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Mixing and Oxygen Transfer Characteristics of a Microplate Bioreactor with Surface-Attached Microposts
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  • Justin Fisher,
  • Travis Gurney,
  • Jay Fisher,
  • Brittany Mason,
  • William. J. Kelly
Justin Fisher
Villanova University

Corresponding Author:jfishe19@villanova.edu

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Travis Gurney
Redbud Labs
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Jay Fisher
Redbud Labs
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Brittany Mason
Redbud Labs
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William. J. Kelly
Villanova University
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Abstract

Bioprocess optimization for cell-based therapies is a resource heavy activity. To reduce the associated cost and time, it is advantageous to carry out process development in small volume systems, with the caveat that such systems be predictive for process scaleup. The transport of oxygen from the gas phase into the culture medium, characterized using the volumetric mass transfer coefficient, kLa, has been identified as a critical parameter for predictive process scaleup. In both large- and small-scale bioreactors, kLa is controlled via mixing, with the method employed dependent upon the size of the reactor. However, existing microplate bioreactor platforms, beneficial for their low working volumes and throughput and automation capabilities, struggle to achieve desired kLa for mammalian cell cultures. Here, we describe the development and testing of a 96-well microplate with integrated Redbud Posts to provide mixing and thus enhanced kLa. Mixing characteristics were investigated, with actuating Redbud Posts shown (visually) to increase convective transport while producing enhanced kLa, providing means to mimic macroscale mammalian cell growth conditions at the microscale. Improved cell growth rates with mixing was demonstrated for two cell types, indicating the potential for this technology to play a valuable role in early stage bioprocess development and optimization.
01 Jun 2020Submitted to Biotechnology Journal
05 Jun 2020Submission Checks Completed
05 Jun 2020Assigned to Editor
06 Jun 2020Reviewer(s) Assigned
06 Jul 2020Editorial Decision: Revise Major
09 Oct 20201st Revision Received
09 Oct 2020Submission Checks Completed
09 Oct 2020Assigned to Editor
09 Oct 2020Reviewer(s) Assigned
19 Nov 2020Editorial Decision: Revise Minor
08 Dec 20202nd Revision Received
09 Dec 2020Submission Checks Completed
09 Dec 2020Assigned to Editor
09 Dec 2020Reviewer(s) Assigned
19 Dec 2020Editorial Decision: Revise Minor
08 Jan 20213rd Revision Received
09 Jan 2021Submission Checks Completed
09 Jan 2021Assigned to Editor
09 Jan 2021Reviewer(s) Assigned
16 Jan 2021Editorial Decision: Accept
11 Mar 2021Published in Biotechnology Journal on pages 2000257. 10.1002/biot.202000257