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Issue 9, 2020

In-flow measurement of cell–cell adhesion using oscillatory inertial microfluidics

Author affiliations

Abstract

Multicellular clusters in circulation can exhibit a substantially different function and biomarker significance compared to individual cells. Notably, clusters of circulating tumor cells (CTCs) are much more effective initiators of metastasis than single CTCs, and correlate with worse patient prognoses. Measuring the cell–cell adhesion strength of CTC clusters is a critical step towards understanding their subsistence in the circulation and mechanism of elevated tumorigenicity. However, measuring cell–cell adhesion forces in flow is elusive using existing methods. Here, we report an oscillatory inertial microfluidics system which exerts a repeating fluidic force profile on suspended cell doublets to determine their cell–cell adhesion strength (Fs), without any biophysical modifications to the cell surface and physiological morphology. Using our system, we analyzed a large number (N > 500) of doublets from a patient-derived breast cancer CTC line. We discovered that the cell–cell adhesion strength of CTC doublets varied almost 20-fold between the weakly adhered (Fs < 28 nN) and strongly bound subpopulations (Fs > 542 nN). Our system can be used with other cancer or noncancer cells without restrictions, and may be used for rapid screening of drugs aiming to disrupt the highly-metastatic CTC clusters in circulation.

Graphical abstract: In-flow measurement of cell–cell adhesion using oscillatory inertial microfluidics

Supplementary files

Article information


Submitted
27 Jan 2020
Accepted
06 Apr 2020
First published
09 Apr 2020

Lab Chip, 2020,20, 1612-1620
Article type
Paper

In-flow measurement of cell–cell adhesion using oscillatory inertial microfluidics

B. R. Mutlu, T. Dubash, C. Dietsche, A. Mishra, A. Ozbey, K. Keim, J. F. Edd, D. A. Haber, S. Maheswaran and M. Toner, Lab Chip, 2020, 20, 1612 DOI: 10.1039/D0LC00089B

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