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Microfluidics-based diagnostics of infectious diseases in the developing world

Abstract

One of the great challenges in science and engineering today is to develop technologies to improve the health of people in the poorest regions of the world. Here we integrated new procedures for manufacturing, fluid handling and signal detection in microfluidics into a single, easy-to-use point-of-care (POC) assay that faithfully replicates all steps of ELISA, at a lower total material cost. We performed this 'mChip' assay in Rwanda on hundreds of locally collected human samples. The chip had excellent performance in the diagnosis of HIV using only 1 μl of unprocessed whole blood and an ability to simultaneously diagnose HIV and syphilis with sensitivities and specificities that rival those of reference benchtop assays. Unlike most current rapid tests, the mChip test does not require user interpretation of the signal. Overall, we demonstrate an integrated strategy for miniaturizing complex laboratory assays using microfluidics and nanoparticles to enable POC diagnostics and early detection of infectious diseases in remote settings.

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Figure 1: Schematic diagram and pictures of microfluidic device, and data on fluid handling of a POC ELISA-like assay.
Figure 2: Results of immunoassays performed at Columbia University on commercial specimen panels.
Figure 3: Field results of the HIV immunoassay collected in Muhima Hospital in Rwanda using <1 μl of unprocessed whole-blood sample.
Figure 4: Field results of a HIV and syphilis duplex immunoassay collected in Projet Ubuzima in Rwanda, using 7 μl of plasma or sera.

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References

  1. Whitesides, G.M. The origins and the future of microfluidics. Nature 442, 368–373 (2006).

    Article  CAS  Google Scholar 

  2. West, J., Becker, M., Tombrink, S. & Manz, A. Micro total analysis systems: Latest achievements. Anal. Chem. 80, 4403–4419 (2008).

    Article  CAS  Google Scholar 

  3. Chin, C.D., Linder, V. & Sia, S.K. Lab-on-a-chip devices for global health: past studies and future opportunities. Lab Chip 7, 41–57 (2007).

    Article  CAS  Google Scholar 

  4. Yager, P. et al. Microfluidic diagnostic technologies for global public health. Nature 442, 412–418 (2006).

    Article  CAS  Google Scholar 

  5. Hay Burgess, D.C., Wasserman, J. & Dahl, C.A. Global health diagnostics. Nature 444 (suppl. 1), 1–2 (2006).

    Article  Google Scholar 

  6. Laxminarayan, R. et al. Advancement of global health: key messages from the Disease Control Priorities Project. Lancet 367, 1193–1208 (2006).

    Article  Google Scholar 

  7. Wootton, R.C.R. & deMello, A.J. Microfluidics: Exploiting elephants in the room. Nature 464, 839–840 (2010).

    Article  CAS  Google Scholar 

  8. Becker, H. & Locascio, L.E. Polymer microfluidic devices. Talanta 56, 267–287 (2002).

    Article  CAS  Google Scholar 

  9. Linder, V., Sia, S.K. & Whitesides, G.M. Reagent-loaded cartridges for valveless and automated fluid delivery in microfluidic devices. Anal. Chem. 77, 64–71 (2005).

    Article  CAS  Google Scholar 

  10. Oh, K.W. & Ahn, C.H. A review of microvalves. J. Micromech. Microeng. 16, R13–R39 (2006).

    Article  Google Scholar 

  11. Thorsen, T., Maerkl, S.J. & Quake, S.R. Microfluidic large-scale integration. Science 298, 580–584 (2002).

    Article  CAS  Google Scholar 

  12. Sia, S.K., Linder, V., Parviz, B.A., Siegel, A. & Whitesides, G.M. An integrated approach to a portable and low-cost immunoassay for resource-poor settings. Angew. Chem. Int. Ed. 16, 498–502 (2004).

    Article  Google Scholar 

  13. Nam, J.M., Thaxton, C.S. & Mirkin, C.A. Nanoparticle-based bio-bar codes for the ultrasensitive detection of proteins. Science 301, 1884–1886 (2003).

    Article  CAS  Google Scholar 

  14. Sia, S.K., Linder, V., Parviz, B.A., Siegel, A. & Whitesides, G.M. An integrated approach to a portable and low-cost immunoassay for resource-poor settings. Angew. Chem. Int. Edn Engl. 43, 498–502 (2004).

    Article  CAS  Google Scholar 

  15. Laksanasopin, T. et al. Microfluidic point-of-care diagnostics for resource-poor environments. Proc. SPIE 7318, 1057–1059 (2009).

    Google Scholar 

  16. Parsa, H. et al. Effect of volume- and time-based constraints on capture of analytes in microfluidic heterogeneous immunoassays. Lab Chip 8, 2062–2070 (2008).

    Article  CAS  Google Scholar 

  17. Patakfalvi, R., Papp, S. & Dekany, I. The kinetics of homogeneous nucleation of silver nanoparticles stabilized by polymers. J. Nanopart. Res. 9, 353–364 (2007).

    Article  CAS  Google Scholar 

  18. Miranda, A.E., Alves, M.C., Neto, R.L., Areal, K.R. & Gerbase, A.C. Seroprevalence of HIV, hepatitis B virus, and syphilis in women at their first visit to public antenatal clinics in Vitoria, Brazil. Sex. Transm. Dis. 28, 710–713 (2001).

    Article  CAS  Google Scholar 

  19. De Cock, K.M. et al. Prevention of mother-to-child HIV transmission in resource-poor countries — translating research into policy and practice. J. Am. Med. Assoc. 283, 1175–1182 (2000).

    Article  CAS  Google Scholar 

  20. Peeling, R.W., Mabey, D., Herring, A. & Hook, E.W. Why do we need quality-assured diagnostic tests for sexually transmitted infections? Nat. Rev. Microbiol. 4, S7–S19 (2006).

    Article  Google Scholar 

  21. Mylonakis, E., Paliou, M., Lally, M., Flanigan, T.P. & Rich, J.D. Laboratory testing for infection with the human immunodeficiency virus: Established and novel approaches. Am. J. Med. 109, 568–576 (2000).

    Article  CAS  Google Scholar 

  22. Herring, A. et al. Evaluation of rapid diagnostic tests: syphilis. Nat. Rev. Microbiol. 4, S33–S40 (2006).

    Article  Google Scholar 

  23. Beelaert, G. et al. Comparative evaluation of eight commercial enzyme linked immunosorbent assays and 14 simple assays for detection of antibodies to HIV. J. Virol. Methods 105, 197–206 (2002).

    Article  CAS  Google Scholar 

  24. Banoo, S. et al. Evaluation of diagnostic tests for infectious diseases: general principles. Nat. Rev. Microbiol. 4, S20–S32 (2006).

    Article  Google Scholar 

  25. Gatarayiha, J.P. et al. Rwanda Demographic and Health Survey 2005. Institut National de la Statistique du Rwanda (INSR) and ORC Macro: Calverton, Maryland, USA (2006).

    Google Scholar 

  26. Posthuma-Trumpie, G.A., Korf, J. & van Amerongen, A. Lateral flow (immuno) assay: its strengths, weaknesses, opportunities and threats. A literature survey. Anal. Bioanal. Chem. 393, 569–582 (2009).

    Article  CAS  Google Scholar 

  27. Gray, R.H. et al. Limitations of rapid HIV-1 tests during screening for trials in Uganda: diagnostic test accuracy study. BMJ 335, 188–190 (2007).

    Article  Google Scholar 

  28. Klarkowski, D.B. et al. The evaluation of a rapid in situ HIV confirmation test in a programme with a high failure rate of the WHO HIV two-test diagnostic algorithm. PLOS One 4, e4351 (2009).

    Article  Google Scholar 

  29. Pavie, J. et al. Sensitivity of five rapid HIV tests on oral fluid or finger-stick whole blood: a real-time comparison in a healthcare setting. PLOS One 5, e11581 (2010).

    Article  Google Scholar 

  30. Jani, I.V., Janossy, G., Brown, D.W.G. & Mandy, F. Multiplexed immunoassays by flow cytometry for diagnosis and surveillance of infectious diseases in resource-poor settings. Lancet Infect. Dis. 2, 243–250 (2002).

    Article  CAS  Google Scholar 

  31. Yager, P., Domingo, G.J. & Gerdes, J. Point-of-care diagnostics for global health. Annu. Rev. Biomed. Eng. 10, 107–144 (2008).

    Article  CAS  Google Scholar 

  32. Martinez, A.W. et al. Simple telemedicine for developing regions: camera phones and paper-based microfluidic devices for real-time, off-site diagnosis. Anal. Chem. 80, 3699–3707 (2008).

    Article  CAS  Google Scholar 

  33. Daar, A.S. et al. Top ten biotechnologies for improving health in developing countries. Nat. Genet. 32, 229–232 (2002).

    Article  CAS  Google Scholar 

  34. Mabey, D., Peeling, R.W., Ustianowski, A. & Perkins, M.D. Diagnostics for the developing world. Nat. Rev. Microbiol. 2, 231–240 (2004).

    Article  CAS  Google Scholar 

  35. Aledort, J.E. et al. Reducing the burden of sexually transmitted infections in resource-limited settings: the role of improved diagnostics. Nature 444 (suppl. 1), 59–72 (2006).

    Article  Google Scholar 

Download references

Acknowledgements

We thank the Wallace H. Coulter Foundation, the US National Institutes of Health (1R41AI076187), a Royal Thai Government Scholarship (to T.L.), a Croucher Foundation Scholarship (to Y.K.C.) and a Frank H. Buck Scholarship (to C.D.C.) for financial support. We thank A. Leek, J. Taylor, N. Karaseva and E. Tan for helping in assay development and data on reagent stability and for assisting in design of the reader. We thank J. Kymissis, M. Steele, R. Peck, G. Whitesides and R. Peeling for helpful discussions. We thank S. Koblavi-Deme, A. Nyaruhirira, J. Kamwesiga, V. Mugisha, N. Micheu, M. Munyangabo, D. Nash, J. Mushingantahe, C. Mutezemariya, A. Binagwaho and N. Veldhuijzen for assistance with the procurement of laboratory supplies and approval of study protocols in Rwanda and for facilitating access to clinical specimens. We thank D. Rouse, R. Satcher, E. Bailey and M. Wirth for assessments of clinical need and social impact.

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Authors and Affiliations

Authors

Contributions

S.K.S. initiated the study; C.D.C. and S.K.S. designed and conducted the study; C.D.C., T.L., J.W., H.M. and R.R. performed microfluidic immunoassays at Columbia; Y.K.C. developed the compact reader; D.S. and V.L. advised on assay development and provided materials and reagents; H.P. performed computational analysis; L.M. performed reference testing of clinical samples; S.L.B., J.v.d.W., R.S., J.E.J. and W.E.-S. acquired clinical samples and assisted with field studies; C.D.C. and T.L. performed microfluidic immunoassays in Rwanda; C.D.C., T.L. and S.K.S. analyzed data; C.D.C. and S.K.S. wrote the paper; all co-authors edited the paper.

Corresponding author

Correspondence to Samuel K Sia.

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Competing interests

S.K.S. is a co-founder of Claros Diagnostics.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–7, Supplementary Tables 1–9 and Supplementary Methods (PDF 4563 kb)

Supplementary Movie 1

Movie of HIV-syphilis duplex test (complete assay). Time lapse over 20 minutes (1200 s) for two duplex immunoassays, one with a sample which is negative for HIV antibodies and positive for syphilis antibodies (top) and another with a sample which is positive for HIV antibodies and negative for syphilis antibodies (bottom). Meandering zones are functionalized with HIV antigen (left), syphilis antigen (middle), and anti-goat IgG antibody (right, positive control) as described in Supplementary Methods. (AVI 9732 kb)

Supplementary Movie 2

Movie of whole blood passing through microchannel. The mChip can test whole blood samples without pre-processing or clogging of microchannels. (AVI 2111 kb)

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Chin, C., Laksanasopin, T., Cheung, Y. et al. Microfluidics-based diagnostics of infectious diseases in the developing world. Nat Med 17, 1015–1019 (2011). https://doi.org/10.1038/nm.2408

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