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The physical characterisation of a microscale parallel bioreactor platform with an industrial CHO cell line expressing an IgG4

Paper ID Volume ID Publish Year Pages File Format Full-Text
3380 167 2013 12 PDF Available
Title
The physical characterisation of a microscale parallel bioreactor platform with an industrial CHO cell line expressing an IgG4
Abstract

•Confirms that unlike shake flasks, ambr™ growth and productivity mimics a 5 L stirred bioreactor.•Physical characteristics in an ambr™ and a 5 L stirred bioreactor are very different.•Transitional rather than turbulent flow with much higher specific power inputs (up to ~400 W/m3).•Surface mass transfer contributes much more to the overall rate of oxygen transfer.•The high specific power input does not lead to a deterioration in performance.

There is a growing body of evidence that the ambr™ workstation from TAP Biosystems performs well in terms of helping to select appropriate clones for scale-up studies. Here we have investigated the physical characteristics of this microscale bioreactor system and found that these are quite different from those that exist in larger scale stirred bioreactors. For example, the flow regime in the ambr™ vessel is transitional rather than turbulent and the sparged air/oxygen superficial gas velocity is relatively very low whilst the specific power input is much higher (~400 W/m3) when compared to that used at larger scales (typically ~20 W/m3). This specific power input is necessary in order to achieve kLa values sufficiently high to satisfy the oxygen demand of the cells and control of dO2. In line with other studies, we find that the culture of CHO cells in a 15 mL ambr™ bioreactor gave similar cell growth and productivity to that achieved in a 5 L stirred bioreactor whilst the results from shake flasks were significantly different. Given the differences in physical characteristics between the ambr™ and larger stirred bioreactors, we suggest that this similarity in biological performance is due to their similar control capabilities and the ‘equivalence of the stress parameters’ across the scales when compared with shake flasks.

Keywords
ambr™, TAP Biosystems trade mark for its advanced micro-bioreactor; CAD, computer-aided design; CFD, computational fluid dynamics; HPLC, high pressure liquid phase chromatography; k–ε, description of turbulence model used in CFD; MRF, moving reference fra
First Page Preview
The physical characterisation of a microscale parallel bioreactor platform with an industrial CHO cell line expressing an IgG4
Publisher
Database: Elsevier - ScienceDirect
Journal: Biochemical Engineering Journal - Volume 76, 15 July 2013, Pages 25–36
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering