Bioengineering | |
Metabolic Control in Mammalian Fed-Batch Cell Cultures for Reduced Lactic Acid Accumulation and Improved Process Robustness | |
Viktor Konakovsky2  Christoph Clemens3  Markus Michael Müller3  Jan Bechmann3  Martina Berger3  Stefan Schlatter3  Christoph Herwig2  Mark Blenner1  | |
[1] Institute of Chemical Engineering, Division of Biochemical Engineering, Vienna University of Technology, Gumpendorfer Strasse 1A 166-4, 1060 Vienna, AustriaInstitute of Chemical Engineering, Division of Biochemical Engineering, Vienna University of Technology, Gumpendorfer Strasse 1A 166-4, 1060 Vienna, Austria;Boehringer Ingelheim Pharma GmbH & Co. KG Dep. Bioprocess Development, Biberach, Germany; | |
关键词: CHO cell culture; scale-down; fed batch; automation; Lactic acid control; pH; metabolic control; MVDA; uncertainty; online analyzer; | |
DOI : 10.3390/bioengineering3010005 | |
来源: mdpi | |
【 摘 要 】
Biomass and cell-specific metabolic rates usually change dynamically over time, making the “feed according to need” strategy difficult to realize in a commercial fed-batch process. We here demonstrate a novel feeding strategy which is designed to hold a particular metabolic state in a fed-batch process by adaptive feeding in real time. The feed rate is calculated with a transferable biomass model based on capacitance, which changes the nutrient flow stoichiometrically in real time. A limited glucose environment was used to confine the cell in a particular metabolic state. In order to cope with uncertainty, two strategies were tested to change the adaptive feed rate and prevent starvation while in limitation: (i) inline pH and online glucose concentration measurement or (ii) inline pH alone, which was shown to be sufficient for the problem statement. In this contribution, we achieved
【 授权许可】
CC BY
© 2016 by the authors; licensee MDPI, Basel, Switzerland.
【 预 览 】
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