CO<sub>2</sub> Control Strategy for Large-Scale Cell Culture Bioreactor Operation

Naveenganesh Muralidharan; Thatsinee Johnson; Emma Bolduc; Mark Davis

doi:doi:10.11648/abb.20241201.11

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CO₂ Control Strategy for Large-Scale Cell Culture Bioreactor Operation

Naveenganesh Muralidharan^*, Thatsinee Johnson, Emma Bolduc, Mark Davis

Published in Advances in Bioscience and Bioengineering (Volume 12, Issue 1)

Received: 3 January 2024 Accepted: 17 January 2024 Published: 1 February 2024

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Abstract

In most mammalian cell culture operations, the pH is targeted to be close to neutral and the dissolved carbon dioxide [dCO₂] concentration is desired to remain between 5 and 15% to avoid any inhibitory effects on cell growth. Typical cell culture scale-up approaches include maintaining constant power by volume (P/V) or a constant tip speed to set the impeller agitation rate or constant vvm to set the gas flow rate. However, these approaches are only focused on keeping the shear in the bioreactor system to a minimum and do not account for controlling the [dCO₂] concentration within the desired range. Process engineers across industries have remediated the elevated [dCO₂] concentration problem in large scale bioreactors by increasing gas flow rates; however, this approach is often trial and error. Therefore, in this article we review the current understanding of various factors that impact the dCO₂ concentration during the scale up of the cell culture process to large-scale bioreactors. This article also describes an easy and practical approach to predict and control the dCO₂ concentration in large-scale cell culture bioreactors using a mathematical predictive model developed based on mass-transfer first principles. We demonstrate the effective application and verification of the model by running a CHO cell culture process with a peak cell density of up to 20 x106 Cells/mL in a 15,000 L bioreactor working volume.

Published in	Advances in Bioscience and Bioengineering (Volume 12, Issue 1)
DOI	10.11648/abb.20241201.11
Page(s)	1-13
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Bioreactor Scale Up, CO₂Control, Kla, Cell Culture CO₂ Concentration, CO₂ Predictive Model, CO₂ Bubble Saturation Time

References

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[2]	Muralidharan, N., Johnson, T., & Davis, M. (2023, November 16). Identifying False Metabolite Measurements During Cell-Culture Monitoring Effective Application of the Multivariate Hotelling’s T2 Statistic. Bioprocess International, 21(11-12), 29-31. Retrieved from https://bioprocessintl.com/2023/november-december-2023/identifying-false-metabolite-measurements-during-cell-culture-monitoring-effective-application-of-the-multivariate-hotellings-t2-statistic/
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Muralidharan, N., Johnson, T., Bolduc, E., Davis, M. (2024). CO2 Control Strategy for Large-Scale Cell Culture Bioreactor Operation. Advances in Bioscience and Bioengineering, 12(1), 1-13. https://doi.org/10.11648/abb.20241201.11

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Muralidharan, N.; Johnson, T.; Bolduc, E.; Davis, M. CO2 Control Strategy for Large-Scale Cell Culture Bioreactor Operation. Adv. BioSci. Bioeng. 2024, 12(1), 1-13. doi: 10.11648/abb.20241201.11

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AMA Style

Muralidharan N, Johnson T, Bolduc E, Davis M. CO2 Control Strategy for Large-Scale Cell Culture Bioreactor Operation. Adv BioSci Bioeng. 2024;12(1):1-13. doi: 10.11648/abb.20241201.11

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@article{10.11648/abb.20241201.11,
  author = {Naveenganesh Muralidharan and Thatsinee Johnson and Emma Bolduc and Mark Davis},
  title = {CO2 Control Strategy for Large-Scale Cell Culture Bioreactor Operation},
  journal = {Advances in Bioscience and Bioengineering},
  volume = {12},
  number = {1},
  pages = {1-13},
  doi = {10.11648/abb.20241201.11},
  url = {https://doi.org/10.11648/abb.20241201.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.abb.20241201.11},
  abstract = {In most mammalian cell culture operations, the pH is targeted to be close to neutral and the dissolved carbon dioxide [dCO2] concentration is desired to remain between 5 and 15% to avoid any inhibitory effects on cell growth. Typical cell culture scale-up approaches include maintaining constant power by volume (P/V) or a constant tip speed to set the impeller agitation rate or constant vvm to set the gas flow rate. However, these approaches are only focused on keeping the shear in the bioreactor system to a minimum and do not account for controlling the [dCO2] concentration within the desired range. Process engineers across industries have remediated the elevated [dCO2] concentration problem in large scale bioreactors by increasing gas flow rates; however, this approach is often trial and error. Therefore, in this article we review the current understanding of various factors that impact the dCO2 concentration during the scale up of the cell culture process to large-scale bioreactors. This article also describes an easy and practical approach to predict and control the dCO2 concentration in large-scale cell culture bioreactors using a mathematical predictive model developed based on mass-transfer first principles. We demonstrate the effective application and verification of the model by running a CHO cell culture process with a peak cell density of up to 20 x106 Cells/mL in a 15,000 L bioreactor working volume.},
 year = {2024}
}

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TY  - JOUR
T1  - CO2 Control Strategy for Large-Scale Cell Culture Bioreactor Operation
AU  - Naveenganesh Muralidharan
AU  - Thatsinee Johnson
AU  - Emma Bolduc
AU  - Mark Davis
Y1  - 2024/02/01
PY  - 2024
N1  - https://doi.org/10.11648/abb.20241201.11
DO  - 10.11648/abb.20241201.11
T2  - Advances in Bioscience and Bioengineering
JF  - Advances in Bioscience and Bioengineering
JO  - Advances in Bioscience and Bioengineering
SP  - 1
EP  - 13
PB  - Science Publishing Group
SN  - 2330-4162
UR  - https://doi.org/10.11648/abb.20241201.11
AB  - In most mammalian cell culture operations, the pH is targeted to be close to neutral and the dissolved carbon dioxide [dCO2] concentration is desired to remain between 5 and 15% to avoid any inhibitory effects on cell growth. Typical cell culture scale-up approaches include maintaining constant power by volume (P/V) or a constant tip speed to set the impeller agitation rate or constant vvm to set the gas flow rate. However, these approaches are only focused on keeping the shear in the bioreactor system to a minimum and do not account for controlling the [dCO2] concentration within the desired range. Process engineers across industries have remediated the elevated [dCO2] concentration problem in large scale bioreactors by increasing gas flow rates; however, this approach is often trial and error. Therefore, in this article we review the current understanding of various factors that impact the dCO2 concentration during the scale up of the cell culture process to large-scale bioreactors. This article also describes an easy and practical approach to predict and control the dCO2 concentration in large-scale cell culture bioreactors using a mathematical predictive model developed based on mass-transfer first principles. We demonstrate the effective application and verification of the model by running a CHO cell culture process with a peak cell density of up to 20 x106 Cells/mL in a 15,000 L bioreactor working volume.
VL  - 12
IS  - 1
ER  -

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Author Information

Naveenganesh Muralidharan

Manufacturing Science and Technology (MSAT), AGC Biologics, Boulder, USA

Contact Email
Thatsinee Johnson

Manufacturing Science and Technology (MSAT), AGC Biologics, Boulder, USA
Emma Bolduc

Manufacturing Science and Technology (MSAT), AGC Biologics, Boulder, USA
Mark Davis

Manufacturing Science and Technology (MSAT), AGC Biologics, Boulder, USA

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Plain Text BibTeX RIS

APA Style

Muralidharan, N., Johnson, T., Bolduc, E., Davis, M. (2024). CO2 Control Strategy for Large-Scale Cell Culture Bioreactor Operation. Advances in Bioscience and Bioengineering, 12(1), 1-13. https://doi.org/10.11648/abb.20241201.11

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ACS Style

Muralidharan, N.; Johnson, T.; Bolduc, E.; Davis, M. CO2 Control Strategy for Large-Scale Cell Culture Bioreactor Operation. Adv. BioSci. Bioeng. 2024, 12(1), 1-13. doi: 10.11648/abb.20241201.11

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AMA Style

Muralidharan N, Johnson T, Bolduc E, Davis M. CO2 Control Strategy for Large-Scale Cell Culture Bioreactor Operation. Adv BioSci Bioeng. 2024;12(1):1-13. doi: 10.11648/abb.20241201.11

Copy | Download

@article{10.11648/abb.20241201.11,
  author = {Naveenganesh Muralidharan and Thatsinee Johnson and Emma Bolduc and Mark Davis},
  title = {CO2 Control Strategy for Large-Scale Cell Culture Bioreactor Operation},
  journal = {Advances in Bioscience and Bioengineering},
  volume = {12},
  number = {1},
  pages = {1-13},
  doi = {10.11648/abb.20241201.11},
  url = {https://doi.org/10.11648/abb.20241201.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.abb.20241201.11},
  abstract = {In most mammalian cell culture operations, the pH is targeted to be close to neutral and the dissolved carbon dioxide [dCO2] concentration is desired to remain between 5 and 15% to avoid any inhibitory effects on cell growth. Typical cell culture scale-up approaches include maintaining constant power by volume (P/V) or a constant tip speed to set the impeller agitation rate or constant vvm to set the gas flow rate. However, these approaches are only focused on keeping the shear in the bioreactor system to a minimum and do not account for controlling the [dCO2] concentration within the desired range. Process engineers across industries have remediated the elevated [dCO2] concentration problem in large scale bioreactors by increasing gas flow rates; however, this approach is often trial and error. Therefore, in this article we review the current understanding of various factors that impact the dCO2 concentration during the scale up of the cell culture process to large-scale bioreactors. This article also describes an easy and practical approach to predict and control the dCO2 concentration in large-scale cell culture bioreactors using a mathematical predictive model developed based on mass-transfer first principles. We demonstrate the effective application and verification of the model by running a CHO cell culture process with a peak cell density of up to 20 x106 Cells/mL in a 15,000 L bioreactor working volume.},
 year = {2024}
}

Copy | Download

TY  - JOUR
T1  - CO2 Control Strategy for Large-Scale Cell Culture Bioreactor Operation
AU  - Naveenganesh Muralidharan
AU  - Thatsinee Johnson
AU  - Emma Bolduc
AU  - Mark Davis
Y1  - 2024/02/01
PY  - 2024
N1  - https://doi.org/10.11648/abb.20241201.11
DO  - 10.11648/abb.20241201.11
T2  - Advances in Bioscience and Bioengineering
JF  - Advances in Bioscience and Bioengineering
JO  - Advances in Bioscience and Bioengineering
SP  - 1
EP  - 13
PB  - Science Publishing Group
SN  - 2330-4162
UR  - https://doi.org/10.11648/abb.20241201.11
AB  - In most mammalian cell culture operations, the pH is targeted to be close to neutral and the dissolved carbon dioxide [dCO2] concentration is desired to remain between 5 and 15% to avoid any inhibitory effects on cell growth. Typical cell culture scale-up approaches include maintaining constant power by volume (P/V) or a constant tip speed to set the impeller agitation rate or constant vvm to set the gas flow rate. However, these approaches are only focused on keeping the shear in the bioreactor system to a minimum and do not account for controlling the [dCO2] concentration within the desired range. Process engineers across industries have remediated the elevated [dCO2] concentration problem in large scale bioreactors by increasing gas flow rates; however, this approach is often trial and error. Therefore, in this article we review the current understanding of various factors that impact the dCO2 concentration during the scale up of the cell culture process to large-scale bioreactors. This article also describes an easy and practical approach to predict and control the dCO2 concentration in large-scale cell culture bioreactors using a mathematical predictive model developed based on mass-transfer first principles. We demonstrate the effective application and verification of the model by running a CHO cell culture process with a peak cell density of up to 20 x106 Cells/mL in a 15,000 L bioreactor working volume.
VL  - 12
IS  - 1
ER  -

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