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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Royal Society of Chemistry, The
2017
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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. |
first_indexed | 2024-09-23T14:25:29Z |
format | Article |
id | mit-1721.1/110937 |
institution | Massachusetts Institute of Technology |
language | en_US |
last_indexed | 2024-09-23T14:25:29Z |
publishDate | 2017 |
publisher | Royal Society of Chemistry, The |
record_format | dspace |
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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