Shaukat Ali and Miguel Angel Perez-Pardo authors contributed equally to this work
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Biocatalysts and Bioreactor Design
Characterization and feasibility of a miniaturized stirred tank bioreactor to perform E. coli high cell density fed-batch fermentations
Article first published online: 23 SEP 2011
DOI: 10.1002/btpr.708
Copyright © 2011 American Institute of Chemical Engineers (AIChE)
Additional Information
How to Cite
Ali, S., Perez-Pardo, M. A., Aucamp, J. P., Craig, A., Bracewell, D. G. and Baganz, F. (2012), Characterization and feasibility of a miniaturized stirred tank bioreactor to perform E. coli high cell density fed-batch fermentations. Biotechnol Progress, 28: 66–75. doi: 10.1002/btpr.708
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Shaukat Ali and Miguel Angel Perez-Pardo authors contributed equally to this work
Publication History
- Issue published online: 2 FEB 2012
- Article first published online: 23 SEP 2011
- Accepted manuscript online: 25 AUG 2011 08:27AM EST
- Manuscript Revised: 18 AUG 2011
- Manuscript Received: 15 JUL 2011
Funded by
- Dow University of Health Sciences, Karachi, Pakistan
- Engineering and Physical Sciences Research Council (EPSRC)
- Innovative Manufacturing Research Centre (IMRC)
- Abstract
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- Cited By
Keywords:
- miniaturized bioreactor;
- Fab′ fermentation;
- scale down;
- high cell density;
- engineering characterization
Abstract
The use of small scale bioreactors that are mechanically and functionally similar to large scale reactors is highly desirable to accelerate bioprocess development because they enable well-defined scale translations. In this study, a 25-mL miniaturized stirred tank bioreactor (MSBR) has been characterized in terms of its power input, hydrodynamics, and volumetric oxygen transfer coefficient (kLa) to assess its potential to grow high cell density (HCD) cultures using adequate scale-down criteria. Engineering characterization results show scale down, based on matched specific power input (PG/V), is feasible from a 20-L pilot scale stirred tank bioreactor. Results from fed-batch fermentations performed using Fab′ producing E. coli W3110 at matched (PG/V) in the MSBR and 20-L STR demonstrated that the MSBR can accurately scale down the 20-L fermentation performance in terms of growth and Fab′ production. Successful implementation of a fed-batch strategy in the MSBR resulted in maximum optical density of ca. 114 and total Fab′ concentration of 940 μg/mL compared with ca. 118 and 990 μg/mL in 20-L STR. Furthermore, the use of the MSBR in conjunction with primary recovery scale-down tools to assess the harvest material of both reactors showed comparable shear sensitivity and centrifugation performance. The conjoint use of the MSBR with ultra scale-down (USD) centrifugation mimics can provide a cost-efficient manner in which to design and develop bioprocesses that account for good upstream performance as well as their manufacturability downstream. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2012