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Shear stress is one of the key factors affecting the large-scale culture of mammalian cells. In this study, numerical simulation based on computational fluid dynamics was used to conduct a flow-field analysis of 7, 50, 200, and 1200 L inverted frusto-conical shaking bioreactors. The results show that the shear rate, specific mass transfer area (a), and volumetric oxygen mass transfer coefficient (k L a) gradually decreased as the scale of the bioreactor increased. Through application of BHK21 and CHO cells in 7, 200, and 1200 L bioreactors, it was found that the cell density and antibody expression level increased as the volume of the bioreactor increased. Moreover, the antibody expression level in a 1200 L bioreactor was nearly 30% and 35% higher than that of 7 and 200 L bioreactors, respectively. The results demonstrate that the environment with a larger volume is more suitable for the growth and antibody expression of CHO cells, indicating shear stress might be the most critical factor affecting the scale-up of mammalian cells.

Numerical simulation of scaling-up an inverted frusto-conical shaking bioreactor with low shear stress for mammalian cell suspension culture