Microfluidics for medical diagnostics and biosensors

Abstract This article reviews the recent development in microfluidics for medical diagnostics and integrations with biosensors. Diagnostic and sensing applications have been the focus of much of the development of the micro-Total-Analysis-Systems (MicroTAS), and have recently enjoyed further development in new fabrication technologies, integrations, and utilities in field- and medical-applications. The challenges for these applications have been to reduce cost, to meet the sensitivity requirements while providing throughput and speed, and to expand the repertoire of applications. This review focuses mostly on new developments in the last 5–10 years in materials development, 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.

[1]  Shuji Aso,et al.  Miniature surface-plasmon resonance immunosensors – rapid and repetitive procedure , 2002, Analytical and bioanalytical chemistry.

[2]  L. Hood,et al.  Integrated barcode chips for rapid, multiplexed analysis of proteins in microliter quantities of blood , 2008, Nature Biotechnology.

[3]  O. Tabata,et al.  Replica multichannel polymer chips with a network of sacrificial channels sealed by adhesive printing method. , 2005, Lab on a chip.

[4]  S. Quake,et al.  Solvent-Resistant Photocurable “Liquid Teflon” for Microfluidic Device Fabrication , 2004 .

[5]  S. Digumarthy,et al.  Isolation of rare circulating tumour cells in cancer patients by microchip technology , 2007, Nature.

[6]  R. Tompkins,et al.  A microfluidics approach for the isolation of nucleated red blood cells (NRBCs) from the peripheral blood of pregnant women , 2008, Prenatal diagnosis.

[7]  R. Mathies,et al.  Integrated affinity capture, purification, and capillary electrophoresis microdevice for quantitative double-stranded DNA analysis. , 2007, Analytical chemistry.

[8]  Martin Moskovits,et al.  Free-surface microfluidic control of surface-enhanced Raman spectroscopy for the optimized detection of airborne molecules , 2007, Proceedings of the National Academy of Sciences.

[9]  B. Balu,et al.  Patterning of superhydrophobic paper to control the mobility of micro-liter drops for two-dimensional lab-on-paper applications. , 2009, Lab on a chip.

[10]  Howard A. Stone,et al.  ENGINEERING FLOWS IN SMALL DEVICES , 2004 .

[11]  Z. Hugh Fan,et al.  Integrating polymerase chain reaction, valving, and electrophoresis in a plastic device for bacterial detection. , 2003, Analytical chemistry.

[12]  E. Mardis The impact of next-generation sequencing technology on genetics. , 2008, Trends in genetics : TIG.

[13]  Ginger M. Denison,et al.  High-resolution soft lithography: enabling materials for nanotechnologies. , 2004, Angewandte Chemie.

[14]  Luke P. Lee,et al.  Optofluidic control using photothermal nanoparticles , 2006, Nature materials.

[15]  G. Whitesides,et al.  Simple telemedicine for developing regions: camera phones and paper-based microfluidic devices for real-time, off-site diagnosis. , 2008, Analytical chemistry.

[16]  Mehmet Toner,et al.  Multifunctional Encoded Particles for High-Throughput Biomolecule Analysis , 2007, Science.

[17]  K. Leong,et al.  Evaluating the intracellular stability and unpacking of DNA nanocomplexes by quantum dots-FRET. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[18]  D. Weitz,et al.  Fluorescence-activated droplet sorting (FADS): efficient microfluidic cell sorting based on enzymatic activity. , 2009, Lab on a chip.

[19]  Vincent Thomy,et al.  SPR biosensing coupled to a digital microfluidic microstreaming system. , 2007, Biosensors & bioelectronics.

[20]  Bartosz A. Grzybowski,et al.  Directing cell motions on micropatterned ratchets , 2009 .

[21]  Hao Li,et al.  PDMS microfludic device for optical detection of protein immunoassay using gold nanoparticles. , 2005, Lab on a chip.

[22]  Donhee Ham,et al.  Chip–NMR biosensor for detection and molecular analysis of cells , 2008, Nature Medicine.

[23]  Demetri Psaltis,et al.  Lensless high-resolution on-chip optofluidic microscopes for Caenorhabditis elegans and cell imaging , 2008, Proceedings of the National Academy of Sciences.

[24]  R Gambari,et al.  Biosensor technology and surface plasmon resonance for real-time detection of HIV-1 genomic sequences amplified by polymerase chain reaction. , 1997, Clinical and diagnostic virology.

[25]  D. Psaltis,et al.  Developing optofluidic technology through the fusion of microfluidics and optics , 2006, Nature.

[26]  Olivier Harismendy,et al.  Microdroplet-based Pcr enrichment for large-scale targeted sequencing , 2016 .

[27]  David J Beebe,et al.  A passive pumping method for microfluidic devices. , 2002, Lab on a chip.

[28]  Patrick Hunziker,et al.  Valves for autonomous capillary systems , 2008 .

[29]  P. Doyle,et al.  Optimization of encoded hydrogel particles for nucleic acid quantification. , 2009, Analytical chemistry.

[30]  C. Klapperich,et al.  Thermoplastic microfluidic device for on-chip purification of nucleic acids for disposable diagnostics. , 2006, Analytical chemistry.

[31]  D. Weitz,et al.  Monodisperse Double Emulsions Generated from a Microcapillary Device , 2005, Science.

[32]  Hsiao-Sheng Liu,et al.  Gold nanoparticles for microfluidics‐based biosensing of PCR products by hybridization‐induced fluorescence quenching , 2005, Electrophoresis.

[33]  G. Whitesides,et al.  Three-dimensional microfluidic devices fabricated in layered paper and tape , 2008, Proceedings of the National Academy of Sciences.

[34]  Andreas Manz,et al.  Single-molecule fluorescence detection in microfluidic channels—the Holy Grail in μTAS? , 2005, Analytical and bioanalytical chemistry.

[35]  Nicole Pamme,et al.  Simultaneous bioassays in a microfluidic channel on plugs of different magnetic particles. , 2008, Analytica chimica acta.

[36]  T. H. Wang,et al.  Coupling confocal fluorescence detection and recirculating microfluidic control for single particle analysis in discrete nanoliter volumes. , 2008, Lab on a chip.

[37]  He Zhu,et al.  Detecting cytokine release from single T-cells. , 2009, Analytical chemistry.

[38]  V. Srinivasan,et al.  Heterogeneous immunoassays using magnetic beads on a digital microfluidic platform. , 2008, Lab on a chip.

[39]  K. Tsukagoshi,et al.  Development of a micro total analysis system incorporating chemiluminescence detection and application to detection of cancer markers. , 2005, Analytical chemistry.

[40]  Yi Zhang,et al.  An integrated fluorescence detection system for lab-on-a-chip applications. , 2007, Lab on a chip.

[41]  Jana Lauzon,et al.  An inexpensive and portable microchip-based platform for integrated RT-PCR and capillary electrophoresis. , 2008, The Analyst.

[42]  N. Zurgil,et al.  Polymer live-cell array for real-time kinetic imaging of immune cells. , 2010, Biomaterials.

[43]  M F Hansen,et al.  On-chip magnetic bead microarray using hydrodynamic focusing in a passive magnetic separator. , 2005, Lab on a chip.

[44]  Edward S. Park,et al.  Packaging for Bio-micro-electro-mechanical Systems (BioMEMS) and Microfluidic Chips , 2021, Nano-Bio- Electronic, Photonic and MEMS Packaging.

[45]  James R Heath,et al.  Quantitative real-time measurements of DNA hybridization with alkylated nonoxidized silicon nanowires in electrolyte solution. , 2006, Journal of the American Chemical Society.

[46]  Christoph A. Merten,et al.  Drop-based microfluidic devices for encapsulation of single cells. , 2008, Lab on a chip.

[47]  G. Whitesides,et al.  Low-cost printing of poly(dimethylsiloxane) barriers to define microchannels in paper. , 2008, Analytical chemistry.

[48]  I-Ming Hsing,et al.  Microfabricated PCR-electrochemical device for simultaneous DNA amplification and detection. , 2003, Lab on a chip.

[49]  Bernhard Weigl,et al.  Towards non- and minimally instrumented, microfluidics-based diagnostic devices. , 2008, Lab on a chip.

[50]  Kristen L. Helton,et al.  Microfluidic Overview of Global Health Issues Microfluidic Diagnostic Technologies for Global Public Health , 2006 .

[51]  Changhuei Yang,et al.  Implementation of a color-capable optofluidic microscope on a RGB CMOS color sensor chip substrate. , 2010, Lab on a chip.

[52]  A. Abate,et al.  Ultrahigh-throughput screening in drop-based microfluidics for directed evolution , 2010, Proceedings of the National Academy of Sciences.

[53]  James P. Landers,et al.  Developments toward a complete micro-total analysis system for Duchenne muscular dystrophy diagnosis , 2003 .

[54]  Rustem F Ismagilov,et al.  Microfluidic cartridges preloaded with nanoliter plugs of reagents: an alternative to 96-well plates for screening. , 2006, Current opinion in chemical biology.

[55]  David A. Weitz,et al.  Controlled production of emulsion drops using an electric field in a flow-focusing microfluidic device , 2007 .

[56]  Lidong Qin,et al.  Self-powered microfluidic chips for multiplexed protein assays from whole blood. , 2009, Lab on a chip.

[57]  G. Whitesides,et al.  Solvent compatibility of poly(dimethylsiloxane)-based microfluidic devices. , 2003, Analytical chemistry.

[58]  M. Natan,et al.  Surface-enhanced Raman scattering tags for rapid and homogeneous detection of circulating tumor cells in the presence of human whole blood. , 2008, Journal of the American Chemical Society.

[59]  W. P. Hall,et al.  A Localized Surface Plasmon Resonance Biosensor: First Steps toward an Assay for Alzheimer's Disease , 2004 .

[60]  H. Yeh,et al.  Single-quantum-dot-based DNA nanosensor , 2005, Nature materials.

[61]  H T Soh,et al.  Integrated microsystem for dielectrophoretic cell concentration and genetic detection. , 2005, Lab on a chip.

[62]  Igor L. Medintz,et al.  Self-assembled nanoscale biosensors based on quantum dot FRET donors , 2003, Nature materials.

[63]  Sindy K. Y. Tang,et al.  Paper-supported 3D cell culture for tissue-based bioassays , 2009, Proceedings of the National Academy of Sciences.

[64]  S. Nie,et al.  Nanotechnology applications in cancer. , 2007, Annual review of biomedical engineering.

[65]  Daniel Malamud,et al.  A Microfluidic System for Saliva‐Based Detection of Infectious Diseases , 2007, Annals of the New York Academy of Sciences.

[66]  Anders Kristensen,et al.  Stretching DNA in polymer nanochannels fabricated by thermal imprint in PMMA , 2008, Nanotechnology.

[67]  K. Jensen,et al.  Cells on chips , 2006, Nature.

[68]  Peter R C Gascoyne,et al.  Dielectric characterization of complete mononuclear and polymorphonuclear blood cell subpopulations for label-free discrimination. , 2009, Integrative biology : quantitative biosciences from nano to macro.

[69]  Unyoung Kim,et al.  Simultaneous sorting of multiple bacterial targets using integrated dielectrophoretic-magnetic activated cell sorter. , 2009, Lab on a chip.

[70]  Eun Kyu Lee,et al.  Highly sensitive signal detection of duplex dye-labelled DNA oligonucleotides in a PDMS microfluidic chip: confocal surface-enhanced Raman spectroscopic study. , 2005, Lab on a chip.

[71]  D. Citterio,et al.  Inkjet-printed microfluidic multianalyte chemical sensing paper. , 2008, Analytical chemistry.

[72]  S. Quake,et al.  Microfluidics: Fluid physics at the nanoliter scale , 2005 .

[73]  Wen-Tso Liu,et al.  Microfluidic device as a new platform for immunofluorescent detection of viruses. , 2005, Lab on a chip.

[74]  T. Matsunaga,et al.  Microfluidic device using chemiluminescence and a DNA-arrayed thin film transistor photosensor for single nucleotide polymorphism genotyping of PCR amplicons from whole blood. , 2009, Lab on a chip.

[75]  Martin A M Gijs,et al.  Microfluidic applications of magnetic particles for biological analysis and catalysis. , 2010, Chemical reviews.

[76]  Shaoyi Jiang,et al.  Label-free biomarker sensing in undiluted serum with suspended microchannel resonators. , 2010, Analytical chemistry.

[77]  Eun Kyu Lee,et al.  Fast and sensitive DNA analysis using changes in the FRET signals of molecular beacons in a PDMS microfluidic channel , 2007, Analytical and bioanalytical chemistry.

[78]  A. Heeger,et al.  Selection of mammalian cells based on their cell-cycle phase using dielectrophoresis , 2007, Proceedings of the National Academy of Sciences of the United States of America.

[79]  Ute Drechsler,et al.  Autonomous microfluidic capillary system. , 2002, Analytical chemistry.

[80]  William H. Grover,et al.  Development and multiplexed control of latching pneumatic valves using microfluidic logical structures. , 2006, Lab on a chip.

[81]  Bingcheng Lin,et al.  Rapid prototyping of paper‐based microfluidics with wax for low‐cost, portable bioassay , 2009, Electrophoresis.

[82]  Samuel K Sia,et al.  Lab-on-a-chip devices for global health: past studies and future opportunities. , 2007, Lab on a chip.

[83]  Jonathan Leach,et al.  An optically driven pump for microfluidics. , 2006, Lab on a chip.

[84]  J. Voldman,et al.  High-throughput cell and particle characterization using isodielectric separation. , 2009, Analytical chemistry.

[85]  D. J. Harrison,et al.  Micromachining a Miniaturized Capillary Electrophoresis-Based Chemical Analysis System on a Chip , 1993, Science.

[86]  Fook Siong Chau,et al.  Microbial detection in microfluidic devices through dual staining of quantum dots-labeled immunoassay and RNA hybridization. , 2006, Analytica chimica acta.

[87]  Gabriel A Kwong,et al.  DNA-encoded antibody libraries: a unified platform for multiplexed cell sorting and detection of genes and proteins. , 2007, Journal of the American Chemical Society.

[88]  Jinjie Shi,et al.  Tunable Liquid Gradient Refractive Index (L-GRIN) lens with two degrees of freedom. , 2009, Lab on a chip.

[89]  G. Gross,et al.  Detection of physiologically active compounds using cell-based biosensors. , 2001, Trends in biotechnology.

[90]  R. Westervelt,et al.  Dielectrophoretic manipulation of drops for high-speed microfluidic sorting devices , 2006 .

[91]  D. Brennan,et al.  An Integrated Optofluidic Platform for DNA Hybridization and Detection , 2008, IEEE Sensors Journal.

[92]  A. deMello Control and detection of chemical reactions in microfluidic systems , 2006, Nature.

[93]  A. Tserepi,et al.  Integration of Microfluidics With a Love Wave Sensor for the Fabrication of a Multisample Analytical Microdevice , 2008, Journal of Microelectromechanical Systems.

[94]  George M Whitesides,et al.  Electrochemical sensing in paper-based microfluidic devices. , 2010, Lab on a chip.

[95]  G. Whitesides,et al.  Understanding wax printing: a simple micropatterning process for paper-based microfluidics. , 2009, Analytical chemistry.

[96]  F. Becker,et al.  Isolation of rare cells from cell mixtures by dielectrophoresis , 2009, Electrophoresis.

[97]  Numrin Thaitrong,et al.  Polymerase chain reaction-capillary electrophoresis genetic analysis microdevice with in-line affinity capture sample injection. , 2009, Analytical chemistry.

[98]  Vincent Studer,et al.  Microfluidic stickers for cell- and tissue-based assays in microchannels. , 2009, Lab on a chip.

[99]  Holger Becker,et al.  Polymer microfabrication technologies for microfluidic systems , 2008, Analytical and bioanalytical chemistry.

[100]  T. Livache,et al.  Polypyrrole DNA chip on a silicon device: example of hepatitis C virus genotyping. , 1998, Analytical biochemistry.

[101]  S. Nie,et al.  Single-molecule and single-nanoparticle SERS: from fundamental mechanisms to biomedical applications. , 2008, Chemical Society reviews.

[102]  David J Beebe,et al.  Cell-free protein expression in a microchannel array with passive pumping. , 2009, Lab on a chip.

[103]  D. Beebe,et al.  Physics and applications of microfluidics in biology. , 2002, Annual review of biomedical engineering.

[104]  G. Whitesides,et al.  Torque-actuated valves for microfluidics. , 2005, Analytical chemistry.

[105]  M. W. Vaughn,et al.  Microfluidic-based diagnostics for cervical cancer cells. , 2006, Biosensors & bioelectronics.

[106]  Xiaolin Zheng,et al.  Numerical characterization and optimization of the microfluidics for nanowire biosensors. , 2008, Nano letters.

[107]  J. Jenkins,et al.  Extracting kinetic rate constants from surface plasmon resonance array systems. , 2008, Analytical biochemistry.

[108]  Sriram Natarajan,et al.  Continuous-flow microfluidic printing of proteins for array-based applications including surface plasmon resonance imaging. , 2008, Analytical biochemistry.

[109]  Andreas Manz,et al.  Scaling and the design of miniaturized chemical-analysis systems , 2006, Nature.

[110]  J. Voldman,et al.  An equilibrium method for continuous-flow cell sorting using dielectrophoresis. , 2008, Analytical chemistry.

[111]  D. Noble,et al.  DNA sequencing on a chip. , 1995, Analytical chemistry.

[112]  D. Weitz,et al.  Geometrically mediated breakup of drops in microfluidic devices. , 2003, Physical review letters.

[113]  Yong Liu,et al.  Integrated cell manipulation system--CMOS/microfluidic hybrid. , 2007, Lab on a chip.

[114]  Chit Yaw Fu,et al.  Integration of optical fiber light guide, fluorescence detection system, and multichannel disposable microfluidic chip , 2007, Biomedical microdevices.

[115]  Nick Harris,et al.  A highly sensitive microsystem based on nanomechanical biosensors for genomics applications , 2006 .

[116]  Javad Alirezaie,et al.  Development of a Nanoparticle-Labeled Microfluidic Immunoassay for Detection of Pathogenic Microorganisms , 2005, Clinical Diagnostic Laboratory Immunology.

[117]  Peter R C Gascoyne,et al.  Quantitative detection of bioassays with a low-cost image-sensor array for integrated microsystems. , 2009, Angewandte Chemie.

[118]  Weihong Tan,et al.  Aptamer-based microfluidic device for enrichment, sorting, and detection of multiple cancer cells. , 2009, Analytical chemistry.

[119]  M. Álvarez,et al.  Rapid generation of protein aerosols and nanoparticles via SAW atomisation , 2008 .

[120]  Handique,et al.  Nanoliter liquid metering in microchannels using hydrophobic patterns , 2000, Analytical chemistry.

[121]  W. Lukosz,et al.  Principles and sensitivities of integrated optical and surface plasmon sensors for direct affinity sensing and immunosensing , 1991 .

[122]  G. Whitesides,et al.  Patterned paper as a platform for inexpensive, low-volume, portable bioassays. , 2007, Angewandte Chemie.

[123]  Demetri Psaltis,et al.  Optofluidic microscopy--a method for implementing a high resolution optical microscope on a chip. , 2006, Lab on a chip.

[124]  Catherine M. Klapperich,et al.  Microfluidics-based extraction of viral RNA from infected mammalian cells for disposable molecular diagnostics , 2008 .

[125]  G. Hansen,et al.  A versatile platform for comprehensive chip‐based explorative cytometry , 2009, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[126]  V. Vandelinder,et al.  Separation of plasma from whole human blood in a continuous cross-flow in a molded microfluidic device. , 2006, Analytical chemistry.

[127]  Nahm-Gyoo Cho,et al.  A novel microfluidic biosensor based on an electrical detection system for alpha-fetoprotein. , 2008, Biosensors & bioelectronics.

[128]  Sang Yup Lee,et al.  Patterned multiplex pathogen DNA detection by Au particle-on-wire SERS sensor. , 2010, Nano letters.

[129]  Samuel M Stavis,et al.  Single molecule studies of quantum dot conjugates in a submicrometer fluidic channel. , 2005, Lab on a chip.

[130]  S. Quake,et al.  Monolithic microfabricated valves and pumps by multilayer soft lithography. , 2000, Science.

[131]  Orawon Chailapakul,et al.  Electrochemical detection for paper-based microfluidics. , 2009, Analytical chemistry.

[132]  Jaebum Choo,et al.  Recent advances in surface‐enhanced Raman scattering detection technology for microfluidic chips , 2008, Electrophoresis.

[133]  George M Whitesides,et al.  FLASH: a rapid method for prototyping paper-based microfluidic devices. , 2008, Lab on a chip.

[134]  S. Manalis,et al.  Weighing of biomolecules, single cells and single nanoparticles in fluid , 2007, Nature.

[135]  R. Divan,et al.  Toward the detection of single virus particle in serum. , 2006, Analytical biochemistry.

[136]  John T McDevitt,et al.  Cell-based sensor for analysis of EGFR biomarker expression in oral cancer. , 2007, Lab on a chip.

[137]  Patrick S Doyle,et al.  High-throughput flow alignment of barcoded hydrogel microparticles. , 2009, Lab on a chip.

[138]  Huabing Yin,et al.  Characterization of cellular chemical dynamics using combined microfluidic and Raman techniques , 2007, Analytical and bioanalytical chemistry.

[139]  Matthew A. Cooper,et al.  Direct and sensitive detection of a human virus by rupture event scanning , 2001, Nature Biotechnology.

[140]  Paul I. Okagbare,et al.  Highly efficient circulating tumor cell isolation from whole blood and label-free enumeration using polymer-based microfluidics with an integrated conductivity sensor. , 2008, Journal of the American Chemical Society.

[141]  Fumihiro Sassa,et al.  Microprocessing of liquid plugs for bio/chemical analyses. , 2008, Analytical chemistry.

[142]  Richard A Mathies,et al.  Inline injection microdevice for attomole-scale sanger DNA sequencing. , 2007, Analytical chemistry.

[143]  Dejiao Lin,et al.  Three-dimensional particle imaging by defocusing method with an annular aperture. , 2008, Optics letters.

[144]  Brian N. Johnson,et al.  An integrated nanoliter DNA analysis device. , 1998, Science.

[145]  Liesbet Lagae,et al.  Cell manipulation with magnetic particles toward microfluidic cytometry , 2009 .

[146]  A. Manz,et al.  Micro total analysis systems. Latest advancements and trends. , 2006, Analytical chemistry.

[147]  T. Park,et al.  Integration of Cell Culture and Microfabrication Technology , 2003, Biotechnology progress.

[148]  Bastian E. Rapp,et al.  Surface acoustic wave biosensors: a review , 2008, Analytical and bioanalytical chemistry.

[149]  Andre Sharon,et al.  Low cost and manufacturable complete microTAS for detecting bacteria. , 2009, Lab on a chip.

[150]  Robert Langer,et al.  Implantable diagnostic device for cancer monitoring. , 2009, Biosensors & bioelectronics.

[151]  J R Scherer,et al.  Integrated portable genetic analysis microsystem for pathogen/infectious disease detection. , 2004, Analytical chemistry.

[152]  Tony Jun Huang,et al.  Hydrodynamically tunable optofluidic cylindrical microlens. , 2007, Lab on a chip.

[153]  R A Mathies,et al.  DNA sequencing using capillary array electrophoresis. , 1992, Analytical chemistry.

[154]  G. Whitesides The origins and the future of microfluidics , 2006, Nature.

[155]  Shantang Liu,et al.  On-chip micropatterning of plastic (cylic olefin copolymer, COC) microfluidic channels for the fabrication of biomolecule microarrays using photografting methods. , 2007, Langmuir : the ACS journal of surfaces and colloids.

[156]  Laura M. Lechuga,et al.  Microfluidic-optical integrated CMOS compatible devices for label-free biochemical sensing , 2006 .

[157]  Gwo-Bin Lee,et al.  Microfluidic systems integrated with two-dimensional surface plasmon resonance phase imaging systems for microarray immunoassay. , 2007, Biosensors & bioelectronics.

[158]  Sylvia Daunert,et al.  Design and Fabrication of CD-Like Microfluidic Platforms for Diagnostics: Polymer-Based Microfabrication , 2001 .

[159]  R. Fair,et al.  An integrated digital microfluidic lab-on-a-chip for clinical diagnostics on human physiological fluids. , 2004, Lab on a chip.

[160]  Daniel C Leslie,et al.  Frequency-specific flow control in microfluidic circuits with passive elastomeric features , 2009 .

[161]  Kwang Bok Kim,et al.  Red blood cell quantification microfluidic chip using polyelectrolytic gel electrodes , 2009, Electrophoresis.

[162]  George M Whitesides,et al.  Thin, lightweight, foldable thermochromic displays on paper. , 2009, Lab on a chip.

[163]  Gengfeng Zheng,et al.  Multiplexed electrical detection of cancer markers with nanowire sensor arrays , 2005, Nature Biotechnology.

[164]  Donghyun Kim,et al.  Fluorescence optical detection in situ for real‐time monitoring of cytochrome P450 enzymatic activity of liver cells in multiple microfluidic devices , 2009, Biotechnology and bioengineering.

[165]  C. Klapperich,et al.  Cell lysis and DNA extraction of gram-positive and gram-negative bacteria from whole blood in a disposable microfluidic chip. , 2009, Lab on a chip.

[166]  Thomas J. Morrow,et al.  Nanowire sensors for multiplexed detection of biomolecules. , 2008, Current opinion in chemical biology.

[167]  Jeffrey R. Alcock,et al.  Micro-injection moulding of polymer microfluidic devices , 2009 .

[168]  Frantisek Svec,et al.  Injection molded microfluidic chips featuring integrated interconnects. , 2006, Lab on a chip.

[169]  Tatsuro Endo,et al.  Multiple label-free detection of antigen-antibody reaction using localized surface plasmon resonance-based core-shell structured nanoparticle layer nanochip. , 2006, Analytical chemistry.

[170]  Aurel Ymeti,et al.  A single platform image cytometer for resource‐poor settings to monitor disease progression in HIV infection , 2007, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[171]  S. Cho,et al.  Creating, transporting, cutting, and merging liquid droplets by electrowetting-based actuation for digital microfluidic circuits , 2003 .

[172]  Ji Hoon Lee,et al.  Microfluidic device capable of sensing ultrafast chemiluminescence. , 2009, Talanta.

[173]  Hanlee P. Ji,et al.  Next-generation DNA sequencing , 2008, Nature Biotechnology.

[174]  J. R. Webster,et al.  An automated microfluidic-based immunoassay cartridge for allergen screening and other multiplexed assays. , 2009, Analytical biochemistry.

[175]  George M Whitesides,et al.  Egg beater as centrifuge: isolating human blood plasma from whole blood in resource-poor settings. , 2008, Lab on a chip.

[176]  Lei Zhai,et al.  Microfluidic valves based on superhydrophobic nanostructures and switchable thermosensitive surface for lab-on-a-chip (LOC) systems , 2008 .

[177]  F. Dickert,et al.  Bioimprinting of polymers and sol-gel phases. Selective detection of yeasts with imprinted polymers. , 2002, Analytical chemistry.

[178]  Liesbet Lagae,et al.  Localized surface plasmon resonance biosensor integrated with microfluidic chip , 2009, Biomedical microdevices.

[179]  Yi Zhang,et al.  Catching bird flu in a droplet , 2007, Nature Medicine.

[180]  David N Breslauer,et al.  Mobile Phone Based Clinical Microscopy for Global Health Applications , 2009, PloS one.

[181]  T. Leary,et al.  A chemiluminescent, magnetic particle‐based immunoassay for the detection of hepatitis C virus core antigen in human serum or plasma , 2006, Journal of medical virology.

[182]  William H. Grover,et al.  Using buoyant mass to measure the growth of single cells , 2010, Nature Methods.

[183]  Mehmet Toner,et al.  Enhancing the performance of a point-of-care CD4+ T-cell counting microchip through monocyte depletion for HIV/AIDS diagnostics. , 2009, Lab on a chip.

[184]  Shuming Nie,et al.  Counting single native biomolecules and intact viruses with color-coded nanoparticles. , 2006, Analytical chemistry.

[185]  C. Klapperich,et al.  Design and testing of a disposable microfluidic chemiluminescent immunoassay for disease biomarkers in human serum samples , 2007, Biomedical microdevices.

[186]  Bernhard H. Weigl,et al.  Design and Rapid Prototyping of Thin-Film Laminate-Based Microfluidic Devices , 2001 .