Abstract
Immunoassays have greatly benefited from miniaturization in microfluidic systems. This review, which summarizes developments in microfluidics-based immunoassays since 2000, includes four sections, focusing on the configurations of immunoassays that have been implemented in microfluidics, the main fluid handling modalities that have been used for microfluidic immunoassays, multiplexed immunoassays in microfluidic platforms, and the emergence of label-free detection techniques. The field of microfluidic immunoassays is continuously improving and has great promise for the future.
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References
Chiem N, Harrison DJ (1997) Anal Chem 69:373–378
Hatch A, Kamholz AE, Hawkins KR, Munson MS, Schilling EA, Weigl BH, Yager P (2001) Nat Biotechnol 19:461–465
Yadavalli VK, Pishko MV (2004) Anal Chim Acta 507:123–128
Bange A, Halsall HB, Heineman WR (2005) Biosens Bioelectron 20:2488–2503
Sia SK, Whitesides GM (2003) Electrophoresis 24:3563–3576
Lee LJ, Yang ST, Lai SY, Bai YL, Huang WC, Juang YJ (2006) Microfluidic enzyme-linked immunosorbent assay technology. Elsevier, San Diego
Xiang Q, Hu G, Gao Y, Li D (2006) Biosens Bioelectron 21:2006–2009
Wolf M, Juncker D, Michel B, Hunziker P, Delamarche E (2004) Biosens Bioelectron 19:1193–1202
Sia SK, Linder V, Parviz BA, Siegel A, Whitesides GM (2004) Angew Chem Int Ed 43:498–502
Yakovleva J, Davidsson R, Lobanova A, Bengtsson M, Eremin S, Laurell T, Emneus J (2002) Anal Chem 74:2994–3004
Yakovleva J, Davidsson R, Bengtsson M, Laurell T, Emneus J (2003) Biosens Bioelectron 19:21–34
Bai YL, Koh CG, Boreman M, Juang YJ, Tang IC, Lee LJ, Yang ST (2006) Langmuir 22:9458–9467
Jonsson C, Aronsson M, Rundstrom G, Pettersson C, Mendel-Hartvig I, Bakker J, Martinsson E, Liedberg B, MacCraith B, Ohman O, Melin J (2008) Lab Chip 8:1191–1197
Yang T, Jung SY, Mao H, Cremer PS (2001) Anal Chem 73:165–169
Cannon B, Weaver N, Pu QS, Thiagarajan V, Liu SR, Huang JY, Vaughn MW, Cheng KH (2005) Langmuir 21:9666–9674
Dong Y, Phillips KS, Cheng Q (2006) Lab Chip 6:675–681
Schroeder H, Adler M, Gerigk K, Muller-Chorus B, Gotz F, Niemeyer CM (2009) Anal Chem 81:1275–1279
Bailey RC, Kwong GA, Radu CG, Witte ON, Heath JR (2007) J Am Chem Soc 129:1959–1967
Sebra RP, Masters KS, Cheung CY, Bowman CN, Anseth KS (2006) Anal Chem 78:3144–3151
Sung WC, Chen HH, Makamba H, Chen SH (2009) Anal Chem 81:7967–7973
Yang D, Niu X, Liu Y, Wang Y, Gu X, Song L, Zhao R, Ma L, Shao Y, Jiang X (2008) Adv Mater 20:4770–4775
Liu Y, Yang D, Yu T, Jiang X (2009) Electrophoresis 30:3269–3275
Delehanty JB, Ligler FS (2002) Anal Chem 74:5681–5687
Stevens DY, Petri CR, Osborn JL, Spicar-Mihalic P, McKenzie KG, Yager P (2008) Lab Chip 8:2038–2045
Wang HX, Meng S, Guo K, Liu Y, Yang PY, Zhong W, Liu BH (2008) Electrochem Commun 10:447–450
Gervais L, Delamarche E (2009) Lab Chip 9:3330–3337
Wen X, He H, Lee LJ (2009) J Immunol Methods 350:97–105
Parsa H, Chin CD, Mongkolwisetwara P, Lee BW, Wang JJ, Sia SK (2008) Lab Chip 8:2062–2070
Hofmann O, Voirin G, Niedermann P, Manz A (2002) Anal Chem 74:5243–5250
Jiang XY, Ng JMK, Stroock AD, Dertinger SKW, Whitesides GM (2003) J Am Chem Soc 125:5294–5295
Golden JP, Floyd-Smith TM, Mott DR, Ligler FS (2007) Biosens Bioelectron 22:2763–2767
Mulvaney SP, Myers KM, Sheehan PE, Whitman LJ (2009) Biosens Bioelectron 24:1109–1115
Mulvaney SP, Cole CL, Kniller MD, Malito M, Tamanaha CR, Rife JC, Stanton MW, Whitman LJ (2007) Biosens Bioelectron 23:191–200
Morozov VN, Groves S, Turell MJ, Bailey C (2007) J Am Chem Soc 129:12628–12629
Lim CT, Zhang Y (2007) Biosens Bioelectron 22:1197–1204
Miyaguchi H, Takahashi H, Ohashi T, Mawatari K, Iwata YT, Inoue H, Kitamori T (2009) Forensic Sci Int 184:1–5
Sato K, Kitamori T (2004) J Nanosci Nanotechnol 4:575–579
Sato K, Tokeshi M, Kimura H, Kitamori T (2001) Anal Chem 73:1213–1218
Sato K, Tokeshi M, Odake T, Kimura H, Ooi T, Nakao M, Kitamori T (2000) Anal Chem 72:1144–1147
Sato K, Yamanaka M, Hagino T, Tokeshi M, Kimura H, Kitamori T (2004) Lab Chip 4:570–575
Sato K, Yamanaka M, Takahashi H, Tokeshi M, Kimura H, Kitamori T (2002) Electrophoresis 23:734–739
Moorthy J, Mensing GA, Kim D, Mohanty S, Eddington DT, Tepp WH, Johnson EA, Beebe DJ (2004) Electrophoresis 25:1705–1713
Murakami Y, Endo T, Yamamura S, Nagatani N, Takamura Y, Tamiya E (2004) Anal Biochem 334:111–116
Endo T, Okuyama A, Matsubara Y, Nishi K, Kobayashi M, Yamamura S, Morita Y, Takamura Y, Mizukami H, Tamiya E (2005) Anal Chim Acta 531:7–13
Honda N, Lindberg U, Andersson P, Hoffman S, Takei H (2005) Clin Chem 51:1955–1961
Liu WT, Zhu L, Qin QW, Zhang Q, Feng HH, Ang S (2005) Lab Chip 5:1327–1330
Kakuta M, Takahashi H, Kazuno S, Murayama K, Ueno T, Tokeshi M (2006) Meas Sci Technol 17:3189–3194
Tsukagoshi K, Jinno N, Nakajima R (2005) Anal Chem 77:1684–1688
Nagai H, Narita Y, Ohtaki M, Saito K, Wakida SI (2007) Anal Sci 23:975–979
Ko YJ, Maeng JH, Ahn Y, Hwang SY, Cho NG, Lee SH (2008) Electrophoresis 29:3466–3476
Haes AJ, Terray A, Collins GE (2006) Anal Chem 78:8412–8420
Hong JW, Chung KH, Yoon HC (2008) Analyst 133:499–504
Messina GA, Panini NV, Martinez NA, Raba J (2008) Anal Biochem 380:262–267
Lee BS, Lee JN, Park JM, Lee JG, Kim S, Cho YK, Ko C (2009) Lab Chip 9:1548–1555
Christodoulides N, Tran M, Floriano PN, Rodriguez M, Goodey A, Ali M, Neikirk D, McDevitt JT (2002) Anal Chem 74:3030–3036
Christodoulides N, Mohanty S, Miller CS, Langub MC, Floriano PN, Dharshan P, Ali MF, Bernard B, Romanovicz D, Anslyn E, Fox PC, McDevitt JT (2005) Lab Chip 5:261–269
Jokerst JV, Raamanathan A, Christodoulides N, Floriano PN, Pollard AA, Simmons GW, Wong J, Gage C, Furmaga WB, Redding SW, McDevitt JT (2009) Biosens Bioelectron 24:3622–3629
Zhou L, Wang K, Tan W, Chen Y, Zuo X, Wen J, Liu B, Tang H, He L, Yang X (2006) Anal Chem 78:6246–6251
Wen JH, Yang XH, Wang KM, Tan WH, Zuo XB, Zhang H (2008) Biosens Bioelectron 23:1788–1792
Yasukawa T, Suzuki M, Sekiya T, Shiku H, Matsue T (2007) Biosens Bioelectron 22:2730–2736
Holmes D, She JK, Roach PL, Morgan H (2007) Lab Chip 7:1048–1056
Sivagnanam V, Song B, Vandevyver C, Gijs MAM (2009) Anal Chem 81:6509–6515
Sivagnanam V, Bouhmad A, Lacharme F, Vandevyver C, Gijs MAM (2009) Microelectron Eng 86:1404–1406
Lucas LJ, Han JH, Yoon JY (2006) Colloids Surf B 49:106–111
Lucas LJ, Han JH, Chesler J, Yoon JY (2007) Biosens Bioelectron 22:2216–2222
Lucas LJ, Chesler JN, Yoon JY (2007) Biosens Bioelectron 23:675–681
Han JH, Kim KS, Yoon JY (2007) Anal Chim Acta 584:252–259
Heinze BC, Song JY, Lee CH, Najam A, Yoon JY (2009) Sens Actuators B 138:491–496
Pamme N, Koyama R, Manz A (2003) Lab Chip 3:187–192
Carbonaro A, Sohn LL (2005) Lab Chip 5:1155–1160
Kim KS, Park JK (2005) Lab Chip 5:657–664
Hahn YK, Jin Z, Kang JH, Oh E, Han MK, Kim HS, Jang JT, Lee JH, Cheon J, Kim SH, Park HS, Park JK (2007) Anal Chem 79:2214–2220
Kim JS, Anderson GP, Erickson JS, Golden JP, Nasir M, Ligler FS (2009) Anal Chem 81:5426–5432
Yang Y, Nam SW, Lee NY, Kim YS, Park S (2008) Ultramicroscopy 108:1384–1389
Shin KS, Lee SW, Han KC, Kim SK, Yang EK, Park JH, Ju BK, Kang JY, Kim TS (2007) Biosens Bioelectron 22:2261–2267
Peoples MC, Karnes HT (2008) Anal Chem 80:3853–3858
Wang YC, Han J (2008) Lab Chip 8:392–394
Goluch ED, Nam JM, Georganopoulou DG, Chiesl TN, Shaikh KA, Ryu KS, Barron AE, Mirkin CA, Liu C (2006) Lab Chip 6:1293–1299
Hayes MA, Polson NA, Phayre AN, Garcia AA (2001) Anal Chem 73:5896–5902
Huang H, Zheng XL, Zheng JS, Pan J, Pu XY (2009) Biomed Microdevices 11:213–216
Cho JH, Han SM, Paek EH, Cho IH, Paek SH (2006) Anal Chem 78:793–800
Do J, Ahn CH (2008) Lab Chip 8:542–549
Rossier JS, Baranek S, Morier P, Vollet C, Vulliet F, De Chastonay Y, Reymond F (2008) J Assoc Lab Autom 13:322–329
Tang D, Yuan R, Chai Y (2007) Clin Chem 53:1323–1329
Thomas JH, Kim SK, Hesketh PJ, Halsall HB, Heineman WR (2004) Anal Chem 76:2700–2707
Sista RS, Eckhardt AE, Srinivasan V, Pollack MG, Palanki S, Pamula VK (2008) Lab Chip 8:2188–2196
Yang SY, Lien KY, Huang KJ, Lei HY, Lee GB (2008) Biosens Bioelectron 24:855–862
Lee YF, Lien KY, Lei HY, Lee GB (2009) Biosens Bioelectron 25:745–752
Lacharme F, Vandevyver C, Gijs MAM (2009) Microfluid Nanofluid 7:479–487
Hatch A, Garcia E, Yager P (2004) Proc IEEE 92:126–139
Lim TK, Ohta H, Matsunaga T (2003) Anal Chem 75:3316–3321
Tachi T, Kaji N, Tokeshi M, Baba Y (2009) Lab Chip 9:966–971
Park H, Lee M, Gi HS, Choo J, Eun KL, Joong YP, Lee S, Lee KH, Choi YW (2008) Bull Korean Chem Soc 29:1297–1298
Tachi T, Kaji N, Tokeshi M, Baba Y (2009) Anal Sci 25:149–151
Qiu CX, Harrison DJ (2001) Electrophoresis 22:3949–3958
Colyer CL, Mangru SD, Harrison DJ (1997) J Chromatogr A 781:271–276
Chiem NH, Harrison DJ (1998) Clin Chem 44:591–598
Cheng SB, Skinner CD, Taylor J, Attiya S, Lee WE, Picelli G, Harrison DJ (2001) Anal Chem 73:1472–1479
Wang J, Ibanez A, Chatrathi MP (2002) Electrophoresis 23:3744–3749
Wang J, Ibanez A, Chatrathi MP (2003) J Am Chem Soc 125:8444–8445
Wang J, Ibanez A, Chatrathi MP, Escarpa A (2001) Anal Chem 73:5323–5327
Bromberg A, Mathies RA (2004) Electrophoresis 25:1895–1900
Bromberg A, Mathies RA (2003) Anal Chem 75:1188–1195
Shackman JG, Munson MS, Ross D (2007) Anal Chem 79:565–571
Reid KR, Kennedy RT (2009) Anal Chem 81:6837–6842
Dishinger JF, Reid KR, Kennedy RT (2009) Anal Chem 81:3119–3127
Dishinger JF, Kennedy RT (2007) Anal Chem 79:947–954
Roper MG, Shackman JG, Dahlgren GM, Kennedy RT (2003) Anal Chem 75:4711–4717
Reichmuth DS, Wang SK, Barrett LM, Throckmorton DJ, Einfeld W, Singh AK (2008) Lab Chip 8:1319–1324
Meagher RJ, Hatch AV, Renzi RF, Singh AK (2008) Lab Chip 8:2046–2053
Mohamadi MR, Kaji N, Tokeshi M, Baba Y (2007) Anal Chem 79:3667–3672
Herr AE, Hatch AV, Throckmorton DJ, Tran HM, Brennan JS, Giannobile WV, Singh AK (2007) Proc Natl Acad Sci U S A 104:5268–5273
Herr AE, Throckmorton DJ, Davenport AA, Singh AK (2005) Anal Chem 77:585–590
Linder V (2007) Analyst 132:1186–1192
Dodge A, Fluri K, Verpoorte E, de Rooij NF (2001) Anal Chem 73:3400–3409
Linder V, Verpoorte E, Thormann W, de Rooij NF, Sigrist M (2001) Anal Chem 73:4181–4189
Gao YL, Shermanb PM, Sun Y, Li D (2008) Anal Chim Acta 606:98–107
Hu GQ, Gao YL, Li DQ (2007) Biosens Bioelectron 22:1403–1409
Madou M, Zoval J, Jia GY, Kido H, Kim J, Kim N (2006) Annu Rev Biomed Eng 8:601–628
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) Anal Biochem 388:306–311
Kawabata T, Wada HG, Watanabe M, Satomura S (2008) Electrophoresis 29:1399–1406
Miller EM, Wheeler AR (2009) Anal Bioanal Chem 393:419–426
Wheeler AR (2008) Science 322:539–540
Abdelgawad M, Wheeler AR (2009) Adv Mater 21:920–925
Sista R, Hua Z, Thwar P, Sudarsan A, Srinivasan V, Eckhardt A, Pollack M, Pamula V (2008) Lab Chip 8:2091–2104
Qiu X, Thompson JA, Chen Z, Liu C, Chen D, Ramprasad S, Mauk MG, Ongagna S, Barber C, Abrams WR, Malamud D, Corstjens PLAM, Bau HH (2009) Biomed Microdevices 11:1175–1186
Park SW, Lee JH, Yoon HC, Kim BW, Sim SJ, Chae H, Yang SS (2008) Biomed Microdevices 10:859–868
Qin LD, Vermesh O, Shi QH, Heath JR (2009) Lab Chip 9:2016–2020
Henares TG, Mizutani F, Hisamoto H (2008) Anal Chim Acta 611:17–30
Kartalov EP, Zhong JF, Scherer A, Quake SR, Taylor CR, Anderson WF (2006) BioTechniques 40:85–90
Lee KH, Su YD, Chen SJ, Tseng FG, Lee GB (2007) Biosens Bioelectron 23:466–472
Kartalov EP, Lin DH, Lee DT, Anderson WF, Taylor CR, Scherer A (2008) Electrophoresis 29:5010–5016
Luo YQ, Yu F, Zare RN (2008) Lab Chip 8:694–700
Diercks AH, Ozinsky A, Hansen CL, Spotts JM, Rodriguez DJ, Aderem A (2009) Anal Biochem 386:30–35
Gao XH, Jiang L, Su XO, Qin JH, Lin BC (2009) Electrophoresis 30:2481–2487
Kong J, Jiang L, Su X, Qin J, Du Y, Lin B (2009) Lab Chip 9:1541–1547
Unger MA, Chou HP, Thorsen T, Scherer A, Quake SR (2000) Science 288:113–116
Quake SR, Scherer A (2000) Science 290:1536–1540
Lu C, Xie Y, Yang Y, Cheng MMC, Koh CG, Bai Y, Lee LJ, Juang YJ (2007) Anal Chem 79:994–1001
Eriksson C, Agaton C, Kånge R, Sundberg M, Nilsson P, Ek B, Uhlén M, Gustafsson M, Hober S (2006) J Proteome Res 5:1568–1574
Lai S, Wang SN, Luo J, Lee LJ, Yang ST, Madou MJ (2004) Anal Chem 76:1832–1837
Zimmermann M, Delamarche E, Wolf M, Hunziker P (2005) Biomed Microdevices 7:99–110
Hosokawa K, Omata M, Sato K, Maeda M (2006) Lab Chip 6:236–241
Hosokawa K, Omata M, Maeda M (2007) Anal Chem 79:6000–6004
Hosokawa K, Maeda M (2009) Lab Chip 9:464–468
Zimmermann M, Hunziker P, Delamarche E (2009) Biomed Microdevices 11:1–8
Ziegler J, Zimmermann M, Hunziker P, Delamarche E (2008) Anal Chem 80:1763–1769
Kim H, Yang Y, Kim M, Nam SW, Lee KM, Lee NY, Kim YS, Park S (2007) Adv Funct Mater 17:3493–3498
Cesaro-Tadic S, Dernick G, Juncker D, Buurman G, Kropshofer H, Michel B, Fattinger C, Delamarche E (2004) Lab Chip 4:563–569
Zimmermann M, Schmid H, Hunziker P, Delamarche E (2007) Lab Chip 7:119–125
Posthuma-Trumpie GA, Korf J, van Amerongen A (2009) Anal Bioanal Chem 393:569–582
Chaerkady R, Pandey A (2008) Annu Rev Pathol Mech Dis 3:485–498
Cretich M, Di Carlo G, Giudici C, Pokoj S, Lauer I, Scheurer S, Chiari M (2009) Proteomics 9:2098–2107
Heyries KA, Loughran MG, Hoffmann D, Homsy A, Blum LJ, Marquette CA (2008) Biosens Bioelectron 23:1812–1818
Delamarche E, Bernard A, Schmid H, Michel B, Biebuyck H (1997) Science 276:779–781
Rowe CA, Scruggs SB, Feldstein MJ, Golden JP, Ligler FS (1999) Anal Chem 71:433–439
Bernard A, Michel B, Delamarche E (2001) Anal Chem 73:8–12
Murphy BM, He XY, Dandy D, Henry CS (2008) Anal Chem 80:444–450
Murphy BM, Dandy DS, Henry CS (2009) Anal Chim Acta 640:1–6
Fan R, Vermesh O, Srivastava A, Yen BKH, Qin LD, Ahmad H, Kwong GA, Liu CC, Gould J, Hood L, Heath JR (2008) Nat Biotechnol 26:1373–1378
Yang S, Undar A, Zahn JD (2006) Lab Chip 6:871–880
Derveaux S, Stubbe BG, Braeckmans K, Roelant C, Sato K, Demeester J, De Smedt SC (2008) Anal Bioanal Chem 391:2453–2467
Ko JS, Yoon HC, Yang H, Pyo HB, Chung KH, Kim SJ, Kim YT (2003) Lab Chip 3:106–113
Braeckmans K, De Smedt SC, Leblans M, Pauwels R, Demeester J (2002) Nat Rev Drug Discov 1:447–456
Riegger L, Grumann M, Nann T, Riegler J, Ehlert O, Bessler W, Mittenbuehler K, Urban G, Pastewka L, Brenner T, Zengerle R, Ducree J (2006) Sens Actuators A 126:455–462
Ray CA, Bowsher RR, Smith WC, Devanarayan V, Willey MB, Brandt JT, Dean RA (2005) J Pharm Biomed Anal 36:1037–1044
Han M, Gao X, Su JZ, Nie S (2001) Nat Biotechnol 19:631–635
Klostranec JM, Xiang Q, Farcas GA, Lee JA, Rhee A, Lafferty EI, Perrault SD, Kain KC, Chan WCW (2007) Nano Lett 7:2812–2818
Nam JM, Thaxton CS, Mirkin CA (2003) Science 301:1884–1886
Stoeva SI, Lee J-S, Smith JE, Rosen ST, Mirkin CA (2006) J Am Chem Soc 128:8378–8379
Qavi AJ, Washburn AL, Byeon JY, Bailey RC (2009) Anal Bioanal Chem 394:121–135
Steiner G (2004) Anal Bioanal Chem 379:328–331
Kanda V, Kariuki JK, Harrison DJ, McDermott MT (2004) Anal Chem 76:7257–7262
Krishnamoorthy G, Carlen ET, Kohlheyer D, Schasfoort RBM, van den Berg A (2009) Anal Chem 81:1957–1963
Sharpe JC, Mitchell JS, Lin L, Sedoglavich H, Blaikie RJ (2008) Anal Chem 80:2244–2249
De Leebeeck A, Kumar LKS, de Lange V, Sinton D, Gordon R, Brolo AG (2007) Anal Chem 79:4094–4100
Ji J, O’Connell JG, Carter DJD, Larson DN (2008) Anal Chem 80:2491–2498
Zheng GF, Patolsky F, Cui Y, Wang WU, Lieber CM (2005) Nat Biotechnol 23:1294–1301
Wang ZH, Jin G (2003) Anal Chem 75:6119–6123
Wang ZH, Meng YH, Ying PQ, Qi C, Jin G (2006) Electrophoresis 27:4078–4085
Markov DA, Swinney K, Bornhop DJ (2004) J Am Chem Soc 126:16659–16664
Suarez G, Jin YH, Auerswald J, Berchtold S, Knapp HF, Diserens JM, Leterrier Y, Manson JAE, Voirin G (2009) Lab Chip 9:1625–1630
Xue CY, Khan SA, Yang KL (2009) Adv Mater 21:198–202
Burg TP, Godin M, Knudsen SM, Shen W, Carlson G, Foster JS, Babcock K, Manalis SR (2007) Nature 446:1066–1069
Gordon R, Sinton D, Kavanagh KL, Brolo AG (2008) Acc Chem Res 41:1049–1057
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We thank the Natural Sciences and Engineering Research Council of Canada for financial support. ARW thanks the CRC for a Canada Research Chair.
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Alphonsus H. C. Ng and Uvaraj Uddayasankar contributed equally to this review.
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Ng, A.H.C., Uddayasankar, U. & Wheeler, A.R. Immunoassays in microfluidic systems. Anal Bioanal Chem 397, 991–1007 (2010). https://doi.org/10.1007/s00216-010-3678-8
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DOI: https://doi.org/10.1007/s00216-010-3678-8