Biomedical Microdevices

, Volume 9, Issue 2, pp 135–141 | Cite as

Screening cell surface receptors using micromosaic immunoassays

  • Marc Wolf
  • Martin Zimmermann
  • Emmanuel DelamarcheEmail author
  • Patrick HunzikerEmail author


This report presents a general method for screening cell surface receptors using so-called micromosaic immunoassays. This method employs a microfluidic chip having n (n = 11) independent flow paths to move cells over m (m = 11) lines of surface-patterned antibodies for screening individual cells in a parallel, combinatorial, fast and flexible manner. The antibodies are patterned as 30-μm-wide lines on a poly(dimethylsiloxane) layer used to seal the area of the chip in which screening is being monitored. Mouse hybridoma cells having CD44 cell surface receptors and anti-CD44 antibodies were used to establish a proof-of-concept for this method. Both the capture antibodies and the cells were fluorescently labelled to allow the position of the cells to be accurately tracked over the binding sites using an inverted fluorescence microscope. The chips and cells were maintained at a constant temperature between 20 to 37°C, and flow velocities of the cells over the capture areas were 100–280 μm~s−1, resulting in a ∼0.1–0.3 s residency time of the cells on each of the eleven 30 × 30 μm s2 capture areas. Binding of the cells appeared to be specific to the capture areas, with a yield of 30% when the assay was performed at a temperature of 37°C and with a slow flow velocity. We suggest that this proof-of-concept is broadly applicable to the screening of cells for medical/diagnostic purposes as well as for basic research on the interaction of cells with surfaces.


Microfluidic Cell Surface receptor Screening Micromosaic immunoassay 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Supplementary material

Quicktime Movie (385 KB)


  1. A. Bernard, B. Michel, and E. Delamarche, Anal. Chem. 73, 8–12 (2001).Google Scholar
  2. S. Cesaro-Tadic, G. Dernick, D. Juncker, G. Buurman, H. Kropshofer, B. Michel, C. Fattinger, and E. Delamarche, Lab Chip 4, 563–569 (2004).Google Scholar
  3. S. Chen, R. Alon, R.C. Fuhlbrigge, and T.A. Springer, Proc Natl Acad Sci USA 94, 3172–3177 (1997).Google Scholar
  4. D.T. Chiu, N.L. Jeon, S. Huang, R.S. Kane, C.J. Wargo, I.S. Choi, D.E. Ingber, and G.M. Whitesides, Proc Natl Acad Sci U S A 97, 2408–2413 (2000).Google Scholar
  5. Comment. Danger: piranha solution is a strong oxidizer and explosions can occur when it is mixed with organic compounds/solvents. A safer alternative for cleaning microfluidic chips is to use a UV/ozone reactor.Google Scholar
  6. E. Delamarche, A. Bernard, H. Schmid, A. Bietsch, B. Michel, and H. Biebuyck, J. Am. Chem. Soc. 120, 500–508 (1998).Google Scholar
  7. E. Delamarche, A. Bernard, H. Schmid, B. Michel, and H. Biebuyck, Science 276, 779–781 (1997).Google Scholar
  8. E. Delamarche, D. Juncker, and H. Schmid, Adv. Mat. 17, 2911–2933 (2005).Google Scholar
  9. A.O. Eniola, P.J. Willcox, and D.A. Hammer, Biophys. J. 85, 2720–2731 (2003).Google Scholar
  10. E. Fitzpatrick, S. McBride, J. Yavelow, S. Najmi, P. Zanzucchi, and R. Wieder, Clin. Chem. 52, 1080–1088 (2006).Google Scholar
  11. A.Y. Fu, C. Spence, A. Scherer, F.H. Arnold, and S.R. Quake, Nat. Biotechnol. 17, 1109–1111 (1999).Google Scholar
  12. N.D. Gallant, J.R. Capadona, A.B. Frazier, D.M. Collard, and A.J. Garcia, Langmuir 18, 5579–5584 (2002).Google Scholar
  13. D. Huh, W. Gu, Y. Kamotani, J.B. Grotberg, and S. Takayama, Physiol. Meas. 26, R73–R98 (2005).Google Scholar
  14. X. Jiang, J.M.K. Ng, A.D. Stroock, S.K.W. Dertinger, and G.M. Whitesides, J. Am. Chem. Soc. 125, 5294–5295 (2003).Google Scholar
  15. D. Juncker, H. Schmid, U. Drechsler, H. Wolf, M. Wolf, B. Michel, N. deRooij, and E. Delamarche, Anal. Chem. 74, 6139–6144 (2002).Google Scholar
  16. V. Kanda, J.K. Kariuki, D.J. Harrison, and M.T. McDermott, Anal. Chem. 76, 7257–7262 (2004).Google Scholar
  17. A. Khademhosseini, J. Yeh, G. Eng, J. Karp, H. Kaji, J. Borenstein, O.C. Farokhzad, and R. Langer, Lab Chip 5, 1380–1386 (2005).Google Scholar
  18. G.C. Koo, and J.R. Peppard, Hybridoma 3, 301–303 (1984).Google Scholar
  19. S.K. Kung, R.C. Su, J. Shannon, and R.G. Miller, Hybridoma 20, 91–101 (2001).Google Scholar
  20. N. Li, A. Tourovskaia, and A. Folch, Crit. Rev. Biomed. Eng. 31, 423–488 (2003).Google Scholar
  21. N. Li Jeon, H. Baskaran, S.K.W. Dertinger, G.M. Whitesides, L. Van De Water, and M. Toner, Nat. Biotech. 20, 826–830 (2002).Google Scholar
  22. D. Mattanovich, and N. Borth, Microb. Cell. Fact. 5, 12 (2006).Google Scholar
  23. K. Miyake, C.B. Underhill, J. Lesley, and P.W. Kincade, J. Exp. Med. 172, 69–75 (1990).Google Scholar
  24. B.P. Nelson, T.E. Grimsrud, M.R. Liles, R.M. Goodman, and R.M. Corn, Anal. Chem. 73, 1–7 (2001).Google Scholar
  25. A. Persidis, Nat. Biotechnol. 16, 488–489 (1998).Google Scholar
  26. J. Pihl, J. Sinclair, E. Sahlin, M. Karlsson, F. Petterson, J. Olofsson, and O. Orwar, Anal. Chem. 77, 3897–3903 (2005).Google Scholar
  27. C.R. Poulsen, C.T. Culbertson, S.C. Jacobson, and J.M. Ramsey, Anal. Chem. 77, 667–672 (2005).Google Scholar
  28. A. Prokop, Z. Prokop, D. Schaffer, E. Kozlov, J. Wikswo, D. Cliffel, and F. Baudenbacher, Biomed. Microdev. 6, 325–339 (2004).Google Scholar
  29. R.M. Rowan, O.W.V. Assendelft, and F.E. Preston, Advances in Laboratory Methods: General Haematology. (Oxford University Press Inc., New York, 2002).Google Scholar
  30. C.A. Rowe, S.B. Scruggs, M.J. Feldstein, J.P. Golden, and F.S. Ligler, Anal. Chem. 71, 433–439 (1999a).Google Scholar
  31. C.A. Rowe, L.M. Tender, M.J. Feldstein, J.P. Golden, S.B. Scruggs, B.D. MacCraith, J.J. Cras, and F.S. Ligler, Anal. Chem. 71, 3846–3852 (1999b).Google Scholar
  32. J.P. Shelby, J. White, K. Ganesan, P.K. Rathod, and D.T. Chiu, Proc Natl Acad Sci U S A 100, 14618–14622 (2003).Google Scholar
  33. S. Takayama, J.C. McDonald, E. Ostuni, M.N. Liang, P.J. Kenis, R.F. Ismagilov, and G.M. Whitesides, Proc Natl Acad Sci U S A 96, 5545–5548 (1999).Google Scholar
  34. A. Tourovskaia, X. Figueroa-Masot, and A. Folch, Lab Chip 5, 14–19 (2005).Google Scholar
  35. A.R. Wheeler, W.R. Throndset, R.J. Whelan, A.M. Leach, R.N. Zare, Y.H. Liao, K. Farrell, I.D. Manger, and A. Daridon, Anal. Chem. 75, 3581–3586 (2003).Google Scholar
  36. M. Wolf, D. Juncker, B. Michel, P. Hunziker, and E. Delamarche, Biosens. Bioelectron. 19, 1193–1202 (2004).Google Scholar
  37. M. Zimmermann, S. Bentley, H. Schmid, P. Hunziker, and E. Delamarche, Lab Chip 5, 1355–1359 (2005).Google Scholar
  38. M. Zimmermann, H. Schmid, P. Hunziker, and E. Delamarche (2006). published in Lab Chip, DOI:10.1039/b609813d.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  1. 1.University Hospital BaselBaselSwitzerland
  2. 2.IBM Research GmbHZürich Research LaboratoryRüschlikonSwitzerland

Personalised recommendations