文献类型：期刊文献

英文题名：CFD-aided design and hydrodynamic characterization of a single-use perfusion bioreactor for high density cell culture

作者：Liu, Yongqiang[1,2];Gu, Qingfeng[1,2];Liu, Yu[3];Xu, Guoqian[3];Zhuang, Yingping[1,2];Guo, Meijin[1,2];Li, Chao[1,2]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, POB 329,130 Meilong Rd, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Biotechnol, 130 Meilong Rd, Shanghai 200237, Peoples R China;[3]Alit Biotech Shanghai Co Ltd, Bldg A8,66 Yunkai Rd, Shanghai 201600, Peoples R China

年份：2026

卷号：13

期号：1

外文期刊名：BIORESOURCES AND BIOPROCESSING

收录：;EI(收录号：20262320845202);WOS:【SCI-EXPANDED(收录号:WOS:001783933200003)】；

基金：This work was supported by the National Natural Science Foundation of China [No. 22208099], Key R&D Program (Science and Technology Demonstration Project) program of Shandong Province, China [No. 2022SFGC0104].

语种：英文

外文关键词：Single-use bioreactor; Computational fluid dynamics; Culture of animal cells; High density culture; Shear strain rate; Perfusion culture

摘要：To address the challenges of high-density animal cell culture, this study developed a high-density culture system comprising a single-use bioreactor (SUB) with a nominal volume of 500 mL and a pulsed tangential flow filtration (ITF) unit. The reactor can be configured with two layers of 35 mm diameter impellers-either double Elephant Ear (EE-EE) or Elephant Ear combined with Ribbon (EE-RB). The flow field characteristics were rigorously characterized through CFD simulations (60-240 rpm; 90-480 mL) validated by experimental data. Engineering analysis revealed the system's robust culture environment: \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${k}_{L}a$$\end{document} values ranging from 2 to 15 h-1 (60-180 rpm; 200-400 mL; 30-150 mL/min aeration), \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$P/V$$\end{document} values from 0.1 to 10 W/m3, and mixing times between 1 and 10 s. Crucially, the system maintains a mild shear environment with an average shear strain rate (SSR) below 25 s-1, fully within the physiological tolerance range for mammalian cells. This low-shear, high-mass-transfer design was validated through perfusion cultures of CHO and HEK293 cells. The system achieved exceptionally high cell densities of 8.32 & times; 107 cells/mL and 1.17 & times; 108 cells/mL, respectively, with cell viability consistently exceeding 90%, demonstrating its suitability for high-intensity biopharmaceutical production.