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Publisher DOI: 10.1002/elsc.202100161
Title: Scaling-down biopharmaceutical production processes via a single multi-compartment bioreactor (SMCB)
Language: English
Authors: Gaugler, Lena 
Mast, Yannic 
Fitschen, Jürgen 
Hofmann, Sebastian  
Schlüter, Michael 
Takors, Ralf 
Keywords: cell culture;compartment discs;mixing times;multi-compartment system;scale-down
Issue Date: 18-Feb-2022
Publisher: Wiley-VCH
Source: Engineering in Life Sciences (2022) (in press ; CC BY 4.0)
Journal: Engineering in life sciences 
Abstract (english): 
Biopharmaceutical production processes often use mammalian cells in bioreactors larger than 10,000 L, where gradients of shear stress, substrate, dissolved oxygen and carbon dioxide, and pH are likely to occur. As former tissue cells, producer cell lines such as Chinese hamster ovary (CHO) cells sensitively respond to these mixing heterogeneities, resulting in related scenarios being mimicked in scale-down reactors. However, commonly applied multi-compartment approaches comprising multiple reactors impose a biasing shear stress caused by pumping. The latter can be prevented using the single multi-compartment bioreactor (SMCB) presented here. The exchange area provided by a disc mounted between the upper and lower compartments in a stirred bioreactor was found to be an essential design parameter. Mimicking the mixing power input at a large scale on a small scale allowed the installation of similar mixing times in the SMCB. The particularities of the disc geometry may also be considered, finally leading to a converged decision tree. The work flow identifies a sharply contoured operational field comprising disc designs and power input to install the same mixing times on a large scale in the SMCB without the additional shear stress caused by pumping. The design principle holds true for both nongassed and gassed systems.
DOI: 10.15480/882.4321
ISSN: 1618-2863
Institute: Mehrphasenströmungen V-5 
Document Type: Article
Project: SPP 2170: Teilprojekt Experimentelle Multiskalenanalyse und Simulation von 'lifelines' in Bioreaktoren um deren Einfluss auf die Kultivierung von Chinese Hamster Ovary (CHO) Zellen zu untersuchen 
Peer Reviewed: Yes
License: CC BY 4.0 (Attribution) CC BY 4.0 (Attribution)
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