Centrifugal microfluidic platform for ultrasensitive detection of botulinum toxin

Koh, Chung -Yan; Schaff, Ulrich Y.; Piccini, Matthew E.; Stanker, Larry H.; Cheng, Luisa W.; Ravichandran, Easwaran; Singh, Bal -Ram; Sommer, Greg J.; Singh, Anup K.

doi:10.1021/ac504054u

Title: Centrifugal microfluidic platform for ultrasensitive detection of botulinum toxin

Journal Article · Thu Dec 18 00:00:00 EST 2014 · Analytical Chemistry

DOI:https://doi.org/10.1021/ac504054u· OSTI ID:1184997

Koh, Chung -Yan ^[1]; Schaff, Ulrich Y. ^[2]; Piccini, Matthew E. ^[3]; Stanker, Larry H. ^[4]; Cheng, Luisa W. ^[4]; Ravichandran, Easwaran ^[5]; Singh, Bal -Ram ^[5]; Sommer, Greg J. ^[2]; Singh, Anup K. ^[1]

Sandia National Lab. (SNL-CA), Livermore, CA (United States)
Sandia National Lab. (SNL-CA), Livermore, CA (United States); Sandstone Diagnostics, Livermore, CA (United States)
Sandia National Lab. (SNL-CA), Livermore, CA (United States); Cepheid, Sunnyvale, CA (United States)
U.S. Dept. of Agriculture - Agricultural Research Service, Albany, CA (United States)
Univ. of Massachusetts, Dartmouth, MA (United States)

In this study, we present an innovative centrifugal microfluidic immunoassay platform (SpinDx) to address the urgent biodefense and public health need for ultrasensitive point-of-care/incident detection of botulinum toxin. The simple, sample-to-answer centrifugal microfluidic immunoassay approach is based on binding of toxins to antibody-laden capture particles followed by sedimentation of the particles through a density-media in a microfluidic disk and quantification by laser-induced fluorescence. A blind, head-to-head comparison study of SpinDx versus the gold-standard mouse bioassay demonstrates 100-fold improvement in sensitivity (limit of detection = 0.09 pg/mL), while achieving total sample-to-answer time of <30 min with 2-μL required volume of the unprocessed sample. We further demonstrate quantification of botulinum toxin in both exogeneous (human blood and serum spiked with toxins) and endogeneous (serum from mice intoxicated via oral, intranasal, and intravenous routes) samples. SpinDx can analyze, without any sample preparation, multiple sample types including whole blood, serum, and food. It is readily expandable to additional analytes as the assay reagents (i.e., the capture beads and detection antibodies) are disconnected from the disk architecture and the reader, facilitating rapid development of new assays. SpinDx can also serve as a general-purpose immunoassay platform applicable to diagnosis of other conditions and diseases.

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Research Organization:: Sandia National Lab. (SNL-CA), Livermore, CA (United States)

Sponsoring Organization:: National Institutes of Health (NIH)

Grant/Contract Number:: AC04-94AL85000

OSTI ID:: 1184997

Report Number(s):: SAND-2014-20313J; 547681

Journal Information:: Analytical Chemistry, Vol. 87, Issue 2; ISSN 0003-2700

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 54 works

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