Microfluidic active loading of single cells enables analysis of complex clinical specimens

Nicholas L. Calistri, Robert J. Kimmerling, Seth W. Malinowski, Mehdi Touat, Mark M. Stevens, Selim Olcum, Keith L. Ligon () and Scott R. Manalis ()
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Nicholas L. Calistri: Massachusetts Institute of Technology
Robert J. Kimmerling: Massachusetts Institute of Technology
Seth W. Malinowski: Dana-Farber Cancer Institute
Mehdi Touat: Dana-Farber Cancer Institute
Mark M. Stevens: Massachusetts Institute of Technology
Selim Olcum: Massachusetts Institute of Technology
Keith L. Ligon: Dana-Farber Cancer Institute
Scott R. Manalis: Massachusetts Institute of Technology

Nature Communications, 2018, vol. 9, issue 1, 1-7

Abstract: Abstract A fundamental trade-off between flow rate and measurement precision limits performance of many single-cell detection strategies, especially for applications that require biophysical measurements from living cells within complex and low-input samples. To address this, we introduce ‘active loading’, an automated, optically-triggered fluidic system that improves measurement throughput and robustness by controlling entry of individual cells into a measurement channel. We apply active loading to samples over a range of concentrations (1–1000 particles μL−1), demonstrate that measurement time can be decreased by up to 20-fold, and show theoretically that performance of some types of existing single-cell microfluidic devices can be improved by implementing active loading. Finally, we demonstrate how active loading improves clinical feasibility for acute, single-cell drug sensitivity measurements by deploying it to a preclinical setting where we assess patient samples from normal brain, primary and metastatic brain cancers containing a complex, difficult-to-measure mixture of confounding biological debris.

Date: 2018
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DOI: 10.1038/s41467-018-07283-x

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