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research article

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

Mutlu, Baris R.
•
Dubash, Taronish D.
•
Dietsche, Claudius
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May 7, 2020
Lab On A Chip

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 (F-s), 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 (F-s < 28 nN) and strongly bound subpopulations (F-s > 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.

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Type
research article
DOI
10.1039/d0lc00089b
Web of Science ID

WOS:000534043300004

Author(s)
Mutlu, Baris R.
Dubash, Taronish D.
Dietsche, Claudius
Mishra, Avanish
Ozbey, Arzu
Keim, Kevin  
Edd, Jon F.
Haber, Daniel A.
Maheswaran, Shyamala
Toner, Mehmet
Date Issued

2020-05-07

Publisher

ROYAL SOC CHEMISTRY

Published in
Lab On A Chip
Volume

20

Issue

9

Start page

1612

End page

1620

Subjects

Biochemical Research Methods

•

Chemistry, Multidisciplinary

•

Chemistry, Analytical

•

Nanoscience & Nanotechnology

•

Instruments & Instrumentation

•

Biochemistry & Molecular Biology

•

Chemistry

•

Science & Technology - Other Topics

•

Instruments & Instrumentation

•

plasma-membrane

•

perspective

•

clusters

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
CLSE  
Available on Infoscience
May 31, 2020
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/169023
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