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Nat Commun. 2018 Nov 14;9(1):4784. doi: 10.1038/s41467-018-07283-x.

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

Author information

1
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
2
Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.
3
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
4
Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA. keith_ligon@dfci.harvard.edu.
5
Department of Pathology, Harvard Medical School, Boston, MA, USA. keith_ligon@dfci.harvard.edu.
6
Department of Pathology, Boston Children's Hospital, Boston, MA, USA. keith_ligon@dfci.harvard.edu.
7
Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA. keith_ligon@dfci.harvard.edu.
8
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA. srm@mit.edu.
9
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. srm@mit.edu.
10
Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. srm@mit.edu.

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.

PMID:
30429479
PMCID:
PMC6235965
DOI:
10.1038/s41467-018-07283-x
[Indexed for MEDLINE]
Free PMC Article

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