Meuwly F, Loviat F, Ruffieux P-A, Bernard A R, Kadouri A, von Stockar U
Serono Biotech Center, Laboratoires Serono S.A., Zone Industrielle B, Fenil-sur-Corsier, Switzerland.
Biotechnol Bioeng. 2006 Mar 5;93(4):791-800. doi: 10.1002/bit.20766.
Packed-bed bioreactors (PBR) have proven to be efficient systems to culture mammalian cells at very high cell density in perfusion mode, thus leading to very high volumetric productivity. However, the immobilized cells must be continuously supplied with all nutrients in sufficient quantities to remain viable and productive over the full duration of the perfusion culture. Among all nutrients, oxygen is the most critical since it is present at very low concentration due to its low solubility in cell culture medium. This work presents the development of a model for oxygenation in a packed-bed bioreactor system. The experimental system used to develop the model was a packed-bed of Fibra-Cel disk carriers used to cultivate Chinese Hamster Ovary cells at high density ( approximately 6.1 x 10(7) cell/mL) in perfusion mode. With the help of this model, it was possible to identify if a PBR system is operated in optimal or sub-optimal conditions. Using the model, two options were proposed, which could improve the performance of the basal system by about twofold, that is, by increasing the density of immobilized cells per carrier volume from 6.1 x 10(7) to 1.2 x 10(8) cell/mL, or by increasing the packed-bed height from 0.2 to 0.4 m. Both strategies would be rather simple to test and implement in the packed-bed bioreactor system used for this study. As a result, it would be possible to achieve a substantial improvement of about twofold higher productivity as compared with the basal conditions.
填充床生物反应器（PBR）已被证明是在灌注模式下以非常高的细胞密度培养哺乳动物细胞的高效系统，从而实现非常高的体积生产率。然而，必须持续为固定化细胞提供足够数量的所有营养物质，以便在灌注培养的整个过程中保持活力和生产力。在所有营养物质中，氧气最为关键，因为它在细胞培养基中的溶解度很低，所以其浓度非常低。本文介绍了一种填充床生物反应器系统中氧合模型的开发。用于开发该模型的实验系统是一个填充有Fibra-Cel圆盘载体的床层，用于在灌注模式下高密度（约6.1×10⁷细胞/毫升）培养中国仓鼠卵巢细胞。借助该模型，可以确定PBR系统是否在最佳或次优条件下运行。使用该模型，提出了两种方案，这可以将基础系统的性能提高约两倍，即通过将每载体体积的固定化细胞密度从6.1×10⁷提高到1.2×10⁸细胞/毫升，或者将填充床高度从0.2米增加到0.4米。这两种策略在本研究使用的填充床生物反应器系统中测试和实施都相当简单。因此，与基础条件相比，有可能实现约两倍的更高生产率的大幅提高。
