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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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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.

Author information

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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