Towards advanced bioprocess optimization: a multiscale modelling approach
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Published version
Author(s)
Monteiro, Mariana
Fadda, Sarah
Kontoravdi, Kleio
Type
Journal Article
Abstract
Mammalian cells produce up to 80% of the commercially available therapeutic proteins, with Chinese Hamster Ovary (CHO) cells being the primary production host. Manufacturing involves a train of reactors, the last of which is typically run in fed-batch mode, where cells grow and produce the required protein. The feeding strategy is decided a priori, from either past operations or the design of experiments and rarely considers the current state of the process. This work proposes a Model Predictive Control (MPC) formulation based on a hybrid kinetic-stoichiometric reactor model to provide optimal feeding policies in real-time, which is agnostic to the culture, hence transferable across CHO cell culture systems. The benefits of the proposed controller formulation are demonstrated through a comparison between an open-loop simulation and closed-loop optimization, using a digital twin as an emulator of the process.
Date Issued
2023
Date Acceptance
2023-07-01
Citation
Computational and Structural Biotechnology Journal, 2023, 21, pp.3639-3655
ISSN
2001-0370
Publisher
Elsevier
Start Page
3639
End Page
3655
Journal / Book Title
Computational and Structural Biotechnology Journal
Volume
21
Copyright Statement
© 2023 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access
article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Identifier
https://www.sciencedirect.com/science/article/pii/S2001037023002362
Publication Status
Published
Date Publish Online
2023-07-08