Biomedical Microdevices

, 11:1175 | Cite as

Finger-actuated, self-contained immunoassay cassettes

  • Xianbo Qiu
  • Jason A. Thompson
  • Zongyuan Chen
  • Changchun Liu
  • Dafeng Chen
  • Sudhir Ramprasad
  • Michael G. Mauk
  • Serge Ongagna
  • Cheryl Barber
  • William R. Abrams
  • Daniel Malamud
  • Paul L. A. M. Corstjens
  • Haim H. Bau
Article

Abstract

The building blocks for an inexpensive, disposable, luminescence-based microfluidic immunoassay cassette are described, and their integration in a point-of-care diagnostic system is demonstrated. Fluid motion in the cassette is driven by depressing finger-actuated pouches. All reagents needed for the immunoassay can be stored in the cassette in liquid form. Prior to use, the cassette consists of two separate parts. A top storage component contains pouches, sealed storage chambers, a metering chamber, and needle seats. The bottom processing component contains connection needles, a mixing chamber, and a detection chamber with immobilized proteins. Subsequent to sample introduction, the storage and processing components are mated. The needles form hydraulic connections between the two parts and, in some cases, close valves. The pouches are then actuated sequentially to induce flow of various reagents and facilitate process operations. The cassette is compatible with different detection modalities. Both a cassette with immunochromatographic-based detection and a cassette with microbead-based detection were constructed and evaluated. The immunochromatographic cassette was used to detect antibodies to HIV in saliva samples. The bead-based cassette was used to detect the proinflammatory chemokine IL-8. The experimental data demonstrates good repeatability and reasonable sensitivity.

Keywords

Microfluidic Finger-actuation Pouch Needle Immunoassay Consecutive flow Immunochromatography Functionalized microbead array 

References

  1. R.C. Anderson, X. Su, G.J. Bogdan, J. Fenton, A miniature integrated device for automated multistep genetic assays. Nucleic Acids Res. 28, i–vi (2000)CrossRefGoogle Scholar
  2. K.D. Barbee, X. Huang, Magnetic assembly of high-density DNA arrays for genomic analyses. Anal. Chem. 80, 2149–2154 (2008)CrossRefGoogle Scholar
  3. H.H. Bau, J. Zhong, M. Yi, A minute magneto hydro dynamic (MHD) mixer. Sens. Actuators B 79, 207–215 (2001)CrossRefGoogle Scholar
  4. A. Bhattacharyya, C.M. Klapperich, Design and testing of a disposable microfluidic chemiluminescent immunoassay for disease biomarkers in human serum samples. Biomedical Microdevices 9, 245–251 (2007)CrossRefGoogle Scholar
  5. T.M. Blicharz, W.L. Siqueira, E.J. Helmerhorst, F.G. Oppenheim, P.J. Wexler, F.F. Little, D.R. Walt, Fiber-optic microsphere-based antibody array for the analysis of inflammatory cytokines in saliva. Anal. Chem. 81, 2106–2114 (2009)CrossRefGoogle Scholar
  6. D.L.N. Cardy, G.J. Allen, Lateral flow assay device and method, International Patent, Publication No.: WO/2004/007078Google Scholar
  7. M.M. Caulum, C.S. Henry, Multi-analyte immunoassay using cleavable tags and microchip micellular electrokinetic chromatography. Analyst 131, 1091–1093 (2006)CrossRefGoogle Scholar
  8. Z. Chen, M.G. Mauk, J. Wang, W.R. Abrams, P.L.A.M. Corstjens, R.S. Niedbala, D. Malamud, H.H. Bau, A microfluidic system for saliva-based detection of infectious diseases, Ann. N.Y. Acad. Sci. 1098, 429-436 (2007)Google Scholar
  9. P.L.A.M. Corstjens, Z. Chen, M. Zuiderwijk, H.H. Bau, W.R. Abrams, D. Malamud, R.S. Niedbala, H.J. Tanke, Rapid assay format for multiplex detection of humoral immune responses to infectious disease pathogens (HIV, HCV, and TB). Ann. N.Y. Acad. Sci 1098, 437–445 (2007)CrossRefGoogle Scholar
  10. P.L.A.M. Corstjens, M. Zuiderwijk, H.J. Tanke, J. van der Ploeg-Schip, T.H.M. Ottenhoff, A. Geluk, A user-friendly, highly sensitive assay to detect the IFN-γ secretion by T cells. Clin. Biochem. 6, 440–444 (2008)CrossRefGoogle Scholar
  11. J.B. Fan, K.L. Gunderson, M. Bibikova, J.M. Yeakley, J. Chen, E. Wickham Garcia, L.L. Lebruska, M. Laurent, R. Shen, D. Barker, Illumina universal bead arrays. Methods Enzymol. 410, 57–73 (2006)CrossRefGoogle Scholar
  12. J.A. Ferguson, F.J. Steemers, D.R. Walt, High-density fiber-optic DNA random microsphere array. Anal. Chem. 72, 5618–5624 (2000)CrossRefGoogle Scholar
  13. H.J.G.E. Gardeniers, R. Luttge, E.J.W. Berenschot, M.J. de Boer, S.Y. Yeshurun, M. Hefetz, R. van’t Oever, A. van den Berg, Silicon micromachined hollow microneedles for transdermal liquid transport. Journal of Microelectromechanical Systems 6, 855–862 (2003)CrossRefGoogle Scholar
  14. A. Goodey, J.J. Lavigne, S.M. Savoy, M.D. Rodriguez, T. Curey, A. Tsao, G. Simmons, J. Wright, S. Yoo, Y. Sohn, E.V. Anslyn, J.B. Shear, D.P. Neikirk, J.T. McDevitt, Development of multianalyte sensor arrays composed of chemically derivatized polymeric microspheres localized in micromachined cavities. J. Am. Chem. Soc. 123, 2559–2570 (2001)CrossRefGoogle Scholar
  15. W. Gu, X. Zhu, N. Futai, B.S. Cho, S. Takayama, Computerized microfluidic cell culture using elastomeric channels and Braille displays. PNAS 45, 15861–15866 (2004)CrossRefGoogle Scholar
  16. G.G. Guilbault, Practical fluorescence, 2nd edition, CRC Press (ISBN 0824783506, 9780824783501) (1990)Google Scholar
  17. S. Haeberle, R. Zengerle, Microfluidic platforms for lab-on-a-chip applications. Lab Chip 7, 1094–1110 (2007)CrossRefGoogle Scholar
  18. J. Hampl, M. Hall, N.A. Mufti, Y.M. Yao, D.B. MacQueen, W.H. Wright, D.E. Cooper, Upconverting phosphor reporters in immunochromatographic assays. Anal. Biochem. 288, 176–187 (2001)CrossRefGoogle Scholar
  19. M. Hashimoto, F. Barany, S.A. Soper, Polymerase chain reaction/ligase detection reaction/hybridization assays using flow-through microfluidic devices for the detection of low-abundant DNA point mutations. Biosens. Bioelectron. 10, 1915–1923 (2006)CrossRefGoogle Scholar
  20. W.Z. Ho, Self-contained microfluidic biochip and apparatus, United States Patent, Patent No.: US 7122153 (2006)Google Scholar
  21. K. Kim, J.B. Lee, High aspect ratio tapered hollow metallic microneedle arrays with microfluidic interconnector. Microsyst. Technol. 13, 231–235 (2007)CrossRefGoogle Scholar
  22. D.S. Kim, S.H. Lee, C.H. Ahn, J.Y. Lee, T.H. Kwon, Disposable integrated microfluidic biochip for blood typing by plastic microinjection molding. Lab Chip 6, 794–802 (2006)CrossRefGoogle Scholar
  23. C.Y. Lee, G.B. Lee, J.L. Lin, F.C. Huang, C.S. Liao, Integrated microfluidic systems for cell lysis, mixing/pumping and DNA amplification. J. Micromechanics Microengineering 15, 1215–1223 (2005)CrossRefGoogle Scholar
  24. S. Li, P.N. Floriano, N. Christodoulides, D.Y. Fozdar, D. Shao, M.F. Ali, P. Dharshan, S. Mohanty, D. Neikirk, J.T. McDevitt, S. Chen, Disposable polydimethylsiloxane/silicon hybrid chips for protein detection. Biosens. Bioelectron 21, 574–580 (2005)CrossRefGoogle Scholar
  25. C.T. Lim, Y. Zhang, Bead-based microfluidic immunoassays: the next generation. Biosens. Bioelectron. 22, 1197–1204 (2007)CrossRefGoogle Scholar
  26. C. Liu, X. Qiu, S. Ongagna, D. Chen, Z. Chen, W.R. Abrams, P.L. Corstjens, H.H. Bau, A timer-actuated immunoassay cassette for detecting molecular markers in oral fluids. Lab Chip 9, 768–776 (2009)CrossRefGoogle Scholar
  27. D. Malamud, H. Bau, S. Niedbala, P. Corstjens, Point detection of pathogens in oral samples. Adv. Dent. Res. 18, 12–16 (2005)CrossRefGoogle Scholar
  28. M.G. Mauk, B.L. Ziober, Z. Chen, J.A. Thompson, H.H. Bau, Lab-on-a-chip technologies for oral-based cancer screening and diagnostics: capabilities, issues, and prospects. Ann. N.Y. Acad. Sci. 1098, 467–475 (2007)CrossRefGoogle Scholar
  29. J.K. Ng, E.S. Selamat, W. Liu, A spatially addressable bead-based biosensor for simple and rapid DNA detection. Biosens. Bioelectron. 23, 803–810 (2008)CrossRefGoogle Scholar
  30. S.J. Paik, S. Byun, J.M. Lim, Y. Park, A. Lee, S. Chung, J. Chang, K. Chun, D. Cho, In-plane single-crystal-silicon microneedles for minimally invasive microfluid systems. Sens. Actuators A 114, 276–284 (2004)CrossRefGoogle Scholar
  31. P.M. Pilarski, S. Adamia, C.J. Backhouse, An adaptable microvalving system for on-chip polymerase chain reactions. J. Immunol. Methods 305, 48–58 (2005)CrossRefGoogle Scholar
  32. S. Qian, H.H. Bau, A mathematical model of lateral flow bio-reactions applied to sandwich assays. Anal. Biochem. 322, 89–98 (2003)CrossRefGoogle Scholar
  33. S. Qian, H.H. Bau, Analysis of lateral flow bio-detectors: competitive format. Anal. Biochem. 326, 211–224 (2004)CrossRefGoogle Scholar
  34. S. Ramachandran, J. Gerdes, P. Tarr, P. Yager, L. Dillman, R. Peck, M. Kokoris, M. Nabavi, F. Battrell, D. Hoekstra, B.H. Weigl, Dry-reagent storage for disposable lab-on-a-card diagnosis of enteric pathogens, Proceedings of the 1st Distributed Diagnosis and Home Healthcare (D2H2) Conference Arlington, 16–19 (2006)Google Scholar
  35. D. Snakenborg, G. Perozziello, O. Geschke, J.P. Kutter, A fast and reliable way to establish fluidic connections to planar microchips. J. Micromechanics Microengineering 17, 98–103 (2007)CrossRefGoogle Scholar
  36. F. van de Rijke, H. Zijlmans, S. Li, T. Vail, A.K. Raap, R.S. Niedbala, H.J. Tanke, Up-converting phosphor reporters for nucleic acid microarrays. Nat. Biotechnol. 19, 273–276 (2001)CrossRefGoogle Scholar
  37. J. Wang, Z. Chen, P.L.A.M. Corstjens, M.G. Mauk, H.H. Bau, A disposable microfluidic cassette for DNA amplification and detection. Lab Chip 6, 46–53 (2006)CrossRefGoogle Scholar
  38. R. Wilkinson, D. Rowland, W.M. Ching, Development of an improved rapid lateral flow assay for the detection of orientia tsutsugamushi-specific IgG/IgM antibodies. Ann. N.Y. Acad. Sci. 990, 386–390 (2003)CrossRefGoogle Scholar
  39. W. Xu, K. Sur, H. Zeng, A. Feinerman, D. Kelso, J.B. Ketterson, A microfluidic approach to assembling ordered microsphere arrays. J. Micromechanics Microengineering 18, 1–6 (2008)Google Scholar
  40. M. Yi, H.H. Bau, The kinematics of bend-induced mixing in micro-conduits. Int. J. Heat Fluid Flow 24, 645–656 (2003)CrossRefGoogle Scholar
  41. C. Zhang, D. Xing, Y. Li, Micropumps, microvalves, and micromixers within PCR microfluidic chips: advances and trends. Biotechnol. Adv. 25, 483–514 (2007)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Xianbo Qiu
    • 1
  • Jason A. Thompson
    • 1
  • Zongyuan Chen
    • 1
    • 5
  • Changchun Liu
    • 1
  • Dafeng Chen
    • 1
  • Sudhir Ramprasad
    • 1
    • 6
  • Michael G. Mauk
    • 1
  • Serge Ongagna
    • 2
  • Cheryl Barber
    • 2
  • William R. Abrams
    • 2
  • Daniel Malamud
    • 2
    • 3
  • Paul L. A. M. Corstjens
    • 4
  • Haim H. Bau
    • 1
  1. 1.Department of Mechanical Engineering and Applied MechanicsUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.Department of Basic SciencesNew York University College of DentistryNew YorkUSA
  3. 3.Department of MedicineNYU School of MedicineNew YorkUSA
  4. 4.Department of Molecular Cell BiologyLeiden University Medical CenterLeidenThe Netherlands
  5. 5.Rheonix, Inc.IthacaUSA
  6. 6.Pacific Northwest National LaboratoryCorvallisUSA

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