Homogenisation and oxygen transfer rates in large agitated and sparged animal cell bioreactors: Some implications for growth and production
Homogenisation and oxygen transfer rates in large agitated and sparged animal cell bioreactors: Some implications for growth and production
复制标题
大型搅拌和喷射动物细胞生物反应器中的均质化和氧转移率：对生长和生产的一些影响
DOI：
10.1007/bf00353927
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发表时间：
2004
期刊：
影响因子：
2.2
通讯作者：
Nigel K. H. Slater
中科院分区：
文献类型：
--
作者：
A. Nienow;C. Langheinrich;N. C. Stevenson;A Nicholas Emery;T. M. Clayton;Nigel K. H. Slater
由于对细胞损伤的关注，工业动物细胞生物反应器中使用了非常低的搅拌能量输入，其典型值比细菌发酵中的能量输入低两个数量级。曝气率也很小。因此，这种生物反应器可能混合不良，也无法提供更密集操作所需的更高氧气吸收率。本文报道了威康（Wellcome）高达8立方米的生物反应器中KL a和混合（通过pH测量）的实验研究，以及伯明翰（Birmingham）此类反应器的缩小模型。除了这些物理测量外，还研究了某些细胞系对连续控制dO2的敏感性，并测量了代表性生长条件下的氧气吸收率。对特征时间和混合理论的分析，以及其他最近的工作表明，特别是在Pluronic F-68存在的情况下，可以使用更有力的搅拌和曝气，指出了改善其性能的方法。pH梯度提供了一个特殊的挑战。
Because of concern for cell damage, very low agitation energy inputs have been used in industrial animal cell bioreactors, typical values being two orders of magnitude less than those found in bacterial fermentations. Aeration rates are also very small. As a result, such bioreactors might be both poorly mixed and also unable to provide the higher oxygen up-take rates demanded by more intensive operation. This paper reports experimental studies both of KL a and of mixing (via pH measurements) in bioreactors up to 8 m3 at Wellcome and of scaled down models of such reactors at Birmingham. Alongside these physical measurements, sensitivity of certain cell lines to continuously controlled dO2 has been studied and the oxygen up-take rates measured in representative growth conditions. An analysis of characteristic times and mixing theory, together with other recent work showing that more vigorous agitation and aeration can be used especially in the presence of Pluronic F-68, indicates ways of improving their performance. pH gradients offer a special challenge.