文献类型：期刊文献

英文题名：Novel scale-up strategy based on three-dimensional shear space for animal cell culture

作者：Li, Chao[1];Teng, Xiaonuo[1];Peng, Huadong[2,3];Yi, Xiaoping[1];Zhuang, Yingping[1];Zhang, Siliang[1];Xia, Jianye[1]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Imperial Coll London, Dept Bioengn, London SW7 2AZ, England;[3]Imperial Coll London, Ctr Synthet Biol, London SW7 2AZ, England

年份：2020

卷号：212

外文期刊名：CHEMICAL ENGINEERING SCIENCE

收录：;EI(收录号：20194607670620);WOS:【SCI-EXPANDED(收录号:WOS:000502034600020)】；

基金：This work was supported by the National Natural Science Foundation of China [grant number 21506052] and the Fundamental Research Funds for the Central Universities [grant number 22221818014].

语种：英文

外文关键词：Shear rate; Animal cell culture; Scale-up; Computational fluid dynamics; Stirred tank bioreactor

摘要：Animal cell cultivations are widely used for producing antibodies, vaccines, and recombinant protein drugs. However, the extreme sensitivity of animal cells to hydrodynamic stress often hinders its scale-up in large-scale stirred tank bioreactors. This study introduced a new scale-up strategy based on three-dimensional (3D) shear space for large-scale animal cell culture. First, the shear environments of bioreactors ranging from lab-scale (7.5 and 42 L) to industrial-scale (30, 90, 350, and 1000 L) were quantitatively analyzed through computational fluid dynamics (CFD) methods and successfully validated by particle image velocimetry (PIV) experiments. Moreover, the quantitative relationships between shear parameters (including shear rates in the impeller and tank zone, overall average shear rate, and maximum shear rate) and impeller tip velocity were established. In addition, a correlation analysis between shear-related parameters and viable cell densities in Spodoptera frugiperda Sf9 cultivations indicated that shear rates in the impeller and tank zone, and the overall average shear rate were the three key shear parameters required for scale-up. Further, an optimized 3D operation space for shear rate was established according to the three key shear parameters obtained under preferable operation conditions in lab-scale bioreactors. Based on the results, agitation rates in large-scale bioreactors were determined using the proposed correlation. Ultimately, we achieved successful scale-up of Spodoptera frugiperda Sf9 in industrial bioreactors with volumes up to 1000 L using this strategy. Thus, this study introduces a highly efficient and economical scale-up strategy for shear-sensitive cells. (C) 2019 Elsevier Ltd. All rights reserved.