Centrifugal microfluidic platform for ultrasensitive detection of botulinum toxin
Abstract
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.
- Authors:
-
- 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)
- Publication Date:
- Research Org.:
- Sandia National Lab. (SNL-CA), Livermore, CA (United States)
- Sponsoring Org.:
- National Institutes of Health (NIH)
- OSTI Identifier:
- 1184997
- Report Number(s):
- SAND-2014-20313J
Journal ID: ISSN 0003-2700; 547681
- Grant/Contract Number:
- AC04-94AL85000
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Analytical Chemistry
- Additional Journal Information:
- Journal Volume: 87; Journal Issue: 2; Journal ID: ISSN 0003-2700
- Publisher:
- American Chemical Society (ACS)
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
Citation Formats
Koh, Chung -Yan, Schaff, Ulrich Y., Piccini, Matthew E., Stanker, Larry H., Cheng, Luisa W., Ravichandran, Easwaran, Singh, Bal -Ram, Sommer, Greg J., and Singh, Anup K. Centrifugal microfluidic platform for ultrasensitive detection of botulinum toxin. United States: N. p., 2014.
Web. doi:10.1021/ac504054u.
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. Centrifugal microfluidic platform for ultrasensitive detection of botulinum toxin. United States. https://doi.org/10.1021/ac504054u
Koh, Chung -Yan, Schaff, Ulrich Y., Piccini, Matthew E., Stanker, Larry H., Cheng, Luisa W., Ravichandran, Easwaran, Singh, Bal -Ram, Sommer, Greg J., and Singh, Anup K. Thu .
"Centrifugal microfluidic platform for ultrasensitive detection of botulinum toxin". United States. https://doi.org/10.1021/ac504054u. https://www.osti.gov/servlets/purl/1184997.
@article{osti_1184997,
title = {Centrifugal microfluidic platform for ultrasensitive detection of botulinum toxin},
author = {Koh, Chung -Yan and Schaff, Ulrich Y. and Piccini, Matthew E. and Stanker, Larry H. and Cheng, Luisa W. and Ravichandran, Easwaran and Singh, Bal -Ram and Sommer, Greg J. and Singh, Anup K.},
abstractNote = {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.},
doi = {10.1021/ac504054u},
journal = {Analytical Chemistry},
number = 2,
volume = 87,
place = {United States},
year = {Thu Dec 18 00:00:00 EST 2014},
month = {Thu Dec 18 00:00:00 EST 2014}
}
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