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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cells, Cultured
  • Equipment Design
  • Humans
  • Mice
  • Microfluidic Analytical Techniques / instrumentation*
  • Microfluidic Analytical Techniques / methods*
  • Reproducibility of Results
  • Single-Cell Analysis / instrumentation*
  • Single-Cell Analysis / methods*
  • Tumor Cells, Cultured