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

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 mo...

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Autores principales: Muhymin Islam, Hannah Brink, Syndey Blanche, Caleb DiPrete, Tom Bongiorno, Nicholas Stone, Anna Liu, Anisha Philip, Gonghao Wang, Wilbur Lam, Alexander Alexeev, Edmund K. Waller, Todd Sulchek
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/9bae05e045644e73b96acd4cee92478b
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spelling oai:doaj.org-article:9bae05e045644e73b96acd4cee92478b2021-12-02T15:05:26ZMicrofluidic Sorting of Cells by Viability Based on Differences in Cell Stiffness10.1038/s41598-017-01807-z2045-2322https://doaj.org/article/9bae05e045644e73b96acd4cee92478b2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01807-zhttps://doaj.org/toc/2045-2322Abstract 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.Muhymin IslamHannah BrinkSyndey BlancheCaleb DiPreteTom BongiornoNicholas StoneAnna LiuAnisha PhilipGonghao WangWilbur LamAlexander AlexeevEdmund K. WallerTodd SulchekNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Muhymin Islam
Hannah Brink
Syndey Blanche
Caleb DiPrete
Tom Bongiorno
Nicholas Stone
Anna Liu
Anisha Philip
Gonghao Wang
Wilbur Lam
Alexander Alexeev
Edmund K. Waller
Todd Sulchek
Microfluidic Sorting of Cells by Viability Based on Differences in Cell Stiffness
description 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.
format article
author Muhymin Islam
Hannah Brink
Syndey Blanche
Caleb DiPrete
Tom Bongiorno
Nicholas Stone
Anna Liu
Anisha Philip
Gonghao Wang
Wilbur Lam
Alexander Alexeev
Edmund K. Waller
Todd Sulchek
author_facet Muhymin Islam
Hannah Brink
Syndey Blanche
Caleb DiPrete
Tom Bongiorno
Nicholas Stone
Anna Liu
Anisha Philip
Gonghao Wang
Wilbur Lam
Alexander Alexeev
Edmund K. Waller
Todd Sulchek
author_sort Muhymin Islam
title Microfluidic Sorting of Cells by Viability Based on Differences in Cell Stiffness
title_short Microfluidic Sorting of Cells by Viability Based on Differences in Cell Stiffness
title_full Microfluidic Sorting of Cells by Viability Based on Differences in Cell Stiffness
title_fullStr Microfluidic Sorting of Cells by Viability Based on Differences in Cell Stiffness
title_full_unstemmed Microfluidic Sorting of Cells by Viability Based on Differences in Cell Stiffness
title_sort microfluidic sorting of cells by viability based on differences in cell stiffness
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/9bae05e045644e73b96acd4cee92478b
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