Application of a two-dimensional disposable rocking bioreactor to bacterial cultivation for recombinant protein production |
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Affiliation: | 1. Department of Chemical Engineering, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada;2. CELLution Biotech BV, Dr. A.F. Philipsweg 15A, AC Assen 9403, The Netherlands;1. Department of Chemical Engineering, National Taiwan University, No. 1, Roosevelt Rd., Sec. 4, Taipei 106, Taiwan;2. R&D Center for Membrane Technology and Department of Chemical Engineering, Chung Yuan Christian University, Chungli, Taoyuan, Taiwan;1. Université Pierre et Marie Curie-Paris 6, Laboratoire Jean Perrin – UMR8237, 4 place Jussieu, Paris F-75005, France;2. CNRS, Laboratoire Jean Perrin, UMR8237, 4 place Jussieu, Paris F-75005, France |
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Abstract: | Disposable rocking bioreactors (RBs) are widely employed for cultivation of recombinant mammalian and insect cell lines, although the perception of inadequate mass transfer has prevented their application to bioprocesses based on microbial platforms. In this study, one-dimensional (1D) and two-dimensional (2D) RBs were assessed and compared with the conventional stirred tank reactor (STR) for recombinant therapeutic protein production in Escherichia coli. The comparison involved: (1) physical characterization of oxygen mass transfer efficiency and mixing intensity, (2) growth characteristics in batch cultivation, and (3) culture performance for the production of recombinant protein. Our results show that oxygen mass transfer was comparable between the 1D RB and STR at low working volume (WV), declining linearly with increasing WV, and was highest in the 2D RB for all tested WVs with the maximum mass transfer coefficient (kLa) at 3 L WV. Well mixing behavior was observed in all three systems for water and aqueous carboxymethylcellulose (CMC) solutions. Batch growth characteristics were similar in all bioreactor systems, although metabolite accumulation was significant in the 1D RB. Culture performance for the production of recombinant GST-hCD83ext (glutathione S-transferase-hCD83ext fusion protein) was similar in terms of soluble protein yield and inclusion body formation for all bioreactor systems. |
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Keywords: | Disposable bioreactor Human CD83 (hCD83) Recombinant protein production Rocking bioreactor Therapeutic protein |
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