Off-Gas-Based Soft Sensor for Real-Time Monitoring of Biomass and Metabolism in Chinese Hamster Ovary Cell Continuous Processes in Single-Use Bioreactors

In mammalian cell culture, especially in pharmaceutical manufacturing and research, biomass and metabolic monitoring are mandatory for various cell culture process steps to develop and, finally, control bioprocesses. As a common measure for biomass, the viable cell density (VCD) or the viable cell v...

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Autores principales:	Tobias Wallocha, Oliver Popp
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	process analytical technologies (PAT) off-gas analytic real-time monitoring viable cell biomass perfusion process continuous process Chemical technology TP1-1185 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/b9d53ce31f8a4f19ac1046401d4a3154
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spelling	oai:doaj.org-article:b9d53ce31f8a4f19ac1046401d4a31542021-11-25T18:52:02ZOff-Gas-Based Soft Sensor for Real-Time Monitoring of Biomass and Metabolism in Chinese Hamster Ovary Cell Continuous Processes in Single-Use Bioreactors10.3390/pr91120732227-9717https://doaj.org/article/b9d53ce31f8a4f19ac1046401d4a31542021-11-01T00:00:00Zhttps://www.mdpi.com/2227-9717/9/11/2073https://doaj.org/toc/2227-9717In mammalian cell culture, especially in pharmaceutical manufacturing and research, biomass and metabolic monitoring are mandatory for various cell culture process steps to develop and, finally, control bioprocesses. As a common measure for biomass, the viable cell density (VCD) or the viable cell volume (VCV) is widely used. This study highlights, for the first time, the advantages of using VCV instead of VCD as a biomass depiction in combination with an oxygen-uptake- rate (OUR)-based soft sensor for real-time biomass estimation and process control in single-use bioreactor (SUBs) continuous processes with Chinese hamster ovary (CHO) cell lines. We investigated a series of 14 technically similar continuous SUB processes, where the same process conditions but different expressing CHO cell lines were used, with respect to biomass growth and oxygen demand to calibrate our model. In addition, we analyzed the key metabolism of the CHO cells in SUB perfusion processes by exometabolomic approaches, highlighting the importance of cell-specific substrate and metabolite consumption and production rate qS analysis to identify distinct metabolic phases. Cell-specific rates for classical mammalian cell culture key substrates and metabolites in CHO perfusion processes showed a good correlation to qOUR, yet, unexpectedly, not for qGluc. Here, we present the soft-sensoring methodology we developed for qPyr to allow for the real-time approximation of cellular metabolism and usage for subsequent, in-depth process monitoring, characterization and optimization.Tobias WallochaOliver PoppMDPI AGarticleprocess analytical technologies (PAT)off-gas analyticreal-time monitoringviable cell biomassperfusion processcontinuous processChemical technologyTP1-1185ChemistryQD1-999ENProcesses, Vol 9, Iss 2073, p 2073 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	process analytical technologies (PAT) off-gas analytic real-time monitoring viable cell biomass perfusion process continuous process Chemical technology TP1-1185 Chemistry QD1-999
spellingShingle	process analytical technologies (PAT) off-gas analytic real-time monitoring viable cell biomass perfusion process continuous process Chemical technology TP1-1185 Chemistry QD1-999 Tobias Wallocha Oliver Popp Off-Gas-Based Soft Sensor for Real-Time Monitoring of Biomass and Metabolism in Chinese Hamster Ovary Cell Continuous Processes in Single-Use Bioreactors
description	In mammalian cell culture, especially in pharmaceutical manufacturing and research, biomass and metabolic monitoring are mandatory for various cell culture process steps to develop and, finally, control bioprocesses. As a common measure for biomass, the viable cell density (VCD) or the viable cell volume (VCV) is widely used. This study highlights, for the first time, the advantages of using VCV instead of VCD as a biomass depiction in combination with an oxygen-uptake- rate (OUR)-based soft sensor for real-time biomass estimation and process control in single-use bioreactor (SUBs) continuous processes with Chinese hamster ovary (CHO) cell lines. We investigated a series of 14 technically similar continuous SUB processes, where the same process conditions but different expressing CHO cell lines were used, with respect to biomass growth and oxygen demand to calibrate our model. In addition, we analyzed the key metabolism of the CHO cells in SUB perfusion processes by exometabolomic approaches, highlighting the importance of cell-specific substrate and metabolite consumption and production rate qS analysis to identify distinct metabolic phases. Cell-specific rates for classical mammalian cell culture key substrates and metabolites in CHO perfusion processes showed a good correlation to qOUR, yet, unexpectedly, not for qGluc. Here, we present the soft-sensoring methodology we developed for qPyr to allow for the real-time approximation of cellular metabolism and usage for subsequent, in-depth process monitoring, characterization and optimization.
format	article
author	Tobias Wallocha Oliver Popp
author_facet	Tobias Wallocha Oliver Popp
author_sort	Tobias Wallocha
title	Off-Gas-Based Soft Sensor for Real-Time Monitoring of Biomass and Metabolism in Chinese Hamster Ovary Cell Continuous Processes in Single-Use Bioreactors
title_short	Off-Gas-Based Soft Sensor for Real-Time Monitoring of Biomass and Metabolism in Chinese Hamster Ovary Cell Continuous Processes in Single-Use Bioreactors
title_full	Off-Gas-Based Soft Sensor for Real-Time Monitoring of Biomass and Metabolism in Chinese Hamster Ovary Cell Continuous Processes in Single-Use Bioreactors
title_fullStr	Off-Gas-Based Soft Sensor for Real-Time Monitoring of Biomass and Metabolism in Chinese Hamster Ovary Cell Continuous Processes in Single-Use Bioreactors
title_full_unstemmed	Off-Gas-Based Soft Sensor for Real-Time Monitoring of Biomass and Metabolism in Chinese Hamster Ovary Cell Continuous Processes in Single-Use Bioreactors
title_sort	off-gas-based soft sensor for real-time monitoring of biomass and metabolism in chinese hamster ovary cell continuous processes in single-use bioreactors
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/b9d53ce31f8a4f19ac1046401d4a3154
work_keys_str_mv	AT tobiaswallocha offgasbasedsoftsensorforrealtimemonitoringofbiomassandmetabolisminchinesehamsterovarycellcontinuousprocessesinsingleusebioreactors AT oliverpopp offgasbasedsoftsensorforrealtimemonitoringofbiomassandmetabolisminchinesehamsterovarycellcontinuousprocessesinsingleusebioreactors
_version_	1718410615517609984

Off-Gas-Based Soft Sensor for Real-Time Monitoring of Biomass and Metabolism in Chinese Hamster Ovary Cell Continuous Processes in Single-Use Bioreactors

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