Continuous removal of small nonviable suspended mammalian cells and debris from bioreactors using inertial microfluidics

Removing nonviable cells from a cell suspension is crucial in biotechnology and biomanufacturing. Label-free microfluidic cell separation devices based on dielectrophoresis, acoustophoresis, and deterministic lateral displacement are used to remove nonviable cells. However, their volumetric throughp...

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Main Authors: Kwon, Taehong, Yao, Rujie, Hamel, Jean-Francois P, Han, Jongyoon
Other Authors: Massachusetts Institute of Technology. Department of Chemical Engineering
Format: Article
Published: Royal Society of Chemistry (RSC) 2018
Online Access:http://hdl.handle.net/1721.1/117504
https://orcid.org/0000-0001-7837-0448
https://orcid.org/0000-0001-7215-1439
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author Kwon, Taehong
Yao, Rujie
Hamel, Jean-Francois P
Han, Jongyoon
author2 Massachusetts Institute of Technology. Department of Chemical Engineering
author_facet Massachusetts Institute of Technology. Department of Chemical Engineering
Kwon, Taehong
Yao, Rujie
Hamel, Jean-Francois P
Han, Jongyoon
author_sort Kwon, Taehong
collection MIT
description Removing nonviable cells from a cell suspension is crucial in biotechnology and biomanufacturing. Label-free microfluidic cell separation devices based on dielectrophoresis, acoustophoresis, and deterministic lateral displacement are used to remove nonviable cells. However, their volumetric throughputs and test cell concentrations are generally too low to be useful in typical bioreactors in biomanufacturing. In this study, we demonstrate the efficient removal of small (<10 μm) nonviable cells from bioreactors while maintaining viable cells using inertial microfluidic cell sorting devices and characterize their performance. Despite the size overlap between viable and nonviable cell populations, the devices demonstrated 3.5-28.0% dead cell removal efficiency with 88.3-83.6% removal purity as well as 97.8-99.8% live cell retention efficiency at 4 million cells per mL with 80% viability. Cascaded and parallel configurations increased the cell concentration capacity (10 million cells per mL) and volumetric throughput (6-8 mL min-1). The system can be used for the removal of small nonviable cells from a cell suspension during continuous perfusion cell culture operations.
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spelling mit-1721.1/1175042022-09-27T19:59:12Z Continuous removal of small nonviable suspended mammalian cells and debris from bioreactors using inertial microfluidics Kwon, Taehong Yao, Rujie Hamel, Jean-Francois P Han, Jongyoon Massachusetts Institute of Technology. Department of Chemical Engineering Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Kwon, Taehong Yao, Rujie Hamel, Jean-Francois P Han, Jongyoon Removing nonviable cells from a cell suspension is crucial in biotechnology and biomanufacturing. Label-free microfluidic cell separation devices based on dielectrophoresis, acoustophoresis, and deterministic lateral displacement are used to remove nonviable cells. However, their volumetric throughputs and test cell concentrations are generally too low to be useful in typical bioreactors in biomanufacturing. In this study, we demonstrate the efficient removal of small (<10 μm) nonviable cells from bioreactors while maintaining viable cells using inertial microfluidic cell sorting devices and characterize their performance. Despite the size overlap between viable and nonviable cell populations, the devices demonstrated 3.5-28.0% dead cell removal efficiency with 88.3-83.6% removal purity as well as 97.8-99.8% live cell retention efficiency at 4 million cells per mL with 80% viability. Cascaded and parallel configurations increased the cell concentration capacity (10 million cells per mL) and volumetric throughput (6-8 mL min-1). The system can be used for the removal of small nonviable cells from a cell suspension during continuous perfusion cell culture operations. 2018-08-24T15:14:25Z 2018-08-24T15:14:25Z 2018-07 2018-03 2018-08-22T15:15:39Z Article http://purl.org/eprint/type/JournalArticle 1473-0197 1473-0189 http://hdl.handle.net/1721.1/117504 Kwon, Taehong et al. “Continuous Removal of Small Nonviable Suspended Mammalian Cells and Debris from Bioreactors Using Inertial Microfluidics.” Lab on a Chip (July 2018) © 2018 Royal Society of Chemistry https://orcid.org/0000-0001-7837-0448 https://orcid.org/0000-0001-7215-1439 http://dx.doi.org/10.1039/c8lc00250a Lab on a Chip Creative Commons Attribution-NonCommercial 3.0 Unported https://creativecommons.org/licenses/by-nc/3.0/ application/pdf Royal Society of Chemistry (RSC) Royal Society of Chemistry
spellingShingle Kwon, Taehong
Yao, Rujie
Hamel, Jean-Francois P
Han, Jongyoon
Continuous removal of small nonviable suspended mammalian cells and debris from bioreactors using inertial microfluidics
title Continuous removal of small nonviable suspended mammalian cells and debris from bioreactors using inertial microfluidics
title_full Continuous removal of small nonviable suspended mammalian cells and debris from bioreactors using inertial microfluidics
title_fullStr Continuous removal of small nonviable suspended mammalian cells and debris from bioreactors using inertial microfluidics
title_full_unstemmed Continuous removal of small nonviable suspended mammalian cells and debris from bioreactors using inertial microfluidics
title_short Continuous removal of small nonviable suspended mammalian cells and debris from bioreactors using inertial microfluidics
title_sort continuous removal of small nonviable suspended mammalian cells and debris from bioreactors using inertial microfluidics
url http://hdl.handle.net/1721.1/117504
https://orcid.org/0000-0001-7837-0448
https://orcid.org/0000-0001-7215-1439
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