The physical characterisation of a microscale parallel bioreactor platform with an industrial CHO cell line expressing an IgG4 |
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| Institution: | 1. Centre for Biological Engineering, Department of Chemical Engineering, Loughborough University, Leicestershire LE11 3TU, UK;2. Centre for Bioprocess Engineering, Department of Chemical Engineering, University of Birmingham, B15 2TT, UK;3. TAP Biosystems, York Way, Royston, Hertfordshire SG8 5WY, UK;1. Novartis Pharma AG, Biologics Process R&D, Basel, Switzerland;2. Institute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zurich, Switzerland;1. State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China;2. Department of Bioengineering, Imperial College London, London SW7 2AZ, UK;3. Centre for Synthetic Biology, Imperial College London, London SW7 2AZ, UK;1. State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China;2. Dalian Practical Biotechnology Co., Ltd., Dalian, China;3. Department of Chemical Engineering, Delft University of Technology, Julianalaan 136, 2628 BL Delft, The Netherlands;1. Department of Chemical Engineering, Ryerson University, 350 Victoria Street, Toronto M5B 2K3, Canada;2. Sanofi Pasteur Company, 1755 Steels Avenue West, North York, Toronto M2R 3T4, Canada;1. Department of Biochemical Engineering, UCL, Gower Street, London WC1E 6BT, UK;2. Bioprocessing Technology Institute, A*STAR, 20 Biopolis Way, Singapore, Singapore;3. Department of Mechanical Engineering, UCL, Torrington Place, London WC1E 7JE, UK |
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| Abstract: | 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. |
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| Keywords: | Ambr? microscale bioreactor CHO cell culture Transitional flow CFD Specific power input Mass transfer |
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