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612 results on '"Omasa, Takeshi"'

12. Metabolomic characterization of monoclonal antibody‐producing Chinese hamster lung (CHL)‐YN cells in glucose‐controlled serum‐free fed‐batch operation.

Author

Sukwattananipaat, Puriwat, Kuroda, Hirotaka, Yamano‐Adachi, Noriko, and Omasa, Takeshi

Abstract

The fast‐growing Chinese hamster lung (CHL)‐YN cell line was recently developed for monoclonal antibody production. In this study, we applied a serum‐free fed‐batch cultivation process to immunoglobulin (Ig)G1‐producing CHL‐YN cells, which were then used to design a dynamic glucose supply system to stabilize the extracellular glucose concentration based on glucose consumption. Glucose consumption of the cultures rapidly oscillated following three phases of glutamine metabolism: consumption, production, and re‐consumption. Use of the dynamic glucose supply prolonged the viability of the CHL‐YN‐IgG1 cell cultures and increased IgG1 production. Liquid chromatography with tandem mass spectrometry‐based target metabolomics analysis of the extracellular metabolites during the first glutamine shift was conducted to search for depleted compounds. The results suggest that the levels of four amino acids, namely arginine, aspartate, methionine, and serine, were sharply decreased in CHL‐YN cells during glutamine production. Supporting evidence from metabolic and gene expression analyses also suggest that CHL‐YN cells acquired ornithine‐ and cystathionine‐production abilities that differed from those in Chinese hamster ovary‐K1 cells, potentially leading to proline and cysteine biosynthesis. [ABSTRACT FROM AUTHOR]

Published
2024
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29. Model‐based control system design to manage process parameters in mammalian cell culture for biopharmaceutical manufacturing.

Author

Sakaki, Ayumu, Namatame, Tetsushi, Nakaya, Makoto, and Omasa, Takeshi

Abstract

To enhance the robustness and flexibility of biopharmaceutical manufacturing, a paradigm shift toward methods of continuous processing, such as perfusion, and fundamental technologies for high‐throughput process development are being actively investigated. The continuous upstream process must establish an advanced control strategy to ensure a "State of Control" before operation. Specifically, feedforward and feedback control must address the complex fluctuations that occur during the culture process and maintain critical process parameters in appropriate states. However, control system design for industry‐standard mammalian cell culture processes is still often performed in a laborious trial‐and‐error manner. This paper provides a novel control approach in which controller specifications to obtain desired control characteristics can be determined systematically by combining a culture model with control theory. In the proposed scheme, control conditions, such as PID parameters, can be specified mechanistically based on process understanding and control requirements without qualitative decision making or specific preliminary experiments. The effectiveness of the model‐based control algorithm was verified by control simulations assuming perfusion Chinese hamster ovary culture. As a tool to assist in the development of control strategies, this study will reduce the high operational workload that is a serious problem in continuous culture and facilitate the digitalization of bioprocesses. [ABSTRACT FROM AUTHOR]

Published
2024
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