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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2025-05-01
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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 |
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| 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. |
| format | Article |
| id | doaj-art-d106f13831c440598a4e05dc00120e31 |
| institution | Kabale University |
| issn | 2305-7084 |
| language | English |
| publishDate | 2025-05-01 |
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| series | ChemEngineering |
| 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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