Influence of Substrate Concentrations on the Performance of Fed-Batch and Perfusion Bioreactors: Insights from Mathematical Modelling

Fed-batch and perfusion bioreactors are commonly used in biopharmaceutical production. This study applies mathematical models to investigate the influence of substrate concentration in the media added (<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="...

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Main Authors: John J. Fitzpatrick, Fionn O'Leary, Ali Hill, James Daly, Fergal Lalor, Edmond P. Byrne
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:ChemEngineering
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Online Access:https://www.mdpi.com/2305-7084/9/3/48
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author John J. Fitzpatrick
Fionn O'Leary
Ali Hill
James Daly
Fergal Lalor
Edmond P. Byrne
author_facet John J. Fitzpatrick
Fionn O'Leary
Ali Hill
James Daly
Fergal Lalor
Edmond P. Byrne
author_sort John J. Fitzpatrick
collection DOAJ
description Fed-batch and perfusion bioreactors are commonly used in biopharmaceutical production. This study applies mathematical models to investigate the influence of substrate concentration in the media added (<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msub><mrow><mi>S</mi></mrow><mrow><mi>m</mi></mrow></msub></mrow></semantics></math></inline-formula>), operating substrate concentration in the bioreactor (<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mi>S</mi></mrow></semantics></math></inline-formula>), and bioreaction time on the performance of both bioreactors. The performance parameters are titer, productivity, product yield, wasted substrate, and mean product residence time. The difference between the substrate concentration in the media and the operating substrate concentration has a major impact on performance parameters. For a fixed <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mi>S</mi></mrow></semantics></math></inline-formula>, operating at higher values of <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msub><mrow><mi>S</mi></mrow><mrow><mi>m</mi></mrow></msub></mrow></semantics></math></inline-formula> is more beneficial to both fed-batch and perfusion performance. Higher productivities are obtained in perfusion, and mean product residence times are shorter. Furthermore, perfusion can obtain titers comparable to fed-batch when operated at similar substrate concentrations. All this suggests that perfusion is more advantageous. It is advantageous to operate the bioreactors over a longer bioreaction time. However, for fed-batch bioreactors, there exists an optimal time after which there is a major progressive reduction in productivity.
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spelling doaj-art-d106f13831c440598a4e05dc00120e312025-08-20T03:26:25ZengMDPI AGChemEngineering2305-70842025-05-01934810.3390/chemengineering9030048Influence of Substrate Concentrations on the Performance of Fed-Batch and Perfusion Bioreactors: Insights from Mathematical ModellingJohn J. Fitzpatrick0Fionn O'Leary1Ali Hill2James Daly3Fergal Lalor4Edmond P. Byrne5Process & Chemical Engineering, School of Engineering & Architecture, University College Cork, T12 K8AF Cork, IrelandProcess & Chemical Engineering, School of Engineering & Architecture, University College Cork, T12 K8AF Cork, IrelandProcess & Chemical Engineering, School of Engineering & Architecture, University College Cork, T12 K8AF Cork, IrelandProcess & Chemical Engineering, School of Engineering & Architecture, University College Cork, T12 K8AF Cork, IrelandProcess & Chemical Engineering, School of Engineering & Architecture, University College Cork, T12 K8AF Cork, IrelandProcess & Chemical Engineering, School of Engineering & Architecture, University College Cork, T12 K8AF Cork, IrelandFed-batch and perfusion bioreactors are commonly used in biopharmaceutical production. This study applies mathematical models to investigate the influence of substrate concentration in the media added (<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msub><mrow><mi>S</mi></mrow><mrow><mi>m</mi></mrow></msub></mrow></semantics></math></inline-formula>), operating substrate concentration in the bioreactor (<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mi>S</mi></mrow></semantics></math></inline-formula>), and bioreaction time on the performance of both bioreactors. The performance parameters are titer, productivity, product yield, wasted substrate, and mean product residence time. The difference between the substrate concentration in the media and the operating substrate concentration has a major impact on performance parameters. For a fixed <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mi>S</mi></mrow></semantics></math></inline-formula>, operating at higher values of <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msub><mrow><mi>S</mi></mrow><mrow><mi>m</mi></mrow></msub></mrow></semantics></math></inline-formula> is more beneficial to both fed-batch and perfusion performance. Higher productivities are obtained in perfusion, and mean product residence times are shorter. Furthermore, perfusion can obtain titers comparable to fed-batch when operated at similar substrate concentrations. All this suggests that perfusion is more advantageous. It is advantageous to operate the bioreactors over a longer bioreaction time. However, for fed-batch bioreactors, there exists an optimal time after which there is a major progressive reduction in productivity.https://www.mdpi.com/2305-7084/9/3/48fed-batchperfusionbioreactor performancebiopharmaceutical
spellingShingle John J. Fitzpatrick
Fionn O'Leary
Ali Hill
James Daly
Fergal Lalor
Edmond P. Byrne
Influence of Substrate Concentrations on the Performance of Fed-Batch and Perfusion Bioreactors: Insights from Mathematical Modelling
ChemEngineering
fed-batch
perfusion
bioreactor performance
biopharmaceutical
title Influence of Substrate Concentrations on the Performance of Fed-Batch and Perfusion Bioreactors: Insights from Mathematical Modelling
title_full Influence of Substrate Concentrations on the Performance of Fed-Batch and Perfusion Bioreactors: Insights from Mathematical Modelling
title_fullStr Influence of Substrate Concentrations on the Performance of Fed-Batch and Perfusion Bioreactors: Insights from Mathematical Modelling
title_full_unstemmed Influence of Substrate Concentrations on the Performance of Fed-Batch and Perfusion Bioreactors: Insights from Mathematical Modelling
title_short Influence of Substrate Concentrations on the Performance of Fed-Batch and Perfusion Bioreactors: Insights from Mathematical Modelling
title_sort influence of substrate concentrations on the performance of fed batch and perfusion bioreactors insights from mathematical modelling
topic fed-batch
perfusion
bioreactor performance
biopharmaceutical
url https://www.mdpi.com/2305-7084/9/3/48
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