动态pH档案带来更高的细胞特异性和体积生产率
Stephanie R Klaubert1, Dylan G Chitwood2, Danqia Peng3
1Department of Chemical and Biomolecular Engineering, Clemson University, Clemson, South Carolina, USA.
Biotechnology progress
|October 20, 2025
概括
在生物反应器中实施动态pH档案减轻了二氧化碳的积累,提高了哺乳动物细胞培养生产率,用于重组蛋白质的生产. 这种方法改善了细胞生长和整体产量.
科学领域:
- 生物技术是生物技术.
- 生物工艺工程 生物工艺工程
- 哺乳动物细胞培养
背景情况:
- 对于生物反应器中的哺乳动物细胞培养来说,关键过程参数控制至关重要,以优化重组治疗性蛋白质的生产.
- 培养 pH 显著影响细胞生长,生产力和关键质量属性.
- 传统的pH控制方法 (设置点或单次转移) 可以导致有害的二氧化碳积累.
研究的目的:
- 在哺乳动物细胞培养物中研究动态pH档案的有效性.
- 为了减轻二氧化碳的积累和提高生物反应器的生产率.
- 评估动态pH控制对产品质量属性的影响.
主要方法:
- 在一个生物反应器中实现了模仿摇动瓶状况的动态pH档案,在生物反应器中实现了动态pH档案.
- 在指数增长阶段,应用了多次pH转移.
- 使用了生产IgG1的中国仓鼠卵巢 (CHO) -K1细胞系.
- 评估了对细胞特异性生产率,整体生产率,糖化和电荷变异的影响.
主要成果:
- 动态pH档案成功地减轻了二氧化碳的积累.
- 观察到细胞特异性和整体培养生产力的显著增加.
- 产品质量属性对糖基化产生混合影响,对充电变量产生积极影响.
结论:
- 动态pH控制是一种可行的策略,可以提高哺乳动物细胞生物反应器的生产率.
- 这种方法有效地管理二氧化碳水平,有利于细胞生长和蛋白质产量.
- 产品质量需要仔细评估每个工艺的基础上,由于对诸如糖化等属性的不同影响.
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