CaltechAUTHORS
  A Caltech Library Service

A digital microfluidic system for serological immunoassays in remote settings

Ng, Alphonsus H. C. and Fobel, Ryan and Fobel, Christian and Lamanna, Julian and Rackus, Darius G. and Summers, Aimee and Dixon, Christopher and Dryden, Michael D. M. and Lam, Charis and Ho, Man and Mufti, Nooman S. and Lee, Victor and Asri, Mohd Afiq Mohd and Sykes, Edward A. and Chamberlain, M. Dean and Joseph, Rachael and Ope, Maurice and Scobie, Heather M. and Knipes, Alaine and Rota, Paul A. and Marano, Nina and Chege, Paul M. and Njuguna, Mary and Nzunza, Rosemary and Kisangau, Ngina and Kiogora, John and Karuingi, Michael and Wagacha Burton, John and Borus, Peter and Lam, Eugene and Wheeler, Aaron R. (2018) A digital microfluidic system for serological immunoassays in remote settings. Science Translational Medicine, 10 (438). Art. No. eaar6076. ISSN 1946-6234. https://resolver.caltech.edu/CaltechAUTHORS:20180426-140925844

[img] PDF - Supplemental Material
See Usage Policy.

1873Kb

Use this Persistent URL to link to this item: https://resolver.caltech.edu/CaltechAUTHORS:20180426-140925844

Abstract

Serosurveys are useful for assessing population susceptibility to vaccine-preventable disease outbreaks. Although at-risk populations in remote areas could benefit from this type of information, they face several logistical barriers to implementation, such as lack of access to centralized laboratories, cold storage, and transport of samples. We describe a potential solution: a compact and portable, field-deployable, point-of-care system relying on digital microfluidics that can rapidly test a small volume of capillary blood for disease-specific antibodies. This system uses inexpensive, inkjet-printed digital microfluidic cartridges together with an integrated instrument to perform enzyme-linked immunosorbent assays (ELISAs). We performed a field validation of the system’s analytical performance at Kakuma refugee camp, a remote setting in northwestern Kenya, where we tested children aged 9 to 59 months and caregivers for measles and rubella immunoglobulin G (IgG). The IgG assays were determined to have sensitivities of 86% [95% confidence interval (CI), 79 to 91% (measles)] and 81% [95% CI, 73 to 88% (rubella)] and specificities of 80% [95% CI, 49 to 94% (measles)] and 91% [95% CI, 76 to 97% (rubella)] (measles, n = 140; rubella, n = 135) compared with reference tests (measles IgG and rubella IgG ELISAs from Siemens Enzygnost) conducted in a centralized laboratory. These results demonstrate a potential role for this point-of-care system in global serological surveillance, particularly in remote areas with limited access to centralized laboratories.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1126/scitranslmed.aar6076DOIArticle
http://www.sciencetranslationalmedicine.org/cgi/content/full/10/438/eaar6076/DC1PublisherSupplementary Materials
ORCID:
AuthorORCID
Ng, Alphonsus H. C.0000-0003-0074-4598
Wheeler, Aaron R.0000-0001-5230-7475
Additional Information:© 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. his is an article distributed under the terms of the Science Journals Default License. Received for publication November 28, 2017. Accepted for publication April 6, 2018. We thank S. Nayak (Columbia University), K. Hayford (Johns Hopkins University), K. Kain (University of Toronto), R. Campos (University of Toronto), and T. Narahari (University of Toronto) for fruitful discussions. We thank C. Okello and J. Sitati [Centers for Disease Control and Prevention (CDC) Kenya] for assistance with the logistics for the field team; E. Ojwang (International Rescue Committee) for assistance in initial planning and field protocol development; P. Kimani (Office of the United Nations High Commissioner for Refugees) for providing an enabling environment for performing the field tests; R. Nyoka (CDC Kenya) for assistance with data management; K. Wannemuehler (CDC Atlanta) for statistical consultation; and L. Ngo (University of Toronto) for assistance with photography, logistics, and personnel support. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the CDC. This work was supported by Stars in Global Health (Grand Challenges Canada), Emergency Response and Recovery Branch (ERRB) Innovation Grant (CDC), Abbott Laboratories, Canada Research Chair Program (Government of Canada) (to A.R.W.), NSERC (Natural Sciences and Engineering Research Council of Canada) E.W.R. Steacie Memorial Fellowship, Queen Elizabeth II Graduate Scholarship in Science and Technology (Government of Ontario) (to D.G.R.), NSERC Postgraduate Scholarship (to M.D.M.D.). Author contributions: A.H.C.N., R.F., and A.R.W. conceived the idea and wrote the initial proposal. A.H.C.N., R.F., C.F., M.D.M.D., E.A.S., N.S.M., M.D.C., and M.A.M.A. designed, optimized, and built the portable DMF control systems. A.H.C.N., C.F., C.D., M.H., and V.L. designed, optimized, and manufactured the DMF cartridges. A.H.C.N., J.L., D.G.R., C.D., C.L., and P.A.R. designed, developed, and optimized the DMF assays and collected the DMF laboratory data. E.L., R.J., M.O., A.S., H.M.S., and J.W.B. planned, scouted, and arranged the field tests. E.L., A.S., A.K., J.K., M.K., and N.M. collected and processed blood and serum field samples and coordinated data collection. A.H.C.N., R.F., C.F., and J.L. conducted the DMF field tests. P.B., N.K., P.M.C., M.N., and R.N. coordinated and conducted the reference laboratory tests. A.H.C.N., C.F., R.F., D.G.R., J.L., A.S., and A.R.W. analyzed the field and laboratory data. A.H.C.N., C.F., D.G.R., and A.R.W. prepared and optimized the figures. D.G.R. and A.R.W. wrote the paper with input from the entire team. Competing interests: R.F., C.F., and A.R.W. are co-founders of Sci-Bots Inc., which sells a commercial version of the open-source DropBot system described here. R.F. and A.R.W. are inventors on issued patent U.S. 9,594,056 B2, which covers methods that can be used to fabricate some of the cartridge components described here. A.H.C.N., R.F., M.H., and A.R.W. are inventors on submitted patent application PCT/CA2017/050398, which covers a droplet additive that was included in some of the assays described here. Data and materials availability: All reagents needed to run assays can be prepared as described here, other than the rubella virus–modified beads and IgG calibrators, which were a gift from Abbott Laboratories. The open-source hardware systems DropBot 3.0 and DStat 1.0 can be assembled as described here and at http://microfluidics.utoronto.ca/dropbot and http://microfluidics.utoronto.ca/dstat, respectively. The source code for the open-source software system MicroDrop 2.0 is available at https://github.com/wheeler-microfluidics.
Funders:
Funding AgencyGrant Number
Grand Challenges CanadaStars in Global Health
Emergency Response and Recovery Branch (ERRB)UNSPECIFIED
Abbott LaboratoriesUNSPECIFIED
Canada Research Chairs ProgramUNSPECIFIED
Natural Sciences and Engineering Research Council of Canada (NSERC)UNSPECIFIED
Government of OntarioUNSPECIFIED
Issue or Number:438
Record Number:CaltechAUTHORS:20180426-140925844
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20180426-140925844
Official Citation:A digital microfluidic system for serological immunoassays in remote settings BY ALPHONSUS H. C. NG, RYAN FOBEL, CHRISTIAN FOBEL, JULIAN LAMANNA, DARIUS G. RACKUS, AIMEE SUMMERS, CHRISTOPHER DIXON, MICHAEL D. M. DRYDEN, CHARIS LAM, MAN HO, NOOMAN S. MUFTI, VICTOR LEE, MOHD AFIQ MOHD ASRI, EDWARD A. SYKES, M. DEAN CHAMBERLAIN, RACHAEL JOSEPH, MAURICE OPE, HEATHER M. SCOBIE, ALAINE KNIPES, PAUL A. ROTA, NINA MARANO, PAUL M. CHEGE, MARY NJUGUNA, ROSEMARY NZUNZA, NGINA KISANGAU, JOHN KIOGORA, MICHAEL KARUINGI, JOHN WAGACHA BURTON, PETER BORUS, EUGENE LAM, AARON R. WHEELER Science Translational Medicine 25 Apr 2018: Vol. 10, Issue 438, eaar6076 DOI: 10.1126/scitranslmed.aar6076
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:86064
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:27 Apr 2018 15:44
Last Modified:03 Oct 2019 19:39

Repository Staff Only: item control page