Oxygen Uptake Rate Soft-Sensing via Dynamic kLa Computation: Cell Volume and Metabolic Transition Prediction in Mammalian Bioprocesses
In aerobic cell cultivation processes, dissolved oxygen is a key process parameter, and an optimal oxygen supply has to be ensured for proper process performance. To achieve optimal growth and/or product formation, the rate of oxygen transfer has to be in right balance with the consumption by cells....
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-08-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fbioe.2019.00195/full |
| _version_ | 1811263812443045888 |
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| author | Magdalena Pappenreiter Bernhard Sissolak Wolfgang Sommeregger Gerald Striedner |
| author_facet | Magdalena Pappenreiter Bernhard Sissolak Wolfgang Sommeregger Gerald Striedner |
| author_sort | Magdalena Pappenreiter |
| collection | DOAJ |
| description | In aerobic cell cultivation processes, dissolved oxygen is a key process parameter, and an optimal oxygen supply has to be ensured for proper process performance. To achieve optimal growth and/or product formation, the rate of oxygen transfer has to be in right balance with the consumption by cells. In this study, a 15 L mammalian cell culture bioreactor was characterized with respect to kLa under varying process conditions. The resulting dynamic kLa description combined with functions for the calculation of oxygen concentrations under prevailing process conditions led to an easy-to-apply model, that allows real-time calculation of the oxygen uptake rate (OUR) throughout the bioprocess without off-gas analyzers. Subsequently, the established OUR soft-sensor was applied in a series of 13 CHO fed-batch cultivations. The OUR was found to be directly associated with the amount of viable biomass in the system, and deploying of cell volumes instead of cell counts led to higher correlations. A two-segment linear model predicted the viable biomass in the system sufficiently. The segmented model was necessary due to a metabolic transition in which the specific consumption of oxygen changed. The aspartate to glutamate ratio was identified as an indicator of this metabolic shift. The detection of such transitions is enabled by a combination of the presented dynamic OUR method with another state-of-the-art viable biomass soft-sensor. In conclusion, this hyphenated technique is a robust and powerful tool for advanced bioprocess monitoring and control based exclusively on bioreactor characteristics. |
| first_indexed | 2024-04-12T19:51:56Z |
| format | Article |
| id | doaj.art-6d2365fb73db4d6aac62887b29a8e13f |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-04-12T19:51:56Z |
| publishDate | 2019-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-6d2365fb73db4d6aac62887b29a8e13f2022-12-22T03:18:48ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852019-08-01710.3389/fbioe.2019.00195466343Oxygen Uptake Rate Soft-Sensing via Dynamic kLa Computation: Cell Volume and Metabolic Transition Prediction in Mammalian BioprocessesMagdalena Pappenreiter0Bernhard Sissolak1Wolfgang Sommeregger2Gerald Striedner3R&D - Bilfinger Industrietechnik Salzburg GmbH, Salzburg, AustriaR&D - Bilfinger Industrietechnik Salzburg GmbH, Salzburg, AustriaR&D - Bilfinger Industrietechnik Salzburg GmbH, Salzburg, AustriaDepartment of Biotechnology (DBT), University of Natural Resources and Life Sciences (BOKU), Vienna, AustriaIn aerobic cell cultivation processes, dissolved oxygen is a key process parameter, and an optimal oxygen supply has to be ensured for proper process performance. To achieve optimal growth and/or product formation, the rate of oxygen transfer has to be in right balance with the consumption by cells. In this study, a 15 L mammalian cell culture bioreactor was characterized with respect to kLa under varying process conditions. The resulting dynamic kLa description combined with functions for the calculation of oxygen concentrations under prevailing process conditions led to an easy-to-apply model, that allows real-time calculation of the oxygen uptake rate (OUR) throughout the bioprocess without off-gas analyzers. Subsequently, the established OUR soft-sensor was applied in a series of 13 CHO fed-batch cultivations. The OUR was found to be directly associated with the amount of viable biomass in the system, and deploying of cell volumes instead of cell counts led to higher correlations. A two-segment linear model predicted the viable biomass in the system sufficiently. The segmented model was necessary due to a metabolic transition in which the specific consumption of oxygen changed. The aspartate to glutamate ratio was identified as an indicator of this metabolic shift. The detection of such transitions is enabled by a combination of the presented dynamic OUR method with another state-of-the-art viable biomass soft-sensor. In conclusion, this hyphenated technique is a robust and powerful tool for advanced bioprocess monitoring and control based exclusively on bioreactor characteristics.https://www.frontiersin.org/article/10.3389/fbioe.2019.00195/fullkLaoxygen transfer rateoxygen uptake ratebiomass predictionmetabolic statesquality by control |
| spellingShingle | Magdalena Pappenreiter Bernhard Sissolak Wolfgang Sommeregger Gerald Striedner Oxygen Uptake Rate Soft-Sensing via Dynamic kLa Computation: Cell Volume and Metabolic Transition Prediction in Mammalian Bioprocesses Frontiers in Bioengineering and Biotechnology kLa oxygen transfer rate oxygen uptake rate biomass prediction metabolic states quality by control |
| title | Oxygen Uptake Rate Soft-Sensing via Dynamic kLa Computation: Cell Volume and Metabolic Transition Prediction in Mammalian Bioprocesses |
| title_full | Oxygen Uptake Rate Soft-Sensing via Dynamic kLa Computation: Cell Volume and Metabolic Transition Prediction in Mammalian Bioprocesses |
| title_fullStr | Oxygen Uptake Rate Soft-Sensing via Dynamic kLa Computation: Cell Volume and Metabolic Transition Prediction in Mammalian Bioprocesses |
| title_full_unstemmed | Oxygen Uptake Rate Soft-Sensing via Dynamic kLa Computation: Cell Volume and Metabolic Transition Prediction in Mammalian Bioprocesses |
| title_short | Oxygen Uptake Rate Soft-Sensing via Dynamic kLa Computation: Cell Volume and Metabolic Transition Prediction in Mammalian Bioprocesses |
| title_sort | oxygen uptake rate soft sensing via dynamic kla computation cell volume and metabolic transition prediction in mammalian bioprocesses |
| topic | kLa oxygen transfer rate oxygen uptake rate biomass prediction metabolic states quality by control |
| url | https://www.frontiersin.org/article/10.3389/fbioe.2019.00195/full |
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