Science.gov

Sample records for based microfluidic elements

  1. Discrete elements for 3D microfluidics

    PubMed Central

    Bhargava, Krisna C.; Thompson, Bryant; Malmstadt, Noah

    2014-01-01

    Microfluidic systems are rapidly becoming commonplace tools for high-precision materials synthesis, biochemical sample preparation, and biophysical analysis. Typically, microfluidic systems are constructed in monolithic form by means of microfabrication and, increasingly, by additive techniques. These methods restrict the design and assembly of truly complex systems by placing unnecessary emphasis on complete functional integration of operational elements in a planar environment. Here, we present a solution based on discrete elements that liberates designers to build large-scale microfluidic systems in three dimensions that are modular, diverse, and predictable by simple network analysis techniques. We develop a sample library of standardized components and connectors manufactured using stereolithography. We predict and validate the flow characteristics of these individual components to design and construct a tunable concentration gradient generator with a scalable number of parallel outputs. We show that these systems are rapidly reconfigurable by constructing three variations of a device for generating monodisperse microdroplets in two distinct size regimes and in a high-throughput mode by simple replacement of emulsifier subcircuits. Finally, we demonstrate the capability for active process monitoring by constructing an optical sensing element for detecting water droplets in a fluorocarbon stream and quantifying their size and frequency. By moving away from large-scale integration toward standardized discrete elements, we demonstrate the potential to reduce the practice of designing and assembling complex 3D microfluidic circuits to a methodology comparable to that found in the electronics industry. PMID:25246553

  2. Microfluidic bioassay system based on microarrays of hydrogel sensing elements entrapping quantum dot-enzyme conjugates.

    PubMed

    Jang, Eunji; Kim, Sinyoung; Koh, Won-Gun

    2012-01-15

    This paper presents a simple method to fabricate a microfluidic biosensor that is able to detect substrates for H(2)O(2)-generating oxidase. The biosensor consists of three components (quantum dot-enzyme conjugates, hydrogel microstructures, and a set of microchannels) that were hierarchically integrated into a microfluidic device. The quantum dot (QD)-enzyme conjugates were entrapped within the poly(ethylene glycol) (PEG)-based hydrogel microstructures that were fabricated within the microchannels by a photopatterning process. Glucose oxidase (GOX) and alcohol oxidase (AOX) were chosen as the model oxidase enzymes, conjugated to carboxyl-terminated CdSe/ZnS QDs, and entrapped within the hydrogel microstructures, which resulted in a fluorescent hydrogel microarray that was responsive to glucose or alcohol. The hydrogel-entrapped GOX and AOX were able to perform enzyme-catalyzed oxidation of glucose and alcohol, respectively, to produce H(2)O(2), which subsequently quenched the fluorescence of the conjugated QDs. The fluorescence intensity of the hydrogel microstructures decreased as the glucose and alcohol concentrations increased, and the detection limits of this system were found to be 50 μM of glucose and 70 μM of alcohol. Because each microchannel was able to carry out different assays independently, the simultaneous detection of glucose and alcohol was possible using our novel microfluidic device composed of multiple microchannels. PMID:22177543

  3. Predicting the behavior of microfluidic circuits made from discrete elements

    PubMed Central

    Bhargava, Krisna C.; Thompson, Bryant; Iqbal, Danish; Malmstadt, Noah

    2015-01-01

    Microfluidic devices can be used to execute a variety of continuous flow analytical and synthetic chemistry protocols with a great degree of precision. The growing availability of additive manufacturing has enabled the design of microfluidic devices with new functionality and complexity. However, these devices are prone to larger manufacturing variation than is typical of those made with micromachining or soft lithography. In this report, we demonstrate a design-for-manufacturing workflow that addresses performance variation at the microfluidic element and circuit level, in context of mass-manufacturing and additive manufacturing. Our approach relies on discrete microfluidic elements that are characterized by their terminal hydraulic resistance and associated tolerance. Network analysis is employed to construct simple analytical design rules for model microfluidic circuits. Monte Carlo analysis is employed at both the individual element and circuit level to establish expected performance metrics for several specific circuit configurations. A protocol based on osmometry is used to experimentally probe mixing behavior in circuits in order to validate these approaches. The overall workflow is applied to two application circuits with immediate use at on the bench-top: series and parallel mixing circuits that are modularly programmable, virtually predictable, highly precise, and operable by hand. PMID:26516059

  4. Predicting the behavior of microfluidic circuits made from discrete elements

    NASA Astrophysics Data System (ADS)

    Bhargava, Krisna C.; Thompson, Bryant; Iqbal, Danish; Malmstadt, Noah

    2015-10-01

    Microfluidic devices can be used to execute a variety of continuous flow analytical and synthetic chemistry protocols with a great degree of precision. The growing availability of additive manufacturing has enabled the design of microfluidic devices with new functionality and complexity. However, these devices are prone to larger manufacturing variation than is typical of those made with micromachining or soft lithography. In this report, we demonstrate a design-for-manufacturing workflow that addresses performance variation at the microfluidic element and circuit level, in context of mass-manufacturing and additive manufacturing. Our approach relies on discrete microfluidic elements that are characterized by their terminal hydraulic resistance and associated tolerance. Network analysis is employed to construct simple analytical design rules for model microfluidic circuits. Monte Carlo analysis is employed at both the individual element and circuit level to establish expected performance metrics for several specific circuit configurations. A protocol based on osmometry is used to experimentally probe mixing behavior in circuits in order to validate these approaches. The overall workflow is applied to two application circuits with immediate use at on the bench-top: series and parallel mixing circuits that are modularly programmable, virtually predictable, highly precise, and operable by hand.

  5. Predicting the behavior of microfluidic circuits made from discrete elements.

    PubMed

    Bhargava, Krisna C; Thompson, Bryant; Iqbal, Danish; Malmstadt, Noah

    2015-01-01

    Microfluidic devices can be used to execute a variety of continuous flow analytical and synthetic chemistry protocols with a great degree of precision. The growing availability of additive manufacturing has enabled the design of microfluidic devices with new functionality and complexity. However, these devices are prone to larger manufacturing variation than is typical of those made with micromachining or soft lithography. In this report, we demonstrate a design-for-manufacturing workflow that addresses performance variation at the microfluidic element and circuit level, in context of mass-manufacturing and additive manufacturing. Our approach relies on discrete microfluidic elements that are characterized by their terminal hydraulic resistance and associated tolerance. Network analysis is employed to construct simple analytical design rules for model microfluidic circuits. Monte Carlo analysis is employed at both the individual element and circuit level to establish expected performance metrics for several specific circuit configurations. A protocol based on osmometry is used to experimentally probe mixing behavior in circuits in order to validate these approaches. The overall workflow is applied to two application circuits with immediate use at on the bench-top: series and parallel mixing circuits that are modularly programmable, virtually predictable, highly precise, and operable by hand. PMID:26516059

  6. A waveguide based microfluidic application

    NASA Astrophysics Data System (ADS)

    Taheri, Nooshin S.; Chan, Peggy; Friend, James R.; Yeo, Leslie

    2013-12-01

    Microfluidics is based on the performance of fluids in a microenvironment. As the microfluidics research advances in the cellular behaviour, the need for improved micro devices grows. This work introduces the design and fabrication of a micro ridge waveguide to be employed in fluids manipulations. Then it investigates the characteristics of the device in order to control the movement of the fluids on top of the ridge of the waveguide. The elastic vibration is excited along the ridge of the guide with the use of thickness poled lead zirconate titanate (PZT) elements attached to both sides of the waveguide. To excite anti-symmetric or flexural mode in the ridge of the guide, the propagation velocity has been kept significantly below the Rayleigh wave velocity. The velocity reduction of 15% is achieved with the high aspect ratio ridge (H/W =3) design. A three dimensional model of the micro waveguide has also been developed to determine the vibration characteristics; the natural frequency and the considered mode of the micro waveguide through finite element analysis using ANSYS. The travelling wave along the ridge of the guide is able to transmit strong vibration to the fluid atop of the substrate. The results represents a promising approach, through recasting the waveguide structure to be suitable in fluids and particle in fluids manipulations in one dimensional environment with the strong confined energy, at smaller scale with higher vibration displacement.

  7. Polymer-based platform for microfluidic systems

    DOEpatents

    Benett, William; Krulevitch, Peter; Maghribi, Mariam; Hamilton, Julie; Rose, Klint; Wang, Amy W.

    2009-10-13

    A method of forming a polymer-based microfluidic system platform using network building blocks selected from a set of interconnectable network building blocks, such as wire, pins, blocks, and interconnects. The selected building blocks are interconnectably assembled and fixedly positioned in precise positions in a mold cavity of a mold frame to construct a three-dimensional model construction of a microfluidic flow path network preferably having meso-scale dimensions. A hardenable liquid, such as poly (dimethylsiloxane) is then introduced into the mold cavity and hardened to form a platform structure as well as to mold the microfluidic flow path network having channels, reservoirs and ports. Pre-fabricated elbows, T's and other joints are used to interconnect various building block elements together. After hardening the liquid the building blocks are removed from the platform structure to make available the channels, cavities and ports within the platform structure. Microdevices may be embedded within the cast polymer-based platform, or bonded to the platform structure subsequent to molding, to create an integrated microfluidic system. In this manner, the new microfluidic platform is versatile and capable of quickly generating prototype systems, and could easily be adapted to a manufacturing setting.

  8. Two dimension (2-D) graphene-based nanomaterials as signal amplification elements in electrochemical microfluidic immune-devices: Recent advances.

    PubMed

    Hasanzadeh, Mohammad; Shadjou, Nasrin; Mokhtarzadeh, Ahad; Ramezani, Mohammad

    2016-11-01

    Graphene is a 2-D carbon nanomaterial with many distinctive properties that are electrochemically beneficial, such as large surface-to-volume ratio, lowered power usage, high conductivity and electron mobility. Graphene-based electrochemical immune-devices have recently gained much importance for detecting antigens and biomarkers responsible for cancer diagnosis. This review describes fabrication and chemical modification of the surfaces of graphene for immunesensing applications. We also present a comprehensive overview of current developments and key issues in the determination of some biological molecules with particular emphasis on evaluating the models. This review focuses mostly on new developments in the last 5years in development of chip architecture and integration, different sensing modes that can be used in conjunction with microfluidics, and new applications that have emerged or have been demonstrated; it also aims to point out where future research can be directed to in these areas. PMID:27524045

  9. A process chain for integrating microfluidic interconnection elements by micro-overmoulding of thermoplastic elastomers

    NASA Astrophysics Data System (ADS)

    Attia, U. M.; Alcock, J. R.

    2010-05-01

    This paper presents a process chain for in-line integration of microfluidic interconnection elements by a variant of micro-injection moulding (µIM). A SEBS-based thermoplastic elastomer (TPE) was moulded over polymethylmethacrylate (PMMA) to produce a hybrid microfluidic structure with an aspect ratio of 2. The process chain implemented micro-milling for fabricating micro-structured tool inserts, and µIM and micro-overmoulding was used for replication. A two-plate mould was used for moulding the substrate, whilst a three-plate mould with a replaceable insert was used for TPE overmoulding. The presented application was an interconnect system for a microfluidic device, which enabled direct fitting of standard tubes into microfluidic substrates. A leakage test showed that the interconnection was leak-proof within a range of flow rates between 0.32 and 0.62 ml min-1.

  10. Mobile monolithic polymer elements for flow control in microfluidic devices

    DOEpatents

    Hasselbrink, Jr., Ernest F.; Rehm, Jason E.; Shepodd, Timothy J.

    2004-08-31

    A cast-in-place and lithographically shaped mobile, monolithic polymer element for fluid flow control in microfluidic devices and method of manufacture. Microfluid flow control devices, or microvalves that provide for control of fluid or ionic current flow can be made incorporating a cast-in-place, mobile monolithic polymer element, disposed within a microchannel, and driven by either fluid or gas pressure against a retaining or sealing surface. The polymer elements are made by the application of lithographic methods to monomer mixtures formulated in such a way that the polymer will not bond to microchannel walls. The polymer elements can seal against pressures greater than 5000 psi, and have a response time on the order of milliseconds. By the use of energetic radiation it is possible to depolymerize selected regions of the polymer element to form shapes that cannot be produced by conventional lithographic patterning and would be impossible to machine.

  11. Mobile Monolith Polymer Elements For Flow Control In Microfluidic Systems

    DOEpatents

    Hasselbrink, Jr., Ernest F.; Rehm, Jason E.; Shepodd, Timothy J.; Kirby, Brian J.

    2006-01-24

    A cast-in-place and lithographically shaped mobile, monolithic polymer element for fluid flow control in microfluidic devices and method of manufacture. Microfluid flow control devices, or microvalves that provide for control of fluid or ionic current flow can be made incorporating a cast-in-place, mobile monolithic polymer element, disposed within a microchannel, and driven by fluid pressure (either liquid or gas) against a retaining or sealing surface. The polymer elements are made by the application of lithographic methods to monomer mixtures formulated in such a way that the polymer will not bond to microchannel walls. The polymer elements can seal against pressures greater than 5000 psi, and have a response time on the order of milliseconds. By the use of energetic radiation it is possible to depolymerize selected regions of the polymer element to form shapes that cannot be produced by conventional lithographic patterning and would be impossible to machine.

  12. Mobile monolithic polymer elements for flow control in microfluidic devices

    DOEpatents

    Hasselbrink, Jr., Ernest F.; Rehm, Jason E.; Shepodd, Timothy J.; Kirby, Brian J.

    2005-11-11

    A cast-in-place and lithographically shaped mobile, monolithic polymer element for fluid flow control in microfluidic devices and method of manufacture. Microfluid flow control devices, or microvalves that provide for control of fluid or ionic current flow can be made incorporating a cast-in-place, mobile monolithic polymer element, disposed within a microchannel, and driven by fluid pressure (either liquid or gas) against a retaining or sealing surface. The polymer elements are made by the application of lithographic methods to monomer mixtures formulated in such a way that the polymer will not bond to microchannel walls. The polymer elements can seal against pressures greater than 5000 psi, and have a response time on the order of milliseconds. By the use of energetic radiation it is possible to depolymerize selected regions of the polymer element to form shapes that cannot be produced by conventional lithographic patterning and would be impossible to machine.

  13. Size-based microfluidic multimodal microparticle sorter.

    PubMed

    Wang, Xiao; Papautsky, Ian

    2015-03-01

    Microfluidic sorting of synthetic and biological microparticles has attracted much interest in recent years. Inertial microfluidics uses hydrodynamic forces to manipulate migration of such microparticles in microfluidic channels to achieve passive sorting based on size with high throughput. However, most inertial microfluidic devices are only capable of bimodal separation with a single cutoff diameter and a well-defined size difference. These limitations inhibit efficient separation of real-world samples that often include heterogeneous mixtures of multiple microparticle components. Our design overcomes these challenges to achieve continuous multimodal sorting of microparticles with high resolution and high tunability of separation cutoff diameters. We demonstrate separations with flexible modulation of the separation bandwidth and the passband location. Our approach offers a number of benefits, including straightforward system design, easily and precisely tuned cutoff diameters, high separation resolution, and high throughput. Ultimately, the unique multimodal separation functionality significantly broadens applications of inertial microfluidics in sorting of complex microparticle samples. PMID:25590954

  14. Magneto-Hydrodynamics Based Microfluidics

    PubMed Central

    Qian, Shizhi; Bau, Haim H.

    2009-01-01

    In microfluidic devices, it is necessary to propel samples and reagents from one part of the device to another, stir fluids, and detect the presence of chemical and biological targets. Given the small size of these devices, the above tasks are far from trivial. Magnetohydrodynamics (MHD) offers an elegant means to control fluid flow in microdevices without a need for mechanical components. In this paper, we review the theory of MHD for low conductivity fluids and describe various applications of MHD such as fluid pumping, flow control in fluidic networks, fluid stirring and mixing, circular liquid chromatography, thermal reactors, and microcoolers. PMID:20046890

  15. Cell-based bioassays in microfluidic systems

    NASA Astrophysics Data System (ADS)

    Itle, Laura J.; Zguris, Jeanna C.; Pishko, Michael V.

    2004-12-01

    The development of cell-based bioassays for high throughput drug screening or the sensing of biotoxins is contingent on the development of whole cell sensors for specific changes in intracellular conditions and the integration of those systems into sample delivery devices. Here we show the feasibility of using a 5-(and-6)-carboxy SNARF-1, acetoxymethyl ester, acetate, a fluorescent dye capable of responding to changes in intracellular pH, as a detection method for the bacterial endotoxin, lipopolysaccharide. We used photolithography to entrap cells with this dye within poly(ethylene) glyocol diacrylate hydrogels in microfluidic channels. After 18 hours of exposure to lipopolysaccharide, we were able to see visible changes in the fluorescent pattern. This work shows the feasibility of using whole cell based biosensors within microfluidic networks to detect cellular changes in response to exogenous agents.

  16. Wearable tactile sensor based on flexible microfluidics.

    PubMed

    Yeo, Joo Chuan; Yu, Jiahao; Koh, Zhao Ming; Wang, Zhiping; Lim, Chwee Teck

    2016-08-16

    In this work, we develop a liquid-based thin film microfluidic tactile sensor of high flexibility, robustness and sensitivity. The microfluidic elastomeric structure comprises a pressure sensitive region and parallel arcs that interface with screen-printed electrodes. The microfluidic sensor is functionalized with a highly conductive metallic liquid, eutectic gallium indium (eGaIn). Microdeformation on the pressure sensor results in fluid displacement which corresponds to a change in electrical resistance. By emulating parallel electrical circuitry in our microchannel design, we reduced the overall electrical resistance of the sensor, therefore enhancing its device sensitivity. Correspondingly, we report a device workable within a range of 4 to 100 kPa and sensitivity of up to 0.05 kPa(-1). We further demonstrate its robustness in withstanding >2500 repeated loading and unloading cycles. Finally, as a proof of concept, we demonstrate that the sensors may be multiplexed to detect forces at multiple regions of the hand. In particular, our sensors registered unique electronic signatures in object grasping, which could provide better assessment of finger dexterity. PMID:27438370

  17. Microfluidic, Bead-Based Assay: Theory and Experiments

    PubMed Central

    Thompson, Jason A.; Bau, Haim H.

    2009-01-01

    Microbeads are frequently used as a solid support for biomolecules such as proteins and nucleic acids in heterogeneous microfluidic assays. However, relatively few studies investigate the binding kinetics on modified bead surfaces in a microfluidics context. In this study, a customized hot embossing technique is used to stamp microwells in a thin plastic substrate where streptavidin-coated agarose beads are selectively placed and subsequently immobilized within a conduit. Biotinylated quantum dots are used as a label to monitor target analyte binding to the bead's surface. Three-dimensional finite element simulations are carried out to model the binding kinetics on the bead's surface. The model accounts for surface exclusion effects resulting from a single quantum dot occluding multiple receptor sites. The theoretical predictions are compared and favorably agree with experimental observations. The theoretical simulations provide a useful tool to predict how varying parameters affect microbead reaction kinetics and sensor performance. This study enhances our understanding of bead-based microfluidic assays and provides a design tool for developers of point-of-care, lab-on-chip devices for medical diagnosis, food and water quality inspection, and environmental monitoring. PMID:19766545

  18. Microfluidic-Based Robotic Sampling System for Radioactive Solutions

    SciTech Connect

    Jack D. Law; Julia L. Tripp; Tara E. Smith; Veronica J. Rutledge; Troy G. Garn; John Svoboda; Larry Macaluso

    2014-02-01

    A novel microfluidic based robotic sampling system has been developed for sampling and analysis of liquid solutions in nuclear processes. This system couples the use of a microfluidic sample chip with a robotic system designed to allow remote, automated sampling of process solutions in-cell and facilitates direct coupling of the microfluidic sample chip with analytical instrumentation. This system provides the capability for near real time analysis, reduces analytical waste, and minimizes the potential for personnel exposure associated with traditional sampling methods. A prototype sampling system was designed, built and tested. System testing demonstrated operability of the microfluidic based sample system and identified system modifications to optimize performance.

  19. Streamline-based microfluidic device

    NASA Technical Reports Server (NTRS)

    Tai, Yu-Chong (Inventor); Zheng, Siyang (Inventor); Kasdan, Harvey (Inventor)

    2013-01-01

    The present invention provides a streamline-based device and a method for using the device for continuous separation of particles including cells in biological fluids. The device includes a main microchannel and an array of side microchannels disposed on a substrate. The main microchannel has a plurality of stagnation points with a predetermined geometric design, for example, each of the stagnation points has a predetermined distance from the upstream edge of each of the side microchannels. The particles are separated and collected in the side microchannels.

  20. Droplet-Based Pyrosequencing Using Digital Microfluidics

    PubMed Central

    Boles, Deborah J.; Benton, Jonathan L.; Siew, Germaine J.; Levy, Miriam H.; Thwar, Prasanna K.; Sandahl, Melissa A.; Rouse, Jeremy L.; Perkins, Lisa C.; Sudarsan, Arjun P.; Jalili, Roxana; Pamula, Vamsee K.; Srinivasan, Vijay; Fair, Richard B.; Griffin, Peter B.; Eckhardt, Allen E.; Pollack, Michael G.

    2013-01-01

    The feasibility of implementing pyrosequencing chemistry within droplets using electrowetting-based digital microfluidics is reported. An array of electrodes patterned on a printed-circuit board was used to control the formation, transportation, merging, mixing, and splitting of submicroliter-sized droplets contained within an oil-filled chamber. A three-enzyme pyrosequencing protocol was implemented in which individual droplets contained enzymes, deoxyribonucleotide triphosphates (dNTPs), and DNA templates. The DNA templates were anchored to magnetic beads which enabled them to be thoroughly washed between nucleotide additions. Reagents and protocols were optimized to maximize signal over background, linearity of response, cycle efficiency, and wash efficiency. As an initial demonstration of feasibility, a portion of a 229 bp Candida parapsilosis template was sequenced using both a de novo protocol and a resequencing protocol. The resequencing protocol generated over 60 bp of sequence with 100% sequence accuracy based on raw pyrogram levels. Excellent linearity was observed for all of the homopolymers (two, three, or four nucleotides) contained in the C. parapsilosis sequence. With improvements in microfluidic design it is expected that longer reads, higher throughput, and improved process integration (i.e., “sample-to-sequence” capability) could eventually be achieved using this low-cost platform. PMID:21932784

  1. Droplet Microfluidics for Chip-Based Diagnostics

    PubMed Central

    Kaler, Karan V. I. S.; Prakash, Ravi

    2014-01-01

    Droplet microfluidics (DMF) is a fluidic handling technology that enables precision control over dispensing and subsequent manipulation of droplets in the volume range of microliters to picoliters, on a micro-fabricated device. There are several different droplet actuation methods, all of which can generate external stimuli, to either actively or passively control the shape and positioning of fluidic droplets over patterned substrates. In this review article, we focus on the operation and utility of electro-actuation-based DMF devices, which utilize one or more micro-/nano-patterned substrates to facilitate electric field-based handling of chemical and/or biological samples. The underlying theory of DMF actuations, device fabrication methods and integration of optical and opto-electronic detectors is discussed in this review. Example applications of such electro-actuation-based DMF devices have also been included, illustrating the various actuation methods and their utility in conducting chip-based laboratory and clinical diagnostic assays. PMID:25490590

  2. Microeddies as microfluidic elements: Reactors and cell traps

    NASA Astrophysics Data System (ADS)

    Lutz, Barry R.

    2003-07-01

    Microfluidic applications generally seek to control fluids, reagents, and objects at the microscale, and the development of individual components to either mimic traditional processes or to realize novel processes remains important to development in the field. This work focuses on microscopic acoustic streaming eddies as hydrodynamic microreactors and traps for microscopic objects including motile cells. Four microeddies were created around a stationary cylinder (radius 406 mum) by oscillating the surrounding fluid (audible frequency). Concentration images measured using Raman spectroscopy show that eddies act as hydrodynamic "vessels" for reagents dosed from the cylinder (an electrode), and the oscillation amplitude and reagent dosing rate quantitatively controlled the eddy composition. These "vessels" were used to quantify the antioxidant properties of vitamin C against an electrogenerated oxidant. Material balances over the eddy yield a reactor model identical to a two-input CSTR (i.e., perfect backmixing model); and the mean reactor residence time, Damkohler number, and reagent feed ratio are quantitatively related to eddy properties. The CSTR model fit to data for a range of reactor conversions gives the homogeneous rate constant for vitamin C oxidation, showing that the composition of microeddy reactors can be controlled quantitatively. The cylinder and oscillating fluid were incorporated into microscale channels to provide a route to integration with more conventional microfluidic applications. Detailed flow measurements describe the three-dimensional acoustic streaming flow structure, and theory relates measured flow features to frequency and geometry through simple scaling. These channel-based microeddies show an impressive ability to trap microscopic objects at fixed positions in three-dimensions. Microeddies formed in a microchannel (425 mum depth) collect and trap motile phytoplankton (P. micans) and microspheres (˜20--0 mum diameter). The trap

  3. Microfluidic System for Solution Array Based Bioassays

    SciTech Connect

    Dougherty, G M; Tok, J B; Pannu, S S; Rose, K A

    2006-02-10

    The objective of this project is to demonstrate new enabling technology for multiplex biodetection systems that are flexible, miniaturizable, highly automated, low cost, and high performance. It builds on prior successes at LLNL with particle-based solution arrays, such as those used in the Autonomous Pathogen Detection System (APDS) successfully field deployed to multiple locations nationwide. We report the development of a multiplex solution array immunoassay based upon engineered metallic nanorod particles. Nanobarcodes{reg_sign} particles are fabricated by sequential electrodeposition of dissimilar metals within porous alumina templates, yielding optically encoded striping patterns that can be read using standard laboratory microscope optics and PC-based image processing software. The addition of self-assembled monolayer (SAM) coatings and target-specific antibodies allows each encoded class of nanorod particles to be directed against a different antigen target. A prototype assay panel directed against bacterial, viral, and soluble protein targets demonstrates simultaneous detection at sensitivities comparable to state of the art immunoassays, with minimal cross-reactivity. Studies have been performed to characterize the colloidal properties (zeta potential) of the suspended nanorod particles as a function of pH, the ionic strength of the suspending solution, and surface functionalization state. Additional studies have produced means for the non-contact manipulation of the particles, including the insertion of magnetic nickel stripes within the encoding pattern, and control via externally applied electromagnetic fields. Using the results of these studies, the novel Nanobarcodes{reg_sign} based assay was implemented in a prototype automated system with the sample processing functions and optical readout performed on a microfluidic card. The unique physical properties of the nanorod particles enable the development of integrated microfluidic systems for

  4. Electrochemical sensing in paper-based microfluidic devices.

    PubMed

    Nie, Zhihong; Nijhuis, Christian A; Gong, Jinlong; Chen, Xin; Kumachev, Alexander; Martinez, Andres W; Narovlyansky, Max; Whitesides, George M

    2010-02-21

    This paper describes the fabrication and the performance of microfluidic paper-based electrochemical sensing devices (we call the microfluidic paper-based electrochemical devices, microPEDs). The microPEDs comprise paper-based microfluidic channels patterned by photolithography or wax printing, and electrodes screen-printed from conducting inks (e.g., carbon or Ag/AgCl). We demonstrated that the microPEDs are capable of quantifying the concentrations of various analytes (e.g., heavy-metal ions and glucose) in aqueous solutions. This low-cost analytical device should be useful for applications in public health, environmental monitoring, and the developing world. PMID:20126688

  5. Reciprocating flow-based centrifugal microfluidics mixer

    NASA Astrophysics Data System (ADS)

    Noroozi, Zahra; Kido, Horacio; Micic, Miodrag; Pan, Hansheng; Bartolome, Christian; Princevac, Marko; Zoval, Jim; Madou, Marc

    2009-07-01

    Proper mixing of reagents is of paramount importance for an efficient chemical reaction. While on a large scale there are many good solutions for quantitative mixing of reagents, as of today, efficient and inexpensive fluid mixing in the nanoliter and microliter volume range is still a challenge. Complete, i.e., quantitative mixing is of special importance in any small-scale analytical application because the scarcity of analytes and the low volume of the reagents demand efficient utilization of all available reaction components. In this paper we demonstrate the design and fabrication of a novel centrifugal force-based unit for fast mixing of fluids in the nanoliter to microliter volume range. The device consists of a number of chambers (including two loading chambers, one pressure chamber, and one mixing chamber) that are connected through a network of microchannels, and is made by bonding a slab of polydimethylsiloxane (PDMS) to a glass slide. The PDMS slab was cast using a SU-8 master mold fabricated by a two-level photolithography process. This microfluidic mixer exploits centrifugal force and pneumatic pressure to reciprocate the flow of fluid samples in order to minimize the amount of sample and the time of mixing. The process of mixing was monitored by utilizing the planar laser induced fluorescence (PLIF) technique. A time series of high resolution images of the mixing chamber were analyzed for the spatial distribution of light intensities as the two fluids (suspension of red fluorescent particles and water) mixed. Histograms of the fluorescent emissions within the mixing chamber during different stages of the mixing process were created to quantify the level of mixing of the mixing fluids. The results suggest that quantitative mixing was achieved in less than 3 min. This device can be employed as a stand alone mixing unit or may be integrated into a disk-based microfluidic system where, in addition to mixing, several other sample preparation steps may be

  6. Electrocoalescence based serial dilution of microfluidic droplets

    PubMed Central

    Bhattacharjee, Biddut; Vanapalli, Siva A.

    2014-01-01

    Dilution of microfluidic droplets where the concentration of a reagent is incrementally varied is a key operation in drop-based biological analysis. Here, we present an electrocoalescence based dilution scheme for droplets based on merging between moving and parked drops. We study the effects of fluidic and electrical parameters on the dilution process. Highly consistent coalescence and fine resolution in dilution factor are achieved with an AC signal as low as 10 V even though the electrodes are separated from the fluidic channel by insulator. We find that the amount of material exchange between the droplets per coalescence event is high for low capillary number. We also observe different types of coalescence depending on the flow and electrical parameters and discuss their influence on the rate of dilution. Overall, we find the key parameter governing the rate of dilution is the duration of coalescence between the moving and parked drop. The proposed design is simple incorporating the channel electrodes in the same layer as that of the fluidic channels. Our approach allows on-demand and controlled dilution of droplets and is simple enough to be useful for assays that require serial dilutions. The approach can also be useful for applications where there is a need to replace or wash fluid from stored drops. PMID:25379096

  7. A hybrid MEMS-based microfluidic system for cancer diagnosis

    NASA Astrophysics Data System (ADS)

    Ortiz, Pedro; Keegan, Neil; Spoors, Julia; Hedley, John; Harris, Alun; Burdess, Jim; Burnett, Richard; Velten, Thomas; Biehl, Margit; Knoll, Thorsten; Haberer, Werner; Solomon, Matthew; Campitelli, Andrew; McNeil, Calum

    2008-12-01

    A microfluidic system for cancer diagnosis based around a core MEMS biosensor technology is presented in this paper. The principle of the MEMS biosensor is introduced and the functionalisation strategy for cancer marker recognition is described. In addition, the successful packaging and integration of functional MEMS biosensor devices are reported herein. This ongoing work represents one of the first hybrid systems to integrate a PCB packaged silicon MEMS device into a disposable microfluidic cartridge.

  8. Silicon based microfluidic cell for terahertz frequencies

    NASA Astrophysics Data System (ADS)

    Baragwanath, A. J.; Swift, G. P.; Dai, D.; Gallant, A. J.; Chamberlain, J. M.

    2010-07-01

    We present a detailed analysis of the design, fabrication and testing of a silicon based, microfluidic cell, for transmission terahertz time-domain spectroscopy. The sensitivity of the device is tested through a range of experiments involving primary alcohol/water mixtures. The dielectric properties of these solutions are subsequently extracted using a Nelder-Mead search algorithm, and are in good agreement with literature values obtained via alternative techniques. Quantities in the order of 2 μmol can be easily distinguished for primary alcohols in solution, even with the subwavelength optical path lengths used. A further display of the device sensitivity is shown through the analysis of commercial whiskeys, where there are clear, detectable differences between samples. Slight absorption variations were identified between samples of the same commercial brand, owing to a 2.5% difference in their alcoholic content. Results from data taken on subsequent days after system realignment are also presented, confirming the robustness of the technique, and the data extraction algorithm used. One final experiment, showing the possible use of this device to analyze aqueous biological samples is detailed; where biotin, a molecule known for its specific terahertz absorptions, is analyzed in solution. The device sensitivity is once again displayed, where quantities of 3 nmol can be clearly detected between samples.

  9. Thermally induced light-driven microfluidics using a MOEMS-based laser scanner for particle manipulation

    NASA Astrophysics Data System (ADS)

    Kremer, Matthias P.; Tortschanoff, Andreas

    2014-03-01

    One key challenge in the field of microfluidics and lab-on-a-chip experiments for biological or chemical applications is the remote manipulation of fluids, droplets and particles. These can be volume elements of reactants, particles coated with markers, cells or many others. Light-driven microfluidics is one way of accomplishing this challenge. In our work, we manipulated micrometre sized polystyrene beads in a microfluidic environment by inducing thermal flows. Therefore, the beads were held statically in an unstructured microfluidic chamber, containing a dyed watery solution. Inside this chamber, the beads were moved along arbitrary trajectories on a micrometre scale. The experiments were performed, using a MOEMS (micro-opto-electro-mechanical-systems)-based laser scanner with a variable focal length. This scanner system is integrated in a compact device, which is flexibly applicable to various microscope setups. The device utilizes a novel approach for varying the focal length, using an electrically tunable lens. A quasi statically driven MOEMS mirror is used for beam steering. The combination of a tunable lens and a dual axis micromirror makes the device very compact and robust and is capable of positioning the laser focus at any arbitrary location within a three dimensional working space. Hence, the developed device constitutes a valuable extension to manually executed microfluidic lab-on-chip experiments.

  10. Microfluidic systems for stem cell-based neural tissue engineering.

    PubMed

    Karimi, Mahdi; Bahrami, Sajad; Mirshekari, Hamed; Basri, Seyed Masoud Moosavi; Nik, Amirala Bakhshian; Aref, Amir R; Akbari, Mohsen; Hamblin, Michael R

    2016-07-01

    Neural tissue engineering aims at developing novel approaches for the treatment of diseases of the nervous system, by providing a permissive environment for the growth and differentiation of neural cells. Three-dimensional (3D) cell culture systems provide a closer biomimetic environment, and promote better cell differentiation and improved cell function, than could be achieved by conventional two-dimensional (2D) culture systems. With the recent advances in the discovery and introduction of different types of stem cells for tissue engineering, microfluidic platforms have provided an improved microenvironment for the 3D-culture of stem cells. Microfluidic systems can provide more precise control over the spatiotemporal distribution of chemical and physical cues at the cellular level compared to traditional systems. Various microsystems have been designed and fabricated for the purpose of neural tissue engineering. Enhanced neural migration and differentiation, and monitoring of these processes, as well as understanding the behavior of stem cells and their microenvironment have been obtained through application of different microfluidic-based stem cell culture and tissue engineering techniques. As the technology advances it may be possible to construct a "brain-on-a-chip". In this review, we describe the basics of stem cells and tissue engineering as well as microfluidics-based tissue engineering approaches. We review recent testing of various microfluidic approaches for stem cell-based neural tissue engineering. PMID:27296463

  11. A novel microfluidic chip based on fiber sensor

    NASA Astrophysics Data System (ADS)

    Su, Bo; Duan, Guoteng; Han, Xue

    2013-08-01

    We have fabricated a novel microfluidic chip based on fiber sensor with casting PDMS method. The optical fiber is used to transmit excitation light, so the diameter of the excitation beam is decreased to 93μm. In order to improve the coupling efficiency of the excitation light in the fiber, the optical fiber collimation device is used to couple beam. The microfluidic chip consists of multimode optical fiber, PDMS cover slab and PDMS base slab. The mould of cover slab is made through twice exposal, however the base slab is achieved using once exposal only. The depths of microfluidic channel and optical fiber channel in the PDMS cover slab are 50μm and 90μm, respectively, and the optical fiber channel in the PDMS base slab is only 40μm. This design can make the centers of the microfluidic channel and the fiber channel in the same point, so the microfluidic channel and the optical fiber can be aimed at easily. In addition, the size of microfluidic channel depth is near the size of light spot of optical fiber, so the detection sensitivity is improved without using the optical focusing system. The detection system of the microfluidic chip is manufactured and it composed of high voltage modules, darkroom, LED light source, photomultiplier and data acquisition circuit, moreover, the software of the detection system is developed. The high voltage modules with four 2kV are used to control the sample amount in the separation channel, so the sensitivity is improved. The microfluidic chip is placed in the darkroom to avoid the interference of external light. The high brightness blue light emitting diode (LED) is used as excitation light sources for inducing fluorescence detection through coupling the LED light into the optical fiber. The photomultiplier is used to amplify the fluorescence signals and the function of data acquisition circuit is data collection and data processing. Under the control of software, the experiment process can be implemented easily. As an

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

    PubMed Central

    Shen, Richang; Gurkan, Umut A.

    2016-01-01

    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.

  13. Microfluidic System for Automated Cell-based Assays.

    PubMed

    Lee, Philip J; Ghorashian, Navid; Gaige, Terry A; Hung, Paul J

    2007-12-01

    Microfluidic cell culture is a promising technology for applications in the drug screening industry. Key benefits include improved biological function, higher quality cell-based data, reduced reagent consumption, and lower cost. In this work, we demonstrate how a microfluidic cell culture design was adapted to be compatible with the standard 96-well plate format. Key design features include the elimination of tubing and connectors, the ability to maintain long term continuous perfusion cell culture using a passive gravity driven pump, and direct analysis on the outlet wells of the microfluidic plate. A single microfluidic culture plate contained 8 independent flow units, each with 10(4) cells at a flow rate of 50 μl/day (6 minute residence time). The cytotoxicity of the anti-cancer drug etoposide was measured on HeLa cells cultured in this format, using a commercial lactate dehydrogenase (LDH) plate reader assay. The integration of microfluidic cell culture methods with commercial automation capabilities offers an exciting opportunity for improved cell-based screening. PMID:18172509

  14. Micro Electromechanical Systems (MEMS) Based Microfluidic Devices for Biomedical Applications

    PubMed Central

    Ashraf, Muhammad Waseem; Tayyaba, Shahzadi; Afzulpurkar, Nitin

    2011-01-01

    Micro Electromechanical Systems (MEMS) based microfluidic devices have gained popularity in biomedicine field over the last few years. In this paper, a comprehensive overview of microfluidic devices such as micropumps and microneedles has been presented for biomedical applications. The aim of this paper is to present the major features and issues related to micropumps and microneedles, e.g., working principles, actuation methods, fabrication techniques, construction, performance parameters, failure analysis, testing, safety issues, applications, commercialization issues and future prospects. Based on the actuation mechanisms, the micropumps are classified into two main types, i.e., mechanical and non-mechanical micropumps. Microneedles can be categorized according to their structure, fabrication process, material, overall shape, tip shape, size, array density and application. The presented literature review on micropumps and microneedles will provide comprehensive information for researchers working on design and development of microfluidic devices for biomedical applications. PMID:21747700

  15. Microfluidic chip-based technologies: emerging platforms for cancer diagnosis

    PubMed Central

    2013-01-01

    The development of early and personalized diagnostic protocols is considered the most promising avenue to decrease mortality from cancer and improve outcome. The emerging microfluidic-based analyzing platforms hold high promises to fulfill high-throughput and high-precision screening with reduced equipment cost and low analysis time, as compared to traditional bulky counterparts in bench-top laboratories. This article overviewed the potential applications of microfluidic technologies for detection and monitoring of cancer through nucleic acid and protein biomarker analysis. The implications of the technologies in cancer cytology that can provide functional personalized diagnosis were highlighted. Finally, the future niches for using microfluidic-based systems in tumor screening were briefly discussed. PMID:24070124

  16. Graphene-based microfluidics for serial crystallography.

    PubMed

    Sui, Shuo; Wang, Yuxi; Kolewe, Kristopher W; Srajer, Vukica; Henning, Robert; Schiffman, Jessica D; Dimitrakopoulos, Christos; Perry, Sarah L

    2016-08-01

    Microfluidic strategies to enable the growth and subsequent serial crystallographic analysis of micro-crystals have the potential to facilitate both structural characterization and dynamic structural studies of protein targets that have been resistant to single-crystal strategies. However, adapting microfluidic crystallization platforms for micro-crystallography requires a dramatic decrease in the overall device thickness. We report a robust strategy for the straightforward incorporation of single-layer graphene into ultra-thin microfluidic devices. This architecture allows for a total material thickness of only ∼1 μm, facilitating on-chip X-ray diffraction analysis while creating a sample environment that is stable against significant water loss over several weeks. We demonstrate excellent signal-to-noise in our X-ray diffraction measurements using a 1.5 μs polychromatic X-ray exposure, and validate our approach via on-chip structure determination using hen egg white lysozyme (HEWL) as a model system. Although this work is focused on the use of graphene for protein crystallography, we anticipate that this technology should find utility in a wide range of both X-ray and other lab on a chip applications. PMID:27241728

  17. Orientation-Based Control of Microfluidics.

    PubMed

    Norouzi, Nazila; Bhakta, Heran C; Grover, William H

    2016-01-01

    Most microfluidic chips utilize off-chip hardware (syringe pumps, computer-controlled solenoid valves, pressure regulators, etc.) to control fluid flow on-chip. This expensive, bulky, and power-consuming hardware severely limits the utility of microfluidic instruments in resource-limited or point-of-care contexts, where the cost, size, and power consumption of the instrument must be limited. In this work, we present a technique for on-chip fluid control that requires no off-chip hardware. We accomplish this by using inert compounds to change the density of one fluid in the chip. If one fluid is made 2% more dense than a second fluid, when the fluids flow together under laminar flow the interface between the fluids quickly reorients to be orthogonal to Earth's gravitational force. If the channel containing the fluids then splits into two channels, the amount of each fluid flowing into each channel is precisely determined by the angle of the channels relative to gravity. Thus, any fluid can be routed in any direction and mixed in any desired ratio on-chip simply by holding the chip at a certain angle. This approach allows for sophisticated control of on-chip fluids with no off-chip control hardware, significantly reducing the cost of microfluidic instruments in point-of-care or resource-limited settings. PMID:26950700

  18. Orientation-Based Control of Microfluidics

    PubMed Central

    Norouzi, Nazila; Bhakta, Heran C.; Grover, William H.

    2016-01-01

    Most microfluidic chips utilize off-chip hardware (syringe pumps, computer-controlled solenoid valves, pressure regulators, etc.) to control fluid flow on-chip. This expensive, bulky, and power-consuming hardware severely limits the utility of microfluidic instruments in resource-limited or point-of-care contexts, where the cost, size, and power consumption of the instrument must be limited. In this work, we present a technique for on-chip fluid control that requires no off-chip hardware. We accomplish this by using inert compounds to change the density of one fluid in the chip. If one fluid is made 2% more dense than a second fluid, when the fluids flow together under laminar flow the interface between the fluids quickly reorients to be orthogonal to Earth’s gravitational force. If the channel containing the fluids then splits into two channels, the amount of each fluid flowing into each channel is precisely determined by the angle of the channels relative to gravity. Thus, any fluid can be routed in any direction and mixed in any desired ratio on-chip simply by holding the chip at a certain angle. This approach allows for sophisticated control of on-chip fluids with no off-chip control hardware, significantly reducing the cost of microfluidic instruments in point-of-care or resource-limited settings. PMID:26950700

  19. Assessment of mesoscopic particle-based methods in microfluidic geometries

    NASA Astrophysics Data System (ADS)

    Zhao, Tongyang; Wang, Xiaogong; Jiang, Lei; Larson, Ronald G.

    2013-08-01

    We assess the accuracy and efficiency of two particle-based mesoscopic simulation methods, namely, Dissipative Particle Dynamics (DPD) and Stochastic Rotation Dynamics (SRD) for predicting a complex flow in a microfluidic geometry. Since both DPD and SRD use soft or weakly interacting particles to carry momentum, both methods contain unavoidable inertial effects and unphysically high fluid compressibility. To assess these effects, we compare the predictions of DPD and SRD for both an exact Stokes-flow solution and nearly exact solutions at finite Reynolds numbers from the finite element method for flow in a straight channel with periodic slip boundary conditions. This flow represents a periodic electro-osmotic flow, which is a complex flow with an analytical solution for zero Reynolds number. We find that SRD is roughly ten-fold faster than DPD in predicting the flow field, with better accuracy at low Reynolds numbers. However, SRD has more severe problems with compressibility effects than does DPD, which limits the Reynolds numbers attainable in SRD to around 25-50, while DPD can achieve Re higher than this before compressibility effects become too large. However, since the SRD method runs much faster than DPD does, we can afford to enlarge the number of grid cells in SRD to reduce the fluid compressibility at high Reynolds number. Our simulations provide a method to estimate the range of conditions for which SRD or DPD is preferable for mesoscopic simulations.

  20. Bead-based microfluidic immunoassay for diagnosis of Johne's disease

    SciTech Connect

    Wadhwa, Ashutosh; Foote, Robert; Shaw, Robert W; Eda, Shigetoshi

    2012-01-01

    Microfluidics technology offers a platform for development of point-of-care diagnostic devices for various infectious diseases. In this study, we examined whether serodiagnosis of Johne s disease (JD) can be conducted in a bead-based microfluidic assay system. Magnetic micro-beads were coated with antigens of the causative agent of JD, Mycobacterium avium subsp. paratuberculosis. The antigen-coated beads were incubated with serum samples of JD-positive or negative serum samples and then with a fluorescently-labeled secondary antibody (SAB). To confirm binding of serum antibodies to the antigen, the beads were subjected to flow cytometric analysis. Different conditions (dilutions of serum and SAB, types of SAB, and types of magnetic beads) were optimized for a great degree of differentiation between the JD-negative and JD-positive samples. Using the optimized conditions, we tested a well-classified set of 155 serum samples from JD negative and JD-positive cattle by using the bead-based flow cytometric assay. Of 105 JD-positive samples, 63 samples (60%) showed higher antibody binding levels than a cut-off value determined by using antibody binding levels of JD-negative samples. In contrast, only 43-49 JD-positive samples showed higher antibody binding levels than the cut-off value when the samples were tested by commercially-available immunoassays. Microfluidic assays were performed by magnetically immobilizing a number of beads within a microchannel of a glass microchip and detecting antibody on the collected beads by laser-induced fluorescence. Antigen-coated magnetic beads treated with bovine serum sample and fluorescently-labeled SAB were loaded into a microchannel to measure the fluorescence (reflecting level of antibody binding) on the beads in the microfluidic system. When the results of five bovine serum samples obtained with the system were compared to those obtained with the flow cytometer, a high level of correlation (linear regression, r2 = 0.994) was

  1. Characterization of light-controlled Volvox as movable microvalve element assembled in multilayer microfluidic device

    NASA Astrophysics Data System (ADS)

    Nagai, Moeto; Oguri, Michihito; Shibata, Takayuki

    2015-06-01

    We report a model of a light-controlled microvalve driven by Volvox and characterization of Volvox as a movable microvalve element in a multilayer microfluidic device for development of the valve. First, a three-layer microfluidic device having a single through-hole was fabricated by a replica molding process. The fabricated devices met the requirements for experiments using Volvox. Second, we used the phototactic behavior of V. carteri and controlled its motions in a microchannel by illuminating light. V. carteri migrated to the light source in the channel. Third, a colony of V. carteri was placed on a microhole, and the colony was found to stop the flow compared to the flow without Volvox on the hole. The integration of all of the obtained findings is expected to lead to the fabrication of the proposed microvalve.

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

    PubMed

    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. PMID:17105183

  3. Towards non- and minimally instrumented, microfluidics-based diagnostic devices†

    PubMed Central

    Weigl, Bernhard; Domingo, Gonzalo; LaBarre, Paul; Gerlach, Jay

    2009-01-01

    In many health care settings, it is uneconomical, impractical, or unaffordable to maintain and access a fully equipped diagnostics laboratory. Examples include home health care, developing-country health care, and emergency situations in which first responders are dealing with pandemics or biowarfare agent release. In those settings, fully disposable diagnostic devices that require no instrument support, reagent, or significant training are well suited. Although the only such technology to have found widespread adoption so far is the immunochromatographic rapid assay strip test, microfluidics holds promise to expand the range of assay technologies that can be performed in formats similar to that of a strip test. In this paper, we review progress toward development of disposable, low-cost, easy-to-use microfluidics-based diagnostics that require no instrument at all. We also present examples of microfluidic functional elements—including mixers, separators, and detectors—as well as complete microfluidic devices that function entirely without any moving parts and external power sources. PMID:19023463

  4. Microfluidics-Based Laser Guided Cell-Micropatterning System

    PubMed Central

    Erdman, Nick; Schmidt, Lucas; Qin, Wan; Yang, Xiaoqi; Lin, Yongliang; DeSilva, Mauris N; Gao, Bruce Z.

    2014-01-01

    The ability to place individual cells into an engineered microenvironment in a cell-culture model is critical for the study of in vivo-relevant cell-cell and cell-extracellular matrix interactions. Microfluidics provides a high-throughput modality to inject various cell types into a microenvironment. Laser guided systems provide the high spatial and temporal resolution necessary for single-cell micropatterning. Combining these two techniques, the authors designed, constructed, tested, and evaluated 1) a novel removable microfluidics-based cell-delivery biochip and 2) a combined system that uses the novel biochip coupled with a laser guided cell-micropatterning system to place individual cells into both 2D and 3D arrays. Cell-suspensions of chick forebrain neurons and glial cells were loaded into their respective inlet reservoirs and traversed the microfluidic channels until reaching the outlet ports. Individual cells were trapped and guided from the outlet of a microfluidic channel to a target site on the cell-culture substrate. At the target site, 2D and 3D pattern arrays were constructed with micron-level accuracy. Single-cell manipulation was accomplished at a rate of 150 μm/s in the radial plane and 50 μm/s in the axial direction of the laser beam. Results demonstrated that a single-cell can typically be patterned in 20-30 seconds, and that highly accurate and reproducible cellular arrays and systems can be achieved through coupling the microfluidics-based cell-delivery biochip with the laser guided system. PMID:25190714

  5. Microfluidics-based laser cell-micropatterning system.

    PubMed

    Erdman, Nick; Schmidt, Lucas; Qin, Wan; Yang, Xiaoqi; Lin, Yongliang; DeSilva, Mauris N; Gao, Bruce Z

    2014-09-01

    The ability to place individual cells into an engineered microenvironment in a cell-culture model is critical for the study of in vivo relevant cell-cell and cell-extracellular matrix interactions. Microfluidics provides a high-throughput modality to inject various cell types into a microenvironment. Laser guided systems provide the high spatial and temporal resolution necessary for single-cell micropatterning. Combining these two techniques, the authors designed, constructed, tested and evaluated (1) a novel removable microfluidics-based cell-delivery biochip and (2) a combined system that uses the novel biochip coupled with a laser guided cell-micropatterning system to place individual cells into both two-dimensional (2D) and three-dimensional (3D) arrays. Cell-suspensions of chick forebrain neurons and glial cells were loaded into their respective inlet reservoirs and traversed the microfluidic channels until reaching the outlet ports. Individual cells were trapped and guided from the outlet of a microfluidic channel to a target site on the cell-culture substrate. At the target site, 2D and 3D pattern arrays were constructed with micron-level accuracy. Single-cell manipulation was accomplished at a rate of 150 μm s(-1) in the radial plane and 50 μm s(-1) in the axial direction of the laser beam. Results demonstrated that a single-cell can typically be patterned in 20-30 s, and that highly accurate and reproducible cellular arrays and systems can be achieved through coupling the microfluidics-based cell-delivery biochip with the laser guided system. PMID:25190714

  6. Computational Analysis of Enhanced Magnetic Bioseparation in Microfluidic Systems with Flow-Invasive Magnetic Elements

    PubMed Central

    Khashan, S. A.; Alazzam, A.; Furlani, E. P.

    2014-01-01

    A microfluidic design is proposed for realizing greatly enhanced separation of magnetically-labeled bioparticles using integrated soft-magnetic elements. The elements are fixed and intersect the carrier fluid (flow-invasive) with their length transverse to the flow. They are magnetized using a bias field to produce a particle capture force. Multiple stair-step elements are used to provide efficient capture throughout the entire flow channel. This is in contrast to conventional systems wherein the elements are integrated into the walls of the channel, which restricts efficient capture to limited regions of the channel due to the short range nature of the magnetic force. This severely limits the channel size and hence throughput. Flow-invasive elements overcome this limitation and enable microfluidic bioseparation systems with superior scalability. This enhanced functionality is quantified for the first time using a computational model that accounts for the dominant mechanisms of particle transport including fully-coupled particle-fluid momentum transfer. PMID:24931437

  7. Flow control concepts for thread-based microfluidic devices

    PubMed Central

    Ballerini, David R.; Li, Xu; Shen, Wei

    2011-01-01

    The emerging concept of thread-based microfluidics has shown great promise for application to inexpensive disease detection and environmental monitoring. To allow the creation of more sophisticated and functional thread-based sensor designs, the ability to better control and understand the flow of fluids in the devices is required. To meet this end, various mechanisms for controlling the flow of reagents and samples in thread-based microfluidic devices are investigated in this study. A study of fluid penetration in single threads and in twined threads provides greater practical understanding of fluid velocity and ultimate penetration for the design of devices. “Switches” which control when or where flow can occur, or allow the mixing of multiple fluids, have been successfully prototyped from multifilament threads, plastic films, and household adhesive. This advancement allows the fabrication of more functional sensory devices which can incorporate more complex detection chemistries, while maintaining low production cost and simplicity of construction. PMID:21483659

  8. Detection of heavy metal by paper-based microfluidics.

    PubMed

    Lin, Yang; Gritsenko, Dmitry; Feng, Shaolong; Teh, Yi Chen; Lu, Xiaonan; Xu, Jie

    2016-09-15

    Heavy metal pollution has shown great threat to the environment and public health worldwide. Current methods for the detection of heavy metals require expensive instrumentation and laborious operation, which can only be accomplished in centralized laboratories. Various microfluidic paper-based analytical devices have been developed recently as simple, cheap and disposable alternatives to conventional ones for on-site detection of heavy metals. In this review, we first summarize current development of paper-based analytical devices and discuss the selection of paper substrates, methods of device fabrication, and relevant theories in these devices. We then compare and categorize recent reports on detection of heavy metals using paper-based microfluidic devices on the basis of various detection mechanisms, such as colorimetric, fluorescent, and electrochemical methods. To finalize, the future development and trend in this field are discussed. PMID:27131999

  9. Evaluating Biomaterial- and Microfluidic-Based 3D Tumor Models.

    PubMed

    Carvalho, Mariana R; Lima, Daniela; Reis, Rui L; Correlo, Vitor M; Oliveira, Joaquim M

    2015-11-01

    Cancer is a major cause of morbidity and mortality worldwide, with a disease burden estimated to increase over the coming decades. Disease heterogeneity and limited information on cancer biology and disease mechanisms are aspects that 2D cell cultures fail to address. Here, we review the current ‘state-of-the-art’ in 3D tissue-engineering (TE) models developed for, and used in, cancer research. We assess the potential for scaffold-based TE models and microfluidics to fill the gap between 2D models and clinical application. We also discuss recent advances in combining the principles of 3D TE models and microfluidics, with a special focus on biomaterials and the most promising chip-based 3D models. PMID:26603572

  10. A frequency reconfigurable antenna based on digital microfluidics.

    PubMed

    Damgaci, Yasin; Cetiner, Bedri A

    2013-08-01

    We present a novel antenna reconfiguration mechanism relying on electrowetting based digital microfluidics to implement a frequency reconfigurable antenna operating in the X-band. The antenna built on a quartz substrate (εr = 3.9, tan δ = 0.0002) is a coplanar waveguide fed annular slot antenna, which is monolithically integrated with a microfluidic chip. This chip establishes an electrowetting on dielectric platform with a mercury droplet placed in it. The base contact area of the mercury droplet can be spread out by electrostatic actuation resulting in a change of loading capacitance. This in turn changes the resonant frequency of the antenna enabling a reversible reconfigurable impedance property. This reconfigurable antenna has been designed, fabricated and measured. The frequency of operation is tuned from around 11 GHz to 13 GHz as demonstrated by simulations and measurements. The design methodology, fabrication processes and the experimental results are given and discussed. PMID:23752978

  11. Fine-tuning of magnetic and microfluidic viscous forces for specific magnetic bead-based immunocomplex formation

    NASA Astrophysics Data System (ADS)

    Cornaglia, M.; Tekin, H. C.; Lehnert, T.; Gijs, M. A. M.

    2013-08-01

    We investigate the working principle of a novel type of microfluidic sandwich immunoassay, as used for the detection of biomarkers. The heterogeneous assay is based on the specific interactions between an array of functionalized superparamagnetic beads and a flow of secondary superparamagnetic beads that carry the antigens and are simultaneously used as detection labels. We identify the main forces governing the immunoassay performance and develop a combined finite element method/analytical model to predict and control these forces. The clue for the improved assay specificity is in the fine-tuning of inter-bead magnetic dipolar and microfluidic viscous forces, which allows strongly reducing non-specific interactions, while enhancing the specific formation of immunocomplexes. We exploit our theoretical model to explain the enhanced sensitivity of magnetic bead-based immunoassay experiments performed in microfluidic chips.

  12. A Microfluidic-based Hydrodynamic Trap for Single Particles

    PubMed Central

    Johnson-Chavarria, Eric M.; Tanyeri, Melikhan; Schroeder, Charles M.

    2011-01-01

    The ability to confine and manipulate single particles in free solution is a key enabling technology for fundamental and applied science. Methods for particle trapping based on optical, magnetic, electrokinetic, and acoustic techniques have led to major advancements in physics and biology ranging from the molecular to cellular level. In this article, we introduce a new microfluidic-based technique for particle trapping and manipulation based solely on hydrodynamic fluid flow. Using this method, we demonstrate trapping of micro- and nano-scale particles in aqueous solutions for long time scales. The hydrodynamic trap consists of an integrated microfluidic device with a cross-slot channel geometry where two opposing laminar streams converge, thereby generating a planar extensional flow with a fluid stagnation point (zero-velocity point). In this device, particles are confined at the trap center by active control of the flow field to maintain particle position at the fluid stagnation point. In this manner, particles are effectively trapped in free solution using a feedback control algorithm implemented with a custom-built LabVIEW code. The control algorithm consists of image acquisition for a particle in the microfluidic device, followed by particle tracking, determination of particle centroid position, and active adjustment of fluid flow by regulating the pressure applied to an on-chip pneumatic valve using a pressure regulator. In this way, the on-chip dynamic metering valve functions to regulate the relative flow rates in the outlet channels, thereby enabling fine-scale control of stagnation point position and particle trapping. The microfluidic-based hydrodynamic trap exhibits several advantages as a method for particle trapping. Hydrodynamic trapping is possible for any arbitrary particle without specific requirements on the physical or chemical properties of the trapped object. In addition, hydrodynamic trapping enables confinement of a "single" target object in

  13. Quantum dot-based microfluidic biosensor for cancer detection

    NASA Astrophysics Data System (ADS)

    Ghrera, Aditya Sharma; Pandey, Chandra Mouli; Ali, Md. Azahar; Malhotra, Bansi Dhar

    2015-05-01

    We report results of the studies relating to fabrication of an impedimetric microfluidic-based nucleic acid sensor for quantification of DNA sequences specific to chronic myelogenous leukemia (CML). The sensor chip is prepared by patterning an indium-tin-oxide (ITO) coated glass substrate via wet chemical etching method followed by sealing with polydimethylsiloxane (PDMS) microchannel for fluid control. The fabricated microfluidic chip comprising of a patterned ITO substrate is modified by depositing cadmium selenide quantum dots (QCdSe) via Langmuir-Blodgett technique. Further, the QCdSe surface has been functionalized with specific DNA probe for CML detection. The probe DNA functionalized QCdSe integrated miniaturized system has been used to monitor target complementary DNA concentration by measuring the interfacial charge transfer resistance via hybridization. The presence of complementary DNA in buffer solution significantly results in decreased electro-conductivity of the interface due to presence of a charge barrier for transport of the redox probe ions. The microfluidic DNA biosensor exhibits improved linearity in the concentration range of 10-15 M to 10-11 M.

  14. Dissecting enzyme function with microfluidic-based deep mutational scanning

    PubMed Central

    Romero, Philip A.; Tran, Tuan M.; Abate, Adam R.

    2015-01-01

    Natural enzymes are incredibly proficient catalysts, but engineering them to have new or improved functions is challenging due to the complexity of how an enzyme’s sequence relates to its biochemical properties. Here, we present an ultrahigh-throughput method for mapping enzyme sequence–function relationships that combines droplet microfluidic screening with next-generation DNA sequencing. We apply our method to map the activity of millions of glycosidase sequence variants. Microfluidic-based deep mutational scanning provides a comprehensive and unbiased view of the enzyme function landscape. The mapping displays expected patterns of mutational tolerance and a strong correspondence to sequence variation within the enzyme family, but also reveals previously unreported sites that are crucial for glycosidase function. We modified the screening protocol to include a high-temperature incubation step, and the resulting thermotolerance landscape allowed the discovery of mutations that enhance enzyme thermostability. Droplet microfluidics provides a general platform for enzyme screening that, when combined with DNA-sequencing technologies, enables high-throughput mapping of enzyme sequence space. PMID:26040002

  15. An embedded microretroreflector-based microfluidic immunoassay platform.

    PubMed

    Raja, Balakrishnan; Pascente, Carmen; Knoop, Jennifer; Shakarisaz, David; Sherlock, Tim; Kemper, Steven; Kourentzi, Katerina; Renzi, Ronald F; Hatch, Anson V; Olano, Juan; Peng, Bi-Hung; Ruchhoeft, Paul; Willson, Richard

    2016-04-26

    We present a microfluidic immunoassay platform based on the use of linear microretroreflectors embedded in a transparent polymer layer as an optical sensing surface, and micron-sized magnetic particles as light-blocking labels. Retroreflectors return light directly to its source and are highly detectable using inexpensive optics. The analyte is immuno-magnetically pre-concentrated from a sample and then captured on an antibody-modified microfluidic substrate comprised of embedded microretroreflectors, thereby blocking reflected light. Fluidic force discrimination is used to increase specificity of the assay, following which a difference imaging algorithm that can see single 3 μm magnetic particles without optical calibration is used to detect and quantify signal intensity from each sub-array of retroreflectors. We demonstrate the utility of embedded microretroreflectors as a new sensing modality through a proof-of-concept immunoassay for a small, obligate intracellular bacterial pathogen, Rickettsia conorii, the causative agent of Mediterranean Spotted Fever. The combination of large sensing area, optimized surface chemistry and microfluidic protocols, automated image capture and analysis, and high sensitivity of the difference imaging results in a sensitive immunoassay with a limit of detection of roughly 4000 R. conorii per mL. PMID:27025227

  16. DIELECTROPHORESIS-BASED MICROFLUIDIC SEPARATION AND DETECTION SYSTEMS

    PubMed Central

    Yang, Jun; Vykoukal, Jody; Noshari, Jamileh; Becker, Frederick; Gascoyne, Peter; Krulevitch, Peter; Fuller, Chris; Ackler, Harold; Hamilton, Julie; Boser, Bernhard; Eldredge, Adam; Hitchens, Duncan; Andrews, Craig

    2009-01-01

    Diagnosis and treatment of human diseases frequently requires isolation and detection of certain cell types from a complex mixture. Compared with traditional separation and detection techniques, microfluidic approaches promise to yield easy-to-use diagnostic instruments tolerant of a wide range of operating environments and capable of accomplishing automated analyses. These approaches will enable diagnostic advances to be disseminated from sophisticated clinical laboratories to the point-of-care. Applications will include the separation and differential analysis of blood cell subpopulations for host-based detection of blood cell changes caused by disease, infection, or exposure to toxins, and the separation and analysis of surface-sensitized, custom dielectric beads for chemical, biological, and biomolecular targets. Here we report a new particle separation and analysis microsystem that uses dielectrophoretic field-flow fractionation (DEP-FFF). The system consists of a microfluidic chip with integrated sample injector, a DEP-FFF separator, and an AC impedance sensor. We show the design of a miniaturized impedance sensor integrated circuit (IC) with improved sensitivity, a new packaging approach for micro-flumes that features a slide-together compression package and novel microfluidic interconnects, and the design, control, integration and packaging of a fieldable prototype. Illustrative applications will be shown, including the separation of different sized beads and different cell types, blood cell differential analysis, and impedance sensing results for beads, spores and cells. PMID:22025905

  17. Suspended microfluidics

    PubMed Central

    Casavant, Benjamin P.; Berthier, Erwin; Theberge, Ashleigh B.; Berthier, Jean; Montanez-Sauri, Sara I.; Bischel, Lauren L.; Brakke, Kenneth; Hedman, Curtis J.; Bushman, Wade; Keller, Nancy P.; Beebe, David J.

    2013-01-01

    Although the field of microfluidics has made significant progress in bringing new tools to address biological questions, the accessibility and adoption of microfluidics within the life sciences are still limited. Open microfluidic systems have the potential to lower the barriers to adoption, but the absence of robust design rules has hindered their use. Here, we present an open microfluidic platform, suspended microfluidics, that uses surface tension to fill and maintain a fluid in microscale structures devoid of a ceiling and floor. We developed a simple and ubiquitous model predicting fluid flow in suspended microfluidic systems and show that it encompasses many known capillary phenomena. Suspended microfluidics was used to create arrays of collagen membranes, mico Dots (μDots), in a horizontal plane separating two fluidic chambers, demonstrating a transwell platform able to discern collective or individual cellular invasion. Further, we demonstrated that μDots can also be used as a simple multiplexed 3D cellular growth platform. Using the μDot array, we probed the combined effects of soluble factors and matrix components, finding that laminin mitigates the growth suppression properties of the matrix metalloproteinase inhibitor GM6001. Based on the same fluidic principles, we created a suspended microfluidic metabolite extraction platform using a multilayer biphasic system that leverages the accessibility of open microchannels to retrieve steroids and other metabolites readily from cell culture. Suspended microfluidics brings the high degree of fluidic control and unique functionality of closed microfluidics into the highly accessible and robust platform of open microfluidics. PMID:23729815

  18. DNA sequence analysis with droplet-based microfluidics

    PubMed Central

    Abate, Adam R.; Hung, Tony; Sperling, Ralph A.; Mary, Pascaline; Rotem, Assaf; Agresti, Jeremy J.; Weiner, Michael A.; Weitz, David A.

    2014-01-01

    Droplet-based microfluidic techniques can form and process micrometer scale droplets at thousands per second. Each droplet can house an individual biochemical reaction, allowing millions of reactions to be performed in minutes with small amounts of total reagent. This versatile approach has been used for engineering enzymes, quantifying concentrations of DNA in solution, and screening protein crystallization conditions. Here, we use it to read the sequences of DNA molecules with a FRET-based assay. Using probes of different sequences, we interrogate a target DNA molecule for polymorphisms. With a larger probe set, additional polymorphisms can be interrogated as well as targets of arbitrary sequence. PMID:24185402

  19. Polydimethylsiloxane-based conducting composites and their applications in microfluidic chip fabrication

    PubMed Central

    Gong, Xiuqing; Wen, Weijia

    2009-01-01

    This paper reviews the design and fabrication of polydimethylsiloxane (PDMS)-based conducting composites and their applications in microfluidic chip fabrication. Owing to their good electrical conductivity and rubberlike elastic characteristics, these composites can be used variously in soft-touch electronic packaging, planar and three-dimensional electronic circuits, and in-chip electrodes. Several microfluidic components fabricated with PDMS-based composites have been introduced, including a microfluidic mixer, a microheater, a micropump, a microdroplet controller, as well as an all-in-one microfluidic chip. PMID:19693388

  20. A New Microfluidics-Based Droplet Dispenser for ICPMS

    PubMed Central

    2014-01-01

    In this work, a novel droplet microfluidic sample introduction system for inductively coupled plasma mass spectrometry (ICPMS) is proposed and characterized. The cheap and disposable microfluidic chip generates droplets of an aqueous sample in a stream of perfluorohexane (PFH), which is also used to eject them as a liquid jet. The aqueous droplets remain intact during the ejection and can be transported into the ICP with >50% efficiency. The transport is realized via a custom-built system, which includes a membrane desolvator necessary for the PFH vapor removal. The introduction system presented here can generate highly monodisperse droplets in the size range of 40–60 μm at frequencies from 90 to 300 Hz. These droplets produced very stable signals with a relative standard deviation (RSD) comparable to the one achieved with a commercial droplet dispenser. Using the current system, samples with a total volume of <1 μL can be analyzed. Moreover, the capabilities of the setup for introduction and quantitative elemental analysis of single cells were described using a test system of bovine red blood cells. In the future, other modules of the modern microfludics can be integrated in the chip, such as on-chip sample pretreatment or parallel introduction of different samples. PMID:24805360

  1. Lossless droplet transfer of droplet-based microfluidic analysis

    DOEpatents

    Kelly, Ryan T; Tang, Keqi; Page, Jason S; Smith, Richard D

    2011-11-22

    A transfer structure for droplet-based microfluidic analysis is characterized by a first conduit containing a first stream having at least one immiscible droplet of aqueous material and a second conduit containing a second stream comprising an aqueous fluid. The interface between the first conduit and the second conduit can define a plurality of apertures, wherein the apertures are sized to prevent exchange of the first and second streams between conduits while allowing lossless transfer of droplets from the first conduit to the second conduit through contact between the first and second streams.

  2. Magnetophoretic-based microfluidic device for DNA Concentration.

    PubMed

    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. PMID:26899965

  3. Microfluidic-Based sample chips for radioactive solutions

    SciTech Connect

    Tripp, J. L.; Law, J. D.; Smith, T. E.; Rutledge, V. J.; Bauer, W. F.; Ball, R. D.; Hahn, P. A.

    2015-01-01

    Historical nuclear fuel cycle process sampling techniques required sample volumes ranging in the tens of milliliters. The radiation levels experienced by analytical personnel and equipment, in addition to the waste volumes generated from analysis of these samples, have been significant. These sample volumes also impacted accountability inventories of required analytes during process operations. To mitigate radiation dose and other issues associated with the historically larger sample volumes, a microcapillary sample chip was chosen for further investigation. The ability to obtain microliter volume samples coupled with a remote automated means of sample loading, tracking, and transporting to the analytical instrument would greatly improve analytical efficiency while reducing both personnel exposure and radioactive waste volumes. Sample chip testing was completed to determine the accuracy, repeatability, and issues associated with the use of microfluidic sample chips used to supply µL sample volumes of lanthanide analytes dissolved in nitric acid for introduction to an analytical instrument for elemental analysis.

  4. Digital Microfluidic Logic Gates

    NASA Astrophysics Data System (ADS)

    Zhao, Yang; Xu, Tao; Chakrabarty, Krishnendu

    Microfluidic computing is an emerging application for microfluidics technology. We propose microfluidic logic gates based on digital microfluidics. Using the principle of electrowetting-on-dielectric, AND, OR, NOT and XOR gates are implemented through basic droplet-handling operations such as transporting, merging and splitting. The same input-output interpretation enables the cascading of gates to create nontrivial computing systems. We present a potential application for microfluidic logic gates by implementing microfluidic logic operations for on-chip HIV test.

  5. Nanomaterial based detection and degradation of biological and chemical contaminants in a microfluidic system

    NASA Astrophysics Data System (ADS)

    Jayamohan, Harikrishnan

    fabricated using non-cleanroom-based methods, making it suitable for economical large-scale manufacture. A computational model of the microfluidic format was developed in COMSOL MultiphysicsRTM finite element software to evaluate the effect of diffusion coefficient and rate constant on the photocatalytic performance. To further enhance the photocatalytic performance of the microfluidic device, TNA synthesized on a mesh was used as the catalyst. The new system was shown to have enhanced photocatalytic performance in comparison to TNA on a foil. The device was then employed in the inactivation of E. coli O157:H7 at different flow rates and light intensities (100, 50, 20, 10 mW/cm2). In the second project, a protocol for ultra-sensitive indirect electrochemical detection of E. coli O157:H7 was reported. The protocol uses antibody functionalized primary (magnetic) beads for capture and polyguanine (polyG) oligonucleotide functionalized secondary (polystyrene) beads as an electrochemical tag. The method was able to detect concentrations of E. coli O157:H7 down to 3 CFU/100 mL (S/N=3). We also demonstrate the use of the protocol for detection of E. coli O157:H7 seeded in wastewater effluent samples.

  6. Microfluidic electronics.

    PubMed

    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. PMID:22711057

  7. Microfluidics based phantoms of superficial vascular network

    PubMed Central

    Luu, Long; Roman, Patrick A.; Mathews, Scott A.; Ramella-Roman, Jessica C.

    2012-01-01

    Several new bio-photonic techniques aim to measure flow in the human vasculature non-destructively. Some of these tools, such as laser speckle imaging or Doppler optical coherence tomography, are now reaching the clinical stage. Therefore appropriate calibration and validation techniques dedicated to these particular measurements are therefore of paramount importance. In this paper we introduce a fast prototyping technique based on laser micromachining for the fabrication of dynamic flow phantoms. Micro-channels smaller than 20 µm in width can be formed in a variety of materials such as epoxies, plastics, and household tape. Vasculature geometries can be easily and quickly modified to accommodate a particular experimental scenario. PMID:22741081

  8. PDMS based microfluidic chips and their application in material synthesis

    NASA Astrophysics Data System (ADS)

    Gong, Xiuqing

    Microfluidics is a highly interdisciplinary science which is to deal with the behavior, control and manipulation of fluids that are constrained to sub-milimeter scale. It incorporates the knowledge and technique intersecting physics, chemistry, mechanics, nanoscience and biotechnology, with practical applications to the design of systems in which small volumes of fluids will be used. In this thesis, we started our research from GER fluid synthesis which then is applied to designing different functions of microfluidic devices, valve, pump, and mixer. We built a way to correlate mechanical signal with electric signal by soft matter. The mechanical devices based GER fluid had good operating stability and mechanical performance. We studied how to improve the performance of GER fluid by increasing the yield stress while avoiding the sendimentation of nanoparticles in GER suspension. The meaning of this work is to enhance the stability and mechanical strength of GER fluid when it is applyed to the microfluidc channels. We tried different oils and studied the particle size for the GER effect. The largest yield stress which amounts to 300 kPa is achievable compared to previous GER fluid with 100 kPa. Microfluidic reactor, directing the flow of microliter volumes along microscale channels, offers the advantages of precise control of reagent loading, fast mixing and an enhanced reaction rate, cessation of the reaction at specific stages, and more. Basically, there are two microfluidic flow regimes, continuous flow and segmented flow (suspended droplets, channel-spanning slug, and wall-wetting films). Both flow regimes offer chemical reaction applications, e.g., continuous flow formation of polymer nanospheres and inorganic nanoparticles, size- and shape-control synthesis by segmented flow, and precipitate-forming reactions in droplets, wherein the segmented flow has gained more popularity in that area. The compartmentalization of segmented flow offers advantages to chemical

  9. Droplet-based microfluidics and the dynamics of emulsions

    NASA Astrophysics Data System (ADS)

    Baret, Jean-Christophe; Brosseau, Quentin; Semin, Benoit; Qu, Xiaopeng

    2012-02-01

    Emulsions are complex fluids already involved for a long time in a wide-range of industrial processes, such as, for example, food, cosmetics or materials synthesis [1]. More recently, applications of emulsions have been extended to new fields like biotechnology or biochemistry where the compartmentalization of compounds in emulsion droplets is used to parallelise (bio-) chemical reactions [2]. Interestingly, these applications pinpoint to fundamental questions dealing with surfactant dynamics, dynamic surface tension, hydrodynamic interactions and electrohydrodynamics. Droplet-based microfluidics is a very powerful tool to quantitatively study the dynamics of emulsions at the single droplet level or even at the single interface level: well-controlled emulsions are produced and manipulated using hydrodynamics, electrical forces, optical actuation and combination of these effects. We will describe here how droplet-based microfluidics is used to extract quantitative informations on the physical-chemistry of emulsions for a better understanding and control of the dynamics of these systems [3].[4pt] [1] J. Bibette et al. Rep. Prog. Phys., 62, 969-1033 (1999)[0pt] [2] A. Theberge et al., Angewandte Chemie Int. Ed. 49, 5846 (2010)[0pt] [3] J.-C. Baret et al., Langmuir, 25, 6088 (2009)

  10. Microfluidic droplet-based liquid-liquid extraction.

    PubMed

    Mary, Pascaline; Studer, Vincent; Tabeling, Patrick

    2008-04-15

    We study microfluidic systems in which mass exchanges take place between moving water droplets, formed on-chip, and an external phase (octanol). Here, no chemical reaction takes place, and the mass exchanges are driven by a contrast in chemical potential between the dispersed and continuous phases. We analyze the case where the microfluidic droplets, occupying the entire width of the channel, extract a solute-fluorescein-from the external phase (extraction) and the opposite case, where droplets reject a solute-rhodamine-into the external phase (purification). Four flow configurations are investigated, based on straight or zigzag microchannels. Additionally to the experimental work, we performed two-dimensional numerical simulations. In the experiments, we analyze the influence of different parameters on the process (channel dimensions, fluid viscosities, flow rates, drop size, droplet spacing, ...). Several regimes are singled out. In agreement with the mass transfer theory of Young et al. (Young, W.; Pumir, A.; Pomeau, Y. Phys. Fluids A 1989, 1, 462), we find that, after a short transient, the amount of matter transferred across the droplet interface grows as the square root of time and the time it takes for the transfer process to be completed decreases as Pe-2/3, where Pe is the Peclet number based on droplet velocity and radius. The numerical simulation is found in excellent consistency with the experiment. In practice, the transfer time ranges between a fraction and a few seconds, which is much faster than conventional systems. PMID:18351786

  11. Quantum dot-based microfluidic biosensor for cancer detection

    SciTech Connect

    Ghrera, Aditya Sharma; Pandey, Chandra Mouli; Ali, Md. Azahar; Malhotra, Bansi Dhar

    2015-05-11

    We report results of the studies relating to fabrication of an impedimetric microfluidic–based nucleic acid sensor for quantification of DNA sequences specific to chronic myelogenous leukemia (CML). The sensor chip is prepared by patterning an indium–tin–oxide (ITO) coated glass substrate via wet chemical etching method followed by sealing with polydimethylsiloxane (PDMS) microchannel for fluid control. The fabricated microfluidic chip comprising of a patterned ITO substrate is modified by depositing cadmium selenide quantum dots (QCdSe) via Langmuir–Blodgett technique. Further, the QCdSe surface has been functionalized with specific DNA probe for CML detection. The probe DNA functionalized QCdSe integrated miniaturized system has been used to monitor target complementary DNA concentration by measuring the interfacial charge transfer resistance via hybridization. The presence of complementary DNA in buffer solution significantly results in decreased electro-conductivity of the interface due to presence of a charge barrier for transport of the redox probe ions. The microfluidic DNA biosensor exhibits improved linearity in the concentration range of 10{sup −15} M to 10{sup −11} M.

  12. Optical detection enhancement in porous volumetric microfluidic capture elements using refractive index matching fluids

    PubMed Central

    Wiederoder, M. S.; Peterken, L.; Lu, A. X.; Rahmanian, O. D.; Raghavan, S. R.; DeVoe, D. L.

    2015-01-01

    Porous volumetric capture elements in microfluidic sensors are advantageous compared to planar capture surfaces due to higher reaction site density and decreased diffusion lengths that can reduce detection limits and total assay time. However a mismatch in refractive indices between the capture matrix and fluid within the porous interstices results in scattering of incident, reflected, or emitted light, significantly reducing the signal for optical detection. Here we demonstrate that perfusion of an index-matching fluid within a porous matrix minimizes scattering, thus enhancing optical signal by enabling the entire capture element volume to be probed. Signal enhancement is demonstrated for both fluorescence and absorbance detection, using porous polymer monoliths in a silica capillary and packed beds of glass beads within thermoplastic microchannels, respectively. Fluorescence signal was improved by a factor of 3.5× when measuring emission from a fluorescent compound attached directly to the polymer monolith, and up to 2.6× for a rapid 10 min direct immunoassay. When combining index matching with a silver enhancement step, a detection limit of 0.1 ng/mL human IgG and a 5 log dynamic range was achieved. The demonstrated technique provides a simple method for enhancing optical sensitivity for a wide range of assays, enabling the full benefits of porous detection elements in miniaturized analytical systems to be realized. PMID:26160546

  13. Optical detection enhancement in porous volumetric microfluidic capture elements using refractive index matching fluids.

    PubMed

    Wiederoder, M S; Peterken, L; Lu, A X; Rahmanian, O D; Raghavan, S R; DeVoe, D L

    2015-08-21

    Porous volumetric capture elements in microfluidic sensors are advantageous compared to planar capture surfaces due to higher reaction site density and decreased diffusion lengths that can reduce detection limits and total assay time. However a mismatch in refractive indices between the capture matrix and fluid within the porous interstices results in scattering of incident, reflected, or emitted light, significantly reducing the signal for optical detection. Here we demonstrate that perfusion of an index-matching fluid within a porous matrix minimizes scattering, thus enhancing optical signal by enabling the entire capture element volume to be probed. Signal enhancement is demonstrated for both fluorescence and absorbance detection, using porous polymer monoliths in a silica capillary and packed beds of glass beads within thermoplastic microchannels, respectively. Fluorescence signal was improved by a factor of 3.5× when measuring emission from a fluorescent compound attached directly to the polymer monolith, and up to 2.6× for a rapid 10 min direct immunoassay. When combining index matching with a silver enhancement step, a detection limit of 0.1 ng mL(-1) human IgG and a 5 log dynamic range was achieved. The demonstrated technique provides a simple method for enhancing optical sensitivity for a wide range of assays, enabling the full benefits of porous detection elements in miniaturized analytical systems to be realized. PMID:26160546

  14. Electrochemiluminescence detection in microfluidic cloth-based analytical devices.

    PubMed

    Guan, Wenrong; Liu, Min; Zhang, Chunsun

    2016-01-15

    This work describes the first approach at combining microfluidic cloth-based analytical devices (μCADs) with electrochemiluminescence (ECL) detection. Wax screen-printing is employed to make cloth-based microfluidic chambers which are patterned with carbon screen-printed electrodes (SPEs) to create truly disposable, simple, inexpensive sensors which can be read with a low-cost, portable charge coupled device (CCD) imaging sensing system. And, the two most commonly used ECL systems of tris(2,2'-bipyridyl)ruthenium(II)/tri-n-propylamine (Ru(bpy)3(2+)/TPA) and 3-aminophthalhydrazide/hydrogen peroxide (luminol/H2O2) are applied to demonstrate the quantitative ability of the ECL μCADs. In this study, the proposed devices have successfully fulfilled the determination of TPA with a linear range from 2.5 to 2500μM with a detection limit of 1.265μM. In addition, the detection of H2O2 can be performed in the linear range of 0.05-2.0mM, with a detection limit of 0.027mM. It has been shown that the ECL emission on the wax-patterned cloth device has an acceptable sensitivity, stability and reproducibility. Finally, the applicability of cloth-based ECL is demonstrated for determination of glucose in phosphate buffer solution (PBS) and artificial urine (AU) samples, with the detection limits of 0.032mM and 0.038mM, respectively. It can be foreseen, therefore, that μCADs with ECL detection could provide a new sensing platform for point-of-care testing, public health, food safety detection and environmental monitoring in remote regions, developing or developed countries. PMID:26319168

  15. Microfluidic droplet-based liquid-liquid extraction: online model validation.

    PubMed

    Lubej, Martin; Novak, Uroš; Liu, Mingqiang; Martelanc, Mitja; Franko, Mladen; Plazl, Igor

    2015-05-21

    Droplet-based liquid-liquid extraction in a microchannel was studied, both theoretically and experimentally. A full 3D mathematical model, incorporating convection and diffusion in all spatial directions along with the velocity profile, was developed to depict the governing transport characteristics of droplet-based microfluidics. The finite elements method, as the most common macroscale simulation technique, was used to solve the set of differential equations regarding conservation of moment, mass and solute concentration in a two-domain system coupled by interfacial surface of droplet-based flow pattern. The model was numerically verified and validated online by following the concentrations of a solute in two phases within the microchannel. The relative azobenzene concentration profiles in a methanol/n-octane two-phase system at different positions along the channel length were retrieved by means of a thermal lens microscopic (TLM) technique coupled to a microfluidic system, which gave results of high spatial and temporal resolution. Very good agreement between model calculations and online experimental data was achieved without applying any fitting procedure to the model parameters. PMID:25850663

  16. Deformability-based microfluidic cell pairing and fusion.

    PubMed

    Dura, Burak; Liu, Yaoping; Voldman, Joel

    2014-08-01

    We present a microfluidic cell pairing device capable of sequential trapping and pairing of hundreds of cells using passive hydrodynamics and flow-induced deformation. We describe the design and operation principles of our device and show its applicability for cell fusion. Using our device, we achieved both homotypic and heterotypic cell pairing, demonstrating efficiencies up to 80%. The platform is compatible with fusion protocols based on biological, chemical and physical stimuli with fusion yields up to 95%. Our device further permits its disconnection from the fluidic hardware enabling its transportation for imaging and culture while maintaining cell registration on chip. Our design principles and cell trapping technique can readily be applied for different cell types and can be extended to trap and fuse multiple (>2) cell partners as demonstrated by our preliminary experiments. PMID:24898933

  17. A self assembled monolayer based microfluidic sensor for urea detection

    NASA Astrophysics Data System (ADS)

    Srivastava, Saurabh; Solanki, Pratima R.; Kaushik, Ajeet; Ali, Md. Azahar; Srivastava, Anchal; Malhotra, B. D.

    2011-07-01

    Urease (Urs) and glutamate dehydrogenase (GLDH) have been covalently co-immobilized onto a self-assembled monolayer (SAM) comprising of 10-carboxy-1-decanthiol (CDT) via EDC-NHS chemistry deposited onto one of the two patterned gold (Au) electrodes for estimation of urea using poly(dimethylsiloxane) based microfluidic channels (2 cm × 200 μm × 200 μm). The CDT/Au and Urs-GLDH/CDT/Au electrodes have been characterized using Fourier transform infrared (FTIR) spectroscopy, contact angle (CA), atomic force microscopy (AFM) and electrochemical cyclic voltammetry (CV) techniques. The electrochemical response measurement of a Urs-GLDH/CDT/Au bioelectrode obtained as a function of urea concentration using CV yield linearity as 10 to 100 mg dl-1, detection limit as 9 mg dl-1 and high sensitivity as 7.5 μA mM-1 cm-2.

  18. Paper-based microfluidic device with upconversion fluorescence assay.

    PubMed

    He, Mengyuan; Liu, Zhihong

    2013-12-17

    A paper-based microfluidic device with upconversion fluorescence assay (named as UC-μPAD) is proposed. The device is fabricated on a normal office printing sheet with a simple plotting method. Upconversion phosphors (UCPs) tagged with specific probes are spotted to the test zones on the μPAD, followed by the introduction of assay targets. Upconversion fluorescence measurements are directly conducted on the test zones after the completion of the probe-to-target reactions, without any post-treatments. The UC-μPAD features very easy fabrication and operation, simple and fast detection, low cost, and high sensitivity. UC-μPAD is a promising prospect for a clinical point-of-care test. PMID:24308347

  19. Exploration of microfluidic devices based on multi-filament threads and textiles: A review.

    PubMed

    Nilghaz, A; Ballerini, D R; Shen, W

    2013-01-01

    In this paper, we review the recent progress in the development of low-cost microfluidic devices based on multifilament threads and textiles for semi-quantitative diagnostic and environmental assays. Hydrophilic multifilament threads are capable of transporting aqueous and non-aqueous fluids via capillary action and possess desirable properties for building fluid transport pathways in microfluidic devices. Thread can be sewn onto various support materials to form fluid transport channels without the need for the patterned hydrophobic barriers essential for paper-based microfluidic devices. Thread can also be used to manufacture fabrics which can be patterned to achieve suitable hydrophilic-hydrophobic contrast, creating hydrophilic channels which allow the control of fluids flow. Furthermore, well established textile patterning methods and combination of hydrophilic and hydrophobic threads can be applied to fabricate low-cost microfluidic devices that meet the low-cost and low-volume requirements. In this paper, we review the current limitations and shortcomings of multifilament thread and textile-based microfluidics, and the research efforts to date on the development of fluid flow control concepts and fabrication methods. We also present a summary of different methods for modelling the fluid capillary flow in microfluidic thread and textile-based systems. Finally, we summarized the published works of thread surface treatment methods and the potential of combining multifilament thread with other materials to construct devices with greater functionality. We believe these will be important research focuses of thread- and textile-based microfluidics in future. PMID:24086179

  20. Exploration of microfluidic devices based on multi-filament threads and textiles: A review

    PubMed Central

    Nilghaz, A.; Ballerini, D. R.; Shen, W.

    2013-01-01

    In this paper, we review the recent progress in the development of low-cost microfluidic devices based on multifilament threads and textiles for semi-quantitative diagnostic and environmental assays. Hydrophilic multifilament threads are capable of transporting aqueous and non-aqueous fluids via capillary action and possess desirable properties for building fluid transport pathways in microfluidic devices. Thread can be sewn onto various support materials to form fluid transport channels without the need for the patterned hydrophobic barriers essential for paper-based microfluidic devices. Thread can also be used to manufacture fabrics which can be patterned to achieve suitable hydrophilic-hydrophobic contrast, creating hydrophilic channels which allow the control of fluids flow. Furthermore, well established textile patterning methods and combination of hydrophilic and hydrophobic threads can be applied to fabricate low-cost microfluidic devices that meet the low-cost and low-volume requirements. In this paper, we review the current limitations and shortcomings of multifilament thread and textile-based microfluidics, and the research efforts to date on the development of fluid flow control concepts and fabrication methods. We also present a summary of different methods for modelling the fluid capillary flow in microfluidic thread and textile-based systems. Finally, we summarized the published works of thread surface treatment methods and the potential of combining multifilament thread with other materials to construct devices with greater functionality. We believe these will be important research focuses of thread- and textile-based microfluidics in future. PMID:24086179

  1. A perspective on paper-based microfluidics: Current status and future trends

    PubMed Central

    Li, Xu; Ballerini, David R.; Shen, Wei

    2012-01-01

    “Paper-based microfluidics” or “lab on paper,” as a burgeoning research field with its beginning in 2007, provides a novel system for fluid handling and fluid analysis for a variety of applications including health diagnostics, environmental monitoring as well as food quality testing. The reasons why paper becomes an attractive substrate for making microfluidic systems include: (1) it is a ubiquitous and extremely cheap cellulosic material; (2) it is compatible with many chemical/biochemical/medical applications; and (3) it transports liquids using capillary forces without the assistance of external forces. By building microfluidic channels on paper, liquid flow is confined within the channels, and therefore, liquid flow can be guided in a controlled manner. A variety of 2D and even 3D microfluidic channels have been created on paper, which are able to transport liquids in the predesigned pathways on paper. At the current stage of its development, paper-based microfluidic system is claimed to be low-cost, easy-to-use, disposable, and equipment-free, and therefore, is a rising technology particularly relevant to improving the healthcare and disease screening in the developing world, especially for those areas with no- or low-infrastructure and limited trained medical and health professionals. The research in paper-based microfluidics is experiencing a period of explosion; most published works have focused on: (1) inventing low-cost and simple fabrication techniques for paper-based microfluidic devices; and (2) exploring new applications of paper-based microfluidics by incorporating efficient detection methods. This paper aims to review both the fabrication techniques and applications of paper-based microfluidics reported to date. This paper also attempts to convey to the readers, from the authors’ point of view the current limitations of paper-based microfluidics which require further research, and a few perspective directions this new analytical system

  2. Microprocessor-based integration of microfluidic control for the implementation of automated sensor monitoring and multithreaded optimization algorithms.

    PubMed

    Ezra, Elishai; Maor, Idan; Bavli, Danny; Shalom, Itai; Levy, Gahl; Prill, Sebastian; Jaeger, Magnus S; Nahmias, Yaakov

    2015-08-01

    Microfluidic applications range from combinatorial synthesis to high throughput screening, with platforms integrating analog perfusion components, digitally controlled micro-valves and a range of sensors that demand a variety of communication protocols. Currently, discrete control units are used to regulate and monitor each component, resulting in scattered control interfaces that limit data integration and synchronization. Here, we present a microprocessor-based control unit, utilizing the MS Gadgeteer open framework that integrates all aspects of microfluidics through a high-current electronic circuit that supports and synchronizes digital and analog signals for perfusion components, pressure elements, and arbitrary sensor communication protocols using a plug-and-play interface. The control unit supports an integrated touch screen and TCP/IP interface that provides local and remote control of flow and data acquisition. To establish the ability of our control unit to integrate and synchronize complex microfluidic circuits we developed an equi-pressure combinatorial mixer. We demonstrate the generation of complex perfusion sequences, allowing the automated sampling, washing, and calibrating of an electrochemical lactate sensor continuously monitoring hepatocyte viability following exposure to the pesticide rotenone. Importantly, integration of an optical sensor allowed us to implement automated optimization protocols that require different computational challenges including: prioritized data structures in a genetic algorithm, distributed computational efforts in multiple-hill climbing searches and real-time realization of probabilistic models in simulated annealing. Our system offers a comprehensive solution for establishing optimization protocols and perfusion sequences in complex microfluidic circuits. PMID:26227212

  3. Biological implications of polydimethylsiloxane-based microfluidic cell culture†

    PubMed Central

    Regehr, Keil J.; Domenech, Maribella; Koepsel, Justin T.; Carver, Kristopher C.; Ellison-Zelski, Stephanie J.; Murphy, William L.; Schuler, Linda A.; Alarid, Elaine T.; Beebe, David J.

    2009-01-01

    Polydimethylsiloxane (PDMS) has become a staple of the microfluidics community by virtue of its simple fabrication process and material attributes, such as gas permeability, optical transparency, and flexibility. As microfluidic systems are put toward biological problems and increasingly utilized as cell culture platforms, the material properties of PDMS must be considered in a biological context. Two properties of PDMS were addressed in this study: the leaching of uncured oligomers from the polymer network into microchannel media, and the absorption of small, hydrophobic molecules (i.e. estrogen) from serum-containing media into the polymer bulk. Uncured PDMS oligomers were detectable via MALDI-MS in microchannel media both before and after Soxhlet extraction of PDMS devices in ethanol. Additionally, PDMS oligomers were identified in the plasma membranes of NMuMG cells cultured in PDMS microchannels for 24 hours. Cells cultured in extracted microchannels also contained a detectable amount of uncured PDMS. It was shown that MCF-7 cells seeded directly on PDMS inserts were responsive to hydrophilic prolactin but not hydrophobic estrogen, reflecting its specificity for absorbing small, hydrophobic molecules; and the presence of PDMS floating in wells significantly reduced cellular response to estrogen in a serum-dependent manner. Quantification of estrogen via ELISA revealed that microchannel estrogen partitioned rapidly into the surrounding PDMS to a ratio of approximately 9:1. Pretreatments such as blocking with serum or pre-absorbing estrogen for 24 hours did not affect estrogen loss from PDMS-based microchannels. These findings highlight the importance of careful consideration of culture system properties when determining an appropriate environment for biological experiments. PMID:19606288

  4. Fabrication of plasmon length-based surface enhanced Raman scattering for multiplex detection on microfluidic device.

    PubMed

    Nguyen, Anh H; Lee, Jeewon; Il Choi, Hong; Seok Kwak, Ho; Jun Sim, Sang

    2015-08-15

    The length of bioreceptors plays an important role in signal enhancement of surface-enhanced Raman scattering (SERS) due to amplification of electromagnetic fields generated by the excitation of localized surface plasmons. Herein, intact antibodies (IgG) and Fab fragments conjugated onto gold nanostar were used to fabricate two kinds of immunosensors for measurement of their SERS signals. Using CA125 as the antigen and Rhodamine-6G (R6G)-conjugated immunogolds, a SERS immunosensor was self-assembled by antigen-antibody interaction. The results showed that the SERS signal from the Fab immunosensor was 2.4 times higher than that of the IgG immunosensor. Furthermore, increased hot-spots by silver atom deposition onto the IgG and Fab immunosensor showed 2.1 and 1.4 times higher signals than before enhancement, respectively. For application, based on the Fab immunosensor, a SERS-compatible microfluidic system was designed for multiplex assays to overcome the drawbacks of conventional assays. This system can measure biological specimens directly from bio fluids instead of using a complex microfluidic device containing separation and detection elements. Four approved biomarkers of breast cancer, including cancer antigen (CA125), HER2, epididymis protein (HE4), and Eotaxin-1, were detected from patient-mimicked serum with limits of 15 fM, 17 fM, 21 fM, and 6.5 fM, respectively. The results indicated that the lengths and geometry of the bioreceptors determined the intensity of SERS signal from the interface and cavity of the sandwich immunosensor. Silver atom deposition at the cavity of the immunosensor increased the SERS signal. Finally, the SERS immunosensor built-in microfluidic system improved the performance of multiplex diagnostics. PMID:25841120

  5. Microfluidic-Based sample chips for radioactive solutions

    DOE PAGESBeta

    Tripp, J. L.; Law, J. D.; Smith, T. E.; Rutledge, V. J.; Bauer, W. F.; Ball, R. D.; Hahn, P. A.

    2015-01-01

    Historical nuclear fuel cycle process sampling techniques required sample volumes ranging in the tens of milliliters. The radiation levels experienced by analytical personnel and equipment, in addition to the waste volumes generated from analysis of these samples, have been significant. These sample volumes also impacted accountability inventories of required analytes during process operations. To mitigate radiation dose and other issues associated with the historically larger sample volumes, a microcapillary sample chip was chosen for further investigation. The ability to obtain microliter volume samples coupled with a remote automated means of sample loading, tracking, and transporting to the analytical instrument wouldmore » greatly improve analytical efficiency while reducing both personnel exposure and radioactive waste volumes. Sample chip testing was completed to determine the accuracy, repeatability, and issues associated with the use of microfluidic sample chips used to supply µL sample volumes of lanthanide analytes dissolved in nitric acid for introduction to an analytical instrument for elemental analysis.« less

  6. On-demand droplet release for droplet-based microfluidic system.

    PubMed

    Wang, Wei; Yang, Chun; Liu, YingShuai; Li, Chang Ming

    2010-03-01

    On-demand droplet release from microwell was successfully implemented and well combined with droplet trapping/fusion functions to make an ideal and integrated droplet based microfluidic system. PMID:20162230

  7. Surface Modified Thread-Based Microfluidic Analytical Device for Selective Potassium Analysis.

    PubMed

    Erenas, Miguel M; de Orbe-Payá, Ignacio; Capitan-Vallvey, Luis Fermin

    2016-05-17

    This paper presents a thread-based microfluidic device (μTAD) that includes ionophore extraction chemistry for the optical recognition of potassium. The device is 1.5 cm × 1.0 cm and includes a cotton thread to transport the aqueous sample via capillary wicking to a 5 mm-long detection area, where the recognition chemistry is deposited that reaches equilibrium in 60 s, changing its color between blue and magenta. A complete characterization of the cotton thread used as well as the sensing element has been carried out. The imaging of the μTAD with a digital camera and the extraction of the H coordinate of the HSV color space used as the analytical parameter make it possible to determine K(I) between 2.4 × 10(-5) and 0.95 M with a precision better than 1.3%. PMID:27077212

  8. Microfluidic-based single cell trapping using a combination of stagnation point flow and physical barrier

    NASA Astrophysics Data System (ADS)

    Yu, Miao; Chen, Zongzheng; Xiang, Cheng; Liu, Bo; Xie, Handi; Qin, Kairong

    2016-06-01

    Single cell trapping in vitro by microfluidic device is an emerging approach for the study of the relationship between single cells and their dynamic biochemical microenvironments. In this paper, a hydrodynamic-based microfluidic device for single cell trapping is designed using a combination of stagnation point flow and physical barrier. The microfluidic device overcomes the weakness of the traditional ones, which have been only based upon either stagnation point flows or physical barriers, and can conveniently load dynamic biochemical signals to the trapped cell. In addition, it can connect with a programmable syringe pump and a microscope to constitute an integrated experimental system. It is experimentally verified that the microfluidic system can trap single cells in vitro even under flow disturbance and conveniently load biochemical signals to the trapped cell. The designed micro-device would provide a simple yet effective experimental platform for further study of the interactions between single cells and their microenvironments.

  9. Microfluidic-based single cell trapping using a combination of stagnation point flow and physical barrier

    NASA Astrophysics Data System (ADS)

    Yu, Miao; Chen, Zongzheng; Xiang, Cheng; Liu, Bo; Xie, Handi; Qin, Kairong

    2016-03-01

    Single cell trapping in vitro by microfluidic device is an emerging approach for the study of the relationship between single cells and their dynamic biochemical microenvironments. In this paper, a hydrodynamic-based microfluidic device for single cell trapping is designed using a combination of stagnation point flow and physical barrier. The microfluidic device overcomes the weakness of the traditional ones, which have been only based upon either stagnation point flows or physical barriers, and can conveniently load dynamic biochemical signals to the trapped cell. In addition, it can connect with a programmable syringe pump and a microscope to constitute an integrated experimental system. It is experimentally verified that the microfluidic system can trap single cells in vitro even under flow disturbance and conveniently load biochemical signals to the trapped cell. The designed micro-device would provide a simple yet effective experimental platform for further study of the interactions between single cells and their microenvironments.

  10. Digital microfluidic magnetic separation for particle-based immunoassays.

    PubMed

    Ng, Alphonsus H C; Choi, Kihwan; Luoma, Robert P; Robinson, John M; Wheeler, Aaron R

    2012-10-16

    We introduce a new format for particle-based immunoassays relying on digital microfluidics (DMF) and magnetic forces to separate and resuspend antibody-coated paramagnetic particles. In DMF, fluids are electrostatically controlled as discrete droplets (picoliters to microliters) on an array of insulated electrodes. By applying appropriate sequences of potentials to these electrodes, multiple droplets can be manipulated simultaneously and various droplet operations can be achieved using the same device design. This flexibility makes DMF well-suited for applications that require complex, multistep protocols such as immunoassays. Here, we report the first particle-based immunoassay on DMF without the aid of oil carrier fluid to enable droplet movement (i.e., droplets are surrounded by air instead of oil). This new format allowed the realization of a novel on-chip particle separation and resuspension method capable of removing greater than 90% of unbound reagents in one step. Using this technique, we developed methods for noncompetitive and competitive immunoassays, using thyroid stimulating hormone (TSH) and 17β-estradiol (E2) as model analytes, respectively. We show that, compared to conventional methods, the new DMF approach reported here reduced reagent volumes and analysis time by 100-fold and 10-fold, respectively, while retaining a level of analytical performance required for clinical screening. Thus, we propose that the new technique has great potential for eventual use in a fast, low-waste, and inexpensive instrument for the quantitative analysis of proteins and small molecules in low sample volumes. PMID:23013543

  11. Coalescing drops in microfluidic parking networks: A multifunctional platform for drop-based microfluidics

    PubMed Central

    Bithi, Swastika S.; Wang, William S.; Sun, Meng; Blawzdziewicz, Jerzy; Vanapalli, Siva A.

    2014-01-01

    Multiwell plate and pipette systems have revolutionized modern biological analysis; however, they have disadvantages because testing in the submicroliter range is challenging, and increasing the number of samples is expensive. We propose a new microfluidic methodology that delivers the functionality of multiwell plates and pipettes at the nanoliter scale by utilizing drop coalescence and confinement-guided breakup in microfluidic parking networks (MPNs). Highly monodisperse arrays of drops obtained using a hydrodynamic self-rectification process are parked at prescribed locations in the device, and our method allows subsequent drop manipulations such as fine-gradation dilutions, reactant addition, and fluid replacement while retaining microparticles contained in the sample. Our devices operate in a quasistatic regime where drop shapes are determined primarily by the channel geometry. Thus, the behavior of parked drops is insensitive to flow conditions. This insensitivity enables highly parallelized manipulation of drop arrays of different composition, without a need for fine-tuning the flow conditions and other system parameters. We also find that drop coalescence can be switched off above a critical capillary number, enabling individual addressability of drops in complex MPNs. The platform demonstrated here is a promising candidate for conducting multistep biological assays in a highly multiplexed manner, using thousands of submicroliter samples. PMID:25379078

  12. Coalescing drops in microfluidic parking networks: A multifunctional platform for drop-based microfluidics.

    PubMed

    Bithi, Swastika S; Wang, William S; Sun, Meng; Blawzdziewicz, Jerzy; Vanapalli, Siva A

    2014-05-01

    Multiwell plate and pipette systems have revolutionized modern biological analysis; however, they have disadvantages because testing in the submicroliter range is challenging, and increasing the number of samples is expensive. We propose a new microfluidic methodology that delivers the functionality of multiwell plates and pipettes at the nanoliter scale by utilizing drop coalescence and confinement-guided breakup in microfluidic parking networks (MPNs). Highly monodisperse arrays of drops obtained using a hydrodynamic self-rectification process are parked at prescribed locations in the device, and our method allows subsequent drop manipulations such as fine-gradation dilutions, reactant addition, and fluid replacement while retaining microparticles contained in the sample. Our devices operate in a quasistatic regime where drop shapes are determined primarily by the channel geometry. Thus, the behavior of parked drops is insensitive to flow conditions. This insensitivity enables highly parallelized manipulation of drop arrays of different composition, without a need for fine-tuning the flow conditions and other system parameters. We also find that drop coalescence can be switched off above a critical capillary number, enabling individual addressability of drops in complex MPNs. The platform demonstrated here is a promising candidate for conducting multistep biological assays in a highly multiplexed manner, using thousands of submicroliter samples. PMID:25379078

  13. Photo-crosslinkable hydrogel-based 3D microfluidic culture device.

    PubMed

    Lee, Youlee; Lee, Jong Min; Bae, Pan-Kee; Chung, Il Yup; Chung, Bong Hyun; Chung, Bong Geun

    2015-04-01

    We developed the photo-crosslinkable hydrogel-based 3D microfluidic device to culture neural stem cells (NSCs) and tumors. The photo-crosslinkable gelatin methacrylate (GelMA) polymer was used as a physical barrier in the microfluidic device and collagen type I gel was employed to culture NSCs in a 3D manner. We demonstrated that the pore size was inversely proportional to concentrations of GelMA hydrogels, showing the pore sizes of 5 and 25 w/v% GelMA hydrogels were 34 and 4 μm, respectively. It also revealed that the morphology of pores in 5 w/v% GelMA hydrogels was elliptical shape, whereas we observed circular-shaped pores in 25 w/v% GelMA hydrogels. To culture NSCs and tumors in the 3D microfluidic device, we investigated the molecular diffusion properties across GelMA hydrogels, indicating that 25 w/v% GelMA hydrogels inhibited the molecular diffusion for 6 days in the 3D microfluidic device. In contrast, the chemicals were diffused in 5 w/v% GelMA hydrogels. Finally, we cultured NSCs and tumors in the hydrogel-based 3D microfluidic device, showing that 53-75% NSCs differentiated into neurons, while tumors were cultured in the collagen gels. Therefore, this photo-crosslinkable hydrogel-based 3D microfluidic culture device could be a potentially powerful tool for regenerative tissue engineering applications. PMID:25641332

  14. Performance of Nanoliter-Sized Droplet-based Microfluidic PCR

    PubMed Central

    Wang, Fang; Burns, Mark A.

    2010-01-01

    A microfluidic device was used to characterize PCR in aqueous-in-oil droplets for potential point-of-care applications. Droplets with a volume range of 5–250nL can be formed on-chip reproducibly, and PCR in the droplets shows amplification efficiencies comparable to benchtop reactions with no evaporation loss. A higher polymerase concentration is required in the reaction droplet while the optimal Magnesium ion concentration is the same for both on-chip and benchtop systems. The optimal hold time is 9 and 30 seconds for denaturation and annealing/extension in thermal cycling, respectively. With the optimized cycling parameters, the total reaction time is reduced to half of that required for benchtop PCR. For the droplets containing the same quantity of template DNA, the PCR yield is approximately the same with either fixed droplet size or fixed template DNA concentration. The droplet-based PCR can be monitored in real time with FRET probes, and provide amplification with a cycle threshold of ~10 cycles earlier than the benchtop instruments. PMID:19479169

  15. Structural studies of enzyme-based microfluidic biofuel cells

    NASA Astrophysics Data System (ADS)

    Togo, Makoto; Takamura, Akimasa; Asai, Tatsuya; Kaji, Hirokazu; Nishizawa, Matsuhiko

    An enzyme-based glucose/O 2 biofuel cell was constructed within a microfluidic channel to study the influence of electrode configuration and fluidic channel height on cell performance. The cell was composed of a bilirubin oxidase (BOD)-adsorbed O 2 cathode and a glucose anode prepared by co-immobilization of glucose dehydrogenase (GDH), diaphorase (Dp) and VK 3-pendant poly- L-lysine. The consumption of O 2 at the upstream cathode protected the downstream anode from interfering O 2 molecules, and consequently improved the cell performance (maximum cell current) ca. 10% for the present cell. The cell performance was also affected by the channel height. The output current and power of a 0.1 mm-height cell was significantly less than those of a 1 mm-height cell because of the depletion of O 2, as determined by the shape of the E- I curve at the cathode. On the other hand, the volume density of current and power was several times higher for the narrower cell.

  16. Development of an evaporation-based microfluidic sample concentrator

    NASA Astrophysics Data System (ADS)

    Sharma, Nigel R.; Lukyanov, Anatoly; Bardell, Ron L.; Seifried, Lynn; Shen, Mingchao

    2008-02-01

    MicroPlumbers Microsciences LLC, has developed a relatively simple concentrator device based on isothermal evaporation. The device allows for rapid concentration of dissolved or dispersed substances or microorganisms (e.g. bacteria, viruses, proteins, toxins, enzymes, antibodies, etc.) under conditions gentle enough to preserve their specific activity or viability. It is capable of removing of 0.8 ml of water per minute at 37°C, and has dimensions compatible with typical microfluidic devices. The concentrator can be used as a stand-alone device or integrated into various processes and analytical instruments, substantially increasing their sensitivity while decreasing processing time. The evaporative concentrator can find applications in many areas such as biothreat detection, environmental monitoring, forensic medicine, pathogen analysis, and agricultural industrial monitoring. In our presentation, we describe the design, fabrication, and testing of the concentrator. We discuss multiphysics simulations of the heat and mass transport in the device that we used to select the design of the concentrator and the protocol of performance testing. We present the results of experiments evaluating water removal performance.

  17. Microfluidic paper-based analytical device for particulate metals.

    PubMed

    Mentele, Mallory M; Cunningham, Josephine; Koehler, Kirsten; Volckens, John; Henry, Charles S

    2012-05-15

    A microfluidic paper-based analytical device (μPAD) fabricated by wax printing was designed to assess occupational exposure to metal-containing aerosols. This method employs rapid digestion of particulate metals using microliters of acid added directly to a punch taken from an air sampling filter. Punches were then placed on a μPAD, and digested metals were transported to detection reservoirs upon addition of water. These reservoirs contained reagents for colorimetric detection of Fe, Cu, and Ni. Dried buffer components were used to set the optimal pH in each detection reservoir, while precomplexation agents were deposited in the channels between the sample and detection zones to minimize interferences from competing metals. Metal concentrations were quantified from color intensity images using a scanner in conjunction with image processing software. Reproducible, log-linear calibration curves were generated for each metal, with method detection limits ranging from 1.0 to 1.5 μg for each metal (i.e., total mass present on the μPAD). Finally, a standard incineration ash sample was aerosolized, collected on filters, and analyzed for the three metals of interest. Analysis of this collected aerosol sample using a μPAD showed good correlation with known amounts of the metals present in the sample. This technology can provide rapid assessment of particulate metal concentrations at or below current regulatory limits and at dramatically reduced cost. PMID:22489881

  18. An integrated microfluidic biochemical detection system for protein analysis with magnetic bead-based sampling capabilities.

    PubMed

    Choi, Jin-Woo; Oh, Kwang W; Thomas, Jennifer H; Heineman, William R; Halsall, H Brian; Nevin, Joseph H; Helmicki, Arthur J; Henderson, H Thurman; Ahn, Chong H

    2002-02-01

    This paper presents the development and characterization of an integrated microfluidic biochemical detection system for fast and low-volume immunoassays using magnetic beads, which are used as both immobilization surfaces and bio-molecule carriers. Microfluidic components have been developed and integrated to construct a microfluidic biochemical detection system. Magnetic bead-based immunoassay, as a typical example of biochemical detection and analysis, has been successfully performed on the integrated microfluidic biochemical analysis system that includes a surface-mounted biofilter and electrochemical sensor on a glass microfluidic motherboard. Total time required for an immunoassay was less than 20 min including sample incubation time, and sample volume wasted was less than 50 microl during five repeated assays. Fast and low-volume biochemical analysis has been successfully achieved with the developed biofilter and immunosensor, which is integrated to the microfluidic system. Such a magnetic bead-based biochemical detection system, described in this paper, can be applied to protein analysis systems. PMID:15100857

  19. Droplet-based microfluidic washing module for magnetic particle-based assays

    PubMed Central

    Lee, Hun; Xu, Linfeng; Oh, Kwang W.

    2014-01-01

    In this paper, we propose a continuous flow droplet-based microfluidic platform for magnetic particle-based assays by employing in-droplet washing. The droplet-based washing was implemented by traversing functionalized magnetic particles across a laterally merged droplet from one side (containing sample and reagent) to the other (containing buffer) by an external magnetic field. Consequently, the magnetic particles were extracted to a parallel-synchronized train of washing buffer droplets, and unbound reagents were left in an original train of sample droplets. To realize the droplet-based washing function, the following four procedures were sequentially carried in a droplet-based microfluidic device: parallel synchronization of two trains of droplets by using a ladder-like channel network; lateral electrocoalescence by an electric field; magnetic particle manipulation by a magnetic field; and asymmetrical splitting of merged droplets. For the stable droplet synchronization and electrocoalescence, we optimized droplet generation conditions by varying the flow rate ratio (or droplet size). Image analysis was carried out to determine the fluorescent intensity of reagents before and after the washing step. As a result, the unbound reagents in sample droplets were significantly removed by more than a factor of 25 in the single washing step, while the magnetic particles were successfully extracted into washing buffer droplets. As a proof-of-principle, we demonstrate a magnetic particle-based immunoassay with streptavidin-coated magnetic particles and fluorescently labelled biotin in the proposed continuous flow droplet-based microfluidic platform. PMID:25379098

  20. Droplet-based microfluidic washing module for magnetic particle-based assays.

    PubMed

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

    2014-07-01

    In this paper, we propose a continuous flow droplet-based microfluidic platform for magnetic particle-based assays by employing in-droplet washing. The droplet-based washing was implemented by traversing functionalized magnetic particles across a laterally merged droplet from one side (containing sample and reagent) to the other (containing buffer) by an external magnetic field. Consequently, the magnetic particles were extracted to a parallel-synchronized train of washing buffer droplets, and unbound reagents were left in an original train of sample droplets. To realize the droplet-based washing function, the following four procedures were sequentially carried in a droplet-based microfluidic device: parallel synchronization of two trains of droplets by using a ladder-like channel network; lateral electrocoalescence by an electric field; magnetic particle manipulation by a magnetic field; and asymmetrical splitting of merged droplets. For the stable droplet synchronization and electrocoalescence, we optimized droplet generation conditions by varying the flow rate ratio (or droplet size). Image analysis was carried out to determine the fluorescent intensity of reagents before and after the washing step. As a result, the unbound reagents in sample droplets were significantly removed by more than a factor of 25 in the single washing step, while the magnetic particles were successfully extracted into washing buffer droplets. As a proof-of-principle, we demonstrate a magnetic particle-based immunoassay with streptavidin-coated magnetic particles and fluorescently labelled biotin in the proposed continuous flow droplet-based microfluidic platform. PMID:25379098

  1. Microfluidics-based integrated airborne pathogen detection systems

    NASA Astrophysics Data System (ADS)

    Northrup, M. Allen; Alleman-Sposito, Jennifer; Austin, Todd; Devitt, Amy; Fong, Donna; Lin, Phil; Nakao, Brian; Pourahmadi, Farzad; Vinas, Mary; Yuan, Bob

    2006-09-01

    Microfluidic Systems is focused on building microfluidic platforms that interface front-end mesofluidics to handle real world sample volumes for optimal sensitivity coupled to microfluidic circuitry to process small liquid volumes for complex reagent metering, mixing, and biochemical analysis, particularly for pathogens. MFSI is the prime contractor on two programs for the US Department of Homeland Security: BAND (Bioagent Autonomous Networked Detector) and IBADS (Instantaneous Bio-Aerosol Detection System). The goal of BAND is to develop an autonomous system for monitoring the air for known biological agents. This consists of air collection, sample lysis, sample purification, detection of DNA, RNA, and toxins, and a networked interface to report the results. For IBADS, MFSI is developing the confirmatory device which must verify the presence of a pathogen with 5 minutes of an air collector/trigger sounding an alarm. Instrument designs and biological assay results from both BAND and IBADS will be presented.

  2. A versatile technology for droplet-based microfluidics: thermomechanical actuation.

    PubMed

    Miralles, Vincent; Huerre, Axel; Williams, Hannah; Fournié, Bastien; Jullien, Marie-Caroline

    2015-05-01

    We report on a versatile technique for microfluidic droplet manipulation that proves effective at every step: from droplet generation to propulsion to sorting, rearrangement or break-up. Non-wetting droplets are thermomechanically actuated in a microfluidic chip using local heating resistors. Controlled temperature variation induces local dilation of the PDMS wall above the resistor, which drives the droplet away from the hot (i.e. constricted) region (B. Selva, I. Cantat and M.-C. Jullien, Phys. Fluids, 2011, 23, 052002). Adapted placing and actuation of such resistors thus allow us to push forward, stop, store and release, or even break up droplets, at the price of low electric power consumption (<150 mW). We believe this technically accessible method to provide a useful tool for droplet microfluidics. PMID:25849442

  3. Mobile phone based electrochemiluminescence detection in paper-based microfluidic sensors.

    PubMed

    Delaney, Jacqui L; Hogan, Conor F

    2015-01-01

    The development of simple, inexpensive paper-based sensors for medical diagnostics and other applications is now an important emerging area in the field of biosensors; however, the electronic instrument or reader used to interrogate such sensors adds significantly to the cost of the analysis. In this chapter we describe the design and construction of novel, low-cost disposable electrochemiluminescent (ECL) sensors based on screen printed carbon electrodes and paper-based microfluidics. Moreover, a method to interrogate these sensors using only a mobile phone is articulated. This is realized by exploiting the audio output of the device to achieve electrochemical control, while using the camera to detect the resulting light emitted during the ECL reaction. The combination of cell phone technology with low-cost paper microfluidic sensors dramatically reduces the cost of sensing and has the potential to enhance health-care outcomes by exploiting the functionality, connectivity, and close to worldwide penetration of mobile phone technology. PMID:25626546

  4. Digital microfluidics for spheroid-based invasion assays.

    PubMed

    Bender, Brian F; Aijian, Andrew P; Garrell, Robin L

    2016-04-21

    Cell invasion is a key process in tissue growth, wound healing, and tumor progression. Most invasion assays examine cells cultured in adherent monolayers, which fail to recapitulate the three-dimensional nuances of the tissue microenvironment. Multicellular cell spheroids have a three-dimensional (3D) morphology and mimic the intercellular interactions found in tissues in vivo, thus providing a more physiologically relevant model for studying the tissue microenvironment and processes such as cell invasion. Spheroid-based invasion assays often require tedious, manually intensive handling protocols or the use of robotic liquid handling systems, which can be expensive to acquire, operate, and maintain. Here we describe a digital microfluidic (DμF) platform that enables formation of spheroids by the hanging drop method, encapsulation of the spheroids in collagen, and the exposure of spheroids to migration-modulating agents. Collagen sol-gel solutions up to 4 mg mL(-1), which form gels with elastic moduli up to ∼50 kPa, can be manipulated on the device. In situ spheroid migration assays show that cells from human fibroblast spheroids exhibit invasion into collagen gels, which can be either enhanced or inhibited by the delivery of exogenous migration modulating agents. Exposing fibroblast spheroids to spheroid secretions from colon cancer spheroids resulted in a >100% increase in fibroblast invasion into the collagen gel, consistent with the cancer-associated fibroblast phenotype. These data show that DμF can be used to automate the liquid handling protocols for spheroid-based invasion assays and create a cell invasion model that mimics the tissue microenvironment more closely than two-dimensional culturing techniques do. A DμF platform that facilitates the creation and assaying of 3D in vitro tissue models has the potential to make automated 3D cell-based assays more accessible to researchers in the life sciences. PMID:27020962

  5. Field-effect flow control in a polydimethylsiloxane-based microfluidic system.

    PubMed

    Buch, J S; Wang, P C; DeVoe, D L; Lee, C S

    2001-10-01

    The application of the field-effect for direct control of electroosmosis in a polydimethylsiloxane (PDMS)-based microfluidic system, constructed on a silicon wafer with a 2.0 microm electrically insulating layer of silicon dioxide, is demonstrated. This microfluidic system consists of a 2.0 cm open microchannel fabricated on a PDMS slab, which can reversibly adhere to the silicon wafer to form a hybrid microfluidic device. Aside from mechanically serving as a robust bottom substrate to seal the channel and support the microfluidic system, the silicon wafer is exploited to achieve field-effect flow control by grounding the semiconductive silicon medium. When an electric field is applied through the channel, a radial electric potential gradient is created across the silicon dioxide layer that allows for direct control of the zeta potential and the resulting electroosmotic flow (EOF). By configuring this microfluidic system with two power supplies at both ends of the microchannel, the applied electric potentials can be varied for manipulating the polarity and the magnitude of the radial electric potential gradient across the silicon dioxide layer. At the same time, the longitudinal potential gradient through the microchannel, which is used to induce EOF, is held constant. The results of EOF control in this hybrid microfluidic system are presented for phosphate buffer at pH 3 and pH 5. It is also demonstrated that EOF control can be performed at higher solution pH of 6 and 7.4 by modifying the silicon wafer surface with cetyltrimethylammonium bromide (CTAB) prior to assembly of the hybrid microfluidic system. Results of EOF control from this study are compared with those reported in the literature involving the use of other microfluidic devices under comparable solution conditions. PMID:11700719

  6. Characterization of a microfluidic microbial fuel cell as a power generator based on a nickel electrode.

    PubMed

    Mardanpour, Mohammad Mahdi; Yaghmaei, Soheila

    2016-05-15

    This study reports the fabrication of a microfluidic microbial fuel cell (MFC) using nickel as a novel alternative for conventional electrodes and a non-phatogenic strain of Escherichia coli as the biocatalyst. The feasibility of a microfluidic MFC as an efficient power generator for production of bioelectricity from glucose and urea as organic substrates in human blood and urine for implantable medical devices (IMDs) was investigated. A maximum open circuit potential of 459 mV was achieved for the batch-fed microfluidic MFC. During continuous mode operation, a maximum power density of 104 Wm(-3) was obtained with nutrient broth. For the glucose-fed microfluidic MFC, the maximum power density of 5.2 μW cm(-2) obtained in this study is significantly greater than the power densities reported previously for microsized MFCs and glucose fuel cells. The maximum power density of 14 Wm(-3) obtained using urea indicates the successful performance of a microfluidic MFC using human excreta. It features high power density, self-regeneration, waste management and a low production cost (<$1), which suggest it as a promising alternative to conventional power supplies for IMDs. The performance of the microfluidic MFC as a power supply was characterized based on polarization behavior and cell potential in different substrates, operational modes, and concentrations. PMID:26720922

  7. Monolithical integration of polymer-based microfluidic structures on application-specific integrated circuits

    NASA Astrophysics Data System (ADS)

    Chemnitz, Steffen; Schafer, Heiko; Schumacher, Stephanie; Koziy, Volodymyr; Fischer, Alexander; Meixner, Alfred J.; Ehrhardt, Dietmar; Bohm, Markus

    2003-04-01

    In this paper, a concept for a monolithically integrated chemical lab on microchip is presented. It contains an ASIC (Application Specific Integrated Circuit), an interface to the polymer based microfluidic layer and a Pyrex glass cap. The top metal layer of the ASIC is etched off and replaced by a double layer metallization, more suitable to microfluidic and electrophoresis systems. The metallization consists of an approximately 50 nm gold layer and a 10 nm chromium layer, acting as adhesion promoter. A necessary prerequisite is a planarized ASIC topography. SU-8 is used to serve as microfluidic structure because of its excellent aspect ratio. This polymer layer contains reservoirs, channels, mixers and electrokinetic micro pumps. The typical channel cross section is 10μm"10μm. First experimental results on a microfluidic pump, consisting of pairs of interdigitated electrodes on the bottom of the channel and without any moving parts show a flow of up to 50μm per second for low AC-voltages in the range of 5 V for aqueous fluids. The microfluidic system is irreversibly sealed with a 150μm thick Pyrex glass plate bonded to the SU-8-layer, supported by oxygen plasma. Due to capillary forces and surfaces properties of the walls the system is self-priming. The technologies for the fabrication of the microfluidic system and the preparation of the interface between the lab layer and the ASIC are presented.

  8. MEMS-based flow cytometry: microfluidics-based cell identification system by fluorescent imaging.

    PubMed

    Wu, W K; Liang, C K; Huang, J Z

    2004-01-01

    This study utilizes MEMS technology to realize a novel low-cost microfluidics-based biochip system for flow-type cell handling. Powered by vacuum pump, the microfluidic driving system enables cells to move in order one by one in the biochip by an effect of sheath flow prefocus. Then, cells are guided to a fluorescent inspection region where two detection tasks such as cell image identification and cell counting are conducted. Currently, the glass-based biochip has been manufactured and all the related devices have been well set up in our laboratory. With this proposed prototype system, typical results about cell separation of yeast cell and PC-3 cell are available and their separated images are also presented, respectively. PMID:17270801

  9. Screening applications in drug discovery based on microfluidic technology.

    PubMed

    Eribol, P; Uguz, A K; Ulgen, K O

    2016-01-01

    Microfluidics has been the focus of interest for the last two decades for all the advantages such as low chemical consumption, reduced analysis time, high throughput, better control of mass and heat transfer, downsizing a bench-top laboratory to a chip, i.e., lab-on-a-chip, and many others it has offered. Microfluidic technology quickly found applications in the pharmaceutical industry, which demands working with leading edge scientific and technological breakthroughs, as drug screening and commercialization are very long and expensive processes and require many tests due to unpredictable results. This review paper is on drug candidate screening methods with microfluidic technology and focuses specifically on fabrication techniques and materials for the microchip, types of flow such as continuous or discrete and their advantages, determination of kinetic parameters and their comparison with conventional systems, assessment of toxicities and cytotoxicities, concentration generations for high throughput, and the computational methods that were employed. An important conclusion of this review is that even though microfluidic technology has been in this field for around 20 years there is still room for research and development, as this cutting edge technology requires ingenuity to design and find solutions for each individual case. Recent extensions of these microsystems are microengineered organs-on-chips and organ arrays. PMID:26865904

  10. Amperometric quantification based on serial dilution microfluidic systems.

    PubMed

    Stephan, Khaled; Pittet, Patrick; Sigaud, Monique; Renaud, Louis; Vittori, Olivier; Morin, Pierre; Ouaini, Naim; Ferrigno, Rosaria

    2009-03-01

    This paper describes a microfluidic device fabricated in poly(dimethylsiloxane) that was employed to perform amperometric quantifications using on-chip calibration curves and on-chip standard addition methods. This device integrated a network of Au electrodes within a microfluidic structure designed for automatic preparation of a series of solutions containing an electroactive molecule at a concentration linearly decreasing. This device was first characterized by fluorescence microscopy and then evaluated with a model electroactive molecule such as Fe(CN(6))(4-). Operating a quantification in this microfluidic parallel approach rather than in batch mode allows a reduced analysis time to be achieved. Moreover, the microfluidic approach is compatible with the on-chip calibration of sensors simultaneously to the analysis, therefore preventing problems due to sensor response deviation with time. When using the on-chip calibration and on-chip standard addition method, we reached concentration estimation better than 5%. We also demonstrated that compared to the calibration curve approach, the standard addition mode is less complex to operate. Indeed, in this case, it is not necessary to take into account flow rate discrepancies as in the calibration approach. PMID:19238282

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

    PubMed

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

    2015-02-01

    Recent progress in thread-based microfluidic devices has provided portable and inexpensive field-based technologies enabling medical diagnostics, environmental monitoring, and food safety analysis. However, capillary-driven liquid flow in a single thread, a crucial aspect of thread-based microfluidics, is difficult to control. Among potential materials, hydrophobic wool thread is an appropriate candidate for liquid flow control in thread-based microfluidics because its wettability can be readily tuned by the introduction of a natural color pigment, thereby manipulating flow. Thus, utilizing natural wool thread as a channel, we demonstrate here that liquid flow manipulations, such as microselecting and micromixing, can be achieved by coating the complex Al(III) (Alum) brazilein onto wool thread. In addition to enabling flow control, the coated wool channels consisting entirely of naturally occurring substances will be beneficial for biological sensing devices. PMID:26349307

  12. Microfluidics-Based Lab-on-Chip Systems in DNA-Based Biosensing: An Overview

    PubMed Central

    Dutse, Sabo Wada; Yusof, Nor Azah

    2011-01-01

    Microfluidics-based lab-on-chip (LOC) systems are an active research area that is revolutionising high-throughput sequencing for the fast, sensitive and accurate detection of a variety of pathogens. LOCs also serve as portable diagnostic tools. The devices provide optimum control of nanolitre volumes of fluids and integrate various bioassay operations that allow the devices to rapidly sense pathogenic threat agents for environmental monitoring. LOC systems, such as microfluidic biochips, offer advantages compared to conventional identification procedures that are tedious, expensive and time consuming. This paper aims to provide a broad overview of the need for devices that are easy to operate, sensitive, fast, portable and sufficiently reliable to be used as complementary tools for the control of pathogenic agents that damage the environment. PMID:22163925

  13. A digital microfluidic method for multiplexed cell-based apoptosis assays.

    PubMed

    Bogojevic, Dario; Chamberlain, M Dean; Barbulovic-Nad, Irena; Wheeler, Aaron R

    2012-02-01

    Digital microfluidics (DMF), a fluid-handling technique in which picolitre-microlitre droplets are manipulated electrostatically on an array of electrodes, has recently become popular for applications in chemistry and biology. DMF devices are reconfigurable, have no moving parts, and are compatible with conventional high-throughput screening infrastructure (e.g., multiwell plate readers). For these and other reasons, digital microfluidics has been touted as being a potentially useful new tool for applications in multiplexed screening. Here, we introduce the first digital microfluidic platform used to implement parallel-scale cell-based assays. A fluorogenic apoptosis assay for caspase-3 activity was chosen as a model system because of the popularity of apoptosis as a target for anti-cancer drug discovery research. Dose-response profiles of caspase-3 activity as a function of staurosporine concentration were generated using both the digital microfluidic method and conventional techniques (i.e., pipetting, aspiration, and 96-well plates.) As expected, the digital microfluidic method had a 33-fold reduction in reagent consumption relative to the conventional technique. Although both types of methods used the same detector (a benchtop multiwell plate reader), the data generated by the digital microfluidic method had lower detection limits and greater dynamic range because apoptotic cells were much less likely to de-laminate when exposed to droplet manipulation by DMF relative to pipetting/aspiration in multiwell plates. We propose that the techniques described here represent an important milestone in the development of digital microfluidics as a useful tool for parallel cell-based screening and other applications. PMID:22159547

  14. Rapid prototyping of arrayed microfluidic systems in polystyrene for cell-based assays

    PubMed Central

    Young, Edmond W.K.; Berthier, Erwin; Guckenberger, David J.; Sackmann, Eric; Lamers, Casey; Meyvantsson, Ivar; Huttenlocher, Anna; Beebe, David J.

    2011-01-01

    Microfluidic cell-based systems have enabled the study of cellular phenomena with improved spatiotemporal control of the microenvironment and at increased throughput. While PDMS has emerged as the most popular material in microfluidics research, it has specific limitations that prevent microfluidic platforms from achieving their full potential. We present here a complete process, ranging from mold design to embossing and bonding, that describes the fabrication of polystyrene (PS) microfluidic devices with similar cost and time expenditures as PDMS-based devices. Emphasis was placed on creating methods that can compete with PDMS fabrication methods in terms of robustness, complexity and time requirements. To achieve this goal several improvements were made to remove critical bottlenecks in existing PS embossing methods. First, traditional lithography techniques were adapted to fabricate bulk epoxy molds capable of resisting high temperatures and pressures. Second, a method was developed to emboss through-holes in a PS layer, enabling creation of large arrays of independent microfluidic systems on a single device without need to manually create access ports. Third, thermal bonding of PS layers was optimized in order to achieve quality bonding over large arrays of microsystems. The choice of materials and methods were validated for biological function using two different cell-based applications to demonstrate the versatility of our streamlined fabrication process. PMID:21261280

  15. 2-layer based microfluidic concentration generator by hybrid serial and volumetric dilutions.

    PubMed

    Lee, Kangsun; Kim, Choong; Kim, Youngeun; Jung, Keunhui; Ahn, Byungwook; Kang, Ji Yoon; Oh, Kwang W

    2010-04-01

    We present a 2-layer based microfluidic concentration generator by a hybrid of a serial and a volumetric dilution for dose-response experiments in drug screening. The hybrid dilution method using 2-layer based microfluidic network significantly reduces the total number of cascaded serial dilution stages. The proposed strategy is capable of generating a large number of universal stepwise monotonic concentrations with a wide range of logarithmic and linear scales. We have studied an equivalent electrical circuit to that of the 2-layer based microfluidic network, where the only variable parameter is channel length. We have designed a microfluidic dilution generator simultaneously covering 14 doses with a combination of 4-order logarithmic and 4-point linear concentrations. The design has been verified by a commercial circuit analysis software (e.g., P-Spice) for the electrical circuit analysis and a computational fluid dynamics software (e.g., CFD-ACE+) for the microfluidic circuit analysis. As a real-life application of the proposed dilution generator, we have successfully performed a dose-response experiment using MCF-7 human breast cancer cells. We expect that the proposed dilution method will be useful to study not only high throughput drug screening but also optimization in biology, chemistry, medicine, and material sciences. PMID:20077018

  16. Product qualification: a barrier to point-of-care microfluidic-based diagnostics?

    PubMed

    Tantra, Ratna; van Heeren, Henne

    2013-06-21

    One of the most exciting applications of microfluidics-based diagnostics is its potential use in next generation point-of-care (POC) devices. Many prototypes are already in existence, but, as of yet, few have achieved commercialisation. In this article, we consider the issue surrounding product qualification as a potential barrier to market success. The study discusses, in the context of POC microfluidics-based diagnostics, what the generic issues are and potential solutions. Our findings underline the need for a community-based effort that is necessary to speed up the product qualification process. PMID:23652789

  17. Fully Automated Quantification of Insulin Concentration Using a Microfluidic-Based Chemiluminescence Immunoassay.

    PubMed

    Yao, Ping; Liu, Zhu; Tung, Steve; Dong, Zaili; Liu, Lianqing

    2016-06-01

    A fully automated microfluidic-based detection system for the rapid determination of insulin concentration through a chemiluminescence immunoassay has been developed. The microfluidic chip used in the system is a double-layered polydimethylsiloxane device embedded with interconnecting micropumps, microvalves, and a micromixer. At a high injection rate of the developing solution, the chemiluminescence signal can be excited and measured within a short period of time. The integral value of the chemiluminescence light signal is used to determine the insulin concentration of the samples, and the results indicate that the measurement is accurate in the range from 1.5 pM to 391 pM. The entire chemiluminescence assay can be completed in less than 10 min. The fully automated microfluidic-based insulin detection system provides a useful platform for rapid determination of insulin in clinical diagnostics for diabetes, which is expected to become increasingly important for future point-of-care applications. PMID:25824205

  18. A SERS-based microfluidic immunoassay using an in-situ synthesized gold substrate

    NASA Astrophysics Data System (ADS)

    Fan, Kequan; Wang, Zhuyuan; Wu, Lei; Zong, Shenfei; Cui, Yiping

    2015-05-01

    A sensitive SERS (surface-enhanced Raman scattering)-based immunoassay in microfluidic system has been developed with in-situ synthesis of gold substrate and immune reporter named as 4MBA (4-Mercaptobenzoic acid)-labeled immuno-Ag aggregates. The gold substrate was fabricated simply by introducing the hydrogen tetrachloroaurate (III) trihydrate (HAuCl4) solution to microchannels using a microfluidic pump. It was found that the obtained deposited gold nanoparticles were uniform in size and shape. Then the sandwich immunoassays were performed using the gold substrates based on SERS signals. In the immunoassay, the gold nanoparticles decorated surface was modified with certain antibodies to recognize the specific kind of antigen, which was flowed through the microfluidic channel afterwards. Then 4MBA-labeled immuno-Ag aggregates were employed as the SERS probes to quantitatively detect the antigen. The experimental results showed a good specificity and limit of detection (LOD) about 1 ng/mL.

  19. Magnetophoretic-based microfluidic device for DNA isolation

    PubMed Central

    Hale, C.; Darabi, J.

    2014-01-01

    This paper presents a continuous flow microfluidic device for the separation of DNA from blood using magnetophoresis for biological applications and analysis. This microfluidic bio-separation device has several benefits, including decreased sample handling, smaller sample and reagent volumes, faster isolation time, and decreased cost to perform DNA isolation. One of the key features of this device is the use of short-range magnetic field gradients, generated by a micro-patterned nickel array on the bottom surface of the separation channel. In addition, the device utilizes an array of oppositely oriented, external permanent magnets to produce strong long-range field gradients at the interfaces between magnets, further increasing the effectiveness of the device. A comprehensive simulation is performed using COMSOL Multiphysics to study the effect of various parameters on the magnetic flux within the separation channel. Additionally, a microfluidic device is designed, fabricated, and tested to isolate DNA from blood. The results show that the device has the capability of separating DNA from a blood sample with a purity of 1.8 or higher, a yield of up to 33 μg of polymerase chain reaction ready DNA per milliliter of blood, and a volumetric throughput of up to 50 ml/h. PMID:25379103

  20. A portable microfluidic-based biophotonic sensor for extracellular H2O2 measurements

    NASA Astrophysics Data System (ADS)

    Koman, V.; Suárez, G.; Santschi, Ch.; Cadarso, V. J.; Brugger, J.; von Moos, N.; Slaveykova, V. I.; Martin, O. J. F.

    2013-03-01

    In this work a portable analytical biosensor for real-time extracellular monitoring of released hydrogen peroxide (H2O2 ) is presented. The biosensor is based on the optical detection of the cytochrome c (cyt c) oxidation state. The setup consists of an integrated microscope combined with a compact spectrometer. The light being absorbed by cyt c is enhanced via multiscattering produced by random aggregates of polystyrene beads in a cross-linked cyt c matrix. Using ink-jet printing technique, the sensing elements, namely cyt c loaded polystyrene aggregates, are fabricated with high reliability in terms of repeatability of size and sensitivity. Additionally, the sensing elements are enclosed in a microfluidic channel assuring a fast and efficient analytes delivery. As an example, the effect of trace concentrations of functionalized cadmium selenide/zinc sulfide (CdSe/ZnS) core shell quantum dots on the green algae Chlamydomonas reinhardtii is investigated, showing extracellular H2O2 release with different production rates over a period of 1 hour. In conclusion, the presented portable biosensor enables the highly sensitive and non-invasive real-time monitoring of the cell metabolism of C. reinhardtii.

  1. A capillary-based microfluidic instrument suitable for immunoaffinity chromatography.

    PubMed

    Peoples, Michael C; Phillips, Terry M; Karnes, H Thomas

    2007-04-01

    The analysis of biological samples to produce clinical or research data often requires measurement of analytes from complex biological matrices and limited volumes. Miniaturized analytical systems capable of minimal sample consumption and reduced analysis times have been employed to meet this need. The small footprint of this technology offers the potential for portability and patient point-of-care testing. A prototype microfluidic system has been developed and is presented for potential rapid assessment of clinical samples. The system has been designed for immunoaffinity chromatography as a means of separating analytes of interest from biological matrices. The instrument is capable of sub-microliter sample injection and detection of labeled antigens by long wavelength laser-induced fluorescence (LIF). The laboratory-constructed device is assembled from an array of components including two syringe pumps, a nano-gradient mixing chip, a micro-injector, a diode laser, and a separation capillary column made from a polymer/silica (PEEKsil) tube. An in-house program written with LabVIEW software controls the syringe pumps to perform step gradient elution and collects the LIF signal as a chromatogram. Initial columns were packed with silica beads to evaluate the system. Optimization of the device has been achieved by measuring flow accuracy with respect to column length and particle size. Syringe size and pressure effects have also been used to characterize the capability of the pumps. Based on test results, a 200-microm x 25-mm column packed with 1-microm silica beads was chosen for use with a 500-microL syringe. The system was tested for mixer proportioning by pumping different compositions of buffer and fluorescent dye solutions in a stepwise fashion. A linear response was achieved for increasing concentrations of fluorescent dye by online mixing (R2=0.9998). The effectiveness of an acidic gradient was confirmed by monitoring pH post-column and measuring premixed

  2. Clogging-free microfluidics for continuous size-based separation of microparticles

    PubMed Central

    Yoon, Yousang; Kim, Seonil; Lee, Jusin; Choi, Jaewoong; Kim, Rae-Kwon; Lee, Su-Jae; Sul, Onejae; Lee, Seung-Beck

    2016-01-01

    In microfluidic filtration systems, one of the leading obstacles to efficient, continuous operation is clogging of the filters. Here, we introduce a lateral flow microfluidic sieving (μ-sieving) technique to overcome clogging and to allow continuous operation of filter based microfluidic separation. A low frequency mechanical oscillation was added to the fluid flow, which made possible the release of aggregated unwanted polystyrene (PS) particles trapped between the larger target PS particles in the filter demonstrating continuous μ-sieving operation. We achieved collection of the target PS particles with 100% separation efficiency. Also, on average, more than 98% of the filtered target particles were retrieved after the filtration showing high retrieval rates. Since the oscillation was applied to the fluid but not to the microfluidic filter system, mechanical stresses to the system was minimized and no additional fabrication procedures were necessary. We also applied the μ-sieving technique to the separation of cancer cells (MDA-MB-231) from whole blood and showed that the fluidic oscillations prevented the filters from being blocked by the filtered cancer cells allowing continuous microfluidic separation with high efficiency. PMID:27198601

  3. A contact line pinning based microfluidic platform for modelling physiological flows.

    PubMed

    Tung, Chih-kuan; Krupa, Oleh; Apaydin, Elif; Liou, Jr-Jiun; Diaz-Santana, Anthony; Kim, Beum Jun; Wu, Mingming

    2013-10-01

    This work introduces a contact line pinning based microfluidic platform for the generation of interstitial and intramural flows within a three dimensional (3D) microenvironment for cellular behaviour studies. A contact line pinning method was used to confine a natively derived biomatrix, collagen, in microfluidic channels without walls. By patterning collagen in designated wall-less channels, we demonstrated and validated the intramural flows through a microfluidic channel bounded by a monolayer of endothelial cells (mimic of a vascular vessel), as well as slow interstitial flows within a cell laden collagen matrix using the same microfluidic platform. The contact line pinning method ensured the generation of an engineered endothelial tube with straight walls, and spatially uniform interstitial fluid flows through the cell embedded 3D collagen matrix. Using this device, we demonstrated that the breast tumour cells' (MDA-MB-231 cell line) morphology and motility were modulated by the interstitial flows, and the motility of a sub-population of the cells was enhanced by the presence of the flow. The presented microfluidic platform provides a basic framework for studies of cellular behaviour including cell transmigration, growth, and adhesion under well controlled interstitial and intramural flows, and within a physiologically realistic 3D co-culture setting. PMID:23917952

  4. Clogging-free microfluidics for continuous size-based separation of microparticles.

    PubMed

    Yoon, Yousang; Kim, Seonil; Lee, Jusin; Choi, Jaewoong; Kim, Rae-Kwon; Lee, Su-Jae; Sul, Onejae; Lee, Seung-Beck

    2016-01-01

    In microfluidic filtration systems, one of the leading obstacles to efficient, continuous operation is clogging of the filters. Here, we introduce a lateral flow microfluidic sieving (μ-sieving) technique to overcome clogging and to allow continuous operation of filter based microfluidic separation. A low frequency mechanical oscillation was added to the fluid flow, which made possible the release of aggregated unwanted polystyrene (PS) particles trapped between the larger target PS particles in the filter demonstrating continuous μ-sieving operation. We achieved collection of the target PS particles with 100% separation efficiency. Also, on average, more than 98% of the filtered target particles were retrieved after the filtration showing high retrieval rates. Since the oscillation was applied to the fluid but not to the microfluidic filter system, mechanical stresses to the system was minimized and no additional fabrication procedures were necessary. We also applied the μ-sieving technique to the separation of cancer cells (MDA-MB-231) from whole blood and showed that the fluidic oscillations prevented the filters from being blocked by the filtered cancer cells allowing continuous microfluidic separation with high efficiency. PMID:27198601

  5. Microfluidic assay-based optical measurement techniques for cell analysis: A review of recent progress.

    PubMed

    Choi, Jong-Ryul; Song, Hyerin; Sung, Jong Hwan; Kim, Donghyun; Kim, Kyujung

    2016-03-15

    Since the early 2000s, microfluidic cell culture systems have attracted significant attention as a promising alternative to conventional cell culture methods and the importance of designing an efficient detection system to analyze cell behavior on a chip in real time is raised. For this reason, various measurement techniques for microfluidic devices have been developed with the development of microfluidic assays for high-throughput screening and mimicking of in vivo conditions. In this review, we discuss optical measurement techniques for microfluidic assays. First of all, the recent development of fluorescence- and absorbance-based optical measurement systems is described. Next, advanced optical detection systems are introduced with respect to three emphases: 1) optimization for long-term, real-time, and in situ measurements; 2) performance improvements; and 3) multimodal analysis conjugations. Moreover, we explore presents future prospects for the establishment of optical detection systems following the development of complex, multi-dimensional microfluidic cell culture assays to mimic in vivo tissue, organ, and human systems. PMID:26409023

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

    PubMed

    Li, Xiao; Liu, Xinyu

    2016-06-01

    The first microfluidic paper-based origami nano-biosensor featuring zinc oxide nanowires and an electrochemical impedance spectroscopy biosensing mechanism, for label-free, ultrasensitive immunoassays is reported by X. Li and X. Liu on page 1326. The sensor consists of cellulose paper, a carbon ink electrode, and zinc oxide nanowires directly grown on the top. Possible parallelization of assays and high storage stability render the sensor promising for clinical diagnostics applications. PMID:27275629

  7. Papers Based Electrochemical Biosensors: From Test Strips to Paper-Based Microfluidics

    SciTech Connect

    Liu, Bingwen; Du, Dan; Hua, Xin; Yu, Xiao-Ying; Lin, Yuehe

    2014-05-08

    Papers based biosensors such as lateral flow test strips and paper-based microfluidic devices (or paperfluidics) are inexpensive, rapid, flexible, and easy-to-use analytical tools. An apparent trend in their detection is to interpret sensing results from qualitative assessment to quantitative determination. Electrochemical detection plays an important role in quantification. This review focuses on electrochemical (EC) detection enabled biosensors. The first part provides detailed examples in paper test strips. The second part gives an overview of paperfluidics engaging EC detections. The outlook and recommendation of future directions of EC enabled biosensors are discussed in the end.

  8. Microfluidic and Label-Free Multi-Immunosensors Based on Carbon Nanotube Microelectrodes

    NASA Astrophysics Data System (ADS)

    Tsujita, Yuichi; Maehashi, Kenzo; Matsumoto, Kazuhiko; Chikae, Miyuki; Takamura, Yuzuru; Tamiya, Eiichi

    2009-06-01

    We fabricated microfluidic and label-free multi-immunosensors by the integration of carbon nanotube (CNT)-arrayed electrodes and microchannels with pneumatic micropumps made of poly(dimethylsiloxane). In the microfluidic systems, four kinds of sample solutions were transported from each liquid inlet to microchannels using six pneumatic micropumps. As a result, two kinds of antibodies were immobilized onto different CNT electrodes using the microfluidic systems. Next, two kinds of cancer markers, prostate specific antigen and human chorionic gonadotropin in phosphate buffer solution, were simultaneously detected by differential pulse voltammetry. Therefore, microfludic multi-immunosensors based on CNT electrodes and pneumatic micropumps are useful for the development of multiplex hand-held biosensors.

  9. Multilayer soft lithography of perfluoropolyether based elastomer for microfluidic device fabrication.

    PubMed

    Devaraju, Naga Sai Gopi Krishna; Unger, Marc Alexander

    2011-06-01

    The compatibility of microfluidic devices with solvents and other chemicals is extremely important for many applications such as organic synthesis in microreactors and drug screening. We report the successful fabrication of microfluidic devices from a novel perfluoropolyether based polymer utilizing the Multilayer Soft Lithography™ (MSL) technique with simple, straightforward processing. The perfluorinated polymer SIFEL X-71 8115 is a highly chemically resistant elastomeric material. We demonstrate fabrication of a microfluidic device using an off-ratio bonding technique to bond multiple SIFEL layers, each patterned lithographically. The mechanical properties of the SIFEL MSL valves (including actuation pressures) are similar to PDMS MSL valves of the same geometry. Chemical compatibility tests highlight SIFEL's remarkable resistance to organic solvents, acids and alkalis. PMID:21503367

  10. Reduction in microparticle adsorption using a lateral interconnection method in a PDMS-based microfluidic device.

    PubMed

    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. PMID:24105848

  11. Microfluidic 3D cell culture: potential application for tissue-based bioassays

    PubMed Central

    Li, XiuJun (James); Valadez, Alejandra V.; Zuo, Peng; Nie, Zhihong

    2014-01-01

    Current fundamental investigations of human biology and the development of therapeutic drugs, commonly rely on two-dimensional (2D) monolayer cell culture systems. However, 2D cell culture systems do not accurately recapitulate the structure, function, physiology of living tissues, as well as highly complex and dynamic three-dimensional (3D) environments in vivo. The microfluidic technology can provide micro-scale complex structures and well-controlled parameters to mimic the in vivo environment of cells. The combination of microfluidic technology with 3D cell culture offers great potential for in vivo-like tissue-based applications, such as the emerging organ-on-a-chip system. This article will review recent advances in microfluidic technology for 3D cell culture and their biological applications. PMID:22793034

  12. Automated cell viability assessment using a microfluidics based portable imaging flow analyzer.

    PubMed

    Jagannadh, Veerendra Kalyan; Adhikari, Jayesh Vasudeva; Gorthi, Sai Siva

    2015-03-01

    In this work, we report a system-level integration of portable microscopy and microfluidics for the realization of optofluidic imaging flow analyzer with a throughput of 450 cells/s. With the use of a cellphone augmented with off-the-shelf optical components and custom designed microfluidics, we demonstrate a portable optofluidic imaging flow analyzer. A multiple microfluidic channel geometry was employed to demonstrate the enhancement of throughput in the context of low frame-rate imaging systems. Using the cell-phone based digital imaging flow analyzer, we have imaged yeast cells present in a suspension. By digitally processing the recorded videos of the flow stream on the cellphone, we demonstrated an automated cell viability assessment of the yeast cell population. In addition, we also demonstrate the suitability of the system for blood cell counting. PMID:26015835

  13. Automated cell viability assessment using a microfluidics based portable imaging flow analyzer

    PubMed Central

    Jagannadh, Veerendra Kalyan; Adhikari, Jayesh Vasudeva; Gorthi, Sai Siva

    2015-01-01

    In this work, we report a system-level integration of portable microscopy and microfluidics for the realization of optofluidic imaging flow analyzer with a throughput of 450 cells/s. With the use of a cellphone augmented with off-the-shelf optical components and custom designed microfluidics, we demonstrate a portable optofluidic imaging flow analyzer. A multiple microfluidic channel geometry was employed to demonstrate the enhancement of throughput in the context of low frame-rate imaging systems. Using the cell-phone based digital imaging flow analyzer, we have imaged yeast cells present in a suspension. By digitally processing the recorded videos of the flow stream on the cellphone, we demonstrated an automated cell viability assessment of the yeast cell population. In addition, we also demonstrate the suitability of the system for blood cell counting. PMID:26015835

  14. Nanostructured anatase-titanium dioxide based platform for application to microfluidics cholesterol biosensor

    NASA Astrophysics Data System (ADS)

    Azahar Ali, Md.; Srivastava, Saurabh; Solanki, Pratima R.; Varun Agrawal, Ved; John, Renu; Malhotra, Bansi D.

    2012-08-01

    We report results of studies relating to the fabrication of a microfluidics cholesterol sensor based on nanocrystalline anatase-titanium dioxide (ant-TiO2) film deposited onto indium tin oxide (ITO) glass. The results of response studies (optimized under the flow rate of 30 μl/min) conducted on cholesterol oxidase (ChOx) immobilized onto crystalline ant-TiO2 nanoparticles (˜27 nm)/ITO microfluidics electrode reveal linearity as 1.3 to 10.3 mM and improved sensitivity of 94.65 μA/mM/cm2. The observed low value of Km (0.14 mM) indicates high affinity of ChOx to cholesterol. No significant changes in current response of this microfluidics sensor are measured in the presence of different interferents.

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

    ERIC Educational Resources Information Center

    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…

  16. A Novel Microfluidic Flow Rate Detection Method Based on Surface Plasmon Resonance Temperature Imaging

    PubMed Central

    Deng, Shijie; Wang, Peng; Liu, Shengnan; Zhao, Tianze; Xu, Shanzhi; Guo, Mingjiang; Yu, Xinglong

    2016-01-01

    A novel microfluidic flow rate detection method based on surface plasmon resonance (SPR) temperature imaging is proposed. The measurement is performed by space-resolved SPR imaging of the flow induced temperature variations. Theoretical simulations and analysis were performed to demonstrate a proof of concept using this approach. Experiments were implemented and results showed that water flow rates within a wide range of tens to hundreds of μL/min could be detected. The flow rate sensor is resistant to disturbances and can be easily integrated into microfluidic lab-on-chip systems. PMID:27347960

  17. Note: A microfluidic freezer based on evaporative cooling of atomized aqueous microdroplets.

    PubMed

    Song, Jin; Chung, Minsub; Kim, Dohyun

    2015-01-01

    We report for the first time water-based evaporative cooling integrated into a microfluidic chip for temperature control and freezing of biological solution. We opt for water as a nontoxic, effective refrigerant. Aqueous solutions are atomized in our device and evaporation of microdroplets under vacuum removes heat effectively. We achieve rapid cooling (-5.1 °C/s) and a low freezing temperature (-14.1 °C). Using this approach, we demonstrate freezing of deionized water and protein solution. Our simple, yet effective cooling device may improve many microfluidic applications currently relying on external power-hungry instruments for cooling and freezing. PMID:25638130

  18. Note: A microfluidic freezer based on evaporative cooling of atomized aqueous microdroplets

    NASA Astrophysics Data System (ADS)

    Song, Jin; Chung, Minsub; Kim, Dohyun

    2015-01-01

    We report for the first time water-based evaporative cooling integrated into a microfluidic chip for temperature control and freezing of biological solution. We opt for water as a nontoxic, effective refrigerant. Aqueous solutions are atomized in our device and evaporation of microdroplets under vacuum removes heat effectively. We achieve rapid cooling (-5.1 °C/s) and a low freezing temperature (-14.1 °C). Using this approach, we demonstrate freezing of deionized water and protein solution. Our simple, yet effective cooling device may improve many microfluidic applications currently relying on external power-hungry instruments for cooling and freezing.

  19. Note: A microfluidic freezer based on evaporative cooling of atomized aqueous microdroplets

    SciTech Connect

    Song, Jin; Kim, Dohyun; Chung, Minsub

    2015-01-15

    We report for the first time water-based evaporative cooling integrated into a microfluidic chip for temperature control and freezing of biological solution. We opt for water as a nontoxic, effective refrigerant. Aqueous solutions are atomized in our device and evaporation of microdroplets under vacuum removes heat effectively. We achieve rapid cooling (−5.1 °C/s) and a low freezing temperature (−14.1 °C). Using this approach, we demonstrate freezing of deionized water and protein solution. Our simple, yet effective cooling device may improve many microfluidic applications currently relying on external power-hungry instruments for cooling and freezing.

  20. A Novel Microfluidic Flow Rate Detection Method Based on Surface Plasmon Resonance Temperature Imaging.

    PubMed

    Deng, Shijie; Wang, Peng; Liu, Shengnan; Zhao, Tianze; Xu, Shanzhi; Guo, Mingjiang; Yu, Xinglong

    2016-01-01

    A novel microfluidic flow rate detection method based on surface plasmon resonance (SPR) temperature imaging is proposed. The measurement is performed by space-resolved SPR imaging of the flow induced temperature variations. Theoretical simulations and analysis were performed to demonstrate a proof of concept using this approach. Experiments were implemented and results showed that water flow rates within a wide range of tens to hundreds of μL/min could be detected. The flow rate sensor is resistant to disturbances and can be easily integrated into microfluidic lab-on-chip systems. PMID:27347960

  1. Flexible microfluidic cloth-based analytical devices using a low-cost wax patterning technique.

    PubMed

    Nilghaz, Azadeh; Wicaksono, Dedy H B; Gustiono, Dwi; Abdul Majid, Fadzilah Adibah; Supriyanto, Eko; Abdul Kadir, Mohammed Rafiq

    2012-01-01

    This paper describes the fabrication of microfluidic cloth-based analytical devices (μCADs) using a simple wax patterning method on cotton cloth for performing colorimetric bioassays. Commercial cotton cloth fabric is proposed as a new inexpensive, lightweight, and flexible platform for fabricating two- (2D) and three-dimensional (3D) microfluidic systems. We demonstrated that the wicking property of the cotton microfluidic channel can be improved by scouring in soda ash (Na(2)CO(3)) solution which will remove the natural surface wax and expose the underlying texture of the cellulose fiber. After this treatment, we fabricated narrow hydrophilic channels with hydrophobic barriers made from patterned wax to define the 2D microfluidic devices. The designed pattern is carved on wax-impregnated paper, and subsequently transferred to attached cotton cloth by heat treatment. To further obtain 3D microfluidic devices having multiple layers of pattern, a single layer of wax patterned cloth can be folded along a predefined folding line and subsequently pressed using mechanical force. All the fabrication steps are simple and low cost since no special equipment is required. Diagnostic application of cloth-based devices is shown by the development of simple devices that wick and distribute microvolumes of simulated body fluids along the hydrophilic channels into reaction zones to react with analytical reagents. Colorimetric detection of bovine serum albumin (BSA) in artificial urine is carried out by direct visual observation of bromophenol blue (BPB) colour change in the reaction zones. Finally, we show the flexibility of the novel microfluidic platform by conducting a similar reaction in a bent pinned μCAD. PMID:22089026

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

    PubMed

    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. PMID:26627046

  3. Thiolene and SIFEL-based Microfluidic Platforms for Liquid-Liquid Extraction

    PubMed Central

    Goyal, Sachit; Desai, Amit V.; Lewis, Robert W.; Ranganathan, David R.; Li, Hairong; Zeng, Dexing; Reichert, David E.; Kenis, Paul J.A.

    2014-01-01

    Microfluidic platforms provide several advantages for liquid-liquid extraction (LLE) processes over conventional methods, for example with respect to lower consumption of solvents and enhanced extraction efficiencies due to the inherent shorter diffusional distances. Here, we report the development of polymer-based parallel-flow microfluidic platforms for LLE. To date, parallel-flow microfluidic platforms have predominantly been made out of silicon or glass due to their compatibility with most organic solvents used for LLE. Fabrication of silicon and glass-based LLE platforms typically requires extensive use of photolithography, plasma or laser-based etching, high temperature (anodic) bonding, and/or wet etching with KOH or HF solutions. In contrast, polymeric microfluidic platforms can be fabricated using less involved processes, typically photolithography in combination with replica molding, hot embossing, and/or bonding at much lower temperatures. Here we report the fabrication and testing of microfluidic LLE platforms comprised of thiolene or a perfluoropolyether-based material, SIFEL, where the choice of materials was mainly guided by the need for solvent compatibility and fabrication amenability. Suitable designs for polymer-based LLE platforms that maximize extraction efficiencies within the constraints of the fabrication methods and feasible operational conditions were obtained using analytical modeling. To optimize the performance of the polymer-based LLE platforms, we systematically studied the effect of surface functionalization and of microstructures on the stability of the liquid-liquid interface and on the ability to separate the phases. As demonstrative examples, we report (i) a thiolene-based platform to determine the lipophilicity of caffeine, and (ii) a SIFEL-based platform to extract radioactive copper from an acidic aqueous solution. PMID:25246730

  4. Thiolene and SIFEL-based Microfluidic Platforms for Liquid-Liquid Extraction.

    PubMed

    Goyal, Sachit; Desai, Amit V; Lewis, Robert W; Ranganathan, David R; Li, Hairong; Zeng, Dexing; Reichert, David E; Kenis, Paul J A

    2014-01-01

    Microfluidic platforms provide several advantages for liquid-liquid extraction (LLE) processes over conventional methods, for example with respect to lower consumption of solvents and enhanced extraction efficiencies due to the inherent shorter diffusional distances. Here, we report the development of polymer-based parallel-flow microfluidic platforms for LLE. To date, parallel-flow microfluidic platforms have predominantly been made out of silicon or glass due to their compatibility with most organic solvents used for LLE. Fabrication of silicon and glass-based LLE platforms typically requires extensive use of photolithography, plasma or laser-based etching, high temperature (anodic) bonding, and/or wet etching with KOH or HF solutions. In contrast, polymeric microfluidic platforms can be fabricated using less involved processes, typically photolithography in combination with replica molding, hot embossing, and/or bonding at much lower temperatures. Here we report the fabrication and testing of microfluidic LLE platforms comprised of thiolene or a perfluoropolyether-based material, SIFEL, where the choice of materials was mainly guided by the need for solvent compatibility and fabrication amenability. Suitable designs for polymer-based LLE platforms that maximize extraction efficiencies within the constraints of the fabrication methods and feasible operational conditions were obtained using analytical modeling. To optimize the performance of the polymer-based LLE platforms, we systematically studied the effect of surface functionalization and of microstructures on the stability of the liquid-liquid interface and on the ability to separate the phases. As demonstrative examples, we report (i) a thiolene-based platform to determine the lipophilicity of caffeine, and (ii) a SIFEL-based platform to extract radioactive copper from an acidic aqueous solution. PMID:25246730

  5. Microfluidic paper-based devices for bioanalytical applications.

    PubMed

    Santhiago, Murilo; Nery, Emilia W; Santos, Glauco P; Kubota, Lauro T

    2014-01-01

    Paper has become increasingly recognized as a very interesting substrate for the construction of microfluidic devices, with potential application in a variety of areas, including health diagnosis, environmental monitoring, immunoassays and food safety. The aim of this review is to present a short history of analytical systems constructed from paper, summarize the main advantages and disadvantages of fabrication techniques, exploit alternative methods of detection such as colorimetric, electrochemical, photoelectrochemical, chemiluminescence and electrochemiluminescence, as well as to take a closer look at the novel achievements in the field of bioanalysis published during the last 2 years. Finally, the future trends for production of such devices are discussed. PMID:24341497

  6. Droplet-based microfluidics for artificial cell generation: a brief review.

    PubMed

    Martino, Chiara; deMello, Andrew J

    2016-08-01

    Artificial cells are best defined as micrometre-sized structures able to mimic many of the morphological and functional characteristics of a living cell. In this mini-review, we describe progress in the application of droplet-based microfluidics for the generation of artificial cells and protocells. PMID:27499841

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

    ERIC Educational Resources Information Center

    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…

  8. FLASH: a rapid method for prototyping paper-based microfluidic devices.

    PubMed

    Martinez, Andres W; Phillips, Scott T; Wiley, Benjamin J; Gupta, Malancha; Whitesides, George M

    2008-12-01

    This article describes FLASH (Fast Lithographic Activation of Sheets), a rapid method for laboratory prototyping of microfluidic devices in paper. Paper-based microfluidic devices are emerging as a new technology for applications in diagnostics for the developing world, where low cost and simplicity are essential. FLASH is based on photolithography, but requires only a UV lamp and a hotplate; no clean-room or special facilities are required (FLASH patterning can even be performed in sunlight if a UV lamp and hotplate are unavailable). The method provides channels in paper with dimensions as small as 200 microm in width and 70 microm in height; the height is defined by the thickness of the paper. Photomasks for patterning paper-based microfluidic devices can be printed using an ink-jet printer or photocopier, or drawn by hand using a waterproof black pen. FLASH provides a straightforward method for prototyping paper-based microfluidic devices in regions where the technological support for conventional photolithography is not available. PMID:19023478

  9. FLASH: A rapid method for prototyping paper-based microfluidic devices‡

    PubMed Central

    Martinez, Andres W.; Phillips, Scott T.; Wiley, Benjamin J.; Gupta, Malancha

    2011-01-01

    This article describes FLASH (Fast Lithographic Activation of Sheets), a rapid method for laboratory prototyping of microfluidic devices in paper. Paper-based microfluidic devices are emerging as a new technology for applications in diagnostics for the developing world, where low cost and simplicity are essential. FLASH is based on photolithography, but requires only a UV lamp and a hotplate; no clean-room or special facilities are required (FLASH patterning can even be performed in sunlight if a UV lamp and hotplate are unavailable). The method provides channels in paper with dimensions as small as 200 μm in width and 70 μm in height; the height is defined by the thickness of the paper. Photomasks for patterning paper-based microfluidic devices can be printed using an ink-jet printer or photocopier, or drawn by hand using a waterproof black pen. FLASH provides a straightforward method for prototyping paper-based microfluidic devices in regions where the technological support for conventional photolithography is not available. PMID:19023478

  10. Low consumption single-use microvalve for microfluidic PCB-based platforms

    NASA Astrophysics Data System (ADS)

    Flores, G.; Aracil, C.; Perdigones, F.; Quero, J. M.

    2014-06-01

    In this paper, a single-use and unidirectional microvalve with low consumption of energy for PCB-based microfluidic platforms is reported. Its activation is easy because it works as a fuse. The fabrication process of the device is based on PCB technology and a typical SU-8 process, using the PCB as a substrate and SU-8 for the microfluidic channels and chambers. The microvalve is intended to be used to impulse small volumes of fluids and it has been designed to be highly integrable in PCB-based microfluidic platforms. The proposed device has been fabricated, integrated and tested in a general purpose microfluidic circuit, resulting in a low activation time, of about 100 μs, and a low consumption of energy, with a maximum of 27 mJ. These results show a significant improvement because the energy consumption is about 84% lower and the time response is about four orders of magnitude shorter if compared with similar microvalves for impulsion of fluids on PCB-based platforms.

  11. Carbon Nanotube Based Microfluidic Elements for Filtration and Concentration

    SciTech Connect

    Bakajin, O; Ben-Barak, N; Peng, J; Noy, A

    2003-06-25

    We have developed a method for integration of patterned arrays of carbon nanotubes or the ''nanotube mesh'' into microfabricated channels. The method includes standard lithographic methods for patterning and etching the substrate, followed by catalyst patterning, CVD deposition of nanotubes, and anodic bonding of coverslip top. We will describe a carbon nanotube filtering device fabricated using this method and discuss the use of carbon nanotube arrays as molecular concentration and separation media.

  12. Microfluidic paper-based biomolecule preconcentrator based on ion concentration polarization.

    PubMed

    Han, Sung Il; Hwang, Kyo Seon; Kwak, Rhokyun; Lee, Jeong Hoon

    2016-06-21

    Microfluidic paper-based analytical devices (μPADs) for molecular detection have great potential in the field of point-of-care diagnostics. Currently, a critical problem being faced by μPADs is improving their detection sensitivity. Various preconcentration processes have been developed, but they still have complicated structures and fabrication processes to integrate into μPADs. To address this issue, we have developed a novel paper-based preconcentrator utilizing ion concentration polarization (ICP) with minimal addition on lateral-flow paper. The cation selective membrane (i.e., Nafion) is patterned on adhesive tape, and this tape is then attached to paper-based channels. When an electric field is applied across the Nafion, ICP is initiated to preconcentrate the biomolecules in the paper channel. Departing from previous paper-based preconcentrators, we maintain steady lateral fluid flow with the separated Nafion layer; as a result, fluorescent dyes and proteins (FITC-albumin and bovine serum albumin) are continuously delivered to the preconcentration zone, achieving high preconcentration performance up to 1000-fold. In addition, we demonstrate that the Nafion-patterned tape can be integrated with various geometries (multiplexed preconcentrator) and platforms (string and polymer microfluidic channel). This work would facilitate integration of various ICP devices, including preconcentrators, pH/concentration modulators, and micro mixers, with steady lateral flows in paper-based platforms. PMID:27199301

  13. Calcium carbonate polymorph control using droplet-based microfluidics.

    PubMed

    Yashina, Alexandra; Meldrum, Fiona; Demello, Andrew

    2012-06-01

    Calcium carbonate (CaCO(3)) is one of the most abundant minerals and of high importance in many areas of science including global CO(2) exchange, industrial water treatment energy storage, and the formation of shells and skeletons. Industrially, calcium carbonate is also used in the production of cement, glasses, paints, plastics, rubbers, ceramics, and steel, as well as being a key material in oil refining and iron ore purification. CaCO(3) displays a complex polymorphic behaviour which, despite numerous experiments, remains poorly characterised. In this paper, we report the use of a segmented-flow microfluidic reactor for the controlled precipitation of calcium carbonate and compare the resulting crystal properties with those obtained using both continuous flow microfluidic reactors and conventional bulk methods. Through combination of equal volumes of equimolar aqueous solutions of calcium chloride and sodium carbonate on the picoliter scale, it was possible to achieve excellent definition of both crystal size and size distribution. Furthermore, highly reproducible control over crystal polymorph could be realised, such that pure calcite, pure vaterite, or a mixture of calcite and vaterite could be precipitated depending on the reaction conditions and droplet-volumes employed. In contrast, the crystals precipitated in the continuous flow and bulk systems comprised of a mixture of calcite and vaterite and exhibited a broad distribution of sizes for all reaction conditions investigated. PMID:22655005

  14. Quantum Dot-Bead-DNA Probe-Based Hybridization Fluorescence Assays on Microfluidic Chips.

    PubMed

    Ankireddy, Seshadri Reddy; Kim, Jongsung

    2015-10-01

    The development of chip-based, quantum dot (QD)-bead-DNA conjugate probes for hybridization detection is a prime research focus in the field of microfluidics. QD-Bead-DNA probe-based hybridization detection methods are often called "bead-based assays," and their success is substantially influenced by the dispensing and manipulation capabilities of microfluidic technology. Met was identified as a prognostic marker in different cancers including lung, renal, liver, head and neck, stomach, and breast. In this report, the cancer causing Met gene was detected with QDs attached to polystyrene microbeads. We constructed a microfluidic platform using a flexible PDMS polymer. The chip consists of two channels, with two inlets and two outlets. The two channels were integrated with QD-bead-DNA probes for simultaneous detection of wild type target DNA and mutant DNA, containing three nucleotide changes compared to the wild type sequence. The fluorescence quenching ability of QDs within the channels of microfluidic chips were compared for both DNAs. PMID:26726440

  15. Bead-based assays for biodetection: from flow-cytometry to microfluidics

    NASA Astrophysics Data System (ADS)

    Ozanich, Richard M., Jr.; Antolick, Kathryn; Bruckner-Lea, Cynthia J.; Bunch, Kyle J.; Dockendorff, Brian P.; Grate, Jay W.; Nash, Michael A.; Tyler, Abby; Warner, Cynthia L.; Warner, Marvin G.

    2009-05-01

    The potential for the use of biological agents by terrorists is a real threat. Two approaches for antibody-based detection of biological species are described in this paper: 1) The use of microbead arrays for multiplexed flow cytometry detection of cytokines and botulinum neurotoxin simulant, and 2) a microfluidic platform for capture and separation of different size superparamagnetic nanoparticles followed by on-chip fluorescence detection of the sandwich complex. These approaches both involve the use of automated fluidic systems for trapping antibody-functionalized microbeads, which allows sample, assay reagents, and wash solutions to be perfused over a micro-column of beads, resulting in faster and more sensitive immunoassays. The automated fluidic approach resulted in up to five-fold improvements in immunoassay sensitivity/speed as compared to identical immunoassays performed in a typical manual batch mode. A second approach for implementing multiplexed bead-based immunoassays without using flow cytometry detection is currently under development. The goal of the microfluidic-based approach is to achieve rapid (<20 minutes), multiplexed (>= 3 bioagents) detection using a simple and low-cost, integrated microfluidic/optical detection platform. Using fiber-optic guided laser-induced fluorescence, assay detection limits were shown to be in the 100's of picomolar range (10's of micrograms per liter) for botulinum neurotoxin simulant without any optimization of the microfluidic device or optical detection approach.

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

    PubMed

    Zhang, He; Fu, Xin; Hu, Jiayi; Zhu, Zhenjun

    2013-05-24

    This study reports the development of a microfluidic bead-based nucleic acid sensor for sensitive detection of circulating tumor cells in blood samples using multienzyme-nanoparticle amplification and quantum dot labels. In this method, the microbeads functionalized with the capture probes and modified electron rich proteins were arrayed within a microfluidic channel as sensing elements, and the gold nanoparticles (AuNPs) functionalized with the horseradish peroxidases (HRP) and DNA probes were used as labels. Hence, two signal amplification approaches are integrated for enhancing the detection sensitivity of circulating tumor cells. First, the large surface area of Au nanoparticle carrier allows several binding events of HRP on each nanosphere. Second, enhanced mass transport capability inherent from microfluidics leads to higher capture efficiency of targets because continuous flow within micro-channel delivers fresh analyte solution to the reaction site which maintains a high concentration gradient differential to enhance mass transport. Based on the dual signal amplification strategy, the developed microfluidic bead-based nucleic acid sensor could discriminate as low as 5 fM (signal-to-noise (S/N)3) of synthesized carcinoembryonic antigen (CEA) gene fragments and showed a 1000-fold increase in detection limit compared to the off-chip test. In addition, using spiked colorectal cancer cell lines (HT29) in the blood as a model system, the detection limit of this chip-based approach was found to be as low as 1 HT29 in 1 mL blood sample. This microfluidic bead-based nucleic acid sensor is a promising platform for disease-related nucleic acid molecules at the lowest level at their earliest incidence. PMID:23663673

  17. Portable Analyzer Based on Microfluidics/Nanoengineered Electrochemical Sensors for in Situ Characterization of Mixed Wastes

    SciTech Connect

    Wang, Joseph

    2006-06-01

    Portable Analyzer Based on Microfluidic/Nanoengineered Electrochemical Sensors for in Situ Characterization of Mixed Wastes PI: Dr. Joseph Wang (In Collaboration with the PNNL PI Dr. Y. Lin). Objective of Research: This research effort aims at developing a portable analytical system for fast, sensitive, and inexpensive, on-site monitoring of toxic transition metals and radionuclides in contaminated DOE Sites. The portable devices will be based on Microscale Total Analytical systems ( -TAS) or 'Lab-on-a-chip' in combination with electrochemical (stripping-voltammetric) sensors. The resulting microfluidics/electrochemical sensor system would allow testing for toxic metals to be performed more rapidly, inexpensively, and reliably in a field setting. Progress Summary/Accomplishments: This report summarizes the ASU activity over the second year of the project. In accordance to our original objectives our studies have focused on various fundamental and practical aspects of sensing and microchip devices for monitoring metal contaminants. As described in this section, we have made a substantial progress, and introduced effective routes for improving the on-site detection of toxic metals and for interfacing microchips with the real world. This activity has already resulted in 7 research papers (published or in press in major international journals). The electrochemical sensors being developed rely on the highly sensitive adsorptive stripping voltammetry (AdSV) technique to detect metal ions of interest to the DOE, particularly uranium and chromium. Traditionally, AdSV measurements of U and Cr require the use of mercury electrodes which are not suitable attractive for field deployment. Our initial goal was thus to replace these toxic mercury electrodes with 'environmentally-friendly' sensor materials. In particular, we demonstrated recently that bismuth-film electrodes offer high-quality measurements of heavy metals that compare favorably with that of mercury electrodes

  18. Bead-Based Assays for Biodetection: From Flow-Cytometry to Microfluidics

    SciTech Connect

    Ozanich, Richard M.; Antolick, Kathryn C.; Bruckner-Lea, Cindy J.; Bunch, Kyle J.; Dockendorff, Brian P.; Grate, Jay W.; Nash, Michael A.; Tyler, Abby J.

    2009-05-04

    ABSTRACT The potential for the use of biological agents by terrorists is a real threat. Two approaches for detection of biological species will be described: 1) The use of microbead arrays for multiplexed flow cytometry detection of cytokines and botulinum neurotoxin simulant, and 2) a microfluidic platform for capture and separation of different size superparamagnetic nanoparticles followed by on-chip fluorescence detection of the sandwich complex. The methods and automated fluidic systems used for trapping functionalized microbeads will be described. This approach allows sample, assay reagents, and wash solutions to be perfused over a micro-column of beads, resulting in faster and more sensitive assays. The automated fluidic approach resulted in up to five-fold improvements in assay sensitivity/speed as compared to identical assays performed in a typical manual batch mode. A second approach for implementing multiplexed bead-based assays without using flow cytometry detection is currently under development. The goal of the microfluidic-based approach is to achieve rapid (<20 minutes), multiplexed (> 3 bioagents) detection using a simple and low-cost, integrated microfluidic/optical detection platform. Using fiber-optic guided laser-induced fluorescence, assay detection limits were shown to be in the 100’s of picomolar range (10’s of micrograms per liter) for botulinum neurotoxin simulant without any optimization of the microfluidic device or optical detection approach. Video taping magnetic nanoparticle capture and release was used to improve understanding of the process and revealed interesting behavior.

  19. Highly Stable Liquid Metal-Based Pressure Sensor Integrated with a Microfluidic Channel

    PubMed Central

    Jung, Taekeon; Yang, Sung

    2015-01-01

    Pressure measurement is considered one of the key parameters in microfluidic systems. It has been widely used in various fields, such as in biology and biomedical fields. The electrical measurement method is the most widely investigated; however, it is unsuitable for microfluidic systems because of a complicated fabrication process and difficult integration. Moreover, it is generally damaged by large deflection. This paper proposes a thin-film-based pressure sensor that is free from these limitations, using a liquid metal called galinstan. The proposed pressure sensor is easily integrated into a microfluidic system using soft lithography because galinstan exists in a liquid phase at room temperature. We investigated the characteristics of the proposed pressure sensor by calibrating for a pressure range from 0 to 230 kPa (R2 > 0.98) using deionized water. Furthermore, the viscosity of various fluid samples was measured for a shear-rate range of 30–1000 s−1. The results of Newtonian and non-Newtonian fluids were evaluated using a commercial viscometer and normalized difference was found to be less than 5.1% and 7.0%, respectively. The galinstan-based pressure sensor can be used in various microfluidic systems for long-term monitoring with high linearity, repeatability, and long-term stability. PMID:26007732

  20. Highly stable liquid metal-based pressure sensor integrated with a microfluidic channel.

    PubMed

    Jung, Taekeon; Yang, Sung

    2015-01-01

    Pressure measurement is considered one of the key parameters in microfluidic systems. It has been widely used in various fields, such as in biology and biomedical fields. The electrical measurement method is the most widely investigated; however, it is unsuitable for microfluidic systems because of a complicated fabrication process and difficult integration. Moreover, it is generally damaged by large deflection. This paper proposes a thin-film-based pressure sensor that is free from these limitations, using a liquid metal called galinstan. The proposed pressure sensor is easily integrated into a microfluidic system using soft lithography because galinstan exists in a liquid phase at room temperature. We investigated the characteristics of the proposed pressure sensor by calibrating for a pressure range from 0 to 230 kPa (R2 > 0.98) using deionized water. Furthermore, the viscosity of various fluid samples was measured for a shear-rate range of 30-1000 s(-1). The results of Newtonian and non-Newtonian fluids were evaluated using a commercial viscometer and normalized difference was found to be less than 5.1% and 7.0%, respectively. The galinstan-based pressure sensor can be used in various microfluidic systems for long-term monitoring with high linearity, repeatability, and long-term stability. PMID:26007732

  1. Entropy-based separation of yeast cells using a microfluidic system of conjoined spheres

    SciTech Connect

    Huang, Kai-Jian; Qin, S.-J. Bai, Zhong-Chen; Zhang, Xin; Mai, John D.

    2013-11-21

    A physical model is derived to create a biological cell separator that is based on controlling the entropy in a microfluidic system having conjoined spherical structures. A one-dimensional simplified model of this three-dimensional problem in terms of the corresponding effects of entropy on the Brownian motion of particles is presented. This dynamic mechanism is based on the Langevin equation from statistical thermodynamics and takes advantage of the characteristics of the Fokker-Planck equation. This mechanism can be applied to manipulate biological particles inside a microfluidic system with identical, conjoined, spherical compartments. This theoretical analysis is verified by performing a rapid and a simple technique for separating yeast cells in these conjoined, spherical microfluidic structures. The experimental results basically match with our theoretical model and we further analyze the parameters which can be used to control this separation mechanism. Both numerical simulations and experimental results show that the motion of the particles depends on the geometrical boundary conditions of the microfluidic system and the initial concentration of the diffusing material. This theoretical model can be implemented in future biophysics devices for the optimized design of passive cell sorters.

  2. Microfluidic-based metal enhanced fluorescence for capillary electrophoresis by Ag nanorod arrays

    NASA Astrophysics Data System (ADS)

    Xiao, Chenyu; Cao, Zhen; Deng, Junhong; Huang, Zhifeng; Xu, Zheng; Fu, Junxue; Yobas, Levent

    2014-06-01

    As metal nanorods show much higher metal enhanced fluorescence (MEF) than metal nanospheres, microfluidic-based MEF is first explored with Ag nanorod (ND) arrays made by oblique angle deposition. By measuring the fluorescein isothiocyanate (FITC) solution sandwiched between the Ag NDs and a piece of cover slip, the enhancement factors (EFs) are found as 3.7 ± 0.64 and 6.74 ± 2.04, for a solution thickness at 20.8 μm and 10 μm, respectively. Because of the strong plasmonic coupling between the adjacent Ag NDs, only the emission of the fluorophores present in the three-dimensional NDs array gets enhanced. Thus, the corresponding effective enhancement factors (EEFs) are revealed to be relatively close, 259 ± 92 and 340 ± 102, respectively. To demonstrate the application of MEF in microfluidic systems, a multilayer of SiO2 NDs/Ag NDs is integrated with a capillary electrophoresis device. At a microchannel depth of 10 μm, an enhancement of 6.5 fold is obtained for amino acids separation detection. These results are very encouraging and open the possibility of MEF applications for the Ag ND arrays decorated microchannels. With the miniaturization of microfluidic devices, microfluidic-based MEF by Ag ND arrays will likely find more applications with further enhancement.

  3. A multiplexed immunoassay system based upon reciprocating centrifugal microfluidics

    PubMed Central

    Noroozi, Zahra; Kido, Horacio; Peytavi, Régis; Nakajima-Sasaki, Rie; Jasinskas, Algimantas; Micic, Miodrag; Felgner, Philip L.; Madou, Marc J.

    2011-01-01

    A novel, centrifugal disk-based micro-total analysis system (μTAS) for low cost and high throughput semi-automated immunoassay processing was developed. A key innovation in the disposable immunoassay disk design is in a fluidic structure that enables very efficient micro-mixing based on a reciprocating mechanism in which centrifugal acceleration acting upon a liquid element first generates and stores pneumatic energy that is then released by a reduction of the centrifugal acceleration, resulting in a reversal of direction of flow of the liquid. Through an alternating sequence of high and low centrifugal acceleration, the system reciprocates the flow of liquid within the disk to maximize incubation/hybridization efficiency between antibodies and antigen macromolecules during the incubation/hybridization stage of the assay. The described reciprocating mechanism results in a reduction in processing time and reagent consumption by one order of magnitude. PMID:21721711

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

    PubMed

    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. PMID:26899264

  5. Microfluidic barcode assay for antibody-based confirmatory diagnostics.

    PubMed

    Araz, M Kursad; Apori, Akwasi A; Salisbury, Cleo M; Herr, Amy E

    2013-10-01

    Confirmatory diagnostics offer high clinical sensitivity and specificity typically by assaying multiple disease biomarkers. Employed in clinical laboratory settings, such assays confirm a positive screening diagnostic result. These important multiplexed confirmatory assays require hours to complete. To address this performance gap, we introduce a simple 'single inlet, single outlet' microchannel architecture with multiplexed analyte detection capability. A streptavidin-functionalized, channel-filling polyacrylamide gel in a straight glass microchannel operates as a 3D scaffold for a purely electrophoretic yet heterogeneous immunoassay. Biotin and biotinylated capture reagents are patterned in discrete regions along the axis of the microchannel resulting in a barcode-like pattern of reagents and spacers. To characterize barcode fabrication, an empirical study of patterning behaviour was conducted across a range of electromigration and binding reaction timescales. We apply the heterogeneous barcode immunoassay to detection of human antibodies against hepatitis C virus and human immunodeficiency virus antigens. Serum was electrophoresed through the barcode patterned gel, allowing capture of antibody targets. We assess assay performance across a range of Damkohler numbers. Compared to clinical immunoblots that require 4-10 h long sample incubation steps with concomitant 8-20 h total assay durations; directed electromigration and reaction in the microfluidic barcode assay leads to a 10 min sample incubation step and a 30 min total assay duration. Further, the barcode assay reports clinically relevant sensitivity (25 ng ml(-1) in 2% human sera) comparable to standard HCV confirmatory diagnostics. Given the low voltage, low power and automated operation, we see the streamlined microfluidic barcode assay as a step towards rapid confirmatory diagnostics for a low-resource clinical laboratory setting. PMID:23925585

  6. A microfluidic paper-based electrochemical biosensor array for multiplexed detection of metabolic biomarkers

    NASA Astrophysics Data System (ADS)

    Zhao, Chen; Thuo, Martin M.; Liu, Xinyu

    2013-10-01

    Paper-based microfluidic devices have emerged as simple yet powerful platforms for performing low-cost analytical tests. This paper reports a microfluidic paper-based electrochemical biosensor array for multiplexed detection of physiologically relevant metabolic biomarkers. Different from existing paper-based electrochemical devices, our device includes an array of eight electrochemical sensors and utilizes a handheld custom-made electrochemical reader (potentiostat) for signal readout. The biosensor array can detect several analytes in a sample solution and produce multiple measurements for each analyte from a single run. Using the device, we demonstrate simultaneous detection of glucose, lactate and uric acid in urine, with analytical performance comparable to that of the existing commercial and paper-based platforms. The paper-based biosensor array and its electrochemical reader will enable the acquisition of high-density, statistically meaningful diagnostic information at the point of care in a rapid and cost-efficient way.

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

    PubMed

    Dak, Piyush; Ebrahimi, Aida; Swaminathan, Vikhram; Duarte-Guevara, Carlos; Bashir, Rashid; Alam, Muhammad A

    2016-01-01

    Low cost, portable sensors can transform health care by bringing easily available diagnostic devices to low and middle income population, particularly in developing countries. Sample preparation, analyte handling and labeling are primary cost concerns for traditional lab-based diagnostic systems. Lab-on-a-chip (LoC) platforms based on droplet-based microfluidics promise to integrate and automate these complex and expensive laboratory procedures onto a single chip; the cost will be further reduced if label-free biosensors could be integrated onto the LoC platforms. Here, we review some recent developments of label-free, droplet-based biosensors, compatible with "open" digital microfluidic systems. These low-cost droplet-based biosensors overcome some of the fundamental limitations of the classical sensors, enabling timely diagnosis. We identify the key challenges that must be addressed to make these sensors commercially viable and summarize a number of promising research directions. PMID:27089377

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

    PubMed Central

    Dak, Piyush; Ebrahimi, Aida; Swaminathan, Vikhram; Duarte-Guevara, Carlos; Bashir, Rashid; Alam, Muhammad A.

    2016-01-01

    Low cost, portable sensors can transform health care by bringing easily available diagnostic devices to low and middle income population, particularly in developing countries. Sample preparation, analyte handling and labeling are primary cost concerns for traditional lab-based diagnostic systems. Lab-on-a-chip (LoC) platforms based on droplet-based microfluidics promise to integrate and automate these complex and expensive laboratory procedures onto a single chip; the cost will be further reduced if label-free biosensors could be integrated onto the LoC platforms. Here, we review some recent developments of label-free, droplet-based biosensors, compatible with “open” digital microfluidic systems. These low-cost droplet-based biosensors overcome some of the fundamental limitations of the classical sensors, enabling timely diagnosis. We identify the key challenges that must be addressed to make these sensors commercially viable and summarize a number of promising research directions. PMID:27089377

  9. A Multi-Phase Based Fluid-Structure-Microfluidic interaction sensor for Aerodynamic Shear Stress

    NASA Astrophysics Data System (ADS)

    Hughes, Christopher; Dutta, Diganta; Bashirzadeh, Yashar; Ahmed, Kareem; Qian, Shizhi

    2014-11-01

    A novel innovative microfluidic shear stress sensor is developed for measuring shear stress through multi-phase fluid-structure-microfluidic interaction. The device is composed of a microfluidic cavity filled with an electrolyte liquid. Inside the cavity, two electrodes make electrochemical velocimetry measurements of the induced convection. The cavity is sealed with a flexible superhydrophobic membrane. The membrane will dynamically stretch and flex as a result of direct shear cross-flow interaction with the seal structure, forming instability wave modes and inducing fluid motion within the microfluidic cavity. The shear stress on the membrane is measured by sensing the induced convection generated by membrane deflections. The advantages of the sensor over current MEMS based shear stress sensor technology are: a simplified design with no moving parts, optimum relationship between size and sensitivity, no gaps such as those created by micromachining sensors in MEMS processes. We present the findings of a feasibility study of the proposed sensor including wind-tunnel tests, microPIV measurements, electrochemical velocimetry, and simulation data results. The study investigates the sensor in the supersonic and subsonic flow regimes. Supported by a NASA SBIR phase 1 contract.

  10. Microfluidic flowmeter based on micro "hot-wire" sandwiched Fabry-Perot interferometer.

    PubMed

    Li, Ying; Yan, Guofeng; Zhang, Liang; He, Sailing

    2015-04-01

    We present a compact microfluidic flowmeter based on Fabry-Perot interferometer (FPI). The FPI was composed by a pair of fiber Bragg grating reflectors and a micro Co(2+)-doped optical fiber cavity, acting as a "hot-wire" sensor. Microfluidic channels made from commercial silica capillaries were integrated with the FPIs on a chip to realize flow-rate sensing system. By utilizing a tunable pump laser with wavelength of 1480 nm, the proposed flowmeter was experimentally demonstrated. The flow rate of the liquid sample is determined by the induced resonance wavelength shift of the FPI. The effect of the pump power, microfluidic channel scale and temperature on the performance of our flowmeter was investigated. The dynamic response was also measured under different flow-rate conditions. The experimental results achieve a sensitivity of 70 pm/(μL/s), a dynamic range up to 1.1 μL/s and response time in the level of seconds, with a spatial resolution ~200 μm. Such good performance renders the sensor a promising supplementary component in microfluidic biochemical sensing system. Furthermore, simulation modal was built up to analyze the heat distribution of the "hot-wire" cavity and optimize the FPI structure as well. PMID:25968776

  11. Continuous isolation of monocytes using a magnetophoretic-based microfluidic Chip.

    PubMed

    Darabi, Jeff; Guo, Chuan

    2016-10-01

    Monocytes play an important role in the immune system and are responsible for phagocytizing and degrading foreign microorganisms in the body. The isolation of monocytes is important in various immunological applications such as in-vitro culture of dendritic cells. We present a magnetophoretic-based microfluidic chip for rapid isolation of highly purified, untouched monocytes from human blood by a negative selection method. This bioseparation platform integrates several unique features into a microfluidic device, including locally engineered magnetic field gradients and a continuous flow with a buffer switching scheme to improve the performance of the cell separation process. The results indicate high monocyte purity and recovery performances at a volumetric flow rate that is nearly an order of magnitude larger than comparable microfluidic devices reported in literature. In addition, a comprehensive 2-D computational modeling is performed to determine the cell trajectory and trapping length within the microfluidic chip. Furthermore, the effects of channel height, substrate thickness, cell size, number of beads per cell, and sample flow rate on the cell separation performance are studied. PMID:27518600

  12. Low cost microfluidic device based on cotton threads for electroanalytical application.

    PubMed

    Agustini, Deonir; Bergamini, Márcio F; Marcolino-Junior, Luiz Humberto

    2016-01-21

    Microfluidic devices are an interesting alternative for performing analytical assays, due to the speed of analyses, reduced sample, reagent and solvent consumption and less waste generation. However, the high manufacturing costs still prevent the massive use of these devices worldwide. Here, we present the construction of a low cost microfluidic thread-based electroanalytical device (μTED), employing extremely cheap materials and a manufacturing process free of equipment. The microfluidic channels were built with cotton threads and the estimated cost per device was only $0.39. The flow of solutions (1.12 μL s(-1)) is generated spontaneously due to the capillary forces, eliminating the use of any pumping system. To demonstrate the analytical performance of the μTED, a simultaneous determination of acetaminophen (ACT) and diclofenac (DCF) was performed by multiple pulse amperometry (MPA). A linear dynamic range (LDR) of 10 to 320 μmol L(-1) for both species, a limit of detection (LOD) and a limit of quantitation (LOQ) of 1.4 and 4.7 μmol L(-1) and 2.5 and 8.3 μmol L(-1) for ACT and DCF, respectively, as well as an analytical frequency of 45 injections per hour were reached. Thus, the proposed device has shown potential to extend the use of microfluidic analytical devices, due to its simplicity, low cost and good analytical performance. PMID:26659997

  13. Continuous perfusion microfluidic cell culture array for high-throughput cell-based assays.

    PubMed

    Hung, Paul J; Lee, Philip J; Sabounchi, Poorya; Lin, Robert; Lee, Luke P

    2005-01-01

    We present for the first time a microfluidic cell culture array for long-term cellular monitoring. The 10 x 10 array could potentially assay 100 different cell-based experiments in parallel. The device was designed to integrate the processes used in typical cell culture experiments on a single self-contained microfluidic system. Major functions include repeated cell growth/passage cycles, reagent introduction, and real-time optical analysis. The single unit of the array consists of a circular microfluidic chamber, multiple narrow perfusion channels surrounding the main chamber, and four ports for fluidic access. Human carcinoma (HeLa) cells were cultured inside the device with continuous perfusion of medium at 37 degrees C. The observed doubling time was 1.4 +/- 0.1 days with a peak cell density of approximately 2.5*10(5) cells/cm(2). Cell assay was demonstrated by monitoring the fluorescence localization of calcein AM from 1 min to 10 days after reagent introduction. Confluent cell cultures were passaged within the microfluidic chambers using trypsin and successfully regrown, suggesting a stable culture environment suitable for continuous operation. The cell culture array could offer a platform for a wide range of assays with applications in drug screening, bioinformatics, and quantitative cell biology. PMID:15580587

  14. Development and Fabrication of Nanoporous Silicon-based Bioreactors within a Microfluidic Chip

    SciTech Connect

    Siuti, Piro; Choi, Chang Kyoung; Doktycz, Mitchel John; Retterer, Scott T

    2010-01-01

    Multi-scale lithography and cryogenic deep reactive ion etching techniques were used to create ensembles of nanoporous, picoliter volume, reaction vessels within a microfluidic system. The fabrication of these vessels is described and how this process can be used to tailor vessel porosity by controlling the width of slits that constitute the vessel pores is demonstrated. Control of pore size allows the containment of nucleic acids and enzymes that are the foundation of biochemical reaction systems, while allowing smaller reaction constituents to traverse the container membrane and continuously supply the reaction. In this work, a 5.4kB DNA plasmid was retained within the reaction vessels and labeled under microfluidic control with ethidium bromide as an initial proof-of-principle. Subsequently, a coupled enzyme reaction, in which glucose oxidase and horseradish peroxidase were contained and fed with a substrate solution of glucose and Amplex Red to produce fluorescent Resorufin, was carried out under microfluidic control and monitored using fluorescent microscopy. The fabrication techniques presented are broadly applicable and can be adapted to produce devices in which a variety of high aspect ratio, nanoporous silicon structures can be integrated within a microfluidic network. The devices shown here are amenable to being scaled in number and organized to implement more complex reaction systems for applications in sensing and production of biologically based therapeutics as well as fundamental studies of biological reaction systems.

  15. Single-cell analysis and sorting using droplet-based microfluidics

    PubMed Central

    Mazutis, Linas; Gilbert, John; Ung, W Lloyd; Weitz, David A; Griffiths, Andrew D; Heyman, John A

    2014-01-01

    We present a droplet-based microfluidics protocol for high-throughput analysis and sorting of single cells. compartmentalization of single cells in droplets enables the analysis of proteins released from or secreted by cells, thereby overcoming one of the major limitations of traditional flow cytometry and fluorescence-activated cell sorting. as an example of this approach, we detail a binding assay for detecting antibodies secreted from single mouse hybridoma cells. secreted antibodies are detected after only 15 min by co-compartmentalizing single mouse hybridoma cells, a fluorescent probe and single beads coated with anti-mouse IgG antibodies in 50-pl droplets. the beads capture the secreted antibodies and, when the captured antibodies bind to the probe, the fluorescence becomes localized on the beads, generating a clearly distinguishable fluorescence signal that enables droplet sorting at ~200 Hz as well as cell enrichment. the microfluidic system described is easily adapted for screening other intracellular, cell-surface or secreted proteins and for quantifying catalytic or regulatory activities. In order to screen ~1 million cells, the microfluidic operations require 2–6 h; the entire process, including preparation of microfluidic devices and mammalian cells, requires 5–7 d. PMID:23558786

  16. Real time culture and analysis of embryo metabolism using a microfluidic device with deformation based actuation.

    PubMed

    Heo, Yun Seok; Cabrera, Lourdes M; Bormann, Charles L; Smith, Gary D; Takayama, Shuichi

    2012-06-21

    We report a computerized microfluidic real time embryo culture and assay device that can perform automated periodic analyses of embryo metabolism. This automated program uses a modified "gated injection" scheme (sample injection, reagent mixing, enzyme reaction of 15 min incubation, and sample detection) to sequentially measure fluorescence from sample, reference, and background (without any analyte) every hour. Measurements assessed with reference solutions demonstrated the stability of these microfluidic measurements over a 24 h period. Furthermore, this system was able to measure time dependent nutrient consumption by single or multiple (10) live mouse blastocyst-stage embryos with pmol h(-1) sensitivity. Mechanical deformation-based microfluidic actuation created by computerized movement of Braille pins enables automated fluid pumping and valving sequences without unwanted gravity-driven backflow or exposure to electrical fields as would be required in electrokinetic schemes. The convenient, non-invasive, and automated nature of these assays open the way for the development of integrated microfluidic platforms for practical single embryo culture and real time biochemical analysis to assess embryo viability and select embryos with the greatest implantation potential, thus improving success in clinical assisted reproductive technology laboratories. PMID:22402469

  17. Laser Ablation of Polymer Microfluidic Devices

    NASA Astrophysics Data System (ADS)

    Killeen, Kevin

    2004-03-01

    Microfluidic technology is ideal for processing precious samples of limited volumes. Some of the most important classes of biological samples are both high in sample complexity and low in concentration. Combining the elements of sample pre-concentration, chemical separation and high sensitivity detection with chemical identification is essential for realizing a functional microfluidic based analysis system. Direct write UV laser ablation has been used to rapidly fabricate microfluidic devices capable of high performance liquid chromatography (HPLC)-MS. These chip-LC/MS devices use bio-compatible, solvent resistant and flexible polymer materials such as polyimide. A novel microfluidic to rotary valve interface enables, leak free, high pressure fluid switching between multiple ports of the microfluidic chip-LC/MS device. Electrospray tips with outer dimension of 50 um and inner of 15 um are formed by ablating the polymer material concentrically around a multilayer laminated channel structure. Biological samples of digested proteins were used to evaluate the performance of these microfluidic devices. Liquid chromatography separation and similar sample pretreatments have been performed using polymeric microfluidic devices with on-chip separation channels. Mass spectrometry was performed using an Agilent Technologies 1100 series ion trap mass spectrometer. Low fmol amounts of protein samples were positively and routinely identified by searching the MS/MS spectral data against protein databases. The sensitivity and separation performance of the chip-LC devices has been found to be comparable to state of the art nano-electrospray systems.

  18. Three-dimensional, paper-based microfluidic devices containing internal timers for running time-based diagnostic assays.

    PubMed

    Phillips, Scott T; Thom, Nicole K

    2013-01-01

    This chapter describes a method for fabricating three-dimensional (3D), paper-based microfluidic devices that contain internal timers for running quantitative, time-based assays. The method involves patterning microfluidic channels into paper, and cutting double-sided adhesive tape into defined patterns. Patterned paper and tape are assembled layer by layer to create 3D microfluidic devices that are capable of distributing microliter volumes of a sample into multiple regions on a device for conducting multiple assays simultaneously. Paraffin wax is incorporated into defined regions within the device to provide control over the distribution rate of a sample, and food coloring is included in defined regions within the device to provide an unambiguous readout when the sample has reached the bottom of the device (this latter feature is the endpoint of the timer). PMID:23329444

  19. Biocompatible fluorinated polyglycerols for droplet microfluidics as an alternative to PEG-based copolymer surfactants.

    PubMed

    Wagner, Olaf; Thiele, Julian; Weinhart, Marie; Mazutis, Linas; Weitz, David A; Huck, Wilhelm T S; Haag, Rainer

    2016-01-01

    In droplet-based microfluidics, non-ionic, high-molecular weight surfactants are required to stabilize droplet interfaces. One of the most common structures that imparts stability as well as biocompatibility to water-in-oil droplets is a triblock copolymer surfactant composed of perfluoropolyether (PFPE) and polyethylene glycol (PEG) blocks. However, the fast growing applications of microdroplets in biology would benefit from a larger choice of specialized surfactants. PEG as a hydrophilic moiety, however, is a very limited tool in surfactant modification as one can only vary the molecular weight and chain-end functionalization. In contrast, linear polyglycerol offers further side-chain functionalization to create custom-tailored, biocompatible droplet interfaces. Herein, we describe the synthesis and characterization of polyglycerol-based triblock surfactants with tailored side-chain composition, and exemplify their application in cell encapsulation and in vitro gene expression studies in droplet-based microfluidics. PMID:26626826

  20. A laser-based technology for fabricating a soda-lime glass based microfluidic device for circulating tumour cell capture.

    PubMed

    Nieto, Daniel; Couceiro, Ramiro; Aymerich, Maria; Lopez-Lopez, Rafael; Abal, Miguel; Flores-Arias, María Teresa

    2015-10-01

    We developed a laser-based technique for fabricating microfluidic microchips on soda-lime glass substrates. The proposed methodology combines a laser direct writing, as a manufacturing tool for the fabrication of the microfluidics structures, followed by a post-thermal treatment with a CO2 laser. This treatment will allow reshaping and improving the morphological (roughness) and optical qualities (transparency) of the generated microfluidics structures. The use of lasers commonly implemented for material processing makes this technique highly competitive when compared with other glass microstructuring approaches. The manufactured chips were tested with tumour cells (Hec 1A) after being functionalized with an epithelial cell adhesion molecule (EpCAM) antibody coating. Cells were successfully arrested on the pillars after being flown through the device giving our technology a translational application in the field of cancer research. PMID:26218523

  1. Hydrogel-based microfluidic incubator for microorganism cultivation and analyses.

    PubMed

    Puchberger-Enengl, Dietmar; van den Driesche, Sander; Krutzler, Christian; Keplinger, Franz; Vellekoop, Michael J

    2015-01-01

    This work presents an array of microfluidic chambers for on-chip culturing of microorganisms in static and continuous shear-free operation modes. The unique design comprises an in-situ polymerized hydrogel that forms gas and reagent permeable culture wells in a glass chip. Utilizing a hydrophilic substrate increases usability by autonomous capillary priming. The thin gel barrier enables efficient oxygen supply and facilitates on-chip analysis by chemical access through the gel without introducing a disturbing flow to the culture. Trapping the suspended microorganisms inside a gel well allows for a much simpler fabrication than in conventional trapping devices as the minimal feature size does not depend on cell size. Nutrients and drugs are provided on-chip in the gel for a self-contained and user-friendly handling. Rapid antibiotic testing in static cultures with strains of Enterococcus faecalis and Escherichia coli is presented. Cell seeding and diffusive medium supply is provided by phaseguide technology, enabling simple operation of continuous culturing with a great flexibility. Cells of Saccharomyces cerevisiae are utilized as a model to demonstrate continuous on-chip culturing. PMID:25784966

  2. An Early-Stage Atherosclerosis Research Model Based on Microfluidics.

    PubMed

    Zheng, Wenfu; Huang, Rong; Jiang, Bo; Zhao, Yuyun; Zhang, Wei; Jiang, Xingyu

    2016-04-01

    The arterial microenvironment plays a vital role in the pathology of atherosclerosis (AS). However, the interplay between the arterial microenvironment and atherogenesis remains unclear, partially due to the gap between cell culture and animal experiments. Addressing this problem, the present study reports a microfluidic AS model reconstituting early-stage AS. Physiological or AS-prone hemodynamic conditions are recapitulated on the model. The on-chip model recaptures the atherogenic responses of endothelial cells (ECs) in ways that the Petri dish could not. Significant cytotoxicity of a clinical anti-atherosclerotic drug probucol is discovered on the model, which does not appear on Petri dish but is supported by previous clinical evidence. Moreover, the anti-AS efficiency of platinum-nanoparticles (Pt-NPs) on the model shows excellent consistency with animal experiments. The early-stage AS model shows an excellent connection between Petri dish and animal experiments and highlights its promising role in bridging fundamental AS research, drug screening, and clinical trials. PMID:26890624

  3. Hydrogel-based microfluidic incubator for microorganism cultivation and analyses

    PubMed Central

    van den Driesche, Sander; Krutzler, Christian; Keplinger, Franz; Vellekoop, Michael J.

    2015-01-01

    This work presents an array of microfluidic chambers for on-chip culturing of microorganisms in static and continuous shear-free operation modes. The unique design comprises an in-situ polymerized hydrogel that forms gas and reagent permeable culture wells in a glass chip. Utilizing a hydrophilic substrate increases usability by autonomous capillary priming. The thin gel barrier enables efficient oxygen supply and facilitates on-chip analysis by chemical access through the gel without introducing a disturbing flow to the culture. Trapping the suspended microorganisms inside a gel well allows for a much simpler fabrication than in conventional trapping devices as the minimal feature size does not depend on cell size. Nutrients and drugs are provided on-chip in the gel for a self-contained and user-friendly handling. Rapid antibiotic testing in static cultures with strains of Enterococcus faecalis and Escherichia coli is presented. Cell seeding and diffusive medium supply is provided by phaseguide technology, enabling simple operation of continuous culturing with a great flexibility. Cells of Saccharomyces cerevisiae are utilized as a model to demonstrate continuous on-chip culturing. PMID:25784966

  4. Fabrication of monodisperse liposomes-in-microgel hybrid microparticles in capillary-based microfluidic devices.

    PubMed

    Jeong, Eun Seon; Son, Han Am; Kim, Min Kyung; Park, Kyoung-Ho; Kay, Sechan; Chae, Pil Seok; Kim, Jin Woong

    2014-11-01

    This study introduces a drop-based microfluidic approach to physically immobilize liposomes in microgel (liposomes-in-microgel) particles. For this, we generate a uniform liposomes-in-water-in-oil emulsion in a capillary-based microfluidic device. Basically, we have investigated how the flow rate and flow composition affect generation of emulsion precursor drops in micro-channels. Then, the precursor emulsion drops are solidified by photo-polymerization. From characterization of hydrogel mesh sizes, we have figured out that the mesh size of the liposomes-in-microgel particles is bigger than that of bare microgel particles, since liposomes take space in the hydrogel phase. In our further study on drug releasing, we have observed that immobilization of liposomes in the microgel particles can not only remarkably retard drug releasing, but also enables a sustained release, which stems from the enhanced matrix viscosity of the surrounding hydrogel phase. PMID:25288532

  5. A Laplace pressure based microfluidic trap for passive droplet trapping and controlled release

    PubMed Central

    Simon, Melinda G.; Lin, Robert; Fisher, Jeffrey S.; Lee, Abraham P.

    2012-01-01

    Here, we present a microfluidic droplet trap that takes advantage of the net Laplace pressure force generated when a droplet is differentially constricted. Mathematical simulations were first used to understand the working range of the component; followed by finite element modeling using the CFD software package to further characterize the behavior of the system. Controlled release of the trapped droplets is also demonstrated through both a mechanical method and a chemical method that manipulates the total pressure exerted on the trapped droplet. The unique design of this trapping device also provides the capability for selection of a single droplet from a train, as well as droplet fusion. PMID:22662095

  6. Uniform mixing in paper-based microfluidic systems using surface acoustic waves.

    PubMed

    Rezk, Amgad R; Qi, Aisha; Friend, James R; Li, Wai Ho; Yeo, Leslie Y

    2012-02-21

    Paper-based microfluidics has recently received considerable interest due to their ease and low cost, making them extremely attractive as point-of-care diagnostic devices. The incorporation of basic fluid actuation and manipulation schemes on paper substrates, however, afford the possibility to extend the functionality of this simple technology to a much wider range of typical lab-on-a-chip operations, given its considerable advantages in terms of cost, size and integrability over conventional microfluidic substrates. We present a convective actuation mechanism in a simple paper-based microfluidic device using surface acoustic waves to drive mixing. Employing a Y-channel structure patterned onto paper, the mixing induced by the 30 MHz acoustic waves is shown to be consistent and rapid, overcoming several limitations associated with its capillary-driven passive mixing counterpart wherein irreproducibilities and nonuniformities are often encountered in the mixing along the channel--capillary-driven passive mixing offers only poor control, is strongly dependent on the paper's texture and fibre alignment, and permits backflow, all due to the scale of the fibres being significant in comparison to the length scales of the features in a microfluidic system. Using a novel hue-based colourimetric technique, the mixing speed and efficiency is compared between the two methods, and used to assess the effects of changing the input power, channel tortuousity and fibre/flow alignment for the acoustically-driven mixing. The hue-based technique offers several advantages over grayscale pixel intensity analysis techniques in facilitating quantification without limitations on the colour contrast of the samples, and can be used, for example, for quantification in on-chip immunochromatographic assays. PMID:22193520

  7. A bubble-based microfluidic gas sensor for gas chromatographs.

    PubMed

    Bulbul, Ashrafuzzaman; Kim, Hanseup

    2015-01-01

    We report a new proof-of-concept bubble-based gas sensor for a gas chromatography system, which utilizes the unique relationship between the diameters of the produced bubbles with the gas types and mixture ratios as a sensing element. The bubble-based gas sensor consists of gas and liquid channels as well as a nozzle to produce gas bubbles through a micro-structure. It utilizes custom-developed software and an optical camera to statistically analyze the diameters of the produced bubbles in flow. The fabricated gas sensor showed that five types of gases (CO2, He, H2, N2, and CH4) produced (1) unique volumes of 0.44, 0.74, 1.03, 1.28, and 1.42 nL (0%, 68%, 134%, 191%, and 223% higher than that of CO2) and (2) characteristic linear expansion coefficients (slope) of 1.38, 2.93, 3.45, 5.06, and 5.44 nL/(kPa (μL s(-1))(-1)). The gas sensor also demonstrated that (3) different gas mixture ratios of CO2 : N2 (100 : 0, 80 : 20, 50 : 50, 20 : 80 and 0 : 100) generated characteristic bubble diameters of 48.95, 77.99, 71.00, 78.53 and 99.50 μm, resulting in a linear coefficient of 10.26 μm (μL s(-1))(-1). It (4) successfully identified an injection (0.01 μL) of pentane (C5) into a continuous carrier gas stream of helium (He) by monitoring bubble diameters and creating a chromatogram and demonstrated (5) the output stability within only 5.60% variation in 67 tests over a month. PMID:25350655

  8. Development of a fast thermal response microfluidic system using liquid metal

    NASA Astrophysics Data System (ADS)

    Gao, Meng; Gui, Lin

    2016-07-01

    Room temperature liquid metal gallium alloy has been widely used in many micro-electromechanical systems applications, such as on-chip electrical microheaters, micro temperature sensors, micro pumps and so on. Injecting liquid metal into microchannels can provide a simple, rapid, low-cost but efficient way to integrate these elements in microfluidic chips with high accuracy. The liquid metal-filled microstructures can be designed in any shape and easily integrated into microfluidic chips. In this paper, an on-chip liquid metal-based thermal microfluidic system is proposed for quick temperature control at the microscale. The micro system utilizes just one microfluidic chip as a basic working platform, which has liquid metal-based on-chip heaters, temperature sensors and electroosmotic flow pumps. Under the comprehensive control of these elements, the micro system can quickly change the temperature of a target fluid in the microfluidic chip. These liquid metal-based on-chip elements are very helpful for the fabrication and miniaturization of the microfluidic chip. In this paper, deionized water is used to test the temperature control performance of the thermal microfluidic system. According to the experimental results, the micro system can efficiently control the temperature of water ranging from 28 °C to 90 °C. The thermal microfluidic system has great potential for use in many microfluidic applications, such as on-chip polymerase chain reaction, temperature gradient focusing, protein crystallization and chemical synthesis.

  9. Capillary-driven surface-enhanced Raman scattering (SERS)-based microfluidic chip for abrin detection

    PubMed Central

    2014-01-01

    Herein, we firstly demonstrate the design and the proof-of-concept use of a capillary-driven surface-enhanced Raman scattering (SERS)-based microfluidic chip for abrin detection. The micropillar array substrate was etched and coated with a gold film by microelectromechanical systems (MEMS) process to integrate into a lateral flow test strip. The detection of abrin solutions of various concentrations was performed by the as-prepared microfluidic chip. It was shown that the correlation between the abrin concentration and SERS signal was found to be linear within the range of 0.1 ng/mL to 1 μg/mL with a limit of detection of 0.1 ng/mL. Our microfluidic chip design enhanced the operability of SERS-based immunodiagnostic techniques, significantly reducing the complication and cost of preparation as compared to previous SERS-based works. Meanwhile, this design proved the superiority to conventional lateral flow test strips in respect of both sensitivity and quantitation and showed great potential in the diagnosis and treatment for abrin poisoning as well as on-site screening of abrin-spiked materials. PMID:24655483

  10. Capillary-driven surface-enhanced Raman scattering (SERS)-based microfluidic chip for abrin detection.

    PubMed

    Yang, Hao; Deng, Min; Ga, Shan; Chen, Shouhui; Kang, Lin; Wang, Junhong; Xin, Wenwen; Zhang, Tao; You, Zherong; An, Yuan; Wang, Jinglin; Cui, Daxiang

    2014-01-01

    Herein, we firstly demonstrate the design and the proof-of-concept use of a capillary-driven surface-enhanced Raman scattering (SERS)-based microfluidic chip for abrin detection. The micropillar array substrate was etched and coated with a gold film by microelectromechanical systems (MEMS) process to integrate into a lateral flow test strip. The detection of abrin solutions of various concentrations was performed by the as-prepared microfluidic chip. It was shown that the correlation between the abrin concentration and SERS signal was found to be linear within the range of 0.1 ng/mL to 1 μg/mL with a limit of detection of 0.1 ng/mL. Our microfluidic chip design enhanced the operability of SERS-based immunodiagnostic techniques, significantly reducing the complication and cost of preparation as compared to previous SERS-based works. Meanwhile, this design proved the superiority to conventional lateral flow test strips in respect of both sensitivity and quantitation and showed great potential in the diagnosis and treatment for abrin poisoning as well as on-site screening of abrin-spiked materials. PMID:24655483

  11. Patterned fluoropolymer barriers for containment of organic solvents within paper-based microfluidic devices.

    PubMed

    Chen, Benny; Kwong, Philip; Gupta, Malancha

    2013-12-11

    In this study, we demonstrate for the first time the ability to pattern lipophobic fluoropolymer barriers for the incorporation of pure organic solvents as operating liquids within paper-based microfluidic devices. Our fabrication method involves replacing traditional wax barriers with fluoropolymer coatings by combining initiated chemical vapor deposition with inhibiting transition metal salt to pattern the polymer. Multiple techniques for patterning the transition metal salt are tested including painting, spray coating, and selective wetting through the use of a photoresist. The efficacy of the barrier coatings to contain organic solvents is found to be dependent on the conformality of the polymer deposited around the paper fibers. We demonstrate examples of the benefits provided by the containment of organic solvents in paper-based microfluidic applications including the ability to tune the separation of analytes by varying the operating solvent and by modifying the channel region of the devices with additional polymer coatings. The work exhibited in this paper has the potential to significantly expand the applications of paper-based microfluidics to include detection of water insoluble analytes. Additionally, the generality of the patterning process allows this technique to be extended to other applications that may require the use of patterned hydrophobic and lipophobic regions, such as biosensing, chemical detection, and optics. PMID:24283374

  12. Cyclic olefin homopolymer-based microfluidics for protein crystallization and in situ X-ray diffraction

    SciTech Connect

    Emamzadah, Soheila; Petty, Tom J.; De Almeida, Victor; Nishimura, Taisuke; Joly, Jacques; Ferrer, Jean-Luc; Halazonetis, Thanos D.

    2009-09-01

    A cyclic olefin homopolymer-based microfluidics system has been established for protein crystallization and in situ X-ray diffraction. Microfluidics is a promising technology for the rapid identification of protein crystallization conditions. However, most of the existing systems utilize silicone elastomers as the chip material which, despite its many benefits, is highly permeable to water vapour. This limits the time available for protein crystallization to less than a week. Here, the use of a cyclic olefin homopolymer-based microfluidics system for protein crystallization and in situ X-ray diffraction is described. Liquid handling in this system is performed in 2 mm thin transparent cards which contain 500 chambers, each with a volume of 320 nl. Microbatch, vapour-diffusion and free-interface diffusion protocols for protein crystallization were implemented and crystals were obtained of a number of proteins, including chicken lysozyme, bovine trypsin, a human p53 protein containing both the DNA-binding and oligomerization domains bound to DNA and a functionally important domain of Arabidopsis Morpheus’ molecule 1 (MOM1). The latter two polypeptides have not been crystallized previously. For X-ray diffraction analysis, either the cards were opened to allow mounting of the crystals on loops or the crystals were exposed to X-rays in situ. For lysozyme, an entire X-ray diffraction data set at 1.5 Å resolution was collected without removing the crystal from the card. Thus, cyclic olefin homopolymer-based microfluidics systems have the potential to further automate protein crystallization and structural genomics efforts.

  13. Open-Source Wax RepRap 3-D Printer for Rapid Prototyping Paper-Based Microfluidics.

    PubMed

    Pearce, J M; Anzalone, N C; Heldt, C L

    2016-08-01

    The open-source release of self-replicating rapid prototypers (RepRaps) has created a rich opportunity for low-cost distributed digital fabrication of complex 3-D objects such as scientific equipment. For example, 3-D printable reactionware devices offer the opportunity to combine open hardware microfluidic handling with lab-on-a-chip reactionware to radically reduce costs and increase the number and complexity of microfluidic applications. To further drive down the cost while improving the performance of lab-on-a-chip paper-based microfluidic prototyping, this study reports on the development of a RepRap upgrade capable of converting a Prusa Mendel RepRap into a wax 3-D printer for paper-based microfluidic applications. An open-source hardware approach is used to demonstrate a 3-D printable upgrade for the 3-D printer, which combines a heated syringe pump with the RepRap/Arduino 3-D control. The bill of materials, designs, basic assembly, and use instructions are provided, along with a completely free and open-source software tool chain. The open-source hardware device described here accelerates the potential of the nascent field of electrochemical detection combined with paper-based microfluidics by dropping the marginal cost of prototyping to nearly zero while accelerating the turnover between paper-based microfluidic designs. PMID:26763294

  14. Modeling and simulation of DNA flow in a microfluidic-based pathogen detection system

    SciTech Connect

    Trebotich, D; Miller, G H

    2005-01-31

    We present simulation results from a new computational model of DNA flow in microfluidic devices. This work is important because computational models are needed to design miniaturized biomedical devices that are becoming the state-of-the-art in many significant applications including pathogen detection as well as continuous monitoring and drug delivery. Currently advanced algorithms in design tools are non-existent but necessary to understand the complex fluid and polymer dynamics involved in biological flow at small scales. Our model is based on a fully coupled fluid-particle numerical algorithm with both stochastic and deterministic components in a bead-rod polymer representation. We have applied this work to DNA extraction configurations in a microfluidic PCR chamber used in a pathogen detection system. We demonstrate our method on the test problem of flow of a single DNA molecule in a 2D packed array microchannel. We are also investigating mechanisms for molecular ''sticking'' using short range forces.

  15. Making a Hybrid Microfluidic Platform Compatible for In Situ Imaging by Vacuum-Based Techniques

    SciTech Connect

    Yang, Li; Yu, Xiao-Ying; Zhu, Zihua; Thevuthasan, Suntharampillai; Cowin, James P.

    2011-10-26

    A self-contained microfluidic-based device was designed and fabricated for in situ imaging of aqueous surfaces using vacuum techniques. The device is a hybrid between a microfluidic PDMS block and external accessories, all portable on a small platform (10 cm-8 cm). The key feature is that a small aperture with a diameter of 2-3 micrometers is opened to the vacuum, which serves as a detection window for in situ imaging of aqueous surfaces. Vacuum compatibility and temperature drop due to water vaporization are the two most important challenges in this invention. Theoretical calculations and fabrication strategies are presented from multiple design aspects. In addition, results from the time-of-flight secondary ion mass spectrometry (ToF-SIMS) of aqueous surfaces are presented.

  16. An integrated software solution for real-time PCR analysis based on microfluidic biochip

    NASA Astrophysics Data System (ADS)

    Wang, Qinghui; Gong, Haiqing

    2003-04-01

    In this paper, we present an integrated and automated prototype system which has been developed for real-time polymerase chain reaction (PCR) analysis based on microfluidic PCR array chips. The system integrates the PCR thermal cycling and optical detection capabilities to enable real-time fluorescence imaging and image processing for data analysis. The main advantage of the system is that it provides a solution that can rapidly perform and evaluate PCR experiment simultaneously on microfluidic PCR array chips. The system has demonstrated fast and efficient on-chip real-time PCR analysis using human genomic DNA samples. The implementation of the system integration is a multi-thread Windows software with component structure which is written in Visual C++.

  17. Volumetric measurement of human red blood cells by MOSFET-based microfluidic gate.

    PubMed

    Guo, Jinhong; Ai, Ye; Cheng, Yuanbing; Li, Chang Ming; Kang, Yuejun; Wang, Zhiming

    2015-08-01

    In this paper, we present a MOSFET-based (metal oxide semiconductor field-effect transistor) microfluidic gate to characterize the translocation of red blood cells (RBCs) through a gate. In the microfluidic system, the bias voltage modulated by the particles or biological cells is connected to the gate of MOSFET. The particles or cells can be detected by monitoring the MOSFET drain current instead of DC/AC-gating method across the electronic gate. Polystyrene particles with various standard sizes are utilized to calibrate the proposed device. Furthermore, RBCs from both adults and newborn blood sample are used to characterize the performance of the device in distinguishing the two types of RBCs. As compared to conventional DC/AC current modulation method, the proposed device demonstrates a higher sensitivity and is capable of being a promising platform for bioassay analysis. PMID:25349117

  18. Ultrasensitive protein detection: a case for microfluidic magnetic bead-based assays.

    PubMed

    Tekin, H Cumhur; Gijs, Martin A M

    2013-12-21

    We review the use of magnetic micro- and nanoparticles ('magnetic beads') in microfluidic systems for ultrasensitive protein detection. During recent years magnetic beads have been used frequently in immunoassays, either as mobile substrates on which the target antigen is captured, as detection labels, or simultaneously as substrates and labels. The major part of the reviewed work has as application the detection of antibodies or disease biomarkers in serum or of biotoxins from food samples. Several of the most sensitive assays allow protein detection down to fg mL(-1) concentrations. We benchmark the performance of these microfluidic magnetic bead-based assays with the most promising earlier work and with alternative solutions. PMID:24145920

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

    PubMed

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

    2016-01-01

    The conventional hanging drop technique is the most widely used method for embryoid body (EB) formation. However, this method is labor intensive and limited by the difficulty in exchanging the medium. Here, we report a microfluidic chip-based approach for high-throughput formation of EBs. The device consists of microfluidic channels with 6 × 12 opening wells in PDMS supported by a glass substrate. The PDMS channels were fabricated by replicating polydimethyl-siloxane (PDMS) from SU-8 mold. The droplet formation in the chip was tested with different hydrostatic pressures to obtain optimal operation pressures for the wells with 1000 μm diameter openings. The droplets formed at the opening wells were used to culture mouse embryonic stem cells which could subsequently developed into EBs in the hanging droplets. This device also allows for medium exchange of the hanging droplets making it possible to perform immunochemistry staining and characterize EBs on chip. PMID:27399655

  20. A fast and switchable microfluidic mixer based on ultrasound-induced vaporization of perfluorocarbon.

    PubMed

    Bezagu, Marine; Arseniyadis, Stellios; Cossy, Janine; Couture, Olivier; Tanter, Mickael; Monti, Fabrice; Tabeling, Patrick

    2015-05-01

    Mixing two fluids together within a microfluidic device still remains a challenging operation today. In order to achieve this goal, a number of effective micromixers have been developed over the years based on the use of either passive or active systems. Typically, passive mixers require no external energy, are more robust, and are easy to manufacture albeit they are poorly flexible. Active mixers, on the other hand, rely on external disturbance and are thus more difficult to use but are proven to have greater efficacy. Here, we report a particularly effective, remotely induced and switchable microfluidic mixer, which relies on the concomitant use of ultrasound and a perfluorocarbon (PFC) phase, with the latter benefiting from its immiscibility with most fluids and its low boiling point. More specifically, our approach is based on localized vaporization of a PFC phase at the focal zone of a transducer leading to efficient mixing of two adjacent fluids. The results show that mixing occurs ~100 ms following the delivery of the acoustic pulse, while a laminar flow is re-established on roughly the same time scale. Overall, this method is simple and effective, does not require tailored channel geometries, is compatible with both hydrophilic and hydrophobic microfluidic systems, and is applicable to a wide range of Reynolds numbers (10(-4) < Re < 2.10(0)), and the PFC phase can be easily separated from the mixed phase at the end of the run. PMID:25778877

  1. 3D printed microfluidic circuitry via multijet-based additive manufacturing†

    PubMed Central

    Sochol, R. D.; Sweet, E.; Glick, C. C.; Venkatesh, S.; Avetisyan, A.; Ekman, K. F.; Raulinaitis, A.; Tsai, A.; Wienkers, A.; Korner, K.; Hanson, K.; Long, A.; Hightower, B. J.; Slatton, G.; Burnett, D. C.; Massey, T. L.; Iwai, K.; Lee, L. P.; Pister, K. S. J.; Lin, L.

    2016-01-01

    The miniaturization of integrated fluidic processors affords extensive benefits for chemical and biological fields, yet traditional, monolithic methods of microfabrication present numerous obstacles for the scaling of fluidic operators. Recently, researchers have investigated the use of additive manufacturing or “three-dimensional (3D) printing” technologies – predominantly stereolithography – as a promising alternative for the construction of submillimeter-scale fluidic components. One challenge, however, is that current stereolithography methods lack the ability to simultaneously print sacrificial support materials, which limits the geometric versatility of such approaches. In this work, we investigate the use of multijet modelling (alternatively, polyjet printing) – a layer-by-layer, multi-material inkjetting process – for 3D printing geometrically complex, yet functionally advantageous fluidic components comprised of both static and dynamic physical elements. We examine a fundamental class of 3D printed microfluidic operators, including fluidic capacitors, fluidic diodes, and fluidic transistors. In addition, we evaluate the potential to advance on-chip automation of integrated fluidic systems via geometric modification of component parameters. Theoretical and experimental results for 3D fluidic capacitors demonstrated that transitioning from planar to non-planar diaphragm architectures improved component performance. Flow rectification experiments for 3D printed fluidic diodes revealed a diodicity of 80.6 ± 1.8. Geometry-based gain enhancement for 3D printed fluidic transistors yielded pressure gain of 3.01 ± 0.78. Consistent with additional additive manufacturing methodologies, the use of digitally-transferrable 3D models of fluidic components combined with commercially-available 3D printers could extend the fluidic routing capabilities presented here to researchers in fields beyond the core engineering community. PMID:26725379

  2. 3D printed microfluidic circuitry via multijet-based additive manufacturing.

    PubMed

    Sochol, R D; Sweet, E; Glick, C C; Venkatesh, S; Avetisyan, A; Ekman, K F; Raulinaitis, A; Tsai, A; Wienkers, A; Korner, K; Hanson, K; Long, A; Hightower, B J; Slatton, G; Burnett, D C; Massey, T L; Iwai, K; Lee, L P; Pister, K S J; Lin, L

    2016-02-21

    The miniaturization of integrated fluidic processors affords extensive benefits for chemical and biological fields, yet traditional, monolithic methods of microfabrication present numerous obstacles for the scaling of fluidic operators. Recently, researchers have investigated the use of additive manufacturing or "three-dimensional (3D) printing" technologies - predominantly stereolithography - as a promising alternative for the construction of submillimeter-scale fluidic components. One challenge, however, is that current stereolithography methods lack the ability to simultaneously print sacrificial support materials, which limits the geometric versatility of such approaches. In this work, we investigate the use of multijet modelling (alternatively, polyjet printing) - a layer-by-layer, multi-material inkjetting process - for 3D printing geometrically complex, yet functionally advantageous fluidic components comprised of both static and dynamic physical elements. We examine a fundamental class of 3D printed microfluidic operators, including fluidic capacitors, fluidic diodes, and fluidic transistors. In addition, we evaluate the potential to advance on-chip automation of integrated fluidic systems via geometric modification of component parameters. Theoretical and experimental results for 3D fluidic capacitors demonstrated that transitioning from planar to non-planar diaphragm architectures improved component performance. Flow rectification experiments for 3D printed fluidic diodes revealed a diodicity of 80.6 ± 1.8. Geometry-based gain enhancement for 3D printed fluidic transistors yielded pressure gain of 3.01 ± 0.78. Consistent with additional additive manufacturing methodologies, the use of digitally-transferrable 3D models of fluidic components combined with commercially-available 3D printers could extend the fluidic routing capabilities presented here to researchers in fields beyond the core engineering community. PMID:26725379

  3. Plug-n-play microfluidic systems from flexible assembly of glass-based flow-control modules.

    PubMed

    Meng, Zhi-Jun; Wang, Wei; Liang, Xuan; Zheng, Wei-Chao; Deng, Nan-Nan; Xie, Rui; Ju, Xiao-Jie; Liu, Zhuang; Chu, Liang-Yin

    2015-04-21

    In this study, we report on a simple and versatile plug-n-play microfluidic system that is fabricated from flexible assembly of glass-based flow-control modules for flexibly manipulating flows for versatile emulsion generation. The microfluidic system consists of three basic functional units: a flow-control module, a positioning groove, and a connection fastener. The flow-control module that is based on simple assembly of low-cost glass slides, coverslips, and glass capillaries provides excellent chemical resistance and optical properties, and easy wettability modification for flow manipulation. The flexible combination of the flow-control modules with 3D-printed positioning grooves and connection fasteners enables creation of versatile microfluidic systems for generating various higher-order multiple emulsions. The simple and reversible connection of the flow-control modules also allows easy disassembly of the microfluidic systems for further scale-up and functionalization. We demonstrate the scalability and controllability of flow manipulation by creating microfluidic systems from flexible assembly of flow-control modules for controllable generation of multiple emulsions from double emulsions to quadruple emulsions. Meanwhile, the flexible flow manipulation in the flow-control module provides advanced functions for improved control of the drop size, and for controllable generation of drops containing distinct components within multiple emulsions to extend the emulsion structure. Such modular microfluidic systems provide flexibility and versatility to flexibly manipulate micro-flows for enhanced and extended applications. PMID:25711675

  4. Design and Evaluation of a Passive Alcove-based Microfluidic Mixer

    PubMed Central

    Egawa, Tsuyoshi; Durand, Jorge L.; Hayden, Eric; Rousseau, Denis L.; Yeh, Syun-Ru

    2012-01-01

    A novel passive microfluidic silicon mixer has been designed, optimized and fabricated. The architecture of the mixer consists of a simple “T” junction, made up by a 20 μm wide by 82 μm deep channel, followed by three repeats of an alcove, each with a triangular obstruction, arranged in a zigzag fashion. Numerical simulations were employed to optimize the geometry, particularly the dimensions of the alcoves, the relative orientation and the spacing between them, and the degree of intrusion associated with them. The simulation results demonstrate that chaotic flow due to recirculation within the alcoves results in transverse velocity that promotes effective fluid mixing. The microfluidic mixer with the simulation-optimized geometry was fabricated with photolithographic techniques and characterized by optical imaging, fluorescence and Raman microscope spectroscopy. At a sample flow rate of 20 μL/s, the mixer exhibits a short mixing deadtime of ~22 μs and a high mixing efficiency under both low and high viscosity conditions. The alcove-based microfluidic silicon mixer offers unique advantages for its short deadtime and slow sample consumption rate. In addition, it provides a valuable component for lab-on-a-chip applications for its ease of development into multiple networks for massively parallel analytical processes. PMID:19140669

  5. Standard and high-throughput microfluidic disposables based on laminar fluid diffusion interfaces

    NASA Astrophysics Data System (ADS)

    Weigl, Bernhard H.; Morris, Chris; Kesler, Natasa; Battrell, Fred; Bardell, Ron L.

    2002-06-01

    Laminar Fluid Diffusion Interfaces are generated when tow or more streams flow in parallel in a microfluidic structure. This technology can be used for diffusion-based separation and detection applications, for example: DNA desalting, the extraction of small proteins from whole-blood samples, and the detection of various constituents in while blood. Additional applications are the establishment of stable concentration gradients, and the exposure of chemical constituents or biological particles to these concentration gradients, enabling the uniform and controlled exposure of cells to lysing agents, allowing the differentiation of cells by their sensitivity to specific agents in an on-chip cytometer coupled directly to the lysing structure. We have developed integrated systems using machine-controlled disposable cartridges and passive self-contained disposable cards including particle separators, flow cytometers, valves, detection channels, mixers, and diluters that are used in a hematology analyzer, stand-alone blood plasma separators, and a variety of chemical and biological assays. Microfluidic arrays compatible with common well-plate formats have been designed for high-throughout toxicology screening applications. All these devices were manufactured using Micronics' unique rapid-prototyping process yielding low-cost plastic disposable microfluidic chips.

  6. Droplet-based microfluidic system to form and separate multicellular spheroids using magnetic nanoparticles.

    PubMed

    Yoon, Sungjun; Kim, Jeong Ah; Lee, Seung Hwan; Kim, Minsoo; Park, Tai Hyun

    2013-04-21

    The importance of creating a three-dimensional (3-D) multicellular spheroid has recently been gaining attention due to the limitations of monolayer cell culture to precisely mimic in vivo structure and cellular interactions. Due to this emerging interest, researchers have utilized new tools, such as microfluidic devices, that allow high-throughput and precise size control to produce multicellular spheroids. We have developed a droplet-based microfluidic system that can encapsulate both cells and magnetic nanoparticles within alginate beads to mimic the function of a multicellular tumor spheroid. Cells were entrapped within the alginate beads along with magnetic nanoparticles, and the beads of a relatively uniform size (diameters of 85% of the beads were 170-190 μm) were formed in the oil phase. These beads were passed through parallel streamlines of oil and culture medium, where the beads were magnetically transferred into the medium phase from the oil phase using an external magnetic force. This microfluidic chip eliminates additional steps for collecting the spheroids from the oil phase and transferring them to culture medium. Ultimately, the overall spheroid formation process can be achieved on a single microchip. PMID:23426090

  7. Purification of microalgae from bacterial contamination using a disposable inertia-based microfluidic device

    NASA Astrophysics Data System (ADS)

    Godino, Neus; Jorde, Felix; Lawlor, Daryl; Jaeger, Magnus; Duschl, Claus

    2015-08-01

    Microalgae are a promising source of bioactive ingredients for the food, pharmaceutical and cosmetic industries. Every microalgae research group or production facility is facing one major problem regarding the potential contamination of the algal cell with bacteria. Prior to the storage of the microalgae in strain collections or to cultivation in bioreactors, it is necessary to carry out laborious purification procedures to separate the microalgae from the undesired bacterial cells. In this work, we present a disposable microfluidic cartridge for the high-throughput purification of microalgae samples based on inertial microfluidics. Some of the most relevant microalgae strains have a larger size than the relatively small, few micron bacterial cells, so making them distinguishable by size. The inertial microfluidic cartridge was fabricated with inexpensive materials, like pressure sensitive adhesive (PSA) and thin plastic layers, which were patterned using a simple cutting plotter. In spite of fabrication restrictions and the intrinsic difficulties of biological samples, the separation of microalgae from bacteria reached values in excess of 99%, previously only achieved using conventional high-end and high cost lithography methods. Moreover, due to the simple and high-throughput characteristic of the separation, it is possible to concatenate serial purification to exponentially decrease the absolute amount of bacteria in the final purified sample.

  8. Design of liquid lens based optical system for microfluidic chip detection

    NASA Astrophysics Data System (ADS)

    Niu, Lijun; Zhou, Ya; Hu, Xiaoming; Zhou, Chang

    2015-08-01

    The precision of manufacturing and installing together with the flexibility is a serious challenge for laser induced fluorescent detector (LIFD) of microfluidic chip. In this paper, a focus tunable liquid lens based on liquid zoom system for LIFD with automatic adjustment is proposed. With the help of liquid zoom lens whose surface curvature can be varied continuously by current, the system can achieve a continuous zoom. Instead of using the traditional mechanical axial displacement scanning motion mechanism, the proposed zoom system can implement axial displacement scan by means of the well-designed autofocus feedback current control function. The simulation results show that the focal length variation range of the designed optical system is 4.87mm~ 8.40mm, which is also the axial scanning displacement range. The size of scanning spot is around 15μm when a 473nm wavelength laser is used, which can meet the demand of microfluidic chip detection. With this design, the required precision of the LIFD could be reduced significantly as well as costs. Moreover, it also makes the detection of microfluidic chip qualified to adapt to different size of detecting channel.

  9. Recombinant Protein-Stabilized Monodisperse Microbubbles with Tunable Size Using a Valve-Based Microfluidic Device

    PubMed Central

    2015-01-01

    Microbubbles are used as contrast enhancing agents in ultrasound sonography and more recently have shown great potential as theranostic agents that enable both diagnostics and therapy. Conventional production methods lead to highly polydisperse microbubbles, which compromise the effectiveness of ultrasound imaging and therapy. Stabilizing microbubbles with surfactant molecules that can impart functionality and properties that are desirable for specific applications would enhance the utility of microbubbles. Here we generate monodisperse microbubbles with a large potential for functionalization by combining a microfluidic method and recombinant protein technology. Our microfluidic device uses an air-actuated membrane valve that enables production of monodisperse microbubbles with narrow size distribution. The size of microbubbles can be precisely tuned by dynamically changing the dimension of the channel using the valve. The microbubbles are stabilized by an amphiphilic protein, oleosin, which provides versatility in controlling the functionalization of microbubbles through recombinant biotechnology. We show that it is critical to control the composition of the stabilizing agents to enable formation of highly stable and monodisperse microbubbles that are echogenic under ultrasound insonation. Our protein-shelled microbubbles based on the combination of microfluidic generation and recombinant protein technology provide a promising platform for ultrasound-related applications. PMID:25265041

  10. [In situ photopolymerization of polyacrylamide-based preconcentrator on a microfluidic chip for capillary electrophoresis].

    PubMed

    Yamamoto, Sachio

    2012-01-01

    Microchip electrophoresis is widely used for microfluidics and has been studied extensively over the past decade. Translation of capillary electrophoresis methods from traditional capillary systems to a microchip platform provides rapid separation and easy quantitation of sample components. However, most microfluidic systems suffer from critical scaling problems. One promising solution to this problem is online sample preconcentration of all analytes in a sample reservoir before the separation channel. Herein, the following three techniques for online preconcentration during microchip electrophoresis are proposed: (1) in situ fabrication of an ionic polyacrylamide-based preconcentrator on a simple poly(methyl methacrylate) microfluidic chip for perm-selective preconcentration and capillary electrophoretic separation of anionic compounds, (2) simultaneous concentration enrichment and electrophoretic separation of weak acids on a microchip using an in situ photopolymerized carboxylate-type polyacrylamide gels as the perm-selective preconcentrator, and (3) microchip electrophoresis of oligosaccharides using lectin-immobilized preconcentrator gels fabricated by in situ photopolymerization. These techniques are expected to be powerful tools for clinical and pharmaceutical studies with on-line preconcentration during microchip electrophoresis. PMID:23023420

  11. A fluorescence-based centrifugal microfluidic system for parallel detection of multiple allergens

    NASA Astrophysics Data System (ADS)

    Chen, Q. L.; Ho, H. P.; Cheung, K. L.; Kong, S. K.; Suen, Y. K.; Kwan, Y. W.; Li, W. J.; Wong, C. K.

    2010-02-01

    This paper reports a robust polymer based centrifugal microfluidic analysis system that can provide parallel detection of multiple allergens in vitro. Many commercial food products (milk, bean, pollen, etc.) may introduce allergy to people. A low-cost device for rapid detection of allergens is highly desirable. With this as the objective, we have studied the feasibility of using a rotating disk device incorporating centrifugal microfluidics for performing actuationfree and multi-analyte detection of different allergen species with minimum sample usage and fast response time. Degranulation in basophils or mast cells is an indicator to demonstrate allergic reaction. In this connection, we used acridine orange (AO) to demonstrate degranulation in KU812 human basophils. It was found that the AO was released from granules when cells were stimulated by ionomycin, thus signifying the release of histamine which accounts for allergy symptoms [1-2]. Within this rotating optical platform, major microfluidic components including sample reservoirs, reaction chambers, microchannel and flow-control compartments are integrated into a single bio-compatible polydimethylsiloxane (PDMS) substrate. The flow sequence and reaction time can be controlled precisely. Sequentially through varying the spinning speed, the disk may perform a variety of steps on sample loading, reaction and detection. Our work demonstrates the feasibility of using centrifugation as a possible immunoassay system in the future.

  12. High throughput multilayer microfluidic particle separation platform using embedded thermoplastic-based micropumping.

    PubMed

    Didar, Tohid Fatanat; Li, Kebin; Tabrizian, Maryam; Veres, Teodor

    2013-07-01

    We present an integrated thermoplastic elastomer (TPE) based multilayer microfluidic device with an embedded peristaltic micropump and through-holes membrane for high throughput particle sorting and separation. Fluidic and pneumatic layers of the device were fabricated using hot-embossing lithography and commercially available polycarbonate membranes were succcessfully sandwiched between two thermoplastic elastomer fluidic layers integrated to a peristaltic micropumping layer. The integrated peristaltic micropump induces turbulence at the top-microfluidic layer ring which successfully avoids particle aggregation and membrane blocking even at nanorange size. We present herein the general design of the device structure and pumping characteristics for three devices with membrane pore sizes of 10 μm, 5 μm and 800 nm. By using this design we have successfully demonstrated a separation efficiency as high as 99% of polystyrene microbeads with different sizes and most importantly the separation of 390 nm particles from 2 μm beads was achieved. Using this device, we were also able to separate red blood cells with size of about 6-8 μm from osteoblasts typically larger than 10 μm to demonstrate the potential applicability of this platform for biological samples. The produced microfluidic chip operating at flow rates up to 100 μl min(-1) allows us to achieve efficient high-throughput sorting and separation of target particles/cells. PMID:23640083

  13. High-performance UV-curable epoxy resin-based microarray and microfluidic immunoassay devices.

    PubMed

    Yu, Ling; Liu, Yingshuai; Gan, Ye; Li, Chang Ming

    2009-06-15

    Immunoassay devices including microarray and microfluidic systems were fabricated with an UV-curable resin by a new economic approach, which can not only simply produce a 3-dimensional (3D) patterned structure, but also simultaneously introduce functional epoxide groups for efficient protein immobilization. The performance of the epoxy resin-based microarray was improved by optimization of printing buffer, probe concentration, and immobilization time, showing a detection dynamic range of 5 orders of magnitude and a limit of detection (LOD) of 10 pg mL(-1) for immunoglobulin G (IgG). The developed microfluidic immunoassay device demonstrates a LOD of 100 pg mL(-1) for IL-5 detection. The device can also be used to colorimetrically detect proteins via naked human eyes for immunoassays. This work provides a simple and inexpensive method to fabricate a sensitive immunoassay device, especially a 3D microfluidic system, which has great potential to develop a portable immunoassay device via human eye detection for point-of-care service and/or high throughput screening of infectious diseases. PMID:19346122

  14. Highly Efficient Bienzyme Functionalized Nanocomposite-Based Microfluidics Biosensor Platform for Biomedical Application

    PubMed Central

    Ali, Md. Azahar; Srivastava, Saurabh; Solanki, Pratima R.; Reddy, Venu; Agrawal, Ved V.; Kim, CheolGi; John, Renu; Malhotra, Bansi D.

    2013-01-01

    This report describes the fabrication of a novel microfluidics nanobiochip based on a composite comprising of nickel oxide nanoparticles (nNiO) and multiwalled carbon nanotubes (MWCNTs), as well as the chip's use in a biomedical application. This nanocomposite was integrated with polydimethylsiloxane (PDMS) microchannels, which were constructed using the photolithographic technique. A structural and morphological characterization of the fabricated microfluidics chip, which was functionalized with a bienzyme containing cholesterol oxidase (ChOx) and cholesterol esterase (ChEt), was accomplished using X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy. The XPS studies revealed that 9.3% of the carboxyl (COOH) groups present in the nNiO-MWCNT composite are used to form amide bonds with the NH2 groups of the bienzyme. The response studies on this nanobiochip reveal good reproducibility and selectivity, and a high sensitivity of 2.2 mA/mM/cm2. This integrated microfluidics biochip provides a promising low-cost platform for the rapid detection of biomolecules using minute samples. PMID:24071971

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

    PubMed

    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. PMID:26477676

  16. Nucleic Acid-based Detection of Bacterial Pathogens Using Integrated Microfluidic Platform Systems

    PubMed Central

    Lui, Clarissa; Cady, Nathaniel C.; Batt, Carl A.

    2009-01-01

    The advent of nucleic acid-based pathogen detection methods offers increased sensitivity and specificity over traditional microbiological techniques, driving the development of portable, integrated biosensors. The miniaturization and automation of integrated detection systems presents a significant advantage for rapid, portable field-based testing. In this review, we highlight current developments and directions in nucleic acid-based micro total analysis systems for the detection of bacterial pathogens. Recent progress in the miniaturization of microfluidic processing steps for cell capture, DNA extraction and purification, polymerase chain reaction, and product detection are detailed. Discussions include strategies and challenges for implementation of an integrated portable platform. PMID:22412335

  17. Protein Microarrays with Novel Microfluidic Methods: Current Advances

    PubMed Central

    Dixit, Chandra K.; Aguirre, Gerson R.

    2014-01-01

    Microfluidic-based micromosaic technology has allowed the pattering of recognition elements in restricted micrometer scale areas with high precision. This controlled patterning enabled the development of highly multiplexed arrays multiple analyte detection. This arraying technology was first introduced in the beginning of 2001 and holds tremendous potential to revolutionize microarray development and analyte detection. Later, several microfluidic methods were developed for microarray application. In this review we discuss these novel methods and approaches which leverage the property of microfluidic technologies to significantly improve various physical aspects of microarray technology, such as enhanced imprinting homogeneity, stability of the immobilized biomolecules, decreasing assay times, and reduction of the costs and of the bulky instrumentation.

  18. Fabrication of digital microfluidic devices on flexible paper-based and rigid substrates via screen printing

    NASA Astrophysics Data System (ADS)

    Yafia, Mohamed; Shukla, Saurabh; Najjaran, Homayoun

    2015-05-01

    In this work, a new fabrication method is presented for digital microfluidic (DMF) devices in which the electrodes are generated using the screen printing technique. This method is applicable to both rigid and flexible substrates. The proposed screen printing approach, as a batch printing technique, is advantageous to the widely reported DMF fabrication methods in terms of fabrication time, cost and capability of mass production. Screen printing provides an effective means for printing different types of conductive materials on a variety of substrates. Specifically, screen printing of conductive silver and carbon based inks is performed on paper, glass and wax paper. As a result, the fabricated DMF devices are characterized by being flexible, disposable and incinerable. Hence, the main advantage of screen printing carbon based inks on paper substrates is more pronounced for point-of-care applications that require a large number of low cost DMF chips, and laboratory setups that lack sophisticated microfabrication facilities. The resolution of the printed DMF electrodes generated by this technique is examined for proof of concept using manual screen printing, but higher resolution screens and automated machines are available off-the-shelf, if needed. Another contribution of this research is the improved actuation techniques that facilitate droplet transport in electrode configurations with relatively large electrode spacing to alleviate the disadvantage of lower resolution screens. Thus, we were able to reduce the cost of fabrication significantly without compromising the DMF performance. The paper-based devices have already shown to be effective in continuous microfluidics domain, so the investigation of their applicability in DMF systems is worthwhile. With this in mind, successful integration of a paper-based microchannel with paper-based digital microfluidic chip is demonstrated in this work.

  19. Streamline based design guideline for deterministic microfluidic hydrodynamic single cell traps

    PubMed Central

    Shenoy, Aditi; Smith, Richard

    2015-01-01

    A prerequisite for single cell study is the capture and isolation of individual cells. In microfluidic devices, cell capture is often achieved by means of trapping. While many microfluidic trapping techniques exist, hydrodynamic methods are particularly attractive due to their simplicity and scalability. However, current design guidelines for single cell hydrodynamic traps predominantly rely on flow resistance manipulation or qualitative streamline analysis without considering the target particle size. This lack of quantitative design criteria from first principles often leads to non-optimal probabilistic trapping. In this work, we describe an analytical design guideline for deterministic single cell hydrodynamic trapping through the optimization of streamline distributions under laminar flow with cell size as a key parameter. Using this guideline, we demonstrate an example design which can achieve 100% capture efficiency for a given particle size. Finite element modelling was used to determine the design parameters necessary for optimal trapping. The simulation results were subsequently confirmed with on-chip microbead and white blood cell trapping experiments. PMID:25825618

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

    NASA Astrophysics Data System (ADS)

    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

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

    NASA Astrophysics Data System (ADS)

    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

  2. Microfluidic waves.

    PubMed

    Utz, Marcel; Begley, Matthew R; Haj-Hariri, Hossein

    2011-11-21

    The propagation of pressure waves in fluidic channels with elastic covers is discussed in view of applications to flow control in microfluidic devices. A theory is presented which describes pressure waves in the fluid that are coupled to bending waves in the elastic cover. At low frequencies, the lateral bending of the cover dominates over longitudinal bending, leading to propagating, non-dispersive longitudinal pressure waves in the channel. The theory addresses effects due to both the finite viscosity and compressibility of the fluid. The coupled waves propagate without dispersion, as long as the wave length is larger than the channel width. It is shown that in channels of typical microfluidic dimensions, wave velocities in the range of a few 10 m s(-1) result if the channels are covered by films of a compliant material such as PDMS. The application of this principle to design microfluidic band pass filters based on standing waves is discussed. Characteristic frequencies in the range of a few kHz are readily achieved with quality factors above 30. PMID:21966667

  3. Single- and two-phase flow in microfluidic porous media analogs based on Voronoi tessellation

    SciTech Connect

    Wu, Mengjie; Xiao, Feng; Johnson-Paben, Rebecca; Retterer, Scott T; Yin, Xiaolong; Neeves, Keith B

    2012-01-01

    The objective of this study was to create a microfluidic model of complex porous media for studying single and multiphase flows. Most experimental porous media models consist of periodic geometries that lend themselves to comparison with well-developed theoretical predictions. However, most real porous media such as geological formations and biological tissues contain a degree of randomness and complexity that is not adequately represented in periodic geometries. To design an experimental tool to study these complex geometries, we created microfluidic models of random homogeneous and heterogeneous networks based on Voronoi tessellations. These networks consisted of approximately 600 grains separated by a highly connected network of channels with an overall porosity of 0.11 0.20. We found that introducing heterogeneities in the form of large cavities within the network changed the permeability in a way that cannot be predicted by the classical porosity-permeability relationship known as the Kozeny equation. The values of permeability found in experiments were in excellent agreement with those calculated from three-dimensional lattice Boltzmann simulations. In two-phase flow experiments of oil displacement with water we found that the surface energy of channel walls determined the pattern of water invasion, while the network topology determined the residual oil saturation. These results suggest that complex network topologies lead to fluid flow behavior that is difficult to predict based solely on porosity. The microfluidic models developed in this study using a novel geometry generation algorithm based on Voronoi tessellation are a new experimental tool for studying fluid and solute transport problems within complex porous media.

  4. TECHNICAL NOTE: Portable audio electronics for impedance-based measurements in microfluidics

    NASA Astrophysics Data System (ADS)

    Wood, Paul; Sinton, David

    2010-08-01

    We demonstrate the use of audio electronics-based signals to perform on-chip electrochemical measurements. Cell phones and portable music players are examples of consumer electronics that are easily operated and are ubiquitous worldwide. Audio output (play) and input (record) signals are voltage based and contain frequency and amplitude information. A cell phone, laptop soundcard and two compact audio players are compared with respect to frequency response; the laptop soundcard provides the most uniform frequency response, while the cell phone performance is found to be insufficient. The audio signals in the common portable music players and laptop soundcard operate in the range of 20 Hz to 20 kHz and are found to be applicable, as voltage input and output signals, to impedance-based electrochemical measurements in microfluidic systems. Validated impedance-based measurements of concentration (0.1-50 mM), flow rate (2-120 µL min-1) and particle detection (32 µm diameter) are demonstrated. The prevailing, lossless, wave audio file format is found to be suitable for data transmission to and from external sources, such as a centralized lab, and the cost of all hardware (in addition to audio devices) is ~10 USD. The utility demonstrated here, in combination with the ubiquitous nature of portable audio electronics, presents new opportunities for impedance-based measurements in portable microfluidic systems.

  5. Microfluidic platform for neurotransmitter sensing based on cyclic voltammetry and dielectrophoresis for in vitro experiments.

    PubMed

    Mathault, Jessy; Zamprogno, Pauline; Greener, Jesse; Miled, Amine

    2015-08-01

    This paper presents a new microfluidic platform that can simultaneously measure and locally modulate neurotransmitter concentration in a neuron network. This work focuses on the development of a first prototype including a potentiostat and electrode functionalization to detect several neurotransmitter's simultaneously. We tested dopamine as proof of concept to validate functionality. The system is based on 320 bidirectional electrode array for dielectrophoretic manipulation and cyclic voltammetry. Each electrode is connected to a mechanical multiplexer in order to reduce noise interference and fully isolate the electrode. The multiplexing rate is 476 kHz and each electrode can drive a signal with an amplitude of 60 V pp for dielectrophoretic manipulation. PMID:26736720

  6. A paper based microfluidic device for easy detection of uric acid using positively charged gold nanoparticles.

    PubMed

    Kumar, Anand; Hens, Abhiram; Arun, Ravi Kumar; Chatterjee, Monosree; Mahato, Kuldeep; Layek, Keya; Chanda, Nripen

    2015-03-21

    A paper based microfluidic device is fabricated that can rapidly detect very low concentrations of uric acid (UA) using 3,5,3',5'-tetramethyl benzidine (TMB), H2O2 and positively charged gold nanoparticles ((+)AuNPs). In the presence of (+)AuNPs, H2O2 reacts with TMB to produce a bluish-green colour which becomes colourless on reaction with UA. This colorimetric method can detect as low as 8.1 ppm of UA within <20 minutes on white filter paper. This technique provides an alternative way for UA detection. PMID:25655365

  7. Development and optimization of an integrated capillary-based opto-microfluidic device for chemiluminescence quantitative detection

    NASA Astrophysics Data System (ADS)

    Honrado, Carlos; Dong, Tao

    2014-12-01

    A capillary-action driven device amenable for integration of organic photodiodes (OPDs) was developed for monitoring parallel chemiluminescence (CL) reactions. Device characterization was conducted using finite element method (FEM) simulations. Definition of the simulation setup, dimensional optimization of the reaction chamber and overall geometrical characterization of the microfluidic device were the main simulation results. Furthermore, a non-uniform filling process was observed during the final simulation of the capillary device. Validation of this result and the proposed capillary-driven filling process was later confirmed by experimental results. Experimental testing performed on a single chamber defined an optimal exposure time to the luminescent substrate of 5 min, indicating a quick analyte detection time. Further tests using one chamber presented a linear relation between the signal-to-noise ratio and increasing concentrations of the protein used. A measured limit of detection of 28 nM was obtained for streptavidin. Regarding the tests performed on the whole device, acceptable values of 39 s ± 5 s were obtained for the luminescent substrate total filling times. Also, the microfluidic device showed the capability to perform a quantitative detection of the occurring CL reactions. Weaker optical signals, due to the occurrence of CL reactions, were detected in the chambers with a later filling process, as predicted by simulation results. Notwithstanding these results, the capillary-based device is promising for quantitative detection of proteins in future point-of-care systems, presenting an unprompted filling process and parallel quantitative detection capability.

  8. A laser microwelding method for assembly of polymer based microfluidic devices

    NASA Astrophysics Data System (ADS)

    Jiang, Xin; Chandrasekar, Soni; Wang, Changhai

    2015-03-01

    This paper presents the development of a laser microwelding method for assembly and packaging of polymer based microfluidic devices. In this approach a diode laser was used to weld two poly(methyl methacrylate) (PMMA) substrates together at the interface using a thin film metal spot based intermediate layer design as a localized absorber. A broad laser beam with a top-hat profile was used to carry out the laser microwelding work. The effects of laser power and processing time on the resultant heated affected zone (HAZ) and the melted zone were investigated. For large area welding, a 2×2 array of thin film metal spots were used to investigate the effect of separation between the spots on the resultant interfacial bond between the two polymer substrates. For comparison, a large area titanium film with a comparable size to that of the 2×2 array was also studied. The results show that the discrete film pattern based design is better than a single large area film in order to reduce the effect of substrate distortion resulting from the higher temperature rise associated with the latter. The tensile strength of the laser welded joints was determined to be about 6 MPa for a sample produced using the 2×2 array of circular titanium spot pattern design. The laser microwelding method has been demonstrated successfully in leak-free encapsulation of a microfluidic channel.

  9. High-throughput screening of filamentous fungi using nanoliter-range droplet-based microfluidics

    PubMed Central

    Beneyton, Thomas; Wijaya, I. Putu Mahendra; Postros, Prexilia; Najah, Majdi; Leblond, Pascal; Couvent, Angélique; Mayot, Estelle; Griffiths, Andrew D.; Drevelle, Antoine

    2016-01-01

    Filamentous fungi are an extremely important source of industrial enzymes because of their capacity to secrete large quantities of proteins. Currently, functional screening of fungi is associated with low throughput and high costs, which severely limits the discovery of novel enzymatic activities and better production strains. Here, we describe a nanoliter-range droplet-based microfluidic system specially adapted for the high-throughput sceening (HTS) of large filamentous fungi libraries for secreted enzyme activities. The platform allowed (i) compartmentalization of single spores in ~10 nl droplets, (ii) germination and mycelium growth and (iii) high-throughput sorting of fungi based on enzymatic activity. A 104 clone UV-mutated library of Aspergillus niger was screened based on α-amylase activity in just 90 minutes. Active clones were enriched 196-fold after a single round of microfluidic HTS. The platform is a powerful tool for the development of new production strains with low cost, space and time footprint and should bring enormous benefit for improving the viability of biotechnological processes. PMID:27270141

  10. High-throughput screening of filamentous fungi using nanoliter-range droplet-based microfluidics.

    PubMed

    Beneyton, Thomas; Wijaya, I Putu Mahendra; Postros, Prexilia; Najah, Majdi; Leblond, Pascal; Couvent, Angélique; Mayot, Estelle; Griffiths, Andrew D; Drevelle, Antoine

    2016-01-01

    Filamentous fungi are an extremely important source of industrial enzymes because of their capacity to secrete large quantities of proteins. Currently, functional screening of fungi is associated with low throughput and high costs, which severely limits the discovery of novel enzymatic activities and better production strains. Here, we describe a nanoliter-range droplet-based microfluidic system specially adapted for the high-throughput sceening (HTS) of large filamentous fungi libraries for secreted enzyme activities. The platform allowed (i) compartmentalization of single spores in ~10 nl droplets, (ii) germination and mycelium growth and (iii) high-throughput sorting of fungi based on enzymatic activity. A 10(4) clone UV-mutated library of Aspergillus niger was screened based on α-amylase activity in just 90 minutes. Active clones were enriched 196-fold after a single round of microfluidic HTS. The platform is a powerful tool for the development of new production strains with low cost, space and time footprint and should bring enormous benefit for improving the viability of biotechnological processes. PMID:27270141

  11. High-throughput screening of filamentous fungi using nanoliter-range droplet-based microfluidics

    NASA Astrophysics Data System (ADS)

    Beneyton, Thomas; Wijaya, I. Putu Mahendra; Postros, Prexilia; Najah, Majdi; Leblond, Pascal; Couvent, Angélique; Mayot, Estelle; Griffiths, Andrew D.; Drevelle, Antoine

    2016-06-01

    Filamentous fungi are an extremely important source of industrial enzymes because of their capacity to secrete large quantities of proteins. Currently, functional screening of fungi is associated with low throughput and high costs, which severely limits the discovery of novel enzymatic activities and better production strains. Here, we describe a nanoliter-range droplet-based microfluidic system specially adapted for the high-throughput sceening (HTS) of large filamentous fungi libraries for secreted enzyme activities. The platform allowed (i) compartmentalization of single spores in ~10 nl droplets, (ii) germination and mycelium growth and (iii) high-throughput sorting of fungi based on enzymatic activity. A 104 clone UV-mutated library of Aspergillus niger was screened based on α-amylase activity in just 90 minutes. Active clones were enriched 196-fold after a single round of microfluidic HTS. The platform is a powerful tool for the development of new production strains with low cost, space and time footprint and should bring enormous benefit for improving the viability of biotechnological processes.

  12. Hot embossed polyethylene through-hole chips for bead-based microfluidic devices

    PubMed Central

    Chou, Jie; Du, Nan; Ou, Tina; Floriano, Pierre N.; Christodoulides, Nicolaos; McDevitt, John T.

    2013-01-01

    Over the past decade, there has been a growth of interest in the translation of microfluidic systems into real-world clinical practice, especially for use in point-of-care or near patient settings. While initial fabrication advances in microfluidics involved mainly the etching of silicon and glass, the economics of scaling of these materials is not amendable for point-of-care usage where single-test applications forces cost considerations to be kept low and throughput high. As such, a materials base more consistent with point-of-care needs is required. In this manuscript, the fabrication of a hot embossed, through-hole low-density polyethylene ensembles derived from an anisotropically etched silicon wafer is discussed. This semi-opaque polymer that can be easily sterilized and recycled provides low background noise for fluorescence measurements and yields more affordable cost than other thermoplastics commonly used for microfluidic applications such as cyclic olefin copolymer (COC). To fabrication through-hole microchips from this alternative material for microfluidics, a fabrication technique that uses a high-temperature, high-pressure resistant mold is described. This aluminum-based epoxy mold, serving as the positive master mold for embossing, is casted over etched arrays of pyramidal pits in a silicon wafer. Methods of surface treatment of the wafer prior to casting and PDMS casting of the epoxy are discussed to preserve the silicon wafer for future use. Changes in the thickness of polyethylene are observed for varying embossing temperatures. The methodology described herein can quickly fabricate 20 disposable, single use chips in less than 30 minutes with the ability to scale up 4x by using multiple molds simultaneously. When coupled as a platform supporting porous bead sensors, as in the recently developed Programmable Bio-Nano-Chip, this bead chip system can achieve limits of detection, for the cardiac biomarker C-reactive protein, of 0.3 ng/mL, thereby

  13. Hot embossed polyethylene through-hole chips for bead-based microfluidic devices.

    PubMed

    Chou, Jie; Du, Nan; Ou, Tina; Floriano, Pierre N; Christodoulides, Nicolaos; McDevitt, John T

    2013-04-15

    Over the past decade, there has been a growth of interest in the translation of microfluidic systems into real-world clinical practice, especially for use in point-of-care or near patient settings. While initial fabrication advances in microfluidics involved mainly the etching of silicon and glass, the economics of scaling of these materials is not amendable for point-of-care usage where single-test applications force cost considerations to be kept low and throughput high. As such, materials base more consistent with point-of-care needs is required. In this manuscript, the fabrication of a hot embossed, through-hole low-density polyethylene ensembles derived from an anisotropically etched silicon wafer is discussed. This semi-opaque polymer that can be easily sterilized and recycled provides low background noise for fluorescence measurements and yields more affordable cost than other thermoplastics commonly used for microfluidic applications such as cyclic olefin copolymer (COC). To fabrication through-hole microchips from this alternative material for microfluidics, a fabrication technique that uses a high-temperature, high-pressure resistant mold is described. This aluminum-based epoxy mold, serving as the positive master mold for embossing, is casted over etched arrays of pyramidal pits in a silicon wafer. Methods of surface treatment of the wafer prior to casting and PDMS casting of the epoxy are discussed to preserve the silicon wafer for future use. Changes in the thickness of polyethylene are observed for varying embossing temperatures. The methodology described herein can quickly fabricate 20 disposable, single use chips in less than 30 min with the ability to scale up 4 times by using multiple molds simultaneously. When coupled as a platform supporting porous bead sensors, as in the recently developed Programmable Bio-Nano-Chip, this bead chip system can achieve limits of detection, for the cardiac biomarker C-reactive protein, of 0.3 ng/mL, thereby

  14. A cell-based sensor of fluid shear stress for microfluidics.

    PubMed

    Varma, Sarvesh; Voldman, Joel

    2015-03-21

    Microsystems designed for cell-based studies or applications inherently require fluid handling. Flows within such systems inevitably generate fluid shear stress (FSS) that may adversely affect cell health. Simple assays of cell viability, morphology or growth are typically reported to indicate any gross disturbances to cell physiology. However, no straightforward metric exists to specifically evaluate physiological implications of FSS within microfluidic devices, or among competing microfluidic technologies. This paper presents the first genetically encoded cell sensors that fluoresce in a quantitative fashion upon FSS pathway activation. We picked a widely used cell line (NIH3T3s) and created a transcriptional cell-sensor where fluorescence turns on when transcription of a relevant FSS-induced protein is initiated. Specifically, we chose Early Growth Factor-1 (a mechanosensitive protein) upregulation as the node for FSS detection. We verified our sensor pathway specificity and functionality by noting induced fluorescence in response to chemical induction of the FSS pathway, seen both through microscopy and flow cytometry. Importantly, we found our cell sensors to be inducible by a range of FSS intensities and durations, with a limit of detection of 2 dynes cm(-2) when applied for 30 minutes. Additionally, our cell-sensors proved their versatility by showing induction sensitivity when made to flow through an inertial microfluidic device environment with typical flow conditions. We anticipate these cell sensors to have wide application in the microsystems community, allowing the device designer to engineer systems with acceptable FSS, and enabling the end-user to evaluate the impact of FSS upon their assay of interest. PMID:25648195

  15. A PDMS-Based Cylindrical Hybrid Lens for Enhanced Fluorescence Detection in Microfluidic Systems

    PubMed Central

    Lin, Bor-Shyh; Yang, Yu-Ching; Ho, Chong-Yi; Yang, Han-Yu; Wang, Hsiang-Yu

    2014-01-01

    Microfluidic systems based on fluorescence detection have been developed and applied for many biological and chemical applications. Because of the tiny amount of sample in the system; the induced fluorescence can be weak. Therefore, most microfluidic systems deploy multiple optical components or sophisticated equipment to enhance the efficiency of fluorescence detection. However, these strategies encounter common issues of complex manufacturing processes and high costs. In this study; a miniature, cylindrical and hybrid lens made of polydimethylsiloxane (PDMS) to improve the fluorescence detection in microfluidic systems is proposed. The hybrid lens integrates a laser focusing lens and a fluorescence collecting lens to achieve dual functions and simplify optical setup. Moreover, PDMS has advantages of low-cost and straightforward fabrication compared with conventional optical components. The performance of the proposed lens is first examined with two fluorescent dyes and the results show that the lens provides satisfactory enhancement for fluorescence detection of Rhodamine 6G and Nile Red. The overall increments in collected fluorescence signal and detection sensitivity are more than 220% of those without lens, and the detection limits of Rhodamine 6G and Nile red are lowered to 0.01 μg/mL and 0.05 μg/mL, respectively. The hybrid lens is further applied to the detection of Nile red-labeled Chlorella vulgaris cells and it increases both signal intensity and detection sensitivity by more than 520%. The proposed hybrid lens also dramatically reduces the variation in detected signal caused by the deviation in incident angle of excitation light. PMID:24531300

  16. Rapid detection of tuberculosis using droplet-based microfluidics

    NASA Astrophysics Data System (ADS)

    Rosenfeld, Liat; Cheng, Yunfeng; Rao, Jianghong; Tang, Sindy K. Y.

    2014-03-01

    Tuberculosis is one of the most deadly diseases that kills over one million people each year and infects one-third of the world's population. The disease is spread by infection with Mycobacterium tuberculosis (Mtb). Owing to its airborne transmission, early diagnosis is critical to the prevention and control of TB. Standard diagnostic methods, acid-fast smear from sputum, often do not become positive until after transmission occurs, which allows the spread of the disease. Culture-based techniques are more sensitive, but take weeks to obtain results because of the extremely slow growth rate of Mtb. In this study a new method to detect indicator enzyme based on the isolation of tubercle bacillus in a large number of picoliter droplets combined with a fluorescent probe has been developed. We use BlaC (an enzyme naturally expressed/secreted by tubercle bacilli) as a marker and a designed BlaC-specific fluorogenic substrates as probes for Mtb detection. We present here a new method to detect the indicator enzyme based on the isolation, digitization and concentration of bacteria samples in a large number of picoliter drops. We show that by controlling the size of the droplets we can control the rate of conversion. Hence rapid increase in signal has been observed as the size of the drops has been decreased. Our vision is that this tool will be able to detect tubercle bacilli in a sensitive, rapid, specific and quantitative manner in vitro at a low cost, particularly in resource limited settings where TB is the most prevalent.

  17. Microfluidic sensor based on integrated optical hollow waveguides.

    PubMed

    Campopiano, Stefania; Bernini, Romeo; Zeni, Luigi; Sarro, Pasqualina M

    2004-08-15

    A simple integrated optical refractometric sensor based on hollow-core antiresonant reflecting optical waveguides is proposed. The sensor uses the antiresonant reflecting guidance mechanism and permits one to measure the refractive index of a liquid filling the core by simply monitoring the transmitted spectrum. The device has been made with standard silicon technology, and the experimental results confirm numerical simulations performed in one- and two-dimensional geometry. The sensor exhibits a linear response over a wide measurement range (1.3330-1.4450) and a resolution of 9 x 10(-4) and requires a small analyte volume. PMID:15357351

  18. A collection of edge-based elements

    NASA Technical Reports Server (NTRS)

    Kempel, Leo C.; Volakis, John L.

    1992-01-01

    Edge-based elements have proved useful in solving electromagnetic problems since they are nondivergent. Previous authors have presented several two and three dimensional elements. Herein, we present four types of elements which are suitable for modeling several types of three dimensional geometries. Distorted brick and triangular prism elements are given in cartesian coordinates as well as the specialized cylindrical shell and pie-shaped prism elements which are suitable for problems best described in polar cylindrical coordinates.

  19. Automated microfluidic platform of bead-based electrochemical immunosensor integrated with bioreactor for continual monitoring of cell secreted biomarkers

    PubMed Central

    Riahi, Reza; Shaegh, Seyed Ali Mousavi; Ghaderi, Masoumeh; Zhang, Yu Shrike; Shin, Su Ryon; Aleman, Julio; Massa, Solange; Kim, Duckjin; Dokmeci, Mehmet Remzi; Khademhosseini, Ali

    2016-01-01

    There is an increasing interest in developing microfluidic bioreactors and organs-on-a-chip platforms combined with sensing capabilities for continual monitoring of cell-secreted biomarkers. Conventional approaches such as ELISA and mass spectroscopy cannot satisfy the needs of continual monitoring as they are labor-intensive and not easily integrable with low-volume bioreactors. This paper reports on the development of an automated microfluidic bead-based electrochemical immunosensor for in-line measurement of cell-secreted biomarkers. For the operation of the multi-use immunosensor, disposable magnetic microbeads were used to immobilize biomarker-recognition molecules. Microvalves were further integrated in the microfluidic immunosensor chip to achieve programmable operations of the immunoassay including bead loading and unloading, binding, washing, and electrochemical sensing. The platform allowed convenient integration of the immunosensor with liver-on-chips to carry out continual quantification of biomarkers secreted from hepatocytes. Transferrin and albumin productions were monitored during a 5-day hepatotoxicity assessment in which human primary hepatocytes cultured in the bioreactor were treated with acetaminophen. Taken together, our unique microfluidic immunosensor provides a new platform for in-line detection of biomarkers in low volumes and long-term in vitro assessments of cellular functions in microfluidic bioreactors and organs-on-chips. PMID:27098564

  20. Automated microfluidic platform of bead-based electrochemical immunosensor integrated with bioreactor for continual monitoring of cell secreted biomarkers.

    PubMed

    Riahi, Reza; Shaegh, Seyed Ali Mousavi; Ghaderi, Masoumeh; Zhang, Yu Shrike; Shin, Su Ryon; Aleman, Julio; Massa, Solange; Kim, Duckjin; Dokmeci, Mehmet Remzi; Khademhosseini, Ali

    2016-01-01

    There is an increasing interest in developing microfluidic bioreactors and organs-on-a-chip platforms combined with sensing capabilities for continual monitoring of cell-secreted biomarkers. Conventional approaches such as ELISA and mass spectroscopy cannot satisfy the needs of continual monitoring as they are labor-intensive and not easily integrable with low-volume bioreactors. This paper reports on the development of an automated microfluidic bead-based electrochemical immunosensor for in-line measurement of cell-secreted biomarkers. For the operation of the multi-use immunosensor, disposable magnetic microbeads were used to immobilize biomarker-recognition molecules. Microvalves were further integrated in the microfluidic immunosensor chip to achieve programmable operations of the immunoassay including bead loading and unloading, binding, washing, and electrochemical sensing. The platform allowed convenient integration of the immunosensor with liver-on-chips to carry out continual quantification of biomarkers secreted from hepatocytes. Transferrin and albumin productions were monitored during a 5-day hepatotoxicity assessment in which human primary hepatocytes cultured in the bioreactor were treated with acetaminophen. Taken together, our unique microfluidic immunosensor provides a new platform for in-line detection of biomarkers in low volumes and long-term in vitro assessments of cellular functions in microfluidic bioreactors and organs-on-chips. PMID:27098564

  1. Automated microfluidic platform of bead-based electrochemical immunosensor integrated with bioreactor for continual monitoring of cell secreted biomarkers

    NASA Astrophysics Data System (ADS)

    Riahi, Reza; Shaegh, Seyed Ali Mousavi; Ghaderi, Masoumeh; Zhang, Yu Shrike; Shin, Su Ryon; Aleman, Julio; Massa, Solange; Kim, Duckjin; Dokmeci, Mehmet Remzi; Khademhosseini, Ali

    2016-04-01

    There is an increasing interest in developing microfluidic bioreactors and organs-on-a-chip platforms combined with sensing capabilities for continual monitoring of cell-secreted biomarkers. Conventional approaches such as ELISA and mass spectroscopy cannot satisfy the needs of continual monitoring as they are labor-intensive and not easily integrable with low-volume bioreactors. This paper reports on the development of an automated microfluidic bead-based electrochemical immunosensor for in-line measurement of cell-secreted biomarkers. For the operation of the multi-use immunosensor, disposable magnetic microbeads were used to immobilize biomarker-recognition molecules. Microvalves were further integrated in the microfluidic immunosensor chip to achieve programmable operations of the immunoassay including bead loading and unloading, binding, washing, and electrochemical sensing. The platform allowed convenient integration of the immunosensor with liver-on-chips to carry out continual quantification of biomarkers secreted from hepatocytes. Transferrin and albumin productions were monitored during a 5-day hepatotoxicity assessment in which human primary hepatocytes cultured in the bioreactor were treated with acetaminophen. Taken together, our unique microfluidic immunosensor provides a new platform for in-line detection of biomarkers in low volumes and long-term in vitro assessments of cellular functions in microfluidic bioreactors and organs-on-chips.

  2. Multiplexed Affinity-Based Separation of Proteins and Cells Using Inertial Microfluidics

    PubMed Central

    Sarkar, Aniruddh; Hou, Han Wei; Mahan, Alison. E.; Han, Jongyoon; Alter, Galit

    2016-01-01

    Isolation of low abundance proteins or rare cells from complex mixtures, such as blood, is required for many diagnostic, therapeutic and research applications. Current affinity-based protein or cell separation methods use binary ‘bind-elute’ separations and are inefficient when applied to the isolation of multiple low-abundance proteins or cell types. We present a method for rapid and multiplexed, yet inexpensive, affinity-based isolation of both proteins and cells, using a size-coded mixture of multiple affinity-capture microbeads and an inertial microfluidic particle sorter device. In a single binding step, different targets–cells or proteins–bind to beads of different sizes, which are then sorted by flowing them through a spiral microfluidic channel. This technique performs continuous-flow, high throughput affinity-separation of milligram-scale protein samples or millions of cells in minutes after binding. We demonstrate the simultaneous isolation of multiple antibodies from serum and multiple cell types from peripheral blood mononuclear cells or whole blood. We use the technique to isolate low abundance antibodies specific to different HIV antigens and rare HIV-specific cells from blood obtained from HIV+ patients. PMID:27026280

  3. A Microfluidic Paper-Based Origami Nanobiosensor for Label-Free, Ultrasensitive Immunoassays.

    PubMed

    Li, Xiao; Liu, Xinyu

    2016-06-01

    Microfluidic paper-based analytical devices (μPADs) represent a promising platform technology for point-of-care diagnosis. Highly sensitive, rapid, and easy-to-perform immunoassays implemented on μPADs are desirable to fulfill the promise of the μPAD technology. This article reports the first microfluidic paper-based origami nanobiosensor (origami μPAD), which integrates zinc oxide nanowires (ZnO NWs) and electrochemical impedance spectroscopy (EIS) biosensing mechanism, for label-free, ultrasensitive immunoassays. The EIS mechanism features simple and label-free assay operations which take less than 25 min to be finished, while the ZnO NWs allow covalent bonding for immobilizing probe proteins and improve the biosensing performance with such features as high surface-area-to-volume ratios and high sensitivity to surface binding. The calibration of the device reveals an ultralow limit of detection (LOD) of 60 fg mL(-1) (>100 times lower than those of existing μPADs) for rabbit immunoglobulin G in phosphate-buffered saline. The detection of human immunodeficiency virus p24 antigen in human serum with a low LOD of 300 fg mL(-1) (>33 times lower than that of a commercial p24 antigen test kit) is also demonstrated. This novel μPAD design offers ultrahigh sensitivity, short assay time, and ease of operation, and thus possesses significant potential for low-cost, rapid molecular diagnosis of early-stage diseases. PMID:27122227

  4. Continuous nanoparticle production by microfluidic-based emulsion, mixing and crystallization

    SciTech Connect

    Su, Y.-F. Kim, H.; Kovenklioglu, S.; Lee, W.Y.

    2007-09-15

    BaSO{sub 4} and 2,2'-dipyridylamine (DPA) nanoparticles were synthesized as reactive crystallization and anti-solvent recrystallization examples, respectively, of using the microfluidic-based emulsion and mixing approach as a new avenue of continuously producing inorganic and organic nanoparticles. BaSO{sub 4} nanoparticles in the size range of 15-100 nm were reactively precipitated within the confinement of an aqueous droplet which was coalesced from two separate aqueous droplets containing BaCl{sub 2} and (NH{sub 4}){sub 2}SO{sub 4} using a three T-junction micromixer configuration constructed with commercially available simple tubing and fitting supplies. Also, DPA nanoparticles of about 200 nm were crystallized by combining DPA+ethanol and water droplets using the same micromixer configuration. - Graphical abstract: BaSO{sub 4} and 2,2'-dipyridylamine (DPA) nanoparticles were synthesized as reactive crystallization and anti-solvent recrystallization examples, respectively, of using the microfluidic-based emulsion and mixing approach as a new avenue of continuously producing inorganic and organic nanoparticles.

  5. Specific capture and temperature-mediated release of cells in an aptamer-based microfluidic device†

    PubMed Central

    Zhu, Jing; Nguyen, ThaiHuu; Pei, Renjun; Stojanovic, Milan; Lin, Qiao

    2014-01-01

    Isolation of cells from heterogeneous mixtures is critically important in both basic cell biology studies and clinical diagnostics. Cell isolation can be realized based on physical properties such as size, density and electrical properties. Alternatively, affinity binding of target cells by surface-immobilized ligands, such as antibodies, can be used to achieve specific cell isolation. Microfluidics technology has recently been used in conjunction with antibody-based affinity isolation methods to capture, purify and isolate cells with higher yield rates, better efficiencies and lower costs. However, a method that allows easy release and collection of live cells from affinity surfaces for subsequent analysis and detection has yet to be developed. This paper presents a microfluidic device that not only achieves specific affinity capture and enrichment, but also enables non-destructive, temperature-mediated release and retrieval of cells. Specific cell capture is achieved using surface-immobilized aptamers in a microchamber. Release of the captured cells is realized by a moderate temperature change, effected via integrated heaters and a temperature sensor, to reversibly disrupt the cell-aptamer interaction. Experimental results with CCRF-CEM cells have demonstrated that the device is capable of specific capture and temperature-mediated release of cells, that the released cells remain viable and that the aptamer-functionalized surface is regenerable. PMID:22854859

  6. A Planar Microfluidic Mixer Based on Logarithmic Spirals

    PubMed Central

    Scherr, Thomas; Quitadamo, Christian; Tesvich, Preston; Park, Daniel Sang-Won; Tiersch, Terrence; Hayes, Daniel; Choi, Jin-Woo; Nandakumar, Krishnaswamy

    2013-01-01

    A passive, planar micromixer design based on logarithmic spirals is presented. The device was fabricated using polydimethylsiloxane soft photolithography techniques, and mixing performance was characterized via numerical simulation and fluorescent microscopy. Mixing efficiency initially declined as Reynolds number increased, and this trend continued until a Reynolds number of 15 where a minimum was reached at 53%. Mixing efficiency then began to increase reaching a maximum mixing efficiency of 86% at Re = 67. Three-dimensional simulations of fluid mixing in this design were compared to other planar geometries such as the Archimedes spiral and Meandering-S mixers. The implementation of logarithmic curvature offers several unique advantages that enhance mixing, namely a variable cross-sectional area and a logarithmically varying radius of curvature that creates 3-D Dean vortices. These flow phenomena were observed in simulations with multilayered fluid folding and validated with confocal microscopy. This design provides improved mixing performance over a broader range of Reynolds numbers than other reported planar mixers, all while avoiding external force fields, more complicated fabrication processes, and the introduction of flow obstructions or cavities that may unintentionally affect sensitive or particulate-containing samples. Due to the planar design requiring only single-step lithographic features, this compact geometry could be easily implemented into existing micro-total analysis systems requiring effective rapid mixing. PMID:23956497

  7. A conductivity-based interface tracking method for microfluidic application

    NASA Astrophysics Data System (ADS)

    Salgado, Juan David; Horiuchi, Keisuke; Dutta, Prashanta

    2006-05-01

    A novel conductivity-based interface tracking method is developed for 'lab-on-a-chip' applications to measure the velocity of the liquid-gas boundary during the filling process. This interface tracking system consists of two basic components: a fluidic circuit and an electronic circuit. The fluidic circuit is composed of a microchannel network where a number of very thin electrodes are placed in the flow path to detect the location of the liquid-gas interface in order to quantify the speed of a traveling liquid front. The electronic circuit is placed on a microelectronic chip that works as a logical switch. This interface tracking method is used to evaluate the performance of planar electrokinetic micropumps formed on a hybrid poly-di-methyl-siloxane (PDMS)-glass platform. In this study, the thickness of the planar micropump is set to be 10 µm, while the externally applied electric field is ranged from 100 V mm-1 to 200 V mm-1. For a particular geometric and electrokinetic condition, repeatable flow results are obtained from the speed of the liquid-gas interface. Flow results obtained from this interface tracking method are compared to those of other existing flow measuring techniques. The maximum error of this interface tracking sensor is less than 5%, even in an ultra low flow velocity.

  8. A droplet-based microfluidic immunosensor for high efficiency melamine analysis.

    PubMed

    Choi, Jae-Won; Min, Kyong-Mi; Hengoju, Sundar; Kim, Gil-Jung; Chang, Soo-Ik; deMello, Andrew J; Choo, Jaebum; Kim, Hak Yong

    2016-06-15

    We report a droplet-based microfluidic immunosensor for the rapid and accurate detection of melamine, an organic base that has been implicated in widescale adulteration of food products such as milk. Our melamine assay is based on the competitive reaction between native melamine and a melamine-fluorescein isothiocyanate (FITC) conjugate against an anti-hapten antibody. The adoption of fluorescence polarization, allows the quantification of melamine in a more direct and rapid manner than established heterogeneous methods based on liquid chromatography, mass spectrometry, and enzyme-linked immunosorbent assay (ELISA). The detection protocol provides a limit of detection of 300 ppb, which is below the maximum allowable melamine levels (2.5 ppm) defined by the U.S. Food and Drug Administration and the European Commission to a significant extent. PMID:26829578

  9. MEMS and microfluidics for diagnostics devices.

    PubMed

    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. PMID:20199381

  10. Microfluidic serpentine antennas with designed mechanical tunability.

    PubMed

    Huang, YongAn; Wang, Yezhou; Xiao, Lin; Liu, Huimin; Dong, Wentao; Yin, Zhouping

    2014-11-01

    This paper describes the design and characterization of microfluidic serpentine antennas with reversible stretchability and designed mechanical frequency modulation (FM). The microfluidic antennas are designed based on the Poisson's ratio of the elastomer in which the liquid alloy antenna is embedded, to controllably decrease, stabilize or increase its resonance frequency when being stretched. Finite element modelling was used in combination with experimental verification to investigate the effects of substrate dimensions and antenna aspect ratios on the FM sensitivity to uniaxial stretching. It could be designed within the range of -1.2 to 0.6 GHz per 100% stretch. When the aspect ratio of the serpentine antenna is between 1.0 and 1.5, the resonance frequency is stable under stretching, bending, and twisting. The presented microfluidic serpentine antenna design could be utilized in the field of wireless mobile communication for the design of wearable electronics, with a stable resonance frequency under dynamic applied strain up to 50%. PMID:25144304