabrication techniques are also discussed.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Acid-base titrations using microfluidic paper-based analytical devices.

    Science.gov (United States)

    Karita, Shingo; Kaneta, Takashi

    2014-12-16

    Rapid and simple acid-base titration was accomplished using a novel microfluidic paper-based analytical device (μPAD). The μPAD was fabricated by wax printing and consisted of ten reservoirs for reaction and detection. The reaction reservoirs contained various amounts of a primary standard substance, potassium hydrogen phthalate (KHPth), whereas a constant amount of phenolphthalein was added to all the detection reservoirs. A sample solution containing NaOH was dropped onto the center of the μPAD and was allowed to spread to the reaction reservoirs where the KHPth neutralized it. When the amount of NaOH exceeded that of the KHPth in the reaction reservoirs, unneutralized hydroxide ion penetrated the detection reservoirs, resulting in a color reaction from the phenolphthalein. Therefore, the number of the detection reservoirs with no color change determined the concentration of the NaOH in the sample solution. The titration was completed within 1 min by visually determining the end point, which required neither instrumentation nor software. The volumes of the KHPth and phenolphthalein solutions added to the corresponding reservoirs were optimized to obtain reproducible and accurate results for the concentration of NaOH. The μPADs determined the concentration of NaOH at orders of magnitude ranging from 0.01 to 1 M. An acid sample, HCl, was also determined using Na2CO3 as a primary standard substance instead of KHPth. Furthermore, the μPAD was applicable to the titrations of nitric acid, sulfuric acid, acetic acid, and ammonia solutions. The μPADs were stable for more than 1 month when stored in darkness at room temperature, although this was reduced to only 5 days under daylight conditions. The analysis of acidic hot spring water was also demonstrated in the field using the μPAD, and the results agreed well with those obtained by classic acid-base titration.

  7. Dry adhesive bonding of nanoporous inorganic membranes to microfluidic devices using the OSTE(+) dual-cure polymer

    Science.gov (United States)

    Saharil, Farizah; Forsberg, Fredrik; Liu, Yitong; Bettotti, Paolo; Kumar, Neeraj; Niklaus, Frank; Haraldsson, Tommy; van der Wijngaart, Wouter; Gylfason, Kristinn B.

    2013-02-01

    We present two transfer bonding schemes for incorporating fragile nanoporous inorganic membranes into microdevices. Such membranes are finding increasing use in microfluidics, due to their precisely controllable nanostructure. Both schemes rely on a novel dual-cure dry adhesive bonding method, enabled by a new polymer formulation: OSTE(+), which can form bonds at room temperature. OSTE(+) is a novel dual-cure ternary monomer system containing epoxy. After the first cure, the OSTE(+) is soft and suitable for bonding, while during the second cure it stiffens and obtains a Young’s modulus of 1.2 GPa. The ability of the epoxy to react with almost any dry surface provides a very versatile fabrication method. We demonstrate the transfer bonding of porous silicon and porous alumina membranes to polymeric microfluidic chips molded into OSTE(+), and of porous alumina membranes to microstructured silicon wafers, by using the OSTE(+) as a thin bonding layer. We discuss the OSTE(+) dual-cure mechanism, describe the device fabrication and evaluate the bond strength and membrane flow properties after bonding. The membranes bonded to OSTE(+) chips delaminate at 520 kPa, and the membranes bonded to silicon delaminate at 750 kPa, well above typical maximum pressures applied to microfluidic circuits. Furthermore, no change in the membrane flow resistance was observed after bonding.

  8. Fluorescence enhancement and multiple protein detection in ZnO nanostructure microfluidic devices.

    Science.gov (United States)

    Sang, Chen-Hsiang; Chou, Shu-Jen; Pan, F M; Sheu, Jeng-Tzong

    2016-01-15

    In this study, different morphological ZnO nanostructures, those of sharp nanowires (NWs), rod NWs, and hexahedral-puncheon nanostructures, were grown in microfluidic channels on the same glass substrate. Characterizations of correspondent biomolecule binding properties were simulated and demonstrated. The surface was modified using 3-ammineopropyl-triethoxysilane (3-APTES) and biotin-N-hydroxysuccinimide ester (NHS-biotin). Different concentrations (4.17pM to 41.7nM) of dye-conjugated streptavidin were simultaneously infused through the second microfluidic channels, which lie 90° from the first microfluidic channels. The florescent intensity at the crossover areas showed good agreement with simulations, with sharp ZnO NWs exhibiting the largest dynamic range and the highest fluorescent intensity. We further characterize correspondent protein detection using sharp ZnO NWs. The surfaces of these ZnO NWs were modified with mouse immunoglobulin G (IgG), infused through the second microfluidic channels with dye-conjugated (Alexa 546) anti-mouse IgG in different concentrations. Concentrations ranging from 417fM to 41.7nM can be resolved using sharp ZnO NWs. Finally, multiple protein detection was demonstrated using a five-by-eight microfluidic channel array. Fluorescence images present clear multiple detections at the crossover areas when using the sharp ZnO NWs for simultaneous dye-conjugated anti-mouse IgG and dye-conjugated anti-rabbit IgG (Alexa 647) detection.

  9. Performance study of acoustophoretic microfluidic silicon-glass devices by characterization of material- and geometry-dependent frequency spectra

    CERN Document Server

    Garofalo, Fabio; Bruus, Henrik

    2016-01-01

    The mechanical and electrical response of acoustophoretic microfluidic devices attached to an ac-voltage-driven piezoelectric transducer is studied by means of numerical simulations. The governing equations are formulated in a variational framework that, introducing Lagrangian and Hamiltonian densities, is used to derive the weak form for the finite element discretization of the equations and to characterize the device response in terms of frequency-dependent figures of merit or indicators. The effectiveness of the device in focusing microparticles is quantified by two mechanical indicators: the average direction of the pressure gradient and the amount of acoustic energy localized in the microchannel. Further, we derive the relations between the Lagrangian, the Hamiltonian and three electrical indicators: the resonance Q-value, the impedance and the electric power. The frequency response of the hard-to-measure mechanical indicators is correlated to that of the easy-to-measure electrical indicators, and by int...

  10. A robust microfluidic device for the synthesis and crystal growth of organometallic polymers with highly organized structures.

    Science.gov (United States)

    Liu, Xiao; Yi, Qiaolian; Han, Yongzhen; Liang, Zhenning; Shen, Chaohua; Zhou, Zhengyang; Sun, Jun-Liang; Li, Yizhi; Du, Wenbin; Cao, Rui

    2015-02-02

    A simple and robust microfluidic device was developed to synthesize organometallic polymers with highly organized structures. The device is compatible with organic solvents. Reactants are loaded into pairs of reservoirs connected by a 15 cm long microchannel prefilled with solvents, thus allowing long-term counter diffusion for self-assembly of organometallic polymers. The process can be monitored, and the resulting crystalline polymers are harvested without damage. The device was used to synthesize three insoluble silver acetylides as single crystals of X-ray diffraction quality. Importantly, for the first time, the single-crystal structure of silver phenylacetylide was determined. The reported approach may have wide applications, such as crystallization of membrane proteins, synthesis and crystal growth of organic, inorganic, and polymeric coordination compounds, whose single crystals cannot be obtained using traditional methods.

  11. Development of an enzymatic reactor applying spontaneously adsorbed trypsin on the surface of a PDMS microfluidic device.

    Science.gov (United States)

    Kecskemeti, Adam; Bako, Jozsef; Csarnovics, Istvan; Csosz, Eva; Gaspar, Attila

    2017-03-15

    Herein, a microfluidic device (MD) containing immobilized trypsin for rapid and efficient proteolysis was described. Trypsin was immobilized via non-specific protein adsorption onto the hydrophobic poly(dimethylsiloxane) (PDMS) channel wall of the MD. Peptide mapping of bovine serum albumin (BSA) samples was carried out to estimate the stability of trypsin adsorbed on PDMS surface. Peptide maps of BSA samples were obtained by capillary zone electrophoresis (CZE), the RSD% for migration times were under 1%. Several proteins (hemoglobin, myoglobin, lysozyme, and BSA) in a wide molecular size range (15-70 kDa) were digested efficiently with ∼50 s contact time. The number of separated peaks correlated well with the expected number of peptides formed in the complete tryptic digestion of the proteins. Peptide mass fingerprinting of BSA and human serum was carried out. Trypsin retained its activity for 2 h; within this period, the MD can be used for multiple digestions. The main properties of this device are simple channel pattern, simple immobilization procedure, regenerability, and disposability; all these features make this MD one of the simplest yet applicable enzymatic microreactors. Graphical abstract Development of microfluidic device including a serpentine channel as an enzyme reactor for protein digestion.

  12. Surface texture change on-demand and microfluidic devices based on thickness mode actuation of dielectric elastomer actuators (DEAs)

    Science.gov (United States)

    Ankit, Ankit; Nguyen, Anh Chien; Mathews, Nripan

    2017-04-01

    Tactile feedback devices and microfluidic devices have huge significance in strengthening the area of robotics, human machine interaction and low cost healthcare. Dielectric Elastomer Actuators (DEAs) are an attractive alternative for both the areas; offering the advantage of low cost and simplistic fabrication in addition to the high actuation strains. The inplane deformations produced by the DEAs can be used to produce out-of-plane deformations by what is known as the thickness mode actuation of DEAs. The thickness mode actuation is achieved by adhering a soft passive layer to the DEA. This enables a wide area of applications in tactile applications without the need of complex systems and multiple actuators. But the thickness mode actuation has not been explored enough to understand how the deformations can be improved without altering the material properties; which is often accompanied with increased cost and a trade off with other closely associated material properties. We have shown the effect of dimensions of active region and non-active region in manipulating the out-of-plane deformation. Making use of this, we have been able to demonstrate large area devices and complex patterns on the passive top layer for the surface texture change on-demand applications. We have also been able to demonstrate on-demand microfluidic channels and micro-chambers without the need of actually fabricating the channels; which is a cost incurring and cumbersome process.

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

    Science.gov (United States)

    Ali, Haider; Park, Cheol Woo

    2016-11-01

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

  14. Development and characterization of an all-solid-state potentiometric biosensor array microfluidic device for multiple ion analysis.

    Science.gov (United States)

    Liao, Wei-Yin; Weng, Chen-Hsun; Lee, Gwo-Bin; Chou, Tse-Chuan

    2006-10-01

    A microfluidic device with an all-solid-state potentiometric biosensor array was developed using microfabrication technology. The sensor array included a pH indicator, and potassium and calcium ion-selective microelectrodes. The pH indicator was an iridium oxide thin film modified platinum microelectrode and the iridium oxide was deposited by an electrochemical method. The potassium and calcium ion-selective microelectrodes were platinum coated with silicon rubber based ion-selective membranes with respectively potassium (valinomycin) and calcium (ETH 1001) ionophores. The detection system was integrated with a micro-pneumatic pump which can continuously drive fluids into the microchannel through sensors at flow rates ranging from 52.4 microl min(-1) to 7.67 microl min(-1). The sensor array microfluidic device showed near-Nernstian responses with slopes of 62.62 mV +/- 2.5 mV pH(-1), 53.76 mV +/- 3 mV -log[K+](-1) and 25.77 mV +/- 2 mV -log[Ca2+](-1) at 25 degrees C +/- 5 degrees C, and a linear response within the pH range of 2-10, with potassium and calcium concentrations between 0.1 M and 10(-6) M. In this study the device provided a convenient way to measure the concentration of hydrogen, potassium and calcium ions, which are important physiological parameters.

  15. Microfluidic devices, systems, and methods for quantifying particles using centrifugal force

    Science.gov (United States)

    Schaff, Ulrich Y.; Sommer, Gregory J.; Singh, Anup K.

    2015-11-17

    Embodiments of the present invention are directed toward microfluidic systems, apparatus, and methods for measuring a quantity of cells in a fluid. Examples include a differential white blood cell measurement using a centrifugal microfluidic system. A method may include introducing a fluid sample containing a quantity of cells into a microfluidic channel defined in part by a substrate. The quantity of cells may be transported toward a detection region defined in part by the substrate, wherein the detection region contains a density media, and wherein the density media has a density lower than a density of the cells and higher than a density of the fluid sample. The substrate may be spun such that at least a portion of the quantity of cells are transported through the density media. Signals may be detected from label moieties affixed to the cells.

  16. Reduction in microparticle adsorption using a lateral interconnection method in a PDMS-based microfluidic device.

    Science.gov (United States)

    Lee, Do-Hyun; Park, Je-Kyun

    2013-12-01

    Microparticle adsorption on microchannel walls occurs frequently due to nonspecific interactions, decreasing operational performance in pressure-driven microfluidic systems. However, it is essential for delicate manipulation of microparticles or cells to maintain smooth fluid traffic. Here, we report a novel microparticle injection technique, which prevents particle loss, assisted by sample injection along the direction of fluid flow. Sample fluids, including microparticles, mammalian (U937), and green algae (Chlorella vulgaris) cells, were injected directly via a through hole drilled in the lateral direction, resulting in a significant reduction in microparticle attachment. For digital microfluidic application, the proposed regime achieved a twofold enhancement of single-cell encapsulation compared to the conventional encapsulation rate, based on a Poisson distribution, by reducing the number of empty droplets. This novel interconnection method can be straightforwardly integrated as a microparticle or cell injection component in integrated microfluidic systems.

  17. Design, fabrication and test of a pneumatically controlled, renewable, microfluidic bead trapping device for sequential injection analysis applications

    Energy Technology Data Exchange (ETDEWEB)

    Shao, Guocheng; Lu, Donglai; Fu, Zhifeng; Du, Dan; Ozanich, Richard M.; Wang, Wanjun; Lin, Yuehe

    2016-01-01

    This paper describes the design, fabrication, and testing of a pneumatically controlled,renewable, microfluidic device for conducting bead-based assays in an automated sequential injection analysis system. The device used a “brick wall”-like pillar array (pillar size: 20 μm length X 50 μm width X 45 μm height) with 5 μm gaps between the pillars serving as the micro filter. The flow channel where bead trapping occurred is 500 μm wide X 75 μm deep. An elastomeric membrane and an air chamber were located underneath the flow channel. By applying pressure to the air chamber, the membrane is deformed and pushed upward against the filter structure. This effectively traps beads larger than 5 μm and creates a “bed” or micro column of beads that can be perfused and washed with liquid samples and reagents. Upon completion of the assay process, the pressure is released and the beads are flushed out from underneath the filter structure to renew the device. Mouse IgG was used as a model analyte to test the feasibility of using the proposed device for immunoassay applications. Resulting microbeads from an on-chip fluorescent immunoassay were individually examined using flow cytometry. The results show that the fluorescence signal intensity distribution is fairly narrow indicating high chemical reaction uniformity among the beads population. Electrochemical onchip assay was also conducted. A detection limit of 0.1 ng/mL1 ppb was achieved and good device reliability and repeatability were demonstrated. The novel microfluidic-based beadstrapping device thus opens up a new pathway to design micro-bead based biosensor immunoassays for clinical and othervarious applications.

  18. Rapid and alternative fabrication method for microfluidic paper based analytical devices.

    Science.gov (United States)

    Malekghasemi, Soheil; Kahveci, Enver; Duman, Memed

    2016-10-01

    A major application of microfluidic paper-based analytical devices (µPADs) includes the field of point-of-care (POC) diagnostics. It is important for POC diagnostics to possess properties such as ease-of-use and low cost. However, µPADs need multiple instruments and fabrication steps. In this study, two different chemicals (Hexamethyldisilazane and Tetra-ethylorthosilicate) were used, and three different methods (heating, plasma treatment, and microwave irradiation) were compared to develop µPADs. Additionally, an inkjet-printing technique was used for generating a hydrophilic channel and printing certain chemical agents on different regions of a modified filter paper. A rapid and effective fabrication method to develop µPADs within 10min was introduced using an inkjet-printing technique in conjunction with a microwave irradiation method. Environmental scanning electron microscope (ESEM) and x-ray photoelectron spectroscopy (XPS) were used for morphology characterization and determining the surface chemical compositions of the modified filter paper, respectively. Contact angle measurements were used to fulfill the hydrophobicity of the treated filter paper. The highest contact angle value (141°±1) was obtained using the microwave irradiation method over a period of 7min, when the filter paper was modified by TEOS. Furthermore, by using this method, the XPS results of TEOS-modified filter paper revealed Si2p (23%) and Si-O bounds (81.55%) indicating the presence of Si-O-Si bridges and Si(OEt) groups, respectively. The ESEM results revealed changes in the porous structures of the papers and decreases in the pore sizes. Washburn assay measurements tested the efficiency of the generated hydrophilic channels in which similar water penetration rates were observed in the TEOS-modified filter paper and unmodified (plain) filter paper. The validation of the developed µPADs was performed by utilizing the rapid urease test as a model test system. The detection limit of

  19. Roll-to-plate fabrication of microfluidic devices with rheology-modified thiol-ene resins

    DEFF Research Database (Denmark)

    Senkbeil, Silja; Aho, Johanna; Yde, Leif

    2016-01-01

    In this paper, the replication possibilities of microfluidic channels by UV-roll-to-plate fabrication were investigated and a study of rheology-modified thiol-ene for the application in such a UV-roll-to-plate setup was conducted. The system allows the manufacture of channels with aspect ratios...

  20. Simulation of the Cystic Fibrosis patient airway habitats using microfluidic devices

    DEFF Research Database (Denmark)

    Skolimowski, Maciej

    2013-01-01

    , and their growth is then monitored using confocal microscopy. However, this is not either a suitable CF model as the human airways are subdivided into aerobic and anaerobic compartments. To investigate the different compartments of the human airways system it is crucial importance to construct a microfluidic model...

  1. Stripline-based microfluidic devices for high-resolution NMR spectroscopy

    NARCIS (Netherlands)

    Bart, J.

    2009-01-01

    A novel route towards microchip integrated NMR analysis was studied. For NMR analysis of mass-limited samples, research has focussed for decennia on microsolenoidal or planar helical detection coils on microfluidic substrates. Since these approaches suffer from static field distortion resulting in

  2. Electron beam fabrication of a microfluidic device for studying submicron-scale bacteria

    NARCIS (Netherlands)

    Moolman, M.C.; Huang, Z.; Krishnan, S.T.; Kerssemakers, J.W.J.; Dekker, N.H.

    2013-01-01

    Background: Controlled restriction of cellular movement using microfluidics allows one to study individual cells to gain insight into aspects of their physiology and behaviour. For example, the use of micron-sized growth channels that confine individual Escherichia coli has yielded novel insights

  3. Rapid photochemical surface patterning of proteins in thiol-ene based microfluidic devices

    DEFF Research Database (Denmark)

    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...

  4. Interconnection blocks with minimal dead volumes permitting planar interconnection to thin microfluidic devices

    DEFF Research Database (Denmark)

    Sabourin, David; Snakenborg, Detlef; Dufva, Martin

    2010-01-01

    We have previously described 'Interconnection Blocks' which are re-usable, non-integrated PDMS blocks which allowing multiple, aligned and planar microfluidic interconnections. Here, we describe Interconnection Block versions with zero dead volumes that allow fluidic interfacing to flat or thin s...

  5. Programmable V-type Valve for Cell and Particle Manipulation in Microfluidic Devices

    NARCIS (Netherlands)

    Rho, Hoon Suk; Yang, Yoon Sun; Hanke, A.T.; Ottens, M.; Terstappen, Leonardus Wendelinus Mathias Marie; Gardeniers, Johannes G.E.

    2016-01-01

    A new microfluidic valve or a “v-type valve” which can be flexibly actuated to focus a fluid flow and block a specific area of a microchannel is demonstrated. Valves with different design parameters were fabricated by multilayer soft lithography and characterized at various operating pressures. To

  6. A Versatile Bonding Method for PDMS and SU-8 and Its Application towards a Multifunctional Microfluidic Device

    Directory of Open Access Journals (Sweden)

    Zhen Zhu

    2016-12-01

    Full Text Available This paper reports a versatile and irreversible bonding method for poly(dimethylsiloxane (PDMS and SU-8. The method is based on epoxide opening and dehydration reactions between surface-modified PDMS and SU-8. A PDMS replica is first activated via the low-cost lab equipment, i.e., the oxygen plasma cleaner or the corona treater. Then both SU-8 and plasma-treated PDMS samples are functionalized using hydrolyzed (3-aminopropyltriethoxysilane (APTES. Ultimately, the samples are simply brought into contact and heated to enable covalent bonding. The molecular coupling and chemical reactions behind the bonding occurring at the surfaces were characterized by water contact angle measurement and X-ray photoelectron spectroscopy (XPS analysis. The reliability of bonded PDMS-SU-8 samples was examined by using tensile strength and leakage tests, which revealed a bonding strength of over 1.4 MPa. The presented bonding method was also applied to create a metal-SU-8-PDMS hybrid device, which integrated SU-8 microfluidic structures and microelectrodes. This hybrid system was used for the effective trapping of microparticles on-chip, and the selective releasing and identification of predefined trapped microparticles. The hybrid fabrication approach presented here, based on the PDMS-SU-8 bonding, enables multifunctional integration in complex microfluidic devices.

  7. Building a better cell trap: Applying Lagrangian modeling to the design of microfluidic devices for cell biology

    Science.gov (United States)

    Kim, Min-Cheol; Wang, Zhanhui; Lam, Raymond H. W.; Thorsen, Todd

    2008-02-01

    In this report, we show how computational fluid dynamics can be applied to the design of efficient hydrodynamic cell traps in microfluidic devices. Modeled hydrodynamic trap designs included a large, multiple-aperture "C-type" sieve for trapping hundreds of cells, flat single-aperture arrays for single cells, and "U-type" hydrodynamic structures with one or two apertures to confine small clusters of cells (˜10-15 cells per trap). Using 3T3 cells as a model system, the motion of each individual cell was calculated using a one-way coupled Lagrangian method. The cell was assumed to be a solid sphere, and interactions with other cells were only considered when a cell sedimented in the trap. The ordinary differential equations were solved along the cell trajectory for the three components of the velocity and location vector by using the Rosenbrock method based on an adaptive time-stepping technique. Validation of the predictive value of modeling, using 3T3 cells flowed through microfluidic devices containing "U-type sieves" under the simulation flow parameters, showed excellent agreement between experiment and simulation with respect to cell number per trap and the uniformity of cell distribution within individual microchambers. For applications such as on-chip cell culture or high-throughput screening of cell populations within a lab-on-a-chip environment, Lagrangian simulations have the potential to greatly simplify the design process.

  8. Investigation of low-voltage pulse parameters on electroporation and electrical lysis using a microfluidic device with interdigitated electrodes.

    Science.gov (United States)

    Morshed, Bashir I; Shams, Maitham; Mussivand, Tofy

    2014-03-01

    Electroporation (EP) of biological cells leads to the exchange of materials through the permeabilized cell membrane, while electrical lysis (EL) irreversibly disrupts the cell membrane. We report a microfluidic device to study these two phenomena with low-voltage excitation for lab-on-a-chip (LOC) applications. For systematic study of EP, we have employed a quantification metric: flow Index (FI) of EP. Simulation and experimental results with the microfluidic device containing interdigitated, coplanar, integrated electrodes to electroporate, and rapidly lyse biological cells are presented. H&E stained human buccal cells were subjected to various pulse magnitudes, pulsewidths, and number of pulses. Simulations show that an electric field of 25 kV/cm with a 20 V applied potential produced 1.3 (°)C temperature rise for a 5 s of excitation. For a 20 V pulse-excitation with pulse-widths between 0.5 to 5 s, EL was observed, whereas for lower excitations, only EP was observed. FI of EP is found to be a direct function of pulse magnitudes, pulsewidths, and numbers of pulses. To release DNA from nucleus, excitation-pulses of 5 s were required. Quantification of EP would be useful for systematic study of EP toward optimization with various excitation pulses, while low-voltage requirement and high yield of EP and EL are critical to develop LOC for drug delivery and cell-sample preparation, respectively.

  9. Capillary-driven microfluidic paper-based analytical devices for lab on a chip screening of explosive residues in soil.

    Science.gov (United States)

    Ueland, Maiken; Blanes, Lucas; Taudte, Regina V; Stuart, Barbara H; Cole, Nerida; Willis, Peter; Roux, Claude; Doble, Philip

    2016-03-04

    A novel microfluidic paper-based analytical device (μPAD) was designed to filter, extract, and pre-concentrate explosives from soil for direct analysis by a lab on a chip (LOC) device. The explosives were extracted via immersion of wax-printed μPADs directly into methanol soil suspensions for 10min, whereby dissolved explosives travelled upwards into the μPAD circular sampling reservoir. A chad was punched from the sampling reservoir and inserted into a LOC well containing the separation buffer for direct analysis, avoiding any further extraction step. Eight target explosives were separated and identified by fluorescence quenching. The minimum detectable amounts for all eight explosives were between 1.4 and 5.6ng with recoveries ranging from 53-82% from the paper chad, and 12-40% from soil. This method provides a robust and simple extraction method for rapid identification of explosives in complex soil samples.

  10. Visual quantification of Hg on a microfluidic paper-based analytical device using distance-based detection technique

    Science.gov (United States)

    Cai, Longfei; Fang, Yanling; Mo, Yuanhui; Huang, Yongshi; Xu, Chunxiu; Zhang, Zhen; Wang, Maoxian

    2017-08-01

    We presented a distance-based detection method for visual quantification of mercury ions on a microfluidic paper-based analytical device (μPAD). Dithizone in NaOH solution was used as chromogenic reagent and deposited onto paper channel delimited by hydrophobic wax barrier. Reactions happened between mercury ions and dithizone to form an insoluble colored complex, producing colored precipitate on the paper channel. The length of colored precipitate could be readily measured using the printed ruler along each device. The length of precipitate increase linearly with the mercury concentrations, mercury in sample solution could be quantified by measuring the length of the colored precipitate. Being free of any electronic instruments, this method has the advantages of portability, ease of use, low cost and disposability. This presented method was used to detect mercury ions in a synthetic sample, demonstrating its potential in on-site and real time analysis.

  11. Enhanced Analytical Performance of Paper Microfluidic Devices by Using Fe3O4 Nanoparticles, MWCNT, and Graphene Oxide.

    Science.gov (United States)

    Figueredo, Federico; Garcia, Paulo T; Cortón, Eduardo; Coltro, Wendell K T

    2016-01-13

    Spheres, tubes, and planar-shaped nanomaterials as Fe3O4 nanoparticles (MNPs), multiwalled carbon nanotubes (MWCNT), and graphene oxide (GO) were used for the first time to treat microfluidic paper-based analytical devices (μPADs) and create a biocompatible layer with high catalytic surface. Once glucose measurements are critical for diabetes or glycosuria detection and monitoring, the analytical performance of the proposed devices was studied by using bienzymatic colorimetric detection of this carbohydrate. The limit of detection values achieved for glucose with μPADs treated with MNPs, MWCNT, and GO were 43, 62, and 18 μM, respectively. The paper surface modification solves problems associated with the lack of homogeneity on color measurements that compromise the sensitivity and detectability levels in clinical diagnosis.

  12. Analysis of Liquid–Liquid Droplets Fission and Encapsulation in Single/Two Layer Microfluidic Devices Fabricated by Xurographic Method

    Directory of Open Access Journals (Sweden)

    Chang Nong Lim

    2017-02-01

    Full Text Available This paper demonstrates a low cost fabrication approach for microscale droplet fission and encapsulation. Using a modified xurography method, rapid yet reliable microfluidic devices with flexible designs (single layer and double layer are developed to enable spatial control of droplet manipulation. In this paper, two different designs are demonstrated, i.e., droplet fission (single layer and droplet encapsulation (double layer. In addition, the current fabrication approach reduces the overall production interval with the introduction of a custom-made polydimethylsiloxane (PDMS aligner. Apart from that, the fabricated device is able to generate daughter droplets with the coefficient of variance (CV below 5% and double emulsions with CV maintained within 10% without involvement of complex surface wettability modification.

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

    Science.gov (United States)

    Surawathanawises, Krissada

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

  14. A Simple and Reliable PDMS and SU-8 Irreversible Bonding Method and Its Application on a Microfluidic-MEA Device for Neuroscience Research

    Directory of Open Access Journals (Sweden)

    Yufei Ren

    2015-12-01

    Full Text Available Polydimethylsiloxane (PDMS and SU-8 are currently two very commonly used polymeric materials in the microfluidics field for biological applications. However; there is a pressing need to find a simple, reliable, irreversible bonding method between these two materials for their combined use in innovative integrated microsystems. In this paper, we attempt to investigate the aminosilane-mediated irreversible bonding method for PDMS and SU-8 with X-Ray Photoelectron Spectroscopy (XPS surface analysis and bonding strength tests. Additionally, the selected bonding method was applied in fabricating a microelectrode array (MEA device, including microfluidic features, which allows electrophysiological observations on compartmentalized neuronal cultures. As there is a growing trend towards microfluidic devices for neuroscience research, this type of integrated microdevice, which can observe functional alterations on compartmentalized neuronal culture, can potentially be used for neurodegenerative disease research and pharmaceutical development.

  15. Monitoring of TGF-β 1-Induced Human Lung Adenocarcinoma A549 Cells Epithelial-Mesenchymal Transformation Process by Measuring Cell Adhesion Force with a Microfluidic Device.

    Science.gov (United States)

    Li, Yuan; Gao, AnXiu; Yu, Ling

    2016-01-01

    The epithelial-mesenchymal transition (EMT) is a process in which epithelial cells lose their cell polarity and cell-cell adhesion, and gain migratory and invasive properties. It is believed that EMT is associated with initiation and completion of the invasion-metastasis cascade. In this study, an economic approach was developed to fabricate a microfluidic device with less instrumentation requirement for the investigation of EMT by quantifying cell adhesion force. Fluid shear force was precisely controlled by a homemade microfluidic perfusion apparatus and interface. The adhesion capability of the human lung adenocarcinoma cell line A549 on different types of extracellular matrix protein was studied. In addition, effects of transforming growth factor-β (TGF-β) on EMT in A549 cells were investigated by characterizing the adhesion force changes and on-chip fluorescent staining. The results demonstrate that the microfluidic device is a potential tool to characterize the epithelial-mesenchymal transition process by measuring cell adhesion force.

  16. Microfluidic chemical reaction circuits

    Science.gov (United States)

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

    2012-06-26

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

  17. Evaluation of passive planar microfluidic devices for mixing of particle flows

    Science.gov (United States)

    Bhagat, Ali Asgar S.; Wurm, K. Teal; Papautsky, Ian

    2008-02-01

    In this paper, the design, modeling, fabrication and characterization of a planar passive microfluidic mixer capable of mixing particulate laden flows at low Reynolds numbers (Re) is reported. Particle-based flow modeling was performed using CFD-ACE+ software to simulate micromixer designs for efficient particle dispersion across microchannel cross-section. The micromixer design developed herein incorporates rectangular shaped obstructions within the microchannel to propel both the particles within the flow and the flow itself into the other half of the channel, thereby achieving mixing. A simple technique to analyze and quantify particle mixing is also proposed. The developed particle micromixer has a simple planar structure, thereby resulting in easy realization and integration with on-chip microfluidic systems, such as micro total analysis systems or lab-on-a-chip.

  18. A Serial Sample Loading System: Interfacing Multi-well plates with Microfluidic Devices

    OpenAIRE

    Rane, Tushar D.; Zec, Helena; Wang, Jeff Tza-Huei

    2012-01-01

    There is an increasing demand for novel high-throughput screening (HTS) technologies in the pharmaceutical and biotechnological industries. The robotic sample handling techniques currently used in these industries, although fast, are still limited to operating in multi-well plates with the sample volumes per reaction in the microliter regime. Digital microfluidics offers an alternative for reduction in sample volume consumption for HTS but lacks a reliable technique for transporting large num...

  19. Toward high-throughput screening of NAD(P)-dependent oxidoreductases using boron-doped diamond microelectrodes and microfluidic devices.

    Science.gov (United States)

    Oyobiki, Ryo; Kato, Taisuke; Katayama, Michinobu; Sugitani, Ai; Watanabe, Takeshi; Einaga, Yasuaki; Matsumoto, Yoshinori; Horisawa, Kenichi; Doi, Nobuhide

    2014-10-07

    Although oxidoreductases are widely used in many applications, such as biosensors and biofuel cells, improvements in the function of existing oxidoreductases or the discovery of novel oxidoreductases with greater activities is desired. To increase the activity of oxidoreductases by directed evolution, a powerful screening technique for oxidoreductases is required. In this study, we demonstrate the utility of boron-doped diamond (BDD) microelectrodes for quantitative and potentially high-throughput measurement of the activity of NAD(P)-dependent oxidoreductases. We first confirmed that BDD microelectrodes can quantify the activity of low concentrations (10-100 pM) of glucose-6-phosphate dehydrogenase and alcohol dehydrogenase with a measuring time of 1 ms per sample. In addition, we found that poisoning of BDD microelectrodes can be repressed by optimizing the pH and by adding l-arginine to the enzyme solution as an antiaggregation agent. Finally, we fabricated a microfluidic device containing a BDD electrode for the first time and observed the elevation of the oxidation current of NADH with increasing flow rate. These results imply that the combination of a BDD microelectrode and microfluidics can be used for high-throughput screening of an oxidoreductase library containing a large number (>10(6)) of samples, each with a small (nanoliter) sample volume.

  20. Volume-of-fluid simulations in microfluidic T-junction devices: Influence of viscosity ratio on droplet size

    Science.gov (United States)

    Nekouei, Mehdi; Vanapalli, Siva A.

    2017-03-01

    We used volume-of-fluid (VOF) method to perform three-dimensional numerical simulations of droplet formation of Newtonian fluids in microfluidic T-junction devices. To evaluate the performance of the VOF method we examined the regimes of drop formation and determined droplet size as a function of system parameters. Comparison of the simulation results with four sets of experimental data from the literature showed good agreement, validating the VOF method. Motivated by the lack of adequate studies investigating the influence of viscosity ratio (λ) on the generated droplet size, we mapped the dependence of drop volume on capillary number (0.001 1. In addition, we find that at a given capillary number, the size of droplets does not vary appreciably when λ 1. We develop an analytical model for predicting the droplet size that includes a viscosity-dependent breakup time for the dispersed phase. This improved model successfully predicts the effects of the viscosity ratio observed in simulations. Results from this study are useful for the design of lab-on-chip technologies and manufacture of microfluidic emulsions, where there is a need to know how system parameters influence the droplet size.

  1. On chip porous polymer membranes for integration of gastrointestinal tract epithelium with microfluidic 'body-on-a-chip' devices.

    Science.gov (United States)

    Esch, Mandy Brigitte; Sung, Jong Hwan; Yang, Jennifer; Yu, Changhao; Yu, Jiajie; March, John C; Shuler, Michael Louis

    2012-10-01

    We describe a novel fabrication method that creates microporous, polymeric membranes that are either flat or contain controllable 3-dimensional shapes that, when populated with Caco-2 cells, mimic key aspects of the intestinal epithelium such as intestinal villi and tight junctions. The developed membranes can be integrated with microfluidic, multi-organ cell culture systems, providing access to both sides, apical and basolateral, of the 3D epithelial cell culture. Partial exposure of photoresist (SU-8) spun on silicon substrates creates flat membranes with micrometer-sized pores (0.5-4.0 μm) that--supported by posts--span across 50 μm deep microfluidic chambers that are 8 mm wide and 10 long. To create three-dimensional shapes the membranes were air dried over silicon pillars with aspect ratios of up to 4:1. Space that provides access to the underside of the shaped membranes can be created by isotropically etching the sacrificial silicon pillars with xenon difluoride. Depending on the size of the supporting posts and the pore sizes the overall porosity of the membranes ranged from 4.4 % to 25.3 %. The microfabricated membranes can be used for integrating barrier tissues such as the gastrointestinal tract epithelium, the lung epithelium, or other barrier tissues with multi-organ "body-on-a-chip" devices.

  2. Magnetic force micropiston: An integrated force/microfluidic device for the application of compressive forces in a confined environment

    Science.gov (United States)

    Fisher, J. K.; Kleckner, N.

    2014-02-01

    Cellular biology takes place inside confining spaces. For example, bacteria grow in crevices, red blood cells squeeze through capillaries, and chromosomes replicate inside the nucleus. Frequently, the extent of this confinement varies. Bacteria grow longer and divide, red blood cells move through smaller and smaller passages as they travel to capillary beds, and replication doubles the amount of DNA inside the nucleus. This increase in confinement, either due to a decrease in the available space or an increase in the amount of material contained in a constant volume, has the potential to squeeze and stress objects in ways that may lead to changes in morphology, dynamics, and ultimately biological function. Here, we describe a device developed to probe the interplay between confinement and the mechanical properties of cells and cellular structures, and forces that arise due to changes in a structure's state. In this system, the manipulation of a magnetic bead exerts a compressive force upon a target contained in the confining space of a microfluidic channel. This magnetic force microfluidic piston is constructed in such a way that we can measure (a) target compliance and changes in compliance as induced by changes in buffer, extract, or biochemical composition, (b) target expansion force generated by changes in the same parameters, and (c) the effects of compression stress on a target's structure and function. Beyond these issues, our system has general applicability to a variety of questions requiring the combination of mechanical forces, confinement, and optical imaging.

  3. Beyond PDMS: off-stoichiometry thiol-ene (OSTE) based soft lithography for rapid prototyping of microfluidic devices.

    Science.gov (United States)

    Carlborg, Carl Fredrik; Haraldsson, Tommy; Öberg, Kim; Malkoch, Michael; van der Wijngaart, Wouter

    2011-09-21

    In this article we introduce a novel polymer platform based on off-stoichiometry thiol-enes (OSTEs), aiming to bridge the gap between research prototyping and commercial production of microfluidic devices. The polymers are based on the versatile UV-curable thiol-ene chemistry but takes advantage of off-stoichiometry ratios to enable important features for a prototyping system, such as one-step surface modifications, tuneable mechanical properties and leakage free sealing through direct UV-bonding. The platform exhibits many similarities with PDMS, such as rapid prototyping and uncomplicated processing but can at the same time mirror the mechanical and chemical properties of both PDMS as well as commercial grade thermoplastics. The OSTE-prepolymer can be cast using standard SU-8 on silicon masters and a table-top UV-lamp, the surface modifications are precisely grafted using a stencil mask and the bonding requires only a single UV-exposure. To illustrate the potential of the material we demonstrate key concepts important in microfluidic chip fabrication such as patterned surface modifications for hydrophobic stops, pneumatic valves using UV-lamination of stiff and rubbery materials as well as micromachining of chip-to-world connectors in the OSTE-materials. This journal is © The Royal Society of Chemistry 2011

  4. Platinum nanoparticle-facilitated reflective surfaces for non-contact temperature control in microfluidic devices for PCR amplification.

    Science.gov (United States)

    Leslie, Daniel C; Seker, Erkin; Bazydlo, Lindsay A L; Strachan, Briony C; Landers, James P

    2012-01-07

    The polymerase chain reaction (PCR) is critical for amplification of target sequences of DNA or RNA that have clinical, biological or forensic relevance. While extrinsic Fabry-Perot interferometry (EFPI) has been shown to be adequate for non-contact temperature sensing, the difficulty in defining a reflective surface that is semi-reflective, non-reactive for PCR compatibility and adherent for thermal bonding has limited its exploitation. Through the incorporation of a reflective surface fabricated using a thermally driven self-assembly of a platinum nanoparticle monolayer on the surface of the microfluidic chamber, an enhanced EFPI signal results, allowing for non-contact microfluidic temperature control instrumentation that uses infrared-mediated heating, convective forced-air cooling, and interferometic temperature sensing. The interferometer is originally calibrated with a miniature copper-constantan thermocouple in the PCR chamber resulting in temperature sensitivities of -22.0 to -32.8 nm·°C(-1), depending on the chamber depth. This universal calibration enables accurate temperature control in any device with arbitrary dimensions, thereby allowing versatility in various applications. Uniquely, this non-contact temperature control for PCR thermocycling is applied to the amplification of STR loci for human genetic profiling, where nine STR loci are successfully amplified for human identification using the EFPI-based non-contact thermocycling.

  5. Hydrogel-Framed Nanofiber Matrix Integrated with a Microfluidic Device for Fluorescence Detection of Matrix Metalloproteinases-9.

    Science.gov (United States)

    Han, Sang Won; Koh, Won-Gun

    2016-06-21

    Matrix metalloproteinases (MMPs) play a pivotal role in regulating the composition of the extracellular matrix and have a critical role in vascular disease, cancer progression, and bone disorders. This paper describes the design and fabrication of a microdevice as a new platform for highly sensitive MMP-9 detection. In this sensing platform, fluorescein isocyanate (FITC)-labeled MMP-9 specific peptides were covalently immobilized on an electrospun nanofiber matrix to utilize an enzymatic cleavage strategy. Prior to peptide immobilization, the nanofiber matrix was incorporated into hydrogel micropatterns for easy size control and handling of the nanofiber matrix. The resultant hydrogel-framed nanofiber matrix immobilizing the peptides was inserted into microfluidic devices consisting of reaction chambers and detection zones. The immobilized peptides were reacted with the MMP-9-containing solution in a reaction chamber, which resulted in the cleavage of the FITC-containing peptide fragments and subsequently generated fluorescent flow at the detection zone. As higher concentrations of the MMP-9 solution were introduced or larger peptide-immobilizing nanofiber areas were used, more peptides were cleaved, and a stronger fluorescence signal was observed. Due to the huge surface area of the nanofiber and small dimensions of the microsystem, a faster response time (30 min) and lower detection limit (10 pM) could be achieved in this study. The hydrogel-framed nanofiber matrix is disposable and can be replaced with new ones immobilizing either the same or different biomolecules for various bioassays, while the microfluidic system can be continuously reused.

  6. Effect of gold nanoparticles on thermal gradient generation and thermotaxis of E. coli cells in microfluidic device.

    Science.gov (United States)

    Murugesan, Nithya; Panda, Tapobrata; Das, Sarit K

    2016-08-01

    Bacteria responds to changing chemical and thermal environment by moving towards or away from a particular location. In this report, we looked into thermal gradient generation and response of E. coli DH5α cells to thermal gradient in the presence and in the absence of spherical gold nanoparticles (size: 15 to 22 nm) in a static microfluidic environment using a polydimethylsiloxane (PDMS) made microfluidic device. A PDMS-agarose based microfluidic device for generating thermal gradient has been developed and the thermal gradient generation in the device has been validated with the numerical simulation. Our studies revealed that the presence of gold nanoparticles, AuNPs (0.649 μg/mL) has no effect on the thermal gradient generation. The E. coli DH5α cells have been treated with AuNPs of two different concentrations (0.649 μg/mL and 0.008 μg/mL). The thermotaxis behavior of cells in the presence of AuNPs has been studied and compared to the thermotaxis of E.coli DH5α cells in the absence of AuNPs. In case of thermotaxis, in the absence of the AuNPs, the E. coli DH5α cells showed better thermotaxis towards lower temperature range, whereas in the presence of AuNPs (0.649 μg/mL and 0.008 μg/mL) thermotaxis of the E. coli DH5α cells has been inhibited. The results show that the spherical AuNPs intervenes in the themotaxis of E. coli DH5α cells and inhibits the cell migration. The reason for the failure in thermotaxis response mechanism may be due to decreased F-type ATP synthase activity and collapse of membrane potential by AuNPs, which, in turn, leads to decreased ATP levels. This has been hypothesized since both thermotaxis and chemotaxis follows the same response mechanism for migration in which ATP plays critical role.

  7. A temperature control method for shortening thermal cycling time to achieve rapid polymerase chain reaction (PCR) in a disposable polymer microfluidic device

    DEFF Research Database (Denmark)

    Bu, Minqiang; Perch-Nielsen, Ivan R.; Sørensen, Karen Skotte

    2013-01-01

    We present a temperature control method capable of effectively shortening the thermal cycling time of polymerase chain reaction (PCR) in a disposable polymer microfluidic device with an external heater and a temperature sensor. The method employs optimized temperature overshooting and undershooting...

  8. Performance of an in-plane detection cell with integrated waveguides for UV/Vis absorbance measurements on microfluidic separation devices

    DEFF Research Database (Denmark)

    Petersen, Nickolaj Jacob; Mogensen, Klaus Bo; Kutter, Jörg Peter

    2002-01-01

    A microfluidic device with integrated waveguides and a long path length detection cell for UV/Vis absorbance detection is presented. The 750 mum U-cell detection geometry was evaluated in terms of its optical performance as well as its influence on efficiency for electrophoretic separations...

  9. One-step patterning of hollow microstructures in paper by laser cutting to create microfluidic analytical devices.

    Science.gov (United States)

    Nie, Jinfang; Liang, Yuanzhi; Zhang, Yun; Le, Shangwang; Li, Dunnan; Zhang, Songbai

    2013-01-21

    In this paper, we report a simple, low-cost method for rapid, highly reproductive fabrication of paper-based microfluidics by using a commercially available, minitype CO(2) laser cutting/engraving machine. This method involves only one operation of cutting a piece of paper by laser according to a predesigned pattern. The hollow microstructures formed in the paper are used as the 'hydrophobic barriers' to define the hydrophilic flowing paths. A typical paper device on a 4 cm × 4 cm piece of paper can be fabricated within ∼7-20 s; it is ready for use once the cutting process is finished. The main fabrication parameters such as the applied current and cutting rate of the laser were optimized. The fabrication resolution and multiplexed analytical capability of the hollow microstructure-patterned paper were also characterized.

  10. Capacitance Variation Induced by Microfluidic Two-Phase Flow across Insulated Interdigital Electrodes in Lab-On-Chip Devices

    Directory of Open Access Journals (Sweden)

    Tao Dong

    2015-01-01

    Full Text Available 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.

  11. Image analysis for a microfluidic paper-based analytical device using the CIE L*a*b* color system.

    Science.gov (United States)

    Komatsu, Takeshi; Mohammadi, Saeed; Busa, Lori Shayne Alamo; Maeki, Masatoshi; Ishida, Akihiko; Tani, Hirofumi; Tokeshi, Manabu

    2016-11-28

    The combination of a microfluidic paper-based analytical device (μPAD) and digital image analysis is widely used for quantitative analysis with μPADs because of its easy and simple operation. Herein, we have demonstrated a quantitative analysis based on multiple color changes on a μPAD. The CIE L*a*b* color system was employed to analyse the digital images obtained with the μPAD. We made pH measurements using a universal pH-indicator showing multiple color changes for various pH values of aqueous test solutions. The detectable pH range of this method was wider than the typical grayscale-based image analysis, and we succeeded in the measurements for a wide pH range of 2-9.

  12. Rational selection of substrates to improve color intensity and uniformity on microfluidic paper-based analytical devices.

    Science.gov (United States)

    Evans, Elizabeth; Gabriel, Ellen Flávia Moreira; Coltro, Wendell Karlos Tomazelli; Garcia, Carlos D

    2014-05-07

    A systematic investigation was conducted to study the effect of paper type on the analytical performance of a series of microfluidic paper-based analytical devices (μPADs) fabricated using a CO2 laser engraver. Samples included three different grades of Whatman chromatography paper, and three grades of Whatman filter paper. According to the data collected and the characterization performed, different papers offer a wide range of flow rate, thickness, and pore size. After optimizing the channel widths on the μPAD, the focus of this study was directed towards the color intensity and color uniformity formed during a colorimetric enzymatic reaction. According to the results herein described, the type of paper and the volume of reagents dispensed in each detection zone can determine the color intensity and uniformity. Therefore, the objective of this communication is to provide rational guidelines for the selection of paper substrates for the fabrication of μPADs.

  13. Sodium chloride precipitation reaction coefficient from crystallization experiment in a microfluidic device

    Science.gov (United States)

    Naillon, A.; Joseph, P.; Prat, M.

    2017-04-01

    The crystal growth of sodium chloride from an aqueous solution is studied from evaporation experiments in microfluidic channels in conjunction with analytical and numerical computations. The crystal growth kinetics is recorded using a high speed camera in order to determine the intrinsic precipitation reaction coefficient. The study reveals that the crystal growth rates determined in previous studies are all affected by the ions transport phenomena in the solution and thus not representative of the precipitation reaction. It is suggested that accurate estimate of sodium chloride precipitation reaction coefficient presented here offers new opportunities for a better understanding of important issues involved in the damages of porous materials induced by the salt crystallization.

  14. Janus droplet parallel arrangements using a simple Y-channel flow-focusing microfluidic device

    Science.gov (United States)

    Cheng, Long; Cai, Bo; Zuo, Yunfeng; Xiao, Liang; Rao, Lang; He, Zhaobo; Yang, Yi; Liu, Wei; Guo, Shishang; Zhao, Xing-Zhong

    2017-04-01

    Due to its unique advantages such as monodispersity and high throughput, droplet microfluidics has been widely used to generate diverse droplets/particles that have specific structures. Herein, we implemented Janus droplet parallel arrangements in a flow-focusing microchip through regulating corresponding fluid flow rates. Initially, fluorescence dye and PBS buffer solution kept laminar flow before the flow-focusing orifice and then was sheared into Janus droplets. Droplet diameter and corresponding generation frequency could be effectively manipulated. Subsequently, the generation of different Janus droplet parallel arrangements (e.g. monolayer, double-layer or three-layer arrangement) could be achieved by fluid regulation.

  15. A computational model of a microfluidic device to measure the dynamics of oxygen-dependent ATP release from erythrocytes.

    Directory of Open Access Journals (Sweden)

    Richard J Sove

    Full Text Available Erythrocytes are proposed to be involved in blood flow regulation through both shear- and oxygen-dependent mechanisms for the release of adenosine triphosphate (ATP, a potent vasodilator. In a recent study, the dynamics of shear-dependent ATP release from erythrocytes was measured using a microfluidic device with a constriction in the channel to increase shear stress. The brief period of increased shear stress resulted in ATP release within 25 to 75 milliseconds downstream of the constriction. The long-term goal of our research is to apply a similar approach to determine the dynamics of oxygen-dependent ATP release. In the place of the constriction, an oxygen permeable membrane would be used to decrease the hemoglobin oxygen saturation of erythrocytes flowing through the channel. This paper describes the first stage in achieving that goal, the development of a computational model of the proposed experimental system to determine the feasibility of altering oxygen saturation rapidly enough to measure ATP release dynamics. The computational model was constructed based on hemodynamics, molecular transport of oxygen and ATP, kinetics of luciferin/luciferase reaction for reporting ATP concentrations, light absorption by hemoglobin, and sensor characteristics. A linear model of oxygen saturation-dependent ATP release with variable time delay was used in this study. The computational results demonstrate that a microfluidic device with a 100 µm deep channel will cause a rapid decrease in oxygen saturation over the oxygen permeable membrane that yields a measurable light intensity profile for a change in rate of ATP release from erythrocytes on a timescale as short as 25 milliseconds. The simulation also demonstrates that the complex dynamics of ATP release from erythrocytes combined with the consumption by luciferin/luciferase in a flowing system results in light intensity values that do not simply correlate with ATP concentrations. A computational

  16. Single-Sided Digital Microfluidic (SDMF Devices for Effective Coolant Delivery and Enhanced Two-Phase Cooling

    Directory of Open Access Journals (Sweden)

    Sung-Yong Park

    2016-12-01

    Full Text Available Digital microfluidics (DMF driven by electrowetting-on-dielectric (EWOD has recently been attracting great attention as an effective liquid-handling platform for on-chip cooling. It enables rapid transportation of coolant liquid sandwiched between two parallel plates and drop-wise thermal rejection from a target heating source without additional mechanical components such as pumps, microchannels, and capillary wicks. However, a typical sandwiched configuration in DMF devices only allows sensible heat transfer, which seriously limits heat rejection capability, particularly for high-heat-flux thermal dissipation. In this paper, we present a single-sided digital microfluidic (SDMF device that enables not only effective liquid handling on a single-sided surface, but also two-phase heat transfer to enhance thermal rejection performance. Several droplet manipulation functions required for two-phase cooling were demonstrated, including continuous droplet injection, rapid transportation as fast as 7.5 cm/s, and immobilization on the target hot spot where heat flux is locally concentrated. Using the SDMF platform, we experimentally demonstrated high-heat-flux cooling on the hydrophilic-coated hot spot. Coolant droplets were continuously transported to the target hot spot which was mitigated below 40 K of the superheat. The effective heat transfer coefficient was stably maintained even at a high heat flux regime over ~130 W/cm2, which will allow us to develop a reliable thermal management module. Our SDMF technology offers an effective on-chip cooling approach, particularly for high-heat-flux thermal management based on two-phase heat transfer.

  17. The application of a new microfluidic device for the simultaneous identification and quantitation of midazolam metabolites obtained from a single micro-litre of chimeric mice blood.

    Science.gov (United States)

    Gallagher, Richard; Dillon, Leonard; Grimsley, Aidan; Murphy, Jim; Samuelsson, Kristin; Douce, David

    2014-06-15

    Improvements in the design of low-flow highly sensitive chromatographic ion source interfaces allow the detection and characterisation of drugs and metabolites from smaller sample volumes. This in turn improves the ethical treatment of animals by reducing both the number of animals needed and the blood sampling volumes required. A new microfluidic device combining an ultra-high pressure liquid chromatography (UHPLC) analytical column with a nano-flow electrospray source is described. All microfluidic, gas and electrical connections are automatically engaged when the ceramic microfluidic device is inserted into the source enclosure. The system was used in conjunction with a hybrid quadrupole-time-of-flight mass spectrometer. The improved sensitivity of the system is highlighted in its application in the quantification and qualification of midazolam and its metabolites detected in whole blood from chimeric and wild-type mice. Metabolite identification and full pharmacokinetic profiles were obtained from a single micro-litre of whole blood at each sampling time and significant pharmacokinetic differences were observed between the two types of mice. Improvements in the enhanced ionisation efficiency from the microfluidic device in conjunction with nanoUHPLC/MS was sufficiently sensitive for the identification and quantification of midazolam metabolites from a single micro-litre of whole blood. Detection of metabolites not previously recorded from the chimeric mouse in vivo model was made. Copyright © 2014 John Wiley & Sons, Ltd.

  18. Assessment of mitochondrial membrane potential using an on-chip microelectrode in a microfluidic device.

    Science.gov (United States)

    Lim, Tae-Sun; Dávila, Antonio; Wallace, Douglas C; Burke, Peter

    2010-07-07

    The mitochondrial membrane potential is used to generate and regulate energy in living systems, driving the conversion of ADP to ATP, regulating ion homeostasis, and controlling apoptosis, all central to human health and disease. Therefore, there is a need for tools to study its regulation in a controlled environment for potential clinical and scientific applications. For this aim, an on-chip tetraphenylphosphonium (TPP(+)) selective microelectrode sensor was constructed in a microfluidic environment. The concentration of isolated mitochondria (Heb7A) used in a membrane potential measurement was 0.3 ng microL(-1), four orders of magnitude smaller than the concentration used in conventional assays (3 microg microL(-1)). In addition, the volume of the chamber (85 microL) is 2 orders of magnitude smaller than traditional experiments. As a demonstration, changes in the membrane potential are clearly measured in response to a barrage of well-known substrates and inhibitors of the electron transport chain. This general approach, which to date has not been demonstrated for study of mitochondrial function and bio-energetics in generally, can be instrumental in advancing the field of mitochondrial research and clinical applications by allowing high throughput studies of the regulation, dynamics, and statistical properties of the mitochondrial membrane potential in response to inhibitors and inducers of apoptosis in a controlled (microfluidic) chemical environment.

  19. Integrated microfluidic devices for the synthesis of nanoscale liposomes and lipoplexes.

    Science.gov (United States)

    Balbino, Tiago A; Serafin, Juliana M; Radaic, Allan; de Jesus, Marcelo B; de la Torre, Lucimara G

    2017-04-01

    In this work, pDNA/cationic liposome (CL) lipoplexes for gene delivery were prepared in one-step using multiple hydrodynamic flow-focusing regions. The microfluidic platform was designed with two distinct regions for the synthesis of liposomes and the subsequent assembly with pDNA, forming lipoplexes. The obtained lipoplexes exhibited appropriate physicochemical characteristics for gene therapy applications under varying conditions of flow rate-ratio (FRR), total volumetric flow rate (QT) and pDNA content (molar charge ratio, R±). The CLs were able to condense and retain the pDNA in the vesicular structures with sizes ranging from 140nm to 250nm. In vitro transfection assays showed that the lipoplexes prepared in one step by the two-stage configuration achieved similar efficiencies as lipoplexes prepared by conventional bulk processes, in which each step comprises a series of manual operations. The integrated microfluidic platform generates lipoplexes with liposome formation combined in-line with lipoplex assembly, significantly reducing the number of steps usually required to form gene carrier systems.

  20. Different migration patterns of sea urchin and mouse sperm revealed by a microfluidic chemotaxis device.

    Directory of Open Access Journals (Sweden)

    Haixin Chang

    Full Text Available Chemotaxis refers to a process whereby cells move up or down a chemical gradient. Sperm chemotaxis is known to be a strategy exploited by marine invertebrates such as sea urchins to reach eggs efficiently in moving water. Less is understood about how or whether chemotaxis is used by mammalian sperm to reach eggs, where fertilization takes place within the confinement of a reproductive tract. In this report, we quantitatively assessed sea urchin and mouse sperm chemotaxis using a recently developed microfluidic model and high-speed imaging. Results demonstrated that sea urchin Arbacia punctulata sperm were chemotactic toward the peptide resact with high chemotactic sensitivity, with an average velocity Vx up the chemical gradient as high as 20% of its average speed (238 μm/s, while mouse sperm displayed no statistically significant chemotactic behavior in progesterone gradients, which had been proposed to guide mammalian sperm toward eggs. This work demonstrates the validity of a microfluidic model for quantitative sperm chemotaxis studies, and reveals a biological insight that chemotaxis up a progesterone gradient may not be a universal strategy for mammalian sperm to reach eggs.

  1. Highly controlled synthesis of nanometric gold particles by citrate reduction using the short mixing, heating and quenching times achievable in a microfluidic device

    Science.gov (United States)

    Ftouni, Jamal; Penhoat, Maël; Addad, Ahmed; Payen, Edmond; Rolando, Christian; Girardon, Jean-Sébastien

    2012-07-01

    Homodispersed 1.8 nm gold nanoparticles were obtained reproducibly in high yields using the classical Turkevich protocol at a high concentration in a continuous flow capillary reactor. The microfluidic reactor made from commercially available items permitted short mixing, heating and quenching times which are the key parameters of this synthesis.Homodispersed 1.8 nm gold nanoparticles were obtained reproducibly in high yields using the classical Turkevich protocol at a high concentration in a continuous flow capillary reactor. The microfluidic reactor made from commercially available items permitted short mixing, heating and quenching times which are the key parameters of this synthesis. Electronic supplementary information (ESI) available: Description of the microfluidic device, protocol for gold nanoparticle synthesis in batch and in the microsystem, and gold nanoparticle size distribution raw data. See DOI: 10.1039/c2nr11666a

  2. A portable microfluidic device for the rapid diagnosis of cancer metastatic potential which is programmable for temperature and CO2.

    Science.gov (United States)

    Yu, I F; Yu, Y H; Chen, L Y; Fan, S K; Chou, H Y E; Yang, J T

    2014-09-21

    If metastasis of lung cancer can be found and treated early, a victim might have an improved chance to prevail over it, but routine examinations such as chest radiography, computed tomography and biopsy cannot characterize the metastatic potential of lung cancer cells; critical diagnoses to define optimal therapeutic strategies are thus lost. We designed a portable microfluidic device for the rapid diagnosis of cancer metastatic potential. Featuring a micro system to control temperature and a bicarbonate buffered environment, our device discriminates a rate of surface detachment as an index of the migratory ability of cells cultured on pH-responsive chitosan. We labeled metastatic subpopulations of lung cancer cell lines, and verified that our device is capable of separating cells according to their metastatic ability. As only few cells are needed, a patient's specimen from biopsies, e.g. from fine-needle aspiration, can be processed on site to offer immediate information to physicians. We expect that our design will provide valuable information in pre-operative evaluations to assist the definition of therapeutic plans for lung cancer, as well as for metastatic tumors of other types.

  3. Microfluidic application-specific integrated device for monitoring direct cell-cell communication via gap junctions between individual cell pairs

    Science.gov (United States)

    Lee, Philip J.; Hung, Paul J.; Shaw, Robin; Jan, Lily; Lee, Luke P.

    2005-05-01

    Direct cell-cell communication between adjacent cells is vital for the development and regulation of functional tissues. However, current biological techniques are difficult to scale up for high-throughput screening of cell-cell communication in an array format. In order to provide an effective biophysical tool for the analysis of molecular mechanisms of gap junctions that underlie intercellular communication, we have developed a microfluidic device for selective trapping of cell-pairs and simultaneous optical characterizations. Two different cell populations can be brought into membrane contact using an array of trapping channels with a 2μm by 2μm cross section. Device operation was verified by observation of dye transfer between mouse fibroblasts (NIH3T3) placed in membrane contact. Integration with lab-on-a-chip technologies offers promising applications for cell-based analytical tools such as drug screening, clinical diagnostics, and soft-state biophysical devices for the study of gap junction protein channels in cellular communications. Understanding electrical transport mechanisms via gap junctions in soft membranes will impact quantitative biomedical sciences as well as clinical applications.

  4. Microfluidic Mechanics and Applications: a Review

    Directory of Open Access Journals (Sweden)

    Sandeep Arya

    2014-01-01

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

  5. 滤纸微流控设备集成电化学检测%Integration of Paper - based Microfluidic Devices with Electrochemical Detection

    Institute of Scientific and Technical Information of China (English)

    唐帆; 邢宏龙; 毕连花; 郑虎祥; 王伟

    2012-01-01

    近年来,人们发现滤纸微流控设备相比于传统的微流控设备来说具有一次性使用、制作简单且成本更低的优点。简单综述了微流控设备的发展现状以及滤纸和电化学检测的相关特点,着重阐明了滤纸在微流控电化学检测中的应用,同时与商品化的检测仪相结合,为微流控设备未来商品化打下了坚实的基础。%Paper - based microfluidic devices are found that they are disposable, easy - to - fabricate, and lower - cost compared to traditional microfluidic devices. This paper presented an overview on the present state of microtluidic devices and the related characteristics of filter paper and electrochemical detection. Filter paper applicated in microfluidie devices coupled with electro- chemical detection is mainly introduced. Meanwhile, the integration of commercial detector will establish a firm foundation for the commercialization of microfluidic devices in the future.

  6. A novel microbead-based microfluidic device for rapid bacterial identification and antibiotic susceptibility testing.

    Science.gov (United States)

    He, J; Mu, X; Guo, Z; Hao, H; Zhang, C; Zhao, Z; Wang, Q

    2014-12-01

    Effective treatment of infectious diseases depends on the ability to rapidly identify the infecting bacteria and the use of sensitive antibiotics. The currently used identification assays usually take more than 72 h to perform and have a low sensitivity. Herein, we present a microbead-based microfluidic platform that is highly sensitive and rapid for bacterial detection and antibiotic sensitivity testing. The platform includes four units, one of which is used for bacterial identification and the other three are used for susceptibility testing. Our results showed that Escherichia coli O157 at a cell density range of 10(1)-10(5) CFU/μL could be detected within 30 min. Additionally, the effects of three antibiotics on E. coli O157 were evaluated within 4-8 h. Overall, this integrated microbead-based microdevice provides a sensitive, rapid, reliable, and highly effective platform for the identification of bacteria, as well as antibiotic sensitivity testing.

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

    Science.gov (United States)

    Tang, Qi; Liang, Min; Lu, Yi; Wong, Pak Kin; Wilmink, Gerald J; Zhang, Donna; Xin, Hao

    2016-04-04

    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.

  8. Rapid photochemical surface patterning of proteins in thiol-ene based microfluidic devices

    DEFF Research Database (Denmark)

    Lafleur, Josiane P.; Kwapiszewski, Radoslaw; Jensen, Thomas Glasdam;

    2013-01-01

    The suitable optical properties of thiol–ene polymers combined with the ease of modifying their surface for the attachment of recognition molecules make them ideal candidates in many biochip applications. This paper reports the rapid one-step photochemical surface patterning of biomolecules...... in microfluidic thiol–ene chips. This work focuses on thiol–ene substrates featuring an excess of thiol groups at their surface. The thiol–ene stoichiometric composition can be varied to precisely control the number of surface thiol groups available for surface modification up to an average surface density of 136...... ! 17 SH nm"2. Biotin alkyne was patterned directly inside thiol–ene microchannels prior to conjugation with fluorescently labelled streptavidin. The surface bound conjugates were detected by evanescent waveinduced fluorescence (EWIF), demonstrating the success of the grafting procedure and its...

  9. Femtosecond laser micromachining for the realization of fully integrated photonic and microfluidic devices

    Science.gov (United States)

    Eaton, S. M.; Osellame, R.; Ramponi, R.

    2015-02-01

    Femtosecond laser microprocessing is a direct, maskless fabrication technique that has attracted much attention in the past 10 years due to its unprecedented versatility in the 3D patterning of transparent materials. Two common modalities of femtosecond laser microfabrication include buried optical waveguide writing and surface laser ablation, which have been applied to a wide range of transparent substrates including glasses, polymers and crystals. In two photon polymerization, a third modality of femtosecond laser fabrication, focused femtosecond laser pulses drive photopolymerization in photoresists, enabling the writing of complex 3D structures with submicrometer resolution. In this paper, we discuss several microdevices realized by these diverse modalities of femtosecond laser microfabrication, for applications in microfluidics, sensing and quantum information.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Tang, Qi; Liang, Min; Lu, Yi; Wong, Pak Kin; Wilmink, Gerald J.; D. Zhang, Donna; Xin, Hao

    2016-01-01

    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. PMID:27049392

  12. Large scale manufacture of magnetic polymer particles using membranes and microfluidic devices

    Institute of Scientific and Technical Information of China (English)

    Qingchun; Yuan; Richard; A.; Williams

    2007-01-01

    Magnetic polymer particles have found applications in diverse areas such as biomedical treatments, diagnosis and separation technology. These applications require the particles to have controlled sizes and narrow size distributions to gain better control and reproducibility in use. This paper reviews recent developments in the preparation of magnetic polymer particles at nano- and micro-scales by encapsulating magnetic components with dissolved or in situ formed polymers. Particle manufacture using emulsification and embedment methods produces magnetic polymer particles at micro-scale dimensions. However, the production of particles in this range using conventional emulsification methods affords very limited control over particle sizes and polydispersity. We report on alternative routes using membrane and microfluidics emulsification techniques, which have a capability to produce monodisperse emulsions and polymer microspheres (with coefficients of variation of less than 10%) in the range from submicrometer to a few 100 μm. The performance of these manufacturing methods is assessed with a view to future applications.

  13. Separation of rare oligodendrocyte progenitor cells from brain using a high-throughput multilayer thermoplastic-based microfluidic device.

    Science.gov (United States)

    Didar, Tohid Fatanat; Li, Kebin; Veres, Teodor; Tabrizian, Maryam

    2013-07-01

    Despite the advances made in the field of regenerative medicine, the progress in cutting-edge technologies for separating target therapeutic cells are still at early stage of development. These cells are often rare, such as stem cells or progenitor cells that their overall properties should be maintained during the separation process for their subsequent application in regenerative medicine. This work, presents separation of oligodendrocyte progenitor cells (OPCs) from rat brain primary cultures using an integrated thermoplastic elastomeric (TPE)- based multilayer microfluidic device fabricated using hot-embossing technology. OPCs are frequently used in recovery, repair and regeneration of central nervous system after injuries. Indeed, their ability to differentiate in vitro into myelinating oligodendrocytes, are extremely important for myelin repair. OPCs form 5-10% of the glial cells population. The traditional macroscale techniques for OPCs separation require pre-processing of cells and/or multiple time consuming steps with low efficiency leading very often to alteration of their properties. The proposed methodology implies to separate OPCs based on their smaller size compared to other cells from the brain tissue mixture. Using aforementioned microfluidic chip embedded with a 5 μm membrane pore size and micropumping system, a separation efficiency more than 99% was achieved. This microchip was able to operate at flow rates up to 100 μl/min, capable of separating OPCs from a confluent 75 cm(2) cell culture flask in less than 10 min, which provides us with a high-throughput and highly efficient separation expected from any cell sorting techniques.

  14. Integrated Microfluidic Reactors.

    Science.gov (United States)

    Lin, Wei-Yu; Wang, Yanju; Wang, Shutao; Tseng, Hsian-Rong

    2009-12-01

    Microfluidic reactors exhibit intrinsic advantages of reduced chemical consumption, safety, high surface-area-to-volume ratios, and improved control over mass and heat transfer superior to the macroscopic reaction setting. In contract to a continuous-flow microfluidic system composed of only a microchannel network, an integrated microfluidic system represents a scalable integration of a microchannel network with functional microfluidic modules, thus enabling the execution and automation of complicated chemical reactions in a single device. In this review, we summarize recent progresses on the development of integrated microfluidics-based chemical reactors for (i) parallel screening of in situ click chemistry libraries, (ii) multistep synthesis of radiolabeled imaging probes for positron emission tomography (PET), (iii) sequential preparation of individually addressable conducting polymer nanowire (CPNW), and (iv) solid-phase synthesis of DNA oligonucleotides. These proof-of-principle demonstrations validate the feasibility and set a solid foundation for exploring a broad application of the integrated microfluidic system.

  15. Performance of a Microfluidic Device for In Situ ToF-SIMS Analysis of Selected Organic Molecules at Aqueous Surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Li; Zhu, Zihua; Yu, Xiao-Ying; Thevuthasan, Suntharampillai; Cowin, James P.

    2013-04-03

    Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is a unique surface analysis technique because it can provide molecular recognition for organic and biological molecules. However, analyzing aqueous solution surfaces by ToF-SIMS is difficult, because ToF-SIMS is a high-vacuum technique, while the vapor pressure of water is about 2.3 kPa at room temperature (20 C). We designed and fabricated a self-contained microfluidic device, enabling in situ analysis of aqueous surfaces by scanning electron microscope (SEM) and ToF-SIMS, which has been briefly reported.1,2 In this study, we report more performance data, focusing on the performance of this device for in situ analysis of organic molecules at aqueous surfaces using ToF-SIMS. Three representative organic compounds (formic acid, glycerol, and glutamic acid) were tested, and their molecular signals were successfully observed. The device can be self-running in vacuum for 8 hours, and SIMS measurements are feasible at any time in this time range. The stability of this device under primary ion beam bombardment is also impressive. High fluence (6 × 1012 ions cm-2 s-1) measurements can be operated continuously for up to 30 minutes without any significant damage to the aperture. However, extra-high fluence measurements (>1 × 1014 ions cm-2 s-1) may lead to liquid bumping in the aperture, and the aqueous solutions may spread out quickly. Signal reproducibility is reasonably good, and relative standard deviation (RSD) for molecular ion signals can be controlled to be smaller than ±15% for consecutive measurements. Measurements at long time intervals (e.g., 60 min) show RSDs of ±40-50%. In addition, the detection limits of formic acid, glycerol, and glutamic acid are estimated to be 0.04%, 0.008%, and 0.002% (weight ratio), respectively.

  16. Development of a Generic Microfluidic Device for Simultaneous Detection of Antibodies and Nucleic Acids in Oral Fluids

    Directory of Open Access Journals (Sweden)

    Zongyuan Chen

    2013-01-01

    Full Text Available A prototype dual-path microfluidic device (Rheonix CARD capable of performing simultaneously screening (antigen or antibody and confirmatory (nucleic acid detection of pathogens is described. The device fully integrates sample processing, antigen or antibody detection, and nucleic acid amplification and detection, demonstrating rapid and inexpensive “sample-to-result” diagnosis with performance comparable to benchtop analysis. For the chip design, a modular approach was followed allowing the optimization of individual steps in the sample processing process. This modular design provides great versatility accommodating different disease targets independently of the production method. In the detection module, a lateral flow (LF protocol utilizing upconverting phosphor (UCP reporters was employed. The nucleic acid (NA module incorporates a generic microtube containing dry reagents. Lateral flow strips and PCR primers determine the target or disease that is diagnosed. Diagnosis of HIV infection was used as a model to investigate the simultaneous detection of both human antibodies against the virus and viral RNA. The serological result is available in less than 30 min, and the confirmation by RNA amplification takes another 60 min. This approach combines a core serological portable diagnostic with a nucleic acid-based confirmatory test.

  17. Capturing CD4 cells using a functionalized circular microfluidic device and glutaraldehyde as biolinker for tuberculosis detection and diagnosis

    Science.gov (United States)

    Shih, Yeu-Farn; Huang, Nien-Tsu; Lee, Chih-Kung

    2015-03-01

    It is estimated that about one-third of the world's population has already been infected by tuberculosis. Mycobacterium tuberculosis, in general, can result in an active case of tuberculosis in approximately 5%-10% of those who suffer from latent tuberculosis and the chance of becoming ill is the highest within one of year of getting the disease. Although a newly developed methods called interferon gamma release assay (IGRA) can monitor CD4 cells secreted cytokine to diagnose tuberculosis (TB) condition. However, it is difficult to count total numbers of cytokine secreted CD4 cells, which make the diagnosis less accurate. Therefore, we develop a functionalized polydimethylsiloxane (PDMS) device using glutaraldehyde to capture CD4 cells. To enhance the capture efficiency, we use COMSOL simulation to optimize the arrangement of PDMS micro pillars to make cells uniformly distributed in the device. Our preliminary data showed the microfluidic configuration in a circular shape with HCP patterned micro pillars turned 30 degrees offers the highest cell capture rate.

  18. Microfluidic paper-based analytical devices for colorimetric detection of urinary tract infection biomarkers on adult diapers.

    Science.gov (United States)

    Chaohao Chen; Tao Dong

    2015-08-01

    Urinary tract infections (UTI) are common infection diseases in elderly patients. The conventional method of detecting UTI involves the collection of significant urine samples from the elderly patients. However, this is a very difficult and time-consuming procedure. This paper addresses the development of a microfluidic paper-based analytical device (μPAD) to detect UTI from urine collected from adult diapers. The design and fabrication for the μPAD is shown. The fabrication process involves melting solid wax on top of filter paper using a hot plate, followed by pattern transfer using a mold with rubbed wax. To demonstrate the feasibility of the proposed method, the μPAD with deposited nitrite reagent had detected different concentrations of nitrite solutions from 0.5 ppm to 100 ppm spiked in urine samples. A calibration curve was obtained by plotting the gray scale intensity values against the various nitrite concentrations. The results showed that the proposed paper-based device holds great potential as low-cost, disposable solution to sensitively detect UTI markers in urine sampled from diapers.

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

    Directory of Open Access Journals (Sweden)

    Priya Gogoi

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

  20. Controlled incremental filtration: a simplified approach to design and fabrication of high-throughput microfluidic devices for selective enrichment of particles.

    Science.gov (United States)

    Gifford, Sean C; Spillane, Angela M; Vignes, Seth M; Shevkoplyas, Sergey S

    2014-12-07

    The number of microfluidic strategies aimed at separating particles or cells of a specific size within a continuous flow system continues to grow. The wide array of biomedical and other applications that would benefit from successful development of such technology has motivated the extensive research in this area over the past 15 years. However, despite promising advancements in microfabrication capabilities, a versatile approach that is suitable for a large range of particle sizes and high levels of enrichment, with a volumetric throughput sufficient for large-scale applications, has yet to emerge. Here we describe a straightforward method that enables the rapid design of microfluidic devices that are capable of enriching/removing particles within a complex aqueous mixture, with an unprecedented range of potential cutoff diameter (below 1 μm to above 100 μm) and an easily scalable degree of enrichment/filtration (up to 10-fold and well beyond). A simplified model of a new approach to crossflow filtration - controlled incremental filtration - was developed and validated for its ability to generate microfluidic devices that efficiently separate particles on the order of 1-10 μm, with throughputs of tens of μL min(-1), without the use of a pump. Precise control of the amount of fluid incrementally diverted at each filtration "gap" of the device allows for the gap size (~20 μm) to be much larger than the particles of interest, while the simplicity of the model allows for many thousands of these filtration points to be readily incorporated into a desired device design. This new approach should enable truly high-throughput microfluidic particle-separation devices to be generated, even by users only minimally experienced in fluid mechanics and microfabrication techniques.