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Microfluidic whole-blood immunoassays

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Abstract

Immunoassay is one of the most widely used biomedical diagnostic methods due to its sensitivity and specificity. Microfluidic lab-on-a-chip technology has the advantages of portability, integration, and automation. The combination of these two technologies leads to a pathway for point-of-care diagnostics using the unprocessed samples such as the whole blood. This article reviews the recent advancement and the major development in the microfluidic-based whole-blood immunoassays. After a survey of the recent studies on microfluidic whole-blood immunoassays, an in-depth review about the detection methods that can be miniaturized and integrated in the immunoassay chips is provided. Point-of-care diagnostics applications require developing a fully integrated, disposable, low-cost, and handheld microfluidic device for the whole-blood immunoassay. In this regard, some comments and suggestions for future research are given.

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References

  • Bard J, Faulkner LR (2001) Electrochemical methods: fundamentals and applications, 2nd edn. Wiley, New York

    Google Scholar 

  • Berti F, Marrazza G et al (2009) Microfluidic-based electrochemical genosensor coupled to magnetic beads for hybridization detection. Talanta 77:971–978

    Google Scholar 

  • Chediak JA, Luo Z, Seo J, Cheung N, Lee LP, Sands TD (2004) Heterogeneous integration of CdS filters with GaN LEDs for fluorescence detection microsystems. Sens Actuator A Phys 111:1–7

    Google Scholar 

  • Chen I-J, Lindner E (2009) Lab-on-chip flow injection analysis system without an external pump and valves and integrated with an in line electrochemical detector. Anal Chem 81:9955–9960

    Google Scholar 

  • Chikkaveeraiah B, Rusling J et al (2009) A microfluidic electrochemical device for high sensitivity biosensing: detection of nanomolar hydrogen peroxide. Electrochem Commun 11:819–822

    Google Scholar 

  • Chin CD, Linder V, Sia SK (2007) Lab-on-a-chip devices for global health: past studies and future opportunities. Lab Chip 7:41–57

    Google Scholar 

  • Chinowsky TM, Grow MS, Johnston KS, Nelson K, Edwards T, Fu E, Yager P (2007a) Compact, high performance surface plasmon resonance imaging system. Biosens Bioelectron 22:2208–2215

    Google Scholar 

  • Chinowsky TM, Soelberg SD, Baker P, Swanson NR, Kauffman P, Mactutis A, Grow MS, Atmar R, Yee SS, Furlong CE (2007b) Portable 24-analyte surface plasmon resonance instruments for rapid, versatile biodetection. Biosens Bioelectron 22:2268–2275

    Google Scholar 

  • Cho JH, Han SM, Paek EH, Cho IH, Paek SH (2006) Plastic ELISA-on-a-chip based on sequential cross-flow chromatography. Anal Chem 78:793–800

    Google Scholar 

  • Cho Y-K, Ko C et al (2007) One-step pathogen specific DNA extraction from whole blood on a centrifugal microfluidic device. Lab Chip 7:565–573

    Google Scholar 

  • Christodoulides N, Tran M, Floriano PN, Rodriguez M, Goodey A, Ali M, Neikirk D, McDevitt JT (2002) A microchip-based multianalyte assay system for the assessment of cardiac risk. Anal Chem 74(13):3030–3036

    Google Scholar 

  • Chumbimuni-Torres K, Bakker E et al (2006) Potentiometric biosensing of proteins with ultrasensitive ion-selective microelectrodes and nanoparticle labels. J Am Chem Soc 128:13676–13677

    Google Scholar 

  • Cooper MA (2002) Optical biosensors in drug discovery. Nat Rev 1:515–528

    Google Scholar 

  • Darain F, Tjin S et al (2009a) Antibody immobilization on to polystyrene substrate––on-chip immunoassay for horse IgG based on fluorescence. Biomed Microdevices 11:653–661

    Google Scholar 

  • Darain F, Tjin S et al (2009b) On-chip detection of myoglobin based on fluorescence. Biosens Bioelectron 24:1744–1750

    Google Scholar 

  • Dittmer WU, Martens MFWC et al (2010) Rapid, high sensitivity, point-of-care test for cardiac troponin based onoptomagnetic biosensor. Clin Chim Acta 411:868–873

    Google Scholar 

  • Ducrée J, Zengerle R et al (2007) The centrifugal microfluidic bio-disk platform. J Micromech Microeng 17:S103–S115

    Google Scholar 

  • Ekins RP (1960) The estimation of thyroxine in human plasma by an electrophoretic technique. Clin Chim Acta 5:453–459

    Google Scholar 

  • Engvall E (1977) Quantitative enzyme immunoassay (ELISA) in microbiology. Med Biol 55:193–200

    Google Scholar 

  • Engvall E, Perlman P (1971) Enzyme-linked immunosorbent assay (ELISA): quantitative assay of immunoglobulin G. Immunochemistry 8(9):871–874

    Google Scholar 

  • Engvall E, Perlmann P (1971) Enzyme-linked immunosorbent assay (ELISA): quantitative assay of immunoglobulin G. Immunochemistry 8:871–874

    Google Scholar 

  • Estmer Nilsson C et al (2010) A novel assay for influenza virus quantification using surface plasmon resonance. Vaccine 28:759–766

    Google Scholar 

  • Fan R, Heath J et al (2008) Integrated barcode chips for rapid, multiplexed analysis of proteins in microliter quantities of blood. Nat Biotechnol 26:1373–1378

    Google Scholar 

  • Feltis B, Sexton B, Glenn F, Best M, Wilkins M, Davis T (2008) A hand-held surface plasmon resonance biosensor for the detection of ricin and other biological agents. Biosens Bioelectron 23:1131–1136

    Google Scholar 

  • Frisk T, Stemme G et al (2008) An integrated QCM-based narcotics sensing microsystem. Lab Chip 8:1648–1657

    Google Scholar 

  • Fu E, Chinowsky T, Nelson K, Johnston K, Edwards T, Helton K, Grow M, Miller J, Yager P (2007) SPR imaging-based salivary diagnostics system for the detection of small molecule analytes. Ann N Y Acad Sci 1098:335–344

    Google Scholar 

  • Fung YC (1973) Stochastic flow in capillary blood vessels. Microvasc Res 5:34–48

    Google Scholar 

  • Gao Y, Hu G, Lin F, Li D (2005a) An electrokinetically-controlled immunoassay for simultaneous detection of multiple microbial antigens. Biomed Microdevices 7(4):301–312

    Google Scholar 

  • Gao Y, Lin F, Hu G, Li D (2005b) Development of a novel electrokinetically driven microfluidic immunoassay for the detection of Helicobacter pylori. Anal Chim Acta 543:109–116

    Google Scholar 

  • Godino N, del Campo FJ et al (2010) Construction and characterisation of a modular microfluidic system: coupling magnetic capture and electrochemical detection. Microfluid Nanofluid 8:393–402

    Google Scholar 

  • Grumann M, Geipel A, Riegger L, Zengerle R, Ducre′e J (2005) Batch-mode mixing on centrifugal microfluidic platforms. Lab Chip 5:560–565

    Google Scholar 

  • Hashimoto M, Kaji H, Kemppinen ME, Nishizawa M (2008) Localized immobilization of proteins onto microstructures within a preassembled microfluidic device. Sens Actuator B Chem 128(2):545–551

    Google Scholar 

  • Hatch AE, Kamholz KR, Hawkins MS, Munson EA, Schilling B, Weigl H, Yager P (2001) A rapid diffusion immunoassay in a T-sensor. Nat Biotechnol 19:461–465

    Google Scholar 

  • Hawkins KR, Yager P et al (2002) Diffusion immunoassay for protein analytes. 2nd annual international IEEE-EMBS special topic conference on microtechnologies in medicine & biology, pp 535–540

  • Henares TG, Funano S-i, Terabe S, Mizutani F, Sekizawa R, Hisamoto H (2007) Multiple enzyme linked immunosorbent assay system on a capillary-assembled microchip integrating valving and immunoreactions functions. Anal Chim Acta 589(2):173–179

    Google Scholar 

  • Herr AE, Anup K (2007) Microfluidic immunoassays as rapid saliva-based clinical diagnostics. PNAS 104:5268–5273

    Google Scholar 

  • Herr AE, Singh AK (2007) Integrated microfluidic platform for oral diagnostics. Ann NY Acad Sci 1098:362–374

    Google Scholar 

  • Herr AE, Hatch AV, Throckmorton DJ, Tran HM, Brennan JS, Giannobile WV, Singh AK (2007) Microfluidic immunoassays as rapid saliva-based clinical diagnostics. Proc Natl Acad Sci USA 104(13):5268–5273

    Google Scholar 

  • Hirsch LR, Jackson JB, Lee A, Halas NJ, West JL (2003) A whole blood immunoassay using gold nanoshells. Anal Chem 75:2377–2381

    Google Scholar 

  • Hirsch LR, Halas NJ, West JL (2005) Whole-blood immunoassay facilitated by gold nanoshell-conjugate antibodies. Methods Mol Biol 303:101–112

    Google Scholar 

  • Hnaiein M, Jaffrezic-Renault N et al (2008) A conductometric immunosensor based on functionalized magnetite nanoparticles for E. coli detection. Electrochem Commun 10:1152–1154

    Google Scholar 

  • Hofmann O, Voirin G, Niedermann P, Manz A (2002) Three-dimensional microfluidic confinement for efficient sample delivery to biosensor surfaces: application to immunoassays on planar optical waveguides. Anal Chem 74:5243–5250

    Google Scholar 

  • Hosokawa K, Omata M, Sato K, Maeda M (2006) Power-free sequential injection for microchip immunoassay toward point-of-care testing. Lab Chip 6(2):236–241

    Google Scholar 

  • Hosokawa K, Omata M, Maeda M (2007) Immunoassay on a power-free microchip with laminar flow-assisted dendritic amplification. Anal Chem 79:6000–6004

    Google Scholar 

  • Hu G, Gao Y, Sherman P, Li D (2005) A microfluidic chip for heterogeneous immunoassay using electrokinetical control. Microfluid Nanofluid 1:346–355

    Google Scholar 

  • Hu G, Gao Y, Li D (2007) Modeling micropatterned antigen–antibody binding kinetics in a microfluidic chip. Biosens Bioelectron 22:1403–1409

    Google Scholar 

  • Huang H, Pu X et al (2009) Rapid analysis of alpha-fetoprotein by chemiluminescence microfluidic immunoassay system based on super-paramagnetic microbeads. Biomed Microdevices 11:213–216

    Google Scholar 

  • Huckle D (2006) Point-of-care diagnostics: will the hurdles be overcome this time? Expert Rev Med Device 3:421–426

    Google Scholar 

  • Huckle D (2008) Point-of-care diagnostics: an advancing sector with nontechnical issues. Expert Rev Mol Diagn 8:679–688

    Google Scholar 

  • Ihara M, Ueda H et al (2010) Micro OS-ELISA: rapid noncompetitive detection of a small biomarker peptide by open-sandwich enzyme-linked immunosorbent assay (OS-ELISA) integrated into microfluidic device. Lab Chip 10:92–100

    Google Scholar 

  • Järås K, Tajudin AA, Ressine A, Soukka T, Marko-Varga G, Bjartell A, Malm J, Laurell T, Lilja H (2008) ENSAM: europium nanoparticles for signal enhancement of antibody microarrays on nanoporous silicon. J Proteome Res 7:1308–1314

    Google Scholar 

  • Kagebayashi C, Yamaguchi I, Akinaga A, Kitano H, Yokoyama K, Satomura M, Kurosawa T, Watanabe M, Kawabata T, Chang W, Li C, Bousse L, Wada HG, Satomura S (2009) Automated immunoassay system for AFP-L3% using on-chip electrokinetic reaction and separation by affinity electrophoresis. Anal Biochem 388(2):306–311

    Google Scholar 

  • Kakehi K, Oda Y et al (2001) Fluorescence polarization: analysis of carbohydrate–protein interaction. Anal Biochem 297(2):111–116

    Google Scholar 

  • Karlsson R (2004) SPR for molecular interaction analysis: a review of emerging application areas. J Mol Recognit 17:151–161

    Google Scholar 

  • Kim N, Kim D-K, Cho Y-J (2009) Development of indirect-competitive quartz crystal microbalance immunosensor for C-reactive protein. Sens Actuator B 143:444–448

    Google Scholar 

  • Kitamori T, Tokeshi M, Hibara A, Sato K (2004) Peer reviewed: thermal lens microscopy and microchip chemistry. Anal Chem 76(3):52A–60A

    Google Scholar 

  • Kong J, Lin B et al (2009) Integrated microfluidic immunoassay for the rapid determination of clenbuterol. Lab Chip 9:1541–1547

    Google Scholar 

  • Kretschmann E (1971) The determination of the optical constants of metals by excitation of surface plasmons. Z Phys 241:313

    Google Scholar 

  • Krishnamoorthy G, Carlen ET, Kohlheyer D, Schasfoort RBM, van den Berg A (2009) Integrated electrokinetic sample focusing and surface plasmon resonance imaging system for measuring biomolecular interactions. Anal Chem 81:1957–1963

    Google Scholar 

  • Krishnamoorthy G et al (2010) Electrokinetic lab-on-a-biochip for multi-ligand/multi-analyte biosensing. Anal Chem 82:4145–4150

    Google Scholar 

  • Kuei-Ling S, Lin Y-C, Chen W-T et al (2009) An immunoassay using an electro-microchip, nanogold probe and silver enhancement. Microfluid Nanofluid 6:93–98

    Google Scholar 

  • Laiwattanapaisal W, Songjaroen T, Maturos T, Lomas T, Sappat A, Tuantranont A (2009) On-chip immunoassay for determination of urinary albumin. Sensors 9:10066–10079

    Google Scholar 

  • Lee K-H, Yuan-Deng S, Chen S-J, Tseng F-G, Lee G-B (2007) Microfluidic systems integrated with two-dimensional surface plasmon resonance phase imaging systems for microarray immunoassay. Biosens Bioelectron 23(4):466–472

    Google Scholar 

  • Lee B, Ko C et al (2009) A fully automated immunoassay from whole blood on a disc. Lab Chip 9:1548–1555

    Google Scholar 

  • Lenshof A, Laurell T et al (2009) Acoustic whole blood plasmapheresis chip for prostate specific antigen microarray diagnostics. Anal Chem 81:6030–6037

    Google Scholar 

  • Liang K-Z, Liu Z-X et al (2009) Conductometric immunoassay for interleukin-6 in human serum based on organic/inorganic hybrid membrane functionalized interface. Bioprocess Biosyst Eng 32:353–359

    Google Scholar 

  • Lim T-K, Ohta H, Matsunaga T (2003) Microfabricated on-chip-type electrochemical flow immunoassay system for the detection of histamine released in whole blood samples. Anal Chem 75:3316–3321

    Google Scholar 

  • Liu C, DafuCui H (2010) A hard–soft microfluidic-based biosensor flow cell for SPR imaging application. Biosens Bioelectron 26(1):255–261

    Google Scholar 

  • Liu C-Yu, Lee G-B et al (2009a) Integrated microfluidic system for electrochemical sensing of urinary proteins. Biomed Microdevices 11:201–211

    Google Scholar 

  • Liu H, Zhong Z et al (2009b) Enhanced conductometric immunoassay for hepatitis B surface antigen using double-codified nanogold particles as labels. Biochem Eng J 45:107–112

    Google Scholar 

  • Ljungstrom I, Engvall E, Ruitenberg EJ (1974) Proceedings: ELISA, enzyme-linked immunosorbent assay—a new technique for serodiagnosis of trichinosis. Parasitology 69:xxiv

    Google Scholar 

  • Luppa PB, Sokoll LJ, Chan DW (2001) Immunosensors—principles and applications to clinical chemistry. Clin Chim Acta 314:1–26

    Google Scholar 

  • Meagher RJ, Hatch AV, Renzi RF, Singh AK (2008) An integrated microfluidic platform for sensitive and rapid detection of biological toxins. Lab Chip 8(12):2046–2053

    Google Scholar 

  • Mecea VM (2005) From quartz crystal microbalance to fundamental principles of mass measurements. Anal Lett 38:753–767

    Google Scholar 

  • Michalzik M, Wilke R, Buttgenbach S (2005) Miniaturized QCM-based flow system for immunosensor application in liquid. Sens Actuator B Chem 111–112(11):410–415

    Google Scholar 

  • Miles LEM, Hales CN (1968) Labelled antibodies and immunological assay systems. Nature 219:186–189

    Google Scholar 

  • Moorthy J, Mensing GA, Kim D, Mohanty S, Eddington DT, Tepp WH, Johnson EA, Beebe DJ (2004) Microfluidic tectonics platform: a colorimetric, disposable botulinum toxin enzyme-linked immunosorbent assay system. Electrophoresis 25:1705

    Google Scholar 

  • Morozov VN, Groves S, Turell MJ, Bailey C (2007) Three minutes-long electrophoretically assisted zeptomolar microfluidic immunoassay with magnetic-beads detection. J Am Chem Soc 129:12628–12629

    Google Scholar 

  • Muhammad-Tahir Z, Alocilja E (2003) A conductometric biosensor for biosecurity. Biosens Bioelectron 18:813–819

    Google Scholar 

  • Mullett WM, Lai EPC, Yeung JM (2000) Surface plasmon resonance-based immunoassays. Methods 22:77–91

    Google Scholar 

  • Nobel Prize home page. http://nobelprize.org/nobel_prizes/medicine/laureates/1977/. Accessed June 2005

  • Pais A, Banerjee A, Klotzkin D, Papautsky I (2008) High-sensitivity, disposable lab on-a-chip with thin-film organic electronics for fluorescence detection. Lab Chip 8:794–800

    Google Scholar 

  • Park SW, Yang SS et al (2009) An electrochemical immunosensing lab-on-a-chip integrated with latch mechanism for hand operation. J Micromech Microeng 19:025024

    Google Scholar 

  • Parsa H, Chin CD, Mongkolwisetwara P, Lee BW, Wang JJ, Sia SK (2008) Effect of volume- and time-based constraints on capture of analytes in microfluidic heterogeneous immunoassays. Lab Chip 8:2062–2070

    Google Scholar 

  • Pereira SV et al (2010a) Integrated microfluidic magnetic immunosensor for quantification of human serum IgG antibodies to Helicobacter pylori. J Chromatogr B Anal Technol Biomed Life Sci 878(2):253–257

    Google Scholar 

  • Pereira S, Raba J, Messina G (2010b) IgG anti-gliadin determination with an immunological microfluidic system applied to the automated diagnostic of the celiac disease. Anal Bioanal Chem 396:2921–2927

    Google Scholar 

  • Petti CA, Polage CR, Quinn TC, Ronald AR, Sande MA (2006) Laboratory medicine in Africa: a barrier to effective health care. Clin Infect Dis 42:377–382

    Google Scholar 

  • Pugia M, Schulman L et al (2005) Microfluidic tool box as technology platform for hand-held diagnostics. Clin Chem 51(10):1923–1932

    Google Scholar 

  • Qin L, Vermesh O, Shi Q, Heath J (2009) Self-powered microfluidic chips for multiplexed protein assays from whole blood. Lab Chip 9:2016–2020

    Google Scholar 

  • Qiu X, Thompson JA, Chen Z et al (2009) Finger-actuated, self-contained immunoassay cassettes. Biomed Microdevices 11(6):1175–1186

    Google Scholar 

  • Rabe J, Buttgenbach S, Zimmermann B, Hauptmann P (2000) Design, manufacturing, and characterization of high-frequency thicknessshear mode resonators. In: Proceedings of the IEEE/EIA international frequency control symposium, pp 106–112

  • Reichmuth DS, Wang SK, Barrett LM, Throckmorton DJ, Einfeld W, Singha AK (2008) Rapid microchip-based electrophoretic immunoassays for the detection of swine influenza virus. Lab Chip 8(8):1319–1324

    Google Scholar 

  • Riegger L, Ducr′ee J et al (2006) Read-out concepts for multiplexed bead-based fluorescence immunoassays on centrifugal microfluidic platforms. Sens Actuator A 126:455–462

    Google Scholar 

  • Sato K, Tokeshi M, Odake T, Kimura H, Ooi T, Nakao M, Kitamori T (2000) Integration of an immunosorbent assay system: analysis of secretory human immunoglobulin A on polystyrene beads in a microchip. Anal Chem 72(6):1144–1147

    Google Scholar 

  • Sato K, Tokeshi M, Kimura H, Kitamori T (2001) Determination of carcinoembryonic antigen in human sera by integrated bead-bed immunoasay in a microchip for cancer diagnosis. Anal Chem 73(6):1213–1218

    Google Scholar 

  • Sato K, Yamanaka M, Takahashi H, Tokeshi M, Kimura H, Kitamori T (2002) Microchip-based immunoassay system with branching multichannels for simultaneous determination of interferon-gamma. Electrophoresis 23(5):734–739

    Google Scholar 

  • Schmid-Schonbein GW, Skalak R, Usami S, Chien S (1980) Cell distribution in capillary networks. Microvasc Res 19:18–44

    Google Scholar 

  • Schmidt O, Bassler M, Kiesel P, Knollenberg C, Johnson N (2007) Fluorescence spectrometer-on-a-fluidic-chip. Lab Chip 7:626–629

    Google Scholar 

  • Schuurs AHWM, van Weemen BK (1980) Enzyme-immunoassay: a powerful analytical tool. J Immunoassay 1:229–249

    Google Scholar 

  • Seo J, Lee LP (2003) Fluorescence amplification by self-aligned integrated microfluidic optical systems. IEEE transducers 2003, solid-state sensors, actuators and microsystems, pp 1136–1139

  • Seo J, Lee LP (2004) Disposable integrated microfluidics with self-aligned planar microlenses. Sens Actuator B Chem 99:615–622

    Google Scholar 

  • Shankaran D, Miura N (2007) Trends in interfacial design for surface plasmon resonance based immunoassays. J Phys D Appl Phys 40:7187–7200

    Google Scholar 

  • Shankaran DR, Gobi KV, Miura N (2007) Recent advancements in surface plasmon resonance immunosensors for detection of small molecules of biomedical, food and environmental interest. Sens Actuator B 12:158–177

    Google Scholar 

  • Singer PA, Taylor AD, Daar AS, Upshur RE, Singh JA, Lavery JV (2007) Grand challenges in global health: the ethical, social and cultural program. PLoS Med 4(9):e265

    Google Scholar 

  • Steigert J, Ducr′ee J et al (2005) Integrated sample preparation, reaction, and detection on a high-frequency centrifugal microfluidic platform. JALA 10(5):331–341

    Google Scholar 

  • Steigert J, Ducr′ee J et al (2006) Fully integrated whole blood testing by real-time absorption measurement on a centrifugal platform. Lab Chip 6:1040–1044

    Google Scholar 

  • Stern E, Fahmy T et al (2010) Label-free biomarker detection from whole blood. Nat Nanotechnol 5:138–142

    Google Scholar 

  • Stevens DY, Petri CR, Osborn JL, Spicar-Mihalic P, McKenzie KG, Yager P (2008) Enabling a microfluidic immunoassay for the developing world by integration of on-card dry reagent storage. Lab Chip 8:2038–2045

    Google Scholar 

  • Tachi T, Baba Y et al (2009) Microchip-based homogeneous immunoassay using fluorescence polarization spectroscopy. Lab Chip 9:966–971

    Google Scholar 

  • Thorslund S, Bergquist J (2006) A hybrid poly (dimethylsiloxane) microsystem for on-chip whole blood filtration optimized for steroid screening. Biomed Microdevices 8:73–79

    Google Scholar 

  • Tokeshi M, Uchida M, Hibara A, Sawada T, Kitamori T (2001) Determination of subyoctomole amounts of nonfluorescent molecules using a thermal lens microscope: subsingle-molecule determination. Anal Chem 73(9):2112–2116

    Google Scholar 

  • Uchiyama K et al (2000) Thermal lens microscope. Jpn J Appl Phys 39:5316–5322

    Google Scholar 

  • Uludag Y, Tothill I (2010) Development of a sensitive detection method of cancer biomarkers in human serum (75%) using a quartz crystal microbalance sensor and nanoparticles amplification system. Talanta 82:277–282

    Google Scholar 

  • Uotila M, Ruoslathi E, Envall E (1981) Two-site sandwich enzyme immunoassay with monoclonal antibodies to human alphafetoprotein. J Immunol Methods 42:11–15

    Google Scholar 

  • Van Weeman BK, Schuurs A (1971) Immunoassay using antigen-enzyme conjugates. FEBS Lett 15(3):232–236

    Google Scholar 

  • Van Weemen BK, Schuurs AHWM (1971) Immunoassay using antigenenzyme conjugates. FEBS Lett 15:232–236

    Google Scholar 

  • Varshney M, Tung S et al (2007) A label-free, microfluidics and interdigitated array microelectrode-based impedance biosensor in combination with nanoparticles immunoseparation for detection of Escherichia coli O157:H7 in food samples. Sens Actuator B 128:99–107

    Google Scholar 

  • Verpoorte E (2003) Beads and chips: new recipes for analysis. Lab Chip 3(4):60N–68N

    Google Scholar 

  • Wang X, Donal D, Bradley C et al (2007) Integrated thin-film polymer/fullerene photodetectors for on-chipmicrofluidic chemiluminescence detection. Lab Chip 7:58–63

    Google Scholar 

  • Wang H, Liu B et al (2008) Microfluidic immunosensor based on stable antibody-patterned surface in PMMA microchip. Electrochem Commun 10:447–450

    Google Scholar 

  • Wang X, de Mello AJ et al (2009) Thin-film organic photodiodes for integrated on-chip chemiluminescencedetection––application to antioxidant capacity screening. Sens Actuator B 140:643–648

    Google Scholar 

  • Wang H, Liu B et al (2010) Microfluidic chip-based aptasensor for amplified electrochemical detection of human thrombin. Electrochem Commun 12:258–261

    Google Scholar 

  • Weigl BH, Yager P (1999) Microfluidic diffusion-based separation and detection. Science 283:346–347

    Google Scholar 

  • Weigl BH, Bardell RL, Cabrera CR (2003) Lab-on-a-chip for drug development. Adv Drug Deliv Rev 55:349–377

    Google Scholar 

  • Wild D (2008) The immunoassay handbook. 3rd edn. Elsevier, Oxford

  • Wolf M, Juncker D et al (2004) Simultaneous detection of C-reactive protein and other cardiac markers in human plasma using micromosaic immunoassays and self-regulating microfluidic networks. Biosens Bioelectron 19(10):1193–1202

    Google Scholar 

  • Xiang Q, Hu G, Gao Y, Li D (2006) Miniaturized immunoassay microfluidic system with electrokinetic control. Biosens Bioelectron 21:2006–2009

    Google Scholar 

  • Yacoub-George E, Hell W, Meixner L, Wenninger F, Bock K, Lindner P, Wolf H, Kloth T, Feller KA (2007) Automated 10-channel capillary chip immunodetector for biological agents detection. Biosens Bioelectron 22:1368–1375

    Google Scholar 

  • Yadavalli VK, Pishko MV (2004) Biosensing in microfluidic channels using fluorescence polarization. Anal Chim Acta 507(1):123–128

    Google Scholar 

  • Yager P, Edwards T, Fu E, Helton K, Nelson K et al (2006) Microfluidic diagnostic technologies for global public health. Nat Insight 442:412–418

    Google Scholar 

  • Yalow RS, Berson SA (1960) Immunoassay of endogenous plasma insulin in man. Clin Invest 39(7):1157–1175

    Google Scholar 

  • Yang S, Ji B, Ündar A, Zahn J (2006a) Microfluidic devices for continuous blood plasma separation and analysis during pediatric cardiopulmonary bypass procedures. ASAIO J 52:698–704

    Google Scholar 

  • Yang S, Undar A, Zahn JD (2006b) A microfluidic device for continuous, real time blood plasma separation. Lab Chip 6:871–880

    Google Scholar 

  • Yang S, Undar A, Zahn J (2007) Continuous cytometric bead processing within a microfluidic device for bead based sensing platforms. Lab Chip 7:588–595

    Google Scholar 

  • Yang S-Y, Lee G-B et al (2008) Micro flow cytometry utilizing a magnetic bead-based immunoassay for rapid virus detection. Biosens Bioelectron 24:855–862

    Google Scholar 

  • Yang Y-N, Lee G-B et al (2009) An integrated microfluidic system for C-reactive protein measurement. Biosens Bioelectron 24:3091–3096

    Google Scholar 

  • Yeh C-H, Lin Y-C et al (2009) Development of an immunoassay based on impedance measurements utilizing an antibody-nanosilver probe, silver enhancement, and electro-microchip. Sens Actuator B 139:387–393

    Google Scholar 

  • Yen RT, Fung YC (1978) Effect of velocity distribution on red cell distribution in capillary blood vessels. Am J Physiol 235(2):H251–H257

    Google Scholar 

  • Yoo S, Lee S-H et al (2009) Microfluidic chip-based electrochemical immunoassay for hippuric acid. Analyst 134:2462–2467

    Google Scholar 

  • Zhang S, Su M et al (2009) MCE enzyme immunoassay for carcinoembryonic antigen and alphafetoprotein using electrochemical detection. Electrophoresis 30:3427–3435

    Google Scholar 

  • Zimmermann M, Delamarche E, Wolf M, Hunziker P (2005) Modeling and optimization of high-sensitivity, low-volume microfluidic-based surface immunoassays. Biomed Microdevices 7:99–110

    Google Scholar 

Download references

Acknowledgments

The authors wish to thank the financial support extended by the Canada Research Chair program and the Natural Sciences and Engineering Research Council (NSERC) of Canada through a research grant to D. Li.

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  1. Department of Mechanical and Mechatronics Engineering, University of Waterloo, Waterloo, ON, N2L 3G1, Canada

    Hai Jiang, Xuan Weng & Dongqing Li

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  2. Xuan Weng
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  3. Dongqing Li
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Correspondence to Dongqing Li.

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Jiang, H., Weng, X. & Li, D. Microfluidic whole-blood immunoassays. Microfluid Nanofluid 10, 941–964 (2011). https://doi.org/10.1007/s10404-010-0718-9

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  • DOI: https://doi.org/10.1007/s10404-010-0718-9

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