Matsunaga Naoki, Kano Kenjiro, Maki Yasuyuki, Dobashi Toshiaki
Bio Process Research and Development Laboratories, Kyowa Hakko Kirin Company, Limited, Hagiwara-cho, Takasaki, Gunma, Japan.
J Biosci Bioeng. 2009 Apr;107(4):419-24. doi: 10.1016/j.jbiosc.2008.11.017.
Dissolved carbon dioxide (dCO(2)) accumulation is one of the most serious problems in the scale-up of industrial cell culture. To predict the effects of dCO(2) stripping in different culture conditions and at different scales, we examined a method of estimation of dCO(2) stripping using a model medium. The operational parameters (e.g., sparging and agitation rate) and the size of the bioreactor (working volume: 80 L, 500 L, 2000 L; aspect ratio: 1.0 approximately 1.6) were varied, and the model medium was prepared by adjusting pH, density, viscosity, surface tension, and buffer conditions. dCO(2) stripping efficiency was evaluated using the index k(L)a(CO)((2)), which was defined in accordance with the volumetric oxygen transfer coefficient k(L)a. The model medium exhibited dCO(2) stripping behavior similar to real culture medium in all experimental conditions tested. It is expected that the use of the model medium to estimate dCO(2) stripping in real cultures will be valuable for determining the culture conditions in bioreactors in scale-up.
溶解二氧化碳(dCO₂)积累是工业细胞培养放大过程中最严重的问题之一。为了预测不同培养条件和不同规模下dCO₂ 脱除的效果,我们研究了一种使用模型培养基估算dCO₂ 脱除的方法。改变操作参数(如鼓泡和搅拌速率)以及生物反应器的尺寸(工作体积:80 L、500 L、2000 L;长宽比:1.0至1.6),并通过调节pH值、密度、粘度、表面张力和缓冲条件来制备模型培养基。使用根据体积氧传递系数k(L)a定义的指标k(L)a(CO₂)评估dCO₂ 脱除效率。在所测试的所有实验条件下,模型培养基表现出与实际培养基相似的dCO₂ 脱除行为。预计使用模型培养基估算实际培养中的dCO₂ 脱除对于确定放大过程中生物反应器的培养条件将具有重要价值。