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Biomedical Microdevices

, Volume 13, Issue 6, pp 1053–1062 | Cite as

Microfluidic LIPS for serum antibody detection: demonstration of a rapid test for HSV-2 infection

  • Adnan Zubair
  • Peter D. Burbelo
  • Ludovic G. Vincent
  • Michael J. Iadarola
  • Paul D. Smith
  • Nicole Y. Morgan
Article

Abstract

There is great interest in point-of-care antibody testing for the diagnosis of infectious and autoimmune diseases. As a first step in the development of self-contained and miniaturized devices for highly quantitative antibody detection, we demonstrate the application of Luciferase Immunoprecipitation Systems (LIPS) technology in a microfluidic format. Protein A/G was immobilized on the walls of PDMS-glass microchannels of 500 nL volume. The assay proceeds with the simultaneous introduction of plasma and Renilla luciferase–tagged antigens. Following washing, coelenterazine substrate was added and bound antigen-luciferase measured by chemiluminescence. Total assay time, including rinsing and detection, is under 10 min. Using these stable microfluidic devices, high diagnostic performance (100% sensitivity and 100% specificity) was achieved for the diagnosis of HSV-2 infection. Based on these findings, the LIPS microfluidic format should readily lend itself to automation and the transfer to portable instrumentation.

Keywords

Antibody detection Biosensor LIPS Microfluidics 

Notes

Acknowledgments

This work was supported by the Intramural Research Program of the National Institutes of Health, including the National Institute of Biomedical Imaging and Bioengineering and the National Institute of Dental and Craniofacial Research. We are grateful to Dr. Jeffrey Cohen for proving the human clinical serum samples.

References

  1. A. Bange, H.B. Halsall, W.R. Heineman, Biosens Bioelectron 20, 2488 (2005)CrossRefGoogle Scholar
  2. A. Bhattacharyya, C.M. Klapperich, Biomed Microdevices 9, 245 (2007)CrossRefGoogle Scholar
  3. P.D. Burbelo, R. Goldman, T.L. Mattson, BMC Biotechnol 5 (2005)Google Scholar
  4. P.D. Burbelo, R. Ramanathan, A.D. Klion, M.J. Iadarola, T.B. Nutman, J Clin Microbiol 46, 2298 (2008)CrossRefGoogle Scholar
  5. P. Burbelo, K. Ching, A. Issa, C. Loftus, Y. Li, M. Satoh, W. Reeves, M. Iadarola, J Transl Med 7, 83 (2009a)CrossRefGoogle Scholar
  6. P.D. Burbelo, Y. Hoshino, H. Leahy, T. Krogmann, R.L. Hornung, M.J. Iadarola, J.I. Cohen, Clin Vaccine Immunol 16, 366 (2009b)CrossRefGoogle Scholar
  7. P.D. Burbelo, H.P. Leahy, M.J. Iadarola, T.B. Nutman, PLoS Negl Trop Dis 3, e438 (2009c)CrossRefGoogle Scholar
  8. P.D. Burbelo, H.P. Leahy, A.T. Issa, S. Groot, J.N. Baraniuk, N.P. Nikolov, G.G. Illei, M.J. Iadarola, Autoimmunity 42, 515 (2009d)CrossRefGoogle Scholar
  9. P.D. Burbelo, K.H. Ching, E.R. Bush, B.L. Han, M.J. Iadarola, Expert Rev Vaccines 9, 567 (2010a)CrossRefGoogle Scholar
  10. P.D. Burbelo, A.T. Issa, K.H. Ching, K.M. Wyvill, R.F. Little, M.J. Iadarola, J.A. Kovacs, R. Yarchoan, J Infect Dis 201, 1919 (2010b)CrossRefGoogle Scholar
  11. P.D. Burbelo, J.A. Kovacs, K.H. Ching, A.T. Issa, M.J. Iadarola, A.A. Murphy, J.F. Schlaak, H. Masur, M.A. Polis, S. Kottilil, J Infect Dis 202, 894 (2010c)CrossRefGoogle Scholar
  12. P.D. Burbelo, K.E. Bren, K.H. Ching, E.S. Gogineni, S. Kottilil, J.I. Cohen, J.A. Kovacs, M.J. Iadarola, Mol Biosyst 7, 1453 (2011)CrossRefGoogle Scholar
  13. K.H. Ching, P.D. Burbelo, M. Gonzalez-Begne, M.E.P. Roberts, A. Coca, I. Sanz, M.J. Iadarola, J Dent Res 90, 445 (2011)CrossRefGoogle Scholar
  14. T. Dubrovsky, A. Tronin, S. Dubrovskaya, O. Guryev, C. Nicolini, Thin Solid Films 284–285, 698 (1996)CrossRefGoogle Scholar
  15. L. Gervais, E. Delamarche, Lab on a Chip 9, 3330 (2009)CrossRefGoogle Scholar
  16. A.E. Herr, A.V. Hatch, D.J. Throckmorton, H.M. Tran, J.S. Brennan, W.V. Giannobile, A.K. Singh, Proc Natl Acad Sci U S A 104, 5268 (2007)CrossRefGoogle Scholar
  17. K.A. Heyries, M.G. Loughran, D. Hoffmann, A. Homsy, L.C.J. Blum, C.A. Marquette, Biosens Bioelectron 23, 1812 (2008)CrossRefGoogle Scholar
  18. C. Hou, A.E. Herr, Electrophoresis 29, 3306 (2008)CrossRefGoogle Scholar
  19. E. Kartalov, D. Lin, D. Lee, W. Anderson, C. Taylor, A. Scherer, Electrophoresis 29, 5010 (2008)CrossRefGoogle Scholar
  20. W.G. Lee, Y.-G. Kim, B.G. Chung, U. Demirci, A. Khademhosseini, Adv Drug Deliv Rev 62, 449 (2010)CrossRefGoogle Scholar
  21. V. Linder, E. Verpoorte, N.F. de Rooij, H. Sigrist, W. Thormann, Electrophoresis 23, 740 (2002)CrossRefGoogle Scholar
  22. E. Liu, G.S. Eisenbarth, Clin Immunol 125, 120 (2007)CrossRefGoogle Scholar
  23. A.H.C. Ng, U. Uddayasankar, A.R. Wheeler, Anal Bioanal Chem 397, 991 (2010)CrossRefGoogle Scholar
  24. T. Ohashi, K. Mawatari, K. Sato, M. Tokeshi, T. Kitamori, Lab on a Chip 9, 991 (2009)CrossRefGoogle Scholar
  25. H. Okada, K. Hosokawa, M. Maeda, Anal Sci 27, 237 (2011)CrossRefGoogle Scholar
  26. S.V. Pereira, G.n.A. Messina, J. Raba. J Chromatogr B 878, 253 (2010)CrossRefGoogle Scholar
  27. B. Weigl, G. Domingo, P. LaBarre, J. Gerlach, Lab on a Chip 8, 1999 (2008)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC (outside the USA) 2011

Authors and Affiliations

  • Adnan Zubair
    • 1
  • Peter D. Burbelo
    • 2
  • Ludovic G. Vincent
    • 1
  • Michael J. Iadarola
    • 2
  • Paul D. Smith
    • 1
  • Nicole Y. Morgan
    • 1
  1. 1.Microfabrication and Microfluidics Unit, Biomedical Engineering and Physical Science Shared Resource, National Institute of Biomedical Imaging and BioengineeringNational Institutes of HealthBethesdaUSA
  2. 2.Neurobiology and Pain Therapeutics Section, Laboratory of Sensory Biology, National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaUSA

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