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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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

Affiliations

  1. Department of Biomedical Engineering, Columbia University, New York, New York, USA.

    • Curtis D Chin
    • , Tassaneewan Laksanasopin
    • , Yuk Kee Cheung
    • , Hesam Parsa
    • , Jennifer Wang
    • , Hannah Moore
    • , Robert Rouse
    •  & Samuel K Sia
  2. Claros Diagnostics, Woburn, Massachusetts, USA.

    • David Steinmiller
    •  & Vincent Linder
  3. Rwanda Zambia HIV Research Group, Projet San Francisco, Kigali, Rwanda.

    • Gisele Umviligihozo
    •  & Etienne Karita
  4. Projet Ubuzima, Kigali, Rwanda.

    • Lambert Mwambarangwe
    •  & Janneke van de Wijgert
  5. Mailman School of Public Health, International Center for AIDS Care and Treatment Programs, Columbia University, New York, New York, USA.

    • Sarah L Braunstein
    • , Ruben Sahabo
    • , Jessica E Justman
    •  & Wafaa El-Sadr
  6. Academic Medical Center of the University of Amsterdam, Department of Internal Medicine, Center for Poverty-related Communicable Diseases and Center for Infection and Immunity, Amsterdam, The Netherlands.

    • Janneke van de Wijgert

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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.

Competing interests

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

Corresponding author

Correspondence to Samuel K Sia.

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–7, Supplementary Tables 1–9 and Supplementary Methods

Videos

  1. 1.

    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.

  2. 2.

    Supplementary Movie 2

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

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DOI

https://doi.org/10.1038/nm.2408

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