Microfluidic Sorting of Cells by Viability Based on Differences in Cell Stiffness

Scientific Reports
Muhymin IslamTodd Sulchek

Abstract

The enrichment of viable cells is an essential step to obtain effective products for cell therapy. While procedures exist to characterize the viability of cells, most methods to exclude nonviable cells require the use of density gradient centrifugation or antibody-based cell sorting with molecular labels of cell viability. We report a label-free microfluidic technique to separate live and dead cells that exploits differences in cellular stiffness. The device uses a channel with repeated ridges that are diagonal with respect to the direction of cell flow. Stiff nonviable cells directed through the channel are compressed and translated orthogonally to the channel length, while soft live cells follow hydrodynamic flow. As a proof of concept, Jurkat cells are enriched to high purity of viable cells by a factor of 185-fold. Cell stiffness was validated as a sorting parameter as nonviable cells were substantially stiffer than live cells. To highlight the utility for hematopoietic stem cell transplantation, frozen samples of cord blood were thawed and the purity of viable nucleated cells was increased from 65% to over 94% with a recovery of 73% of the viable cells. Thus, the microfluidic stiffness sorting can simply and efficiently ob...Continue Reading

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Citations

Apr 18, 2018·Apoptosis : an International Journal on Programmed Cell Death·Jingwen FengYuanming Feng
Jun 24, 2019·European Biophysics Journal : EBJ·Elena GioloLaura Andolfi
Nov 22, 2019·MRS Communications·Anton Kan, Neel S Joshi
Jan 23, 2020·Integrative Biology : Quantitative Biosciences From Nano to Macro·Efraín A CermeñoAndrés J García
Jul 9, 2020·APL Bioengineering·Muhymin IslamTodd Sulchek
Jun 27, 2021·Experimental Cell Research·Tibor TeplickýBeata Čunderlíková
Jun 14, 2021·European Biophysics Journal : EBJ·Ilaria TortorellaFrancesco Morena
Oct 5, 2018·Analytical Chemistry·Laura PasitkaCarl-Fredrik Mandenius
Oct 27, 2018·Analytical Chemistry·Pieter E OomenAndrew G Ewing
Nov 9, 2018·Analytical Chemistry·Gongchen Sun, Hang Lu
Jul 15, 2020·Accounts of Chemical Research·Mahmoud LabibShana O Kelley
Sep 11, 2021·Scientific Reports·Nicholas E StoneTodd Sulchek
Sep 18, 2021·Science Advances·Benjamin B YellenJeff Hammerbacher
Dec 10, 2021·Advanced Biology·Mona T ElsemaryBenjamin Thierry

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Methods Mentioned

BETA
flow
pull down
flow cytometry
biopsy
chemical treatments
chip
atomic force microscopy
AFM

Software Mentioned

AutoCAD
ANSYS Fluent
ImageJ

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