Microfluidic chips for immunoassays.

The use of microfluidic chips for immunoassays has been extensively explored in recent years. The combination of immunoassays and microfluidics affords a promising platform for multiple, sensitive, and automatic point-of-care (POC) diagnostics. In this review, we focus on the description of recent achievements in microfluidic chips for immunoassays categorized by their detection method. Following a brief introduction to the basic principles of each detection method, we examine current microfluidic immunosensor detection systems in detail. We also highlight interesting strategies for sensitive immunosensing configurations, multiplexed analysis, and POC diagnostics in microfluidic immunosensors.

[1]  Rodica Elena Ionescu,et al.  EIS microfluidic chips for flow immunoassay and ultrasensitive cholera toxin detection. , 2011, Lab on a chip.

[2]  Christof M. Niemeyer,et al.  User configurable microfluidic device for multiplexed immunoassays based on DNA-directed assembly. , 2009, Analytical chemistry.

[3]  Albert van den Berg,et al.  Electrokinetic lab-on-a-biochip for multi-ligand/multi-analyte biosensing. , 2010, Analytical chemistry.

[4]  V. Dravid,et al.  MOSFET-Embedded Microcantilevers for Measuring Deflection in Biomolecular Sensors , 2006, Science.

[5]  Eun Kyu Lee,et al.  On-chip immunoassay using surface-enhanced Raman scattering of hollow gold nanospheres. , 2010, Analytical chemistry.

[6]  Kak Namkoong,et al.  Surface acoustic wave immunosensor for real-time detection of hepatitis B surface antibodies in whole blood samples. , 2009, Biosensors & bioelectronics.

[7]  N. Pourmand,et al.  Label-Free Impedance Biosensors: Opportunities and Challenges. , 2007, Electroanalysis.

[8]  R. Crooks,et al.  Three-dimensional paper microfluidic devices assembled using the principles of origami. , 2011, Journal of the American Chemical Society.

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

[10]  Jinghua Yu,et al.  Paper-based three-dimensional electrochemical immunodevice based on multi-walled carbon nanotubes functionalized paper for sensitive point-of-care testing. , 2012, Biosensors & bioelectronics.

[11]  H. Lang,et al.  A label-free immunosensor array using single-chain antibody fragments. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[12]  D D Stubbs,et al.  Investigation of cocaine plumes using surface acoustic wave immunoassay sensors. , 2003, Analytical chemistry.

[13]  Lidan You,et al.  Effect of nanowire number, diameter, and doping density on nano-FET biosensor sensitivity. , 2011, ACS nano.

[14]  Abraham J. Qavi,et al.  Label-free technologies for quantitative multiparameter biological analysis , 2009, Analytical and bioanalytical chemistry.

[15]  Rostislav Bukasov,et al.  In situ microarray fabrication and analysis using a microfluidic flow cell array integrated with surface plasmon resonance microscopy. , 2009, Analytical chemistry.

[16]  Chao Ma,et al.  A self-powered, one-step chip for rapid, quantitative and multiplexed detection of proteins from pinpricks of whole blood. , 2010, Lab on a chip.

[17]  S. Manalis,et al.  Suspended microchannel resonators with piezoresistive sensors. , 2011, Lab on a chip.

[18]  Minbaek Lee,et al.  Nanowire and nanotube transistors for lab-on-a-chip applications. , 2009, Lab on a chip.

[19]  Jun Kondoh,et al.  Parametric study of SH-SAW device response to various types of surface perturbations , 2009 .

[20]  Xiaodong Xia,et al.  A novel label-free multi-throughput optical biosensor based on localized surface plasmon resonance. , 2009, Biosensors & bioelectronics.

[21]  Hua Dong,et al.  Screen-printed microfluidic device for electrochemical immunoassay. , 2007, Lab on a chip.

[22]  Jun‐Jie Zhu,et al.  Electrochemical immunosensor for simultaneous detection of dual cardiac markers based on a poly(dimethylsiloxane)-gold nanoparticles composite microfluidic chip: a proof of principle. , 2010, Clinical chemistry.

[23]  Baohong Liu,et al.  Microfluidic immunosensor based on stable antibody-patterned surface in PMMA microchip , 2008 .

[24]  Arben Merkoçi,et al.  Magnetic and electrokinetic manipulations on a microchip device for bead‐based immunosensing applications , 2011, Electrophoresis.

[25]  Joseph Wang.  Nanomaterial-based electrochemical biosensors. , 2005, The Analyst.

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

[27]  Jaebum Choo,et al.  Optoelectrofluidic sandwich immunoassays for detection of human tumor marker using surface-enhanced Raman scattering. , 2010, Analytical chemistry.

[28]  Klaus Drese,et al.  Automated microsystem for electrochemical detection of cancer markers , 2011, Electrophoresis.

[29]  E. Delamarche,et al.  Microfluidics for Processing Surfaces and Miniaturizing Biological Assays , 2005 .

[30]  Ruo Yuan,et al.  Magnetic control of an electrochemical microfluidic device with an arrayed immunosensor for simultaneous multiple immunoassays. , 2007, Clinical chemistry.

[31]  Takamichi Nakamoto,et al.  Prediction of QCM gas sensor responses and calculation of electrostatic contribution to sensor responses using a computational chemistry method , 2000 .

[32]  Wei Wang,et al.  Flow-through functionalized PDMS microfluidic channels with dextran derivative for ELISAs. , 2009, Lab on a chip.

[33]  Julio Raba,et al.  Citrinin (CIT) determination in rice samples using a micro fluidic electrochemical immunosensor. , 2011, Talanta.

[34]  Vijay Srinivasan,et al.  Development of a digital microfluidic platform for point of care testing. , 2008, Lab on a chip.

[35]  Guodong Liu,et al.  Aptamer-functionalized gold nanoparticles as probes in a dry-reagent strip biosensor for protein analysis. , 2009, Analytical chemistry.

[36]  Alberto Escarpa,et al.  Electrochemical immunosensing on board microfluidic chip platforms , 2012 .

[37]  Huangxian Ju,et al.  Layer-by-layer hydroxymethyl ferrocene modified sensor for one-step flow/stop-flow injection amperometric immunoassay of alpha-fetoprotein. , 2007, Biosensors & bioelectronics.

[38]  J. Rusling,et al.  Fabrication of immunosensor microwell arrays from gold compact discs for detection of cancer biomarker proteins. , 2012, Lab on a chip.

[39]  Gibum Kim,et al.  SPR microscopy and its applications to high-throughput analyses of biomolecular binding events and their kinetics. , 2007, Biomaterials.

[40]  Wei-Wei Zhao,et al.  Highly sensitive photoelectrochemical immunoassay with enhanced amplification using horseradish peroxidase induced biocatalytic precipitation on a CdS quantum dots multilayer electrode. , 2012, Analytical chemistry.

[41]  Ajay Agarwal,et al.  Label-free electrical detection of cardiac biomarker with complementary metal-oxide semiconductor-compatible silicon nanowire sensor arrays. , 2009, Analytical chemistry.

[42]  Chan Woo Park,et al.  Ultrasensitive, label-free, and real-time immunodetection using silicon field-effect transistors , 2007 .

[43]  Jing-Juan Xu,et al.  Microchip device with 64-site electrode array for multiplexed immunoassay of cell surface antigens based on electrochemiluminescence resonance energy transfer. , 2012, Analytical chemistry.

[44]  G. Whitesides,et al.  Poly(dimethylsiloxane) as a material for fabricating microfluidic devices. , 2002, Accounts of chemical research.

[45]  Feng Yan,et al.  Automated support-resolution strategy for a one-way chemiluminescent multiplex immunoassay. , 2009, Analytical chemistry.

[46]  João Pedro Conde,et al.  Microspot-based ELISA in microfluidics: chemiluminescence and colorimetry detection using integrated thin-film hydrogenated amorphous silicon photodiodes. , 2011, Lab on a chip.

[47]  C. Fan,et al.  Ultrasensitive, multiplexed detection of cancer biomarkers directly in serum by using a quantum dot-based microfluidic protein chip. , 2010, ACS nano.

[48]  Charles S Henry,et al.  Competitive immunoassays for simultaneous detection of metabolites and proteins using micromosaic patterning. , 2008, Analytical chemistry.

[49]  Albena Ivanisevic,et al.  Molecular analysis of blood with micro-/nanoscale field-effect-transistor biosensors. , 2011, Small.

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

[51]  Michael S. Wilson,et al.  Multiplex measurement of seven tumor markers using an electrochemical protein chip. , 2006, Analytical chemistry.

[52]  Jinghua Yu,et al.  Three-dimensional paper-based electrochemiluminescence immunodevice for multiplexed measurement of biomarkers and point-of-care testing. , 2012, Biomaterials.

[53]  T. Gronewold,et al.  Surface acoustic wave sensors in the bioanalytical field: recent trends and challenges. , 2007, Analytica chimica acta.

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

[55]  H. Lang,et al.  Multiple label-free biodetection and quantitative DNA-binding assays on a nanomechanical cantilever array , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[56]  Sang Jun Sim,et al.  Fabrication and testing of a PDMS multi-stacked hand-operated LOC for use in portable immunosensing systems , 2008, Biomedical microdevices.

[57]  W. Verboom,et al.  Optical sensing systems for microfluidic devices: a review. , 2007, Analytica chimica acta.

[58]  Hongping Wei,et al.  Rapid detection of Bacillus anthracis using monoclonal antibody functionalized QCM sensor. , 2009, Biosensors & bioelectronics.

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

[60]  Julio Raba,et al.  IgG anti-gliadin determination with an immunological microfluidic system applied to the automated diagnostic of the celiac disease , 2010, Analytical and bioanalytical chemistry.

[61]  R. V. Van Duyne,et al.  Localized surface plasmon resonance spectroscopy and sensing. , 2007, Annual review of physical chemistry.

[62]  David Juncker,et al.  Immunochromatographic assay on thread. , 2012, Analytical chemistry.

[63]  Seung-Man Yang,et al.  Microfluidic multicolor encoding of microspheres with nanoscopic surface complexity for multiplex immunoassays. , 2011, Angewandte Chemie.

[64]  Itamar Willner,et al.  Nucleic acid-functionalized Pt nanoparticles: Catalytic labels for the amplified electrochemical detection of biomolecules. , 2006, Analytical chemistry.

[65]  Jung Ho Park,et al.  In-situ quantitative analysis of a prostate-specific antigen (PSA) using a nanomechanical PZT cantilever. , 2004, Lab on a chip.

[66]  Zsolt Tulassay,et al.  Protein microchips in biomedicine and biomarker discovery , 2007, Electrophoresis.

[67]  Wang Li,et al.  SERS-fluorescence joint spectral encoding using organic-metal-QD hybrid nanoparticles with a huge encoding capacity for high-throughput biodetection: putting theory into practice. , 2012, Journal of the American Chemical Society.

[68]  B. Lin,et al.  Low cost, portable detection of gold nanoparticle‐labeled microfluidic immunoassay with camera cell phone , 2009, Electrophoresis.

[69]  Fred J Sigworth,et al.  Importance of the Debye screening length on nanowire field effect transistor sensors. , 2007, Nano letters.

[70]  Dong-Kyung Kim,et al.  Development of indirect-competitive quartz crystal microbalance immunosensor for C-reactive protein , 2009 .

[71]  H. B. Halsall,et al.  Microfluidic immunosensor systems. , 2005, Biosensors & bioelectronics.

[72]  Matthew A Cooper,et al.  Profiling of molecular interactions in real time using acoustic detection. , 2007, Biosensors & bioelectronics.

[73]  Konstantinos Mitsakakis,et al.  Detection of multiple cardiac markers with an integrated acoustic platform for cardiovascular risk assessment. , 2011, Analytica chimica acta.

[74]  Alberto Escarpa,et al.  Electrochemical microfluidic chips coupled to magnetic bead-based ELISA to control allowable levels of zearalenone in baby foods using simplified calibration. , 2009, The Analyst.

[75]  Tae-Kyu Lim,et al.  Microfabricated on-chip-type electrochemical flow immunoassay system for the detection of histamine released in whole blood samples. , 2003, Analytical chemistry.

[76]  Patrick S Doyle,et al.  Multiplexed protein quantification with barcoded hydrogel microparticles. , 2010, Analytical chemistry.

[77]  Maryam Tabrizian,et al.  Patterning multiplex protein microarrays in a single microfluidic channel. , 2012, Analytical chemistry.

[78]  Jean-Michel Savéant,et al.  Theory and practice of enzyme bioaffinity electrodes. Direct electrochemical product detection. , 2008, Journal of the American Chemical Society.

[79]  Stephanus Büttgenbach,et al.  Miniaturized QCM-based flow system for immunosensor application in liquid , 2005 .

[80]  James F Rusling,et al.  Microfluidic electrochemical immunoarray for ultrasensitive detection of two cancer biomarker proteins in serum. , 2011, Biosensors & bioelectronics.

[81]  Feng Guo,et al.  On-demand preparation of quantum dot-encoded microparticles using a droplet microfluidic system. , 2011, Lab on a chip.

[82]  Hirotsugu Ogi,et al.  Multichannel wireless-electrodeless quartz-crystal microbalance immunosensor. , 2010, Analytical chemistry.

[83]  Julio Raba,et al.  Integrated microfluidic systems with an immunosensor modified with carbon nanotubes for detection of prostate specific antigen (PSA) in human serum samples. , 2008, Biosensors & bioelectronics.

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

[85]  Baohong Liu,et al.  Microchip-based ELISA strategy for the detection of low-level disease biomarker in serum. , 2009, Analytica chimica acta.

[86]  G. Whitesides,et al.  Diagnostics for the developing world: microfluidic paper-based analytical devices. , 2010, Analytical chemistry.

[87]  Charles J. Choi,et al.  A 96-well microplate incorporating a replica molded microfluidic network integrated with photonic crystal biosensors for high throughput kinetic biomolecular interaction analysis. , 2007, Lab on a chip.

[88]  Isao Karube,et al.  Electrochemical protein chip with arrayed immunosensors with antibodies immobilized in a plasma-polymerized film. , 2003, Analytical chemistry.

[89]  Charles M Lieber,et al.  Label-free detection of small-molecule-protein interactions by using nanowire nanosensors. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[90]  Terence G. Henares,et al.  Current development in microfluidic immunosensing chip. , 2008, Analytica chimica acta.

[91]  Göran Stemme,et al.  An integrated QCM-based narcotics sensing microsystem. , 2008, Lab on a chip.

[92]  Paul Winterrowd,et al.  Ultra-sensitive detection of bacterial toxin with silicon nanowire transistor. , 2008, Lab on a chip.

[93]  Hans Lehrach,et al.  Miniaturization in functional genomics and proteomics , 2005, Nature Reviews Genetics.

[94]  Paul A. Millner,et al.  Development of a myoglobin impedimetric immunosensor based on mixed self-assembled monolayer onto gold , 2008 .

[95]  Eun Kyu Lee,et al.  Fabrication of SERS-fluorescence dual modal nanoprobes and application to multiplex cancer cell imaging. , 2012, Nanoscale.

[96]  Arun Majumdar,et al.  Label-free protein recognition two-dimensional array using nanomechanical sensors. , 2008, Nano letters.

[97]  D. Cliffel,et al.  Electrochemical sensors and biosensors. , 2012, Analytical chemistry.

[98]  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.

[99]  Karlheinz Bock,et al.  Automated 10-channel capillary chip immunodetector for biological agents detection. , 2007, Biosensors & bioelectronics.

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

[101]  Shenguang Ge,et al.  Paper-based chemiluminescence ELISA: lab-on-paper based on chitosan modified paper device and wax-screen-printing. , 2012, Biosensors & bioelectronics.

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

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

[104]  K. Rose,et al.  Metallic striped nanowires as multiplexed immunoassay platforms for pathogen detection. , 2006, Angewandte Chemie.

[105]  Julio Raba,et al.  A microfluidic device based on a screen-printed carbon electrode with electrodeposited gold nanoparticles for the detection of IgG anti-Trypanosoma cruzi antibodies. , 2011, The Analyst.

[106]  Julio Raba,et al.  Microfluidic immunosensor with gold nanoparticle platform for the determination of immunoglobulin G anti-Echinococcus granulosus antibodies. , 2011, Analytical biochemistry.

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

[108]  Juan Tang,et al.  Nanoparticle-based sandwich electrochemical immunoassay for carbohydrate antigen 125 with signal enhancement using enzyme-coated nanometer-sized enzyme-doped silica beads. , 2010, Analytical chemistry.

[109]  Gun-Sik Tae,et al.  Microfluidic chip-based electrochemical immunoassay for hippuric acid. , 2009, The Analyst.

[110]  Noritada Kaji,et al.  Immuno-pillar chip: a new platform for rapid and easy-to-use immunoassay. , 2010, Lab on a chip.

[111]  Albert van den Berg,et al.  Electrokinetic label-free screening chip: a marriage of multiplexing and high throughput analysis using surface plasmon resonance imaging. , 2010, Lab on a chip.

[112]  J. Rossier,et al.  Enzyme linked immunosorbent assay on a microchip with electrochemical detection. , 2001, Lab on a chip.

[113]  Wei Yan,et al.  Electrochemical impedance immunosensor based on three-dimensionally ordered macroporous gold film. , 2008, Analytical chemistry.

[114]  Alex Rhee,et al.  Convergence of quantum dot barcodes with microfluidics and signal processing for multiplexed high-throughput infectious disease diagnostics. , 2007, Nano letters.

[115]  Tomoyuki Taguchi,et al.  Construction of an electrochemical probe for on chip type flow immunoassay , 2005 .

[116]  Se Young Oh,et al.  Electrochemical detection of cardiac troponin I using a microchip with the surface-functionalized poly(dimethylsiloxane) channel. , 2007, Biosensors & bioelectronics.

[117]  Se Young Oh,et al.  In situ electrochemical enzyme immunoassay on a microchip with surface-functionalized poly(dimethylsiloxane) channel , 2006 .

[118]  Mark A. Reed,et al.  Label-free immunodetection with CMOS-compatible semiconducting nanowires , 2007, Nature.

[119]  Aldo Roda,et al.  Portable device based on chemiluminescence lensless imaging for personalized diagnostics through multiplex bioanalysis. , 2011, Analytical chemistry.

[120]  Jing Wang,et al.  Immunogold labeling-induced synergy effect for amplified photoelectrochemical immunoassay of prostate-specific antigen. , 2012, Chemical communications.