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.
At a glance
- The origins and the future of microfluidics. Nature 442, 368–373 (2006).
- Micro total analysis systems: Latest achievements. Anal. Chem. 80, 4403–4419 (2008). , , &
- Lab-on-a-chip devices for global health: past studies and future opportunities. Lab Chip 7, 41–57 (2007). , &
- Microfluidic diagnostic technologies for global public health. Nature 442, 412–418 (2006). et al.
- Global health diagnostics. Nature 444 (suppl. 1), 1–2 (2006). , &
- Advancement of global health: key messages from the Disease Control Priorities Project. Lancet 367, 1193–1208 (2006). et al.
- Microfluidics: Exploiting elephants in the room. Nature 464, 839–840 (2010). &
- Polymer microfluidic devices. Talanta 56, 267–287 (2002). &
- Reagent-loaded cartridges for valveless and automated fluid delivery in microfluidic devices. Anal. Chem. 77, 64–71 (2005). , &
- A review of microvalves. J. Micromech. Microeng. 16, R13–R39 (2006). &
- Microfluidic large-scale integration. Science 298, 580–584 (2002). , &
- An integrated approach to a portable and low-cost immunoassay for resource-poor settings. Angew. Chem. Int. Ed. 16, 498–502 (2004). , , , &
- Nanoparticle-based bio-bar codes for the ultrasensitive detection of proteins. Science 301, 1884–1886 (2003). , &
- An integrated approach to a portable and low-cost immunoassay for resource-poor settings. Angew. Chem. Int. Edn Engl. 43, 498–502 (2004). , , , &
- Microfluidic point-of-care diagnostics for resource-poor environments. Proc. SPIE 7318, 1057–1059 (2009). et al.
- Effect of volume- and time-based constraints on capture of analytes in microfluidic heterogeneous immunoassays. Lab Chip 8, 2062–2070 (2008). et al.
- The kinetics of homogeneous nucleation of silver nanoparticles stabilized by polymers. J. Nanopart. Res. 9, 353–364 (2007). , &
- 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). , , , &
- 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). et al.
- Why do we need quality-assured diagnostic tests for sexually transmitted infections? Nat. Rev. Microbiol. 4, S7–S19 (2006). , , &
- Laboratory testing for infection with the human immunodeficiency virus: Established and novel approaches. Am. J. Med. 109, 568–576 (2000). , , , &
- Evaluation of rapid diagnostic tests: syphilis. Nat. Rev. Microbiol. 4, S33–S40 (2006). 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). et al.
- Evaluation of diagnostic tests for infectious diseases: general principles. Nat. Rev. Microbiol. 4, S20–S32 (2006). et al.
- 2006). et al. Rwanda Demographic and Health Survey 2005. Institut National de la Statistique du Rwanda (INSR) and ORC Macro: Calverton, Maryland, USA (
- Lateral flow (immuno) assay: its strengths, weaknesses, opportunities and threats. A literature survey. Anal. Bioanal. Chem. 393, 569–582 (2009). , &
- Limitations of rapid HIV-1 tests during screening for trials in Uganda: diagnostic test accuracy study. BMJ 335, 188–190 (2007). 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). 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). et al.
- Multiplexed immunoassays by flow cytometry for diagnosis and surveillance of infectious diseases in resource-poor settings. Lancet Infect. Dis. 2, 243–250 (2002). , , &
- Point-of-care diagnostics for global health. Annu. Rev. Biomed. Eng. 10, 107–144 (2008). , &
- Simple telemedicine for developing regions: camera phones and paper-based microfluidic devices for real-time, off-site diagnosis. Anal. Chem. 80, 3699–3707 (2008). et al.
- Top ten biotechnologies for improving health in developing countries. Nat. Genet. 32, 229–232 (2002). et al.
- Diagnostics for the developing world. Nat. Rev. Microbiol. 2, 231–240 (2004). , , &
- Reducing the burden of sexually transmitted infections in resource-limited settings: the role of improved diagnostics. Nature 444 (suppl. 1), 59–72 (2006). et al.
- Supplementary Text and Figures (5M)
Supplementary Figures 1–7, Supplementary Tables 1–9 and Supplementary Methods
- Supplementary Movie 1 (10M)
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.
- Supplementary Movie 2 (2M)
Movie of whole blood passing through microchannel. The mChip can test whole blood samples without pre-processing or clogging of microchannels.