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Using computational fluid dynamics simulation improves the design and subsequent characterization of a plug-flow type scale-down reactor for microbial cultivation processes
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  • Florian Mayer,
  • Monika Cserjan-Puschmann,
  • Benedikt Haslinger,
  • Anton Shpylovyi,
  • Christian Sam,
  • Miroslav Soos,
  • Rainer Hahn,
  • Gerald Striedner
Florian Mayer
University of Natural Resources and Life Sciences Vienna

Corresponding Author:florian.mayer@boku.ac.at

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Monika Cserjan-Puschmann
University of Natural Resources and Life Sciences Vienna
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Benedikt Haslinger
University of Natural Resources and Life Sciences Vienna
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Anton Shpylovyi
University of Natural Resources and Life Sciences Vienna
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Christian Sam
Boehringer Ingelheim RCV GmbH und Co KG
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Miroslav Soos
University of Chemistry and Technology Prague
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Rainer Hahn
University of Natural Resources and Life Sciences Vienna
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Gerald Striedner
University of Natural Resources and Life Sciences Vienna
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Abstract

The scale-up of bioprocesses is still one of the major obstacles in biotechnological industry. Scale-down bioreactors were identified as valuable tools to investigate the heterogeneities observed in large-scale tanks in laboratory-scale. Additionally, computational fluid dynamics (CFD) simulations can be used to gain information about fluid flow in tanks used for production. Here we present the rational design and comprehensive characterization of a scale-down setup, in which a flexible and modular plug-flow reactor is connected to a stirred tank bioreactor. With the help of CFD the mixing time difference between differently scaled bioreactors were evaluated and used as scale-down criterium. Additionally, it was used to characterize the setup at conditions were experiments could technically not be performed. This was the first time a scale-down setup was tested on high cell density Escherichia coli cultivations to produce industrial relevant antigen-binding fragments (Fab). Reduced biomass and product yields were observed during the scale-down cultivations. Additionally, the intracellular Fab fraction was increased by using the setup. The results show that including CFD in the design and characterization of a scale-down reactor can help to keep a connection to production scale and also gain intensive knowledge about the setup, which enhances usability.
25 Mar 2022Submitted to Biotechnology Journal
26 Mar 2022Submission Checks Completed
26 Mar 2022Assigned to Editor
20 Apr 2022Reviewer(s) Assigned
24 May 2022Editorial Decision: Revise Major
03 Aug 20221st Revision Received
05 Aug 2022Submission Checks Completed
05 Aug 2022Assigned to Editor
11 Aug 2022Reviewer(s) Assigned
30 Sep 2022Editorial Decision: Accept