Direct detection and drug-resistance profiling of bacteremias using inertial microfluidics

Detection of bacteria in bloodstream infections and their antibiotic susceptibility patterns is critical to guide therapeutic decision-making for optimal patient care. Current culture-based assays are too slow (>48 h), leading to excessive up-front use of broad-spectrum antibiotics and/or incorre...

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Main Authors: Hou, Han Wei, Bhattacharyya, Roby P., Hung, Deborah T., Han, Jongyoon
Other Authors: Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Format: Article
Language:en_US
Published: Royal Society of Chemistry, The 2017
Online Access:http://hdl.handle.net/1721.1/110937
https://orcid.org/0000-0001-7215-1439
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author Hou, Han Wei
Bhattacharyya, Roby P.
Hung, Deborah T.
Han, Jongyoon
author2 Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
author_facet Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Hou, Han Wei
Bhattacharyya, Roby P.
Hung, Deborah T.
Han, Jongyoon
author_sort Hou, Han Wei
collection MIT
description Detection of bacteria in bloodstream infections and their antibiotic susceptibility patterns is critical to guide therapeutic decision-making for optimal patient care. Current culture-based assays are too slow (>48 h), leading to excessive up-front use of broad-spectrum antibiotics and/or incorrect antibiotic choices due to resistant bacteria, each with deleterious consequences for patient care and public health. To approach this problem, we describe a method to rapidly isolate bacteria from whole blood using inertial microfluidics and directly determine pathogen identity and antibiotic susceptibility with hybridization-based RNA detection. Using the principle of Dean flow fractionation, bacteria are separated from host blood cells in a label-free separation method with efficient recovery of even low abundance bacteria. Ribosomal RNA detection can then be applied for direct identification of low abundance pathogens (~100 per mL) from blood without culturing or enzymatic amplification. Messenger RNA detection of antibiotic-responsive transcripts after brief drug exposure permits rapid susceptibility determination from bacteria with minimal culturing (~105 per mL). This unique coupling of microfluidic cell separation with RNA-based molecular detection techniques represents significant progress towards faster diagnostics (~8 hours) to guide antibiotic therapy.
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spelling mit-1721.1/1109372022-09-29T09:23:59Z Direct detection and drug-resistance profiling of bacteremias using inertial microfluidics Hou, Han Wei Bhattacharyya, Roby P. Hung, Deborah T. Han, Jongyoon Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Massachusetts Institute of Technology. Research Laboratory of Electronics Hou, Han Wei Han, Jongyoon Detection of bacteria in bloodstream infections and their antibiotic susceptibility patterns is critical to guide therapeutic decision-making for optimal patient care. Current culture-based assays are too slow (>48 h), leading to excessive up-front use of broad-spectrum antibiotics and/or incorrect antibiotic choices due to resistant bacteria, each with deleterious consequences for patient care and public health. To approach this problem, we describe a method to rapidly isolate bacteria from whole blood using inertial microfluidics and directly determine pathogen identity and antibiotic susceptibility with hybridization-based RNA detection. Using the principle of Dean flow fractionation, bacteria are separated from host blood cells in a label-free separation method with efficient recovery of even low abundance bacteria. Ribosomal RNA detection can then be applied for direct identification of low abundance pathogens (~100 per mL) from blood without culturing or enzymatic amplification. Messenger RNA detection of antibiotic-responsive transcripts after brief drug exposure permits rapid susceptibility determination from bacteria with minimal culturing (~105 per mL). This unique coupling of microfluidic cell separation with RNA-based molecular detection techniques represents significant progress towards faster diagnostics (~8 hours) to guide antibiotic therapy. United States. Defense Advanced Research Projects Agency (N66001-11-1-4182) 2017-08-14T14:22:50Z 2017-08-14T14:22:50Z 2015-04 2015-03 Article http://purl.org/eprint/type/JournalArticle 1473-0197 1473-0189 http://hdl.handle.net/1721.1/110937 Hou, Han Wei, et al. “Direct Detection and Drug-Resistance Profiling of Bacteremias Using Inertial Microfluidics.” Lab on a Chip 15, 10 (May 2015): 2297–2307 © 2015 The Royal Society of Chemistry https://orcid.org/0000-0001-7215-1439 en_US http://dx.doi.org/10.1039/c5lc00311c Lab on a Chip Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Royal Society of Chemistry, The PMC
spellingShingle Hou, Han Wei
Bhattacharyya, Roby P.
Hung, Deborah T.
Han, Jongyoon
Direct detection and drug-resistance profiling of bacteremias using inertial microfluidics
title Direct detection and drug-resistance profiling of bacteremias using inertial microfluidics
title_full Direct detection and drug-resistance profiling of bacteremias using inertial microfluidics
title_fullStr Direct detection and drug-resistance profiling of bacteremias using inertial microfluidics
title_full_unstemmed Direct detection and drug-resistance profiling of bacteremias using inertial microfluidics
title_short Direct detection and drug-resistance profiling of bacteremias using inertial microfluidics
title_sort direct detection and drug resistance profiling of bacteremias using inertial microfluidics
url http://hdl.handle.net/1721.1/110937
https://orcid.org/0000-0001-7215-1439
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