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

• Type of Material: Article
• Authors: Muhymin Islam, Georgia Institute of Technology; Hannah Brink, Georgia Institute of Technology; Sydney Blanche, Georgia Institute of Technology; Caleb DiPrete, Georgia Institute of Technology; Tom Bongiorno, Georgia Institute of Technology; Nicholas Stone, Georgia Institute of Technology; Anna Liu, Georgia Institute of Technology; Anisha Philip, Emory University; Gonghao Wang, Georgia Institute of Technology; Wilbur Lam, Emory University; Alexander Alexeev, Georgia Institute of Technology; Edmund Waller, Emory University; Todd Sulchek, Georgia Institute of Technology
• Language: English
• Date: 2017-05-17
• Publisher: Nature Publishing Group
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2017
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41598-017-01807-z
• Title of Journal or Parent Work: Scientific Reports
• ISSN: 2045-2322
• Volume: 7
• Issue: 1997
• Grant/Funding Information: This research was supported by National Institute of Health (1R21EB020977-01).
• Keywords: Biosensors; Cell delivery
• Research Categories: Engineering, Mechanical; Health Sciences, Oncology; Engineering, Biomedical

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 obtain highly pure populations of viable cells.