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Characterization and feasibility of a miniaturized stirred tank bioreactor to perform E. coli high cell density fed-batch fermentations

Authors

  • Shaukat Ali,

    1. The Advanced Centre for Biochemical Engineering, Dept. of Biochemical Engineering, University College London, Torrington Place, London WC1E 7JE, U.K.
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    • Shaukat Ali and Miguel Angel Perez-Pardo authors contributed equally to this work

  • Miguel Angel Perez-Pardo,

    1. The Advanced Centre for Biochemical Engineering, Dept. of Biochemical Engineering, University College London, Torrington Place, London WC1E 7JE, U.K.
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    • Shaukat Ali and Miguel Angel Perez-Pardo authors contributed equally to this work

  • Jean P. Aucamp,

    1. The Advanced Centre for Biochemical Engineering, Dept. of Biochemical Engineering, University College London, Torrington Place, London WC1E 7JE, U.K.
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  • Alan Craig,

    1. The Advanced Centre for Biochemical Engineering, Dept. of Biochemical Engineering, University College London, Torrington Place, London WC1E 7JE, U.K.
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  • Daniel G. Bracewell,

    1. The Advanced Centre for Biochemical Engineering, Dept. of Biochemical Engineering, University College London, Torrington Place, London WC1E 7JE, U.K.
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  • Frank Baganz

    Corresponding author
    1. The Advanced Centre for Biochemical Engineering, Dept. of Biochemical Engineering, University College London, Torrington Place, London WC1E 7JE, U.K.
    • The Advanced Centre for Biochemical Engineering, Department of Biochemical Engineering, University College London, Torrington Place, London WC1E 7JE, U.K.
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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

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