High-throughput measurement of single-cell growth rates using serial microfluidic mass sensor arrays

Heterogeneity in growth phenotypes and drug susceptibility in bacterial and mammalian cells are assayed at the single-cell level using multiplexed resonant mass sensors. Methods to rapidly assess cell growth would be useful for many applications, including drug susceptibility testing, but current te...

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Bibliographic Details
Published in:	Nature biotechnology Vol. 34; no. 10; pp. 1052 - 1059
Main Authors:	Cermak, Nathan, Olcum, Selim, Delgado, Francisco Feijó, Wasserman, Steven C, Payer, Kristofor R, A Murakami, Mark, Knudsen, Scott M, Kimmerling, Robert J, Stevens, Mark M, Kikuchi, Yuki, Sandikci, Arzu, Ogawa, Masaaki, Agache, Vincent, Baléras, François, Weinstock, David M, Manalis, Scott R
Format:	Journal Article
Language:	English
Published:	New York Nature Publishing Group US 01.10.2016 Nature Publishing Group
Subjects:	13/31 631/57 631/80 639/166/985 Agriculture Antibiotics Bioinformatics Biomedical engineering Biomedical Engineering/Biotechnology Biomedicine Biophysics Biotechnology Cell growth Cell Proliferation - drug effects Cell Proliferation - physiology Drug Evaluation, Preclinical - instrumentation Drug Evaluation, Preclinical - methods E coli Enterococcus faecalis Equipment Design Equipment Failure Analysis Escherichia coli Fluid mechanics Growth Growth kinetics High-Throughput Screening Assays - instrumentation High-Throughput Screening Assays - methods Lab-On-A-Chip Devices Leukemia Life Sciences Mammals Measurement Micro-Electrical-Mechanical Systems - instrumentation Micro-Electrical-Mechanical Systems - methods Peptides Physiological aspects Reproducibility of Results Sensitivity and Specificity Sensors Subpopulations T cells Transducers Yeasts
ISSN:	1087-0156, 1546-1696, 1546-1696
Online Access:	Get full text
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Summary:	Heterogeneity in growth phenotypes and drug susceptibility in bacterial and mammalian cells are assayed at the single-cell level using multiplexed resonant mass sensors. Methods to rapidly assess cell growth would be useful for many applications, including drug susceptibility testing, but current technologies have limited sensitivity or throughput. Here we present an approach to precisely and rapidly measure growth rates of many individual cells simultaneously. We flow cells in suspension through a microfluidic channel with 10–12 resonant mass sensors distributed along its length, weighing each cell repeatedly over the 4–20 min it spends in the channel. Because multiple cells traverse the channel at the same time, we obtain growth rates for >60 cells/h with a resolution of 0.2 pg/h for mammalian cells and 0.02 pg/h for bacteria. We measure the growth of single lymphocytic cells, mouse and human T cells, primary human leukemia cells, yeast, Escherichia coli and Enterococcus faecalis . Our system reveals subpopulations of cells with divergent growth kinetics and enables assessment of cellular responses to antibiotics and antimicrobial peptides within minutes.
Bibliography:	SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 14 ObjectType-Article-2 ObjectType-Undefined-1 ObjectType-Feature-3 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 These authors contributed equally to this work. Present Address: Hitachi High-Technologies Corp, Ibaraki-ken, Japan.
ISSN:	1087-0156 1546-1696 1546-1696
DOI:	10.1038/nbt.3666