Computational fluid dynamics modeling of an inverted frustoconical shaking bioreactor for mammalian cell suspension culture |
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Authors: | Haifeng Hang Yuanxin Guo Jian Liu Li Bai Jianye Xia Meijin Guo Matthew Hui |
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Institution: | 1.State Key Laboratory of Bioreactor Engineering,East China University of Science and Technology,Shanghai,China;2.National Key Laboratory of Biochemical Engineering, Institute of Process Engineering,Chinese Academy of Sciences,Beijing,China |
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Abstract: | We previously developed an inverted frustoconical shaking bioreactor (IFSB) which had high mammalian cell culture performance
when compared with a mechanically stirred tank reactor (STR) or a flat-bottom shaking bioreactor (FBSB). Here, we determined
the mixing time (t) and volumetric oxygen transfer coefficient (k
La) of this IFSB at various speeds, and simulated the fluid hydrodynamics, including the shear stress and specific surface
area, by computational fluid dynamics. The shortest mixing time was observed in a STR. The maximum kLa value of 12/h was achieved
in the IFSB at an aeration rate of 4 L/h, demonstrating that our IFSB has enhanced oxygen transfer capabilities needed to
meet the demands of mammalian cells. Simulation studies revealed a 3% greater specific surface area and a 21% lower shear
strain in the IFSB compared to an FBSB under the same conditions. Additionally, the conical angle of the vessel, which significantly
affected cell growth and recombinant protein production, was tested here. We conclude that, compared to the STR and FBSB,
the IFSB has an increased liquid surface area for oxygen uptake and exhaust CO2 stripping, an enhanced k
La for cell robust growth to a high cell density, and a lower shear stress to alleviate cell damage. |
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