[Numerical simulation and optimization of impeller combination used in stirred bioreactor].

Bioreactors have been central in monoclonal antibodies and vaccines manufacturing by mammalian cells in suspension culture. Numerical simulation of five impeller combinations in a stirred bioreactor was conducted, and characteristics of velocity vectors, distributions of gas hold-up, distributions of shear rate in the bioreactor using 5 impeller combinations were numerically elucidated. In addition, genetically engineered CHO cells were cultivated in bioreactor installed with 5 different impeller combinations in fed-batch culture mode. The cell growth and antibody level were directly related to the maximum shear rate in the bioreactor, and the highest viable cell density and the peak antibody level were achieved in FBMI3 impeller combination, indicating that CHO cells are sensitive to shear force produced by impeller movement when cells were cultivated in bioreactor at large scale, and the maximum shear rate would play key roles in scaling-up of bioreactor at industrial scale.生物反应器已成为哺乳动物细胞生产治疗性抗体药物和疫苗的核心。文中采用CFD 数值模拟方法对目前常用的机械搅拌式生物反应器在不同的搅拌形式下的流场进行了分析，获得了5 种搅拌桨型组合条件下的速率矢量、持气率、含气率和剪切力分布的特征。通过构建的重组CHO 细胞在不同搅拌形式条件下的流加分批培养发现，细胞密度和抗体表达水平与反应器内的最大剪切率直接相关，在FBMI3 搅拌形式下细胞密度和抗体表达水平均最高。结果表明该CHO 细胞在悬浮培养时对剪切环境比较敏感，且最大剪切力是工业规模放大的关键因素。.