Applications of improved stoichiometric model in medium design and fed-batch cultivation of animal cells in bioreactor
Applications of improved stoichiometric model in medium design and fed-batch cultivation of animal cells in bioreactor
复制标题
改进的化学计量模型在生物反应器动物细胞培养基设计和补料分批培养中的应用
DOI：
--
复制
发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Daniel I. C. Wang
中科院分区：
文献类型：
--
作者：
Liangzhi Xie;Daniel I. C. Wang
在我们以前的工作（谢和王，1994年a），简化的化学计量模型的能量代谢的动物细胞培养。在补充培养基设计中使用该模型在T瓶中进行补料分批实验（Xie和Wang，1994 b）。在这项工作中，葡萄糖和谷氨酰胺代谢的主要途径纳入化学计量模型。采用适当的工艺控制策略，在2升生物反应器中进行分批补料培养。营养物质的浓度，特别是葡萄糖和谷氨酰胺，保持在恒定的，但低水平，通过使用改进的化学计量模型配制的补充培养基的自动进料。有毒副产物如氨和乳酸盐的形成（Hassellet al.，1991年，大幅减少。比乳酸生产速率降低了62倍，相比分批培养在生物反应器和8倍相比，流加培养在T-烧瓶中使用以前的化学计量模型。与分批培养和补料分批培养相比，氨形成也减少。最重要的是，单克隆抗体浓度达到900 mg l-1，与分批培养和补料分批培养相比分别增加了17倍和1.6倍。
In our previous work (Xie and Wang, 1994a), a simplified stoichiometric model on energy metabolism for animal cell cultivation was developed. Fed-batch experiments were performed in T-flasks using this model in supplemental medium design (Xie and Wang, 1994b). In this work, the major pathways of glucose and glutamine metabolism were incorporated into the stoichiometric model. Fed-batch culture was conducted in a 2-liter bioreactor with appropriate process control strategies. Nutrient concentrations, especially glucose and glutamine, were maintained at constant but low levels through the automated feeding of a supplemental medium formulated using the improved stoichiometric model. The formation of toxic byproducts, such as ammonia and lactate (Hassellet al., 1991), was greatly reduced. The specific lactate production rate was decreased by 62-fold compared with batch culture in bioreactor and by 8-fold compared to fed-batch culture in T-flask using the previous stoichiometric model. Ammonia formation was also decreased compared with both the batch and fed-batch cultures. Most importantly, the monoclonal antibody concentration reached 900 mg l−1, an increase of 17- and 1.6-fold compared with the batch and fed-batch cultures respectively.