A Novel Microfluidic Dielectrophoresis Technology to Enable Rapid Diagnosis of Mycobacteria tuberculosis in Clinical Samples

Catherine M. Moore, Jasvir Dhillon, Rebecca Flynn, Krzysztof Gizynski, Candice Adams, George Morgan, David McGurk, Eduardo Boada, Shireen Shabestary, Jonathan Peat, Jonathan O'Halloran, Neil G. Stoker, Philip D. Butcher, Heather Murton and Moore, C. 2023. A Novel Microfluidic Dielectrophoresis Technology to Enable Rapid Diagnosis of Mycobacteria tuberculosis in Clinical Samples. Journal of Molecular Diagnostics. 25 (7), pp. 513-523. https://doi.org/10.1016/j.jmoldx.2023.04.005

TitleA Novel Microfluidic Dielectrophoresis Technology to Enable Rapid Diagnosis of Mycobacteria tuberculosis in Clinical Samples
TypeJournal article
AuthorsCatherine M. Moore, Jasvir Dhillon, Rebecca Flynn, Krzysztof Gizynski, Candice Adams, George Morgan, David McGurk, Eduardo Boada, Shireen Shabestary, Jonathan Peat, Jonathan O'Halloran, Neil G. Stoker, Philip D. Butcher, Heather Murton and Moore, C.
Abstract

To achieve the global efforts to end tuberculosis, affordable diagnostics suitable for true point-of-care implementation are required to reach the missing millions. In addition, diagnostics with increased sensitivity and expanded drug susceptibility testing are needed to address drug resistance and to diagnose low-bacterial burden cases. The laboratory-on-a-chip technology described herein used dielectrophoresis to selectively isolate Mycobacterium tuberculosis from sputum samples, purifying the bacterial population ahead of molecular confirmation by multiplex real-time quantitative PCR. After optimization using a panel of 50 characterized sputum samples, the performance of the prototype was assessed against the current gold standards, screening 100 blinded sputum samples using characterized and biobanked sputum provided by Foundation for Innovative New Diagnostics. Concordance with culture diagnosis was 100% for smear-negative samples and 87% for smear-positive samples. Of the smear-positive samples, the high burden sample concordance was 100%. Samples were diagnosed on the basis of visual assessment of the dielectrophoresis array and by multiplex real-time quantitative PCR assay. The results described herein demonstrate the potential of the CAPTURE-XT technology to provide a powerful sample preparation tool that could function as a front-end platform for molecular detection. This versatile tool could equally be applied as a visual detection diagnostic, potentially associated with bacterial identification for low-cost screening or coupled with an expanded PCR assay for genotypic drug susceptibility testing.

JournalJournal of Molecular Diagnostics
Journal citation25 (7), pp. 513-523
Year2023
PublisherElsevier
Association for Molecular Biology
Publisher's version
License
CC BY 4.0
File Access Level
Open (open metadata and files)
Digital Object Identifier (DOI)https://doi.org/10.1016/j.jmoldx.2023.04.005
Web address (URL)https://doi.org/10.1016/j.jmoldx.2023.04.005
Publication dates
Published in printJul 2023
Published online22 Jun 2023

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