Department of Chemistry and Applied Biosciences, Institute for Chemical and Bioengineering, ETH Zurich, Zurich, Switzerland.
Biotechnol J. 2011 Dec;6(12):1504-15. doi: 10.1002/biot.201000477. Epub 2011 Aug 15.
The objective of the present study was to investigate the effect of hydrodynamic stress heterogeneity on metabolism and productivity of an industrial mammalian cell line. For this purpose, a novel Lobed Taylor-Couette (LTC) mixing unit combining a narrow distribution of hydrodynamic stresses and a membrane aeration system to prevent cell damage by bubble bursting was developed. A hydrodynamic analysis of the LTC was developed to reproduce, in a uniform hydrodynamic environment, the same hydrodynamic stress encountered locally by cells in a stirred tank, particularly at the large scale, e.g., close and far from the impeller. The developed LTC was used to simulate the stress values near the impeller of a laboratory stirred tank bioreactor, equal to about 0.4 Pa, which is however below the threshold value leading to cell death. It was found that the cells actively change their metabolism by increasing lactate production and decreasing titer while the consumption of the main nutrients remains substantially unchanged. When considering average stress values ranging from 1 to 10 Pa found by other researchers to cause physiological response of cells to the hydrodynamic stress in heterogeneous stirred vessels, our results are close to the lower boundary of this interval.
本研究的目的是研究流体动力应力异质性对工业哺乳动物细胞系代谢和生产力的影响。为此，开发了一种新型的叶状泰勒-库埃特（LTC）混合单元，该单元结合了流体动力应力的窄分布和膜曝气系统，以防止气泡破裂对细胞造成损伤。对 LTC 进行了流体动力学分析，以在均匀的流体动力学环境中重现搅拌罐中细胞局部遇到的相同流体动力应力，特别是在大尺度下，例如靠近和远离叶轮处。开发的 LTC 用于模拟实验室搅拌罐生物反应器中叶轮附近的应力值，约为 0.4 Pa，但低于导致细胞死亡的阈值。结果发现，细胞通过增加乳酸产量和降低效价来主动改变其代谢，而主要营养物质的消耗基本保持不变。当考虑到其他研究人员发现的导致细胞对异质搅拌容器中流体动力应力产生生理反应的 1 至 10 Pa 的平均应力值时，我们的结果接近该区间的下限。
