细胞生理状态对超高种植密度的强化食批次培养的影响
Qingyuan Ran1, Ying Su1, Weijian Zhang1
1The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China.
Biotechnology and applied biochemistry
|January 21, 2025
概括
在超高播种密度的强化料批次培养中优化种子细胞条件和空气化策略显著提高了生产力. 呈指数增长阶段的细胞具有高透率和双气化,从而产生更高的可活细胞密度和产品标位.
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
- 细胞培养技术 细胞培养技术
背景情况:
- 为了提高生产力,越来越多地采用了超高种植密度 (uHSD-IFB) 的强化料批次培养.
- 在uHSD-IFB过程中,种子细胞的生理状态和通风策略尚不清楚.
- 目前的生产前注射剂 (N-1) 制备依赖于经验方法,缺乏合理的基础.
研究的目的:
- 研究 perfusion 速率和细胞生长状态对随后的 uHSD-IFB 过程的影响.
- 探索不同通风策略对uHSD-IFB过程结果的影响.
- 在uHSD-IFB培养中建立合理播种和工艺设计的指南.
主要方法:
- 探索了种子细胞生理状态 (生长阶段) 和N-1 perfusion rate. 种子细胞生理状态 (生长阶段) 和N-1 perfusion rate. 种子细胞生理状态 (生长阶段) 和N-1 perfusion rate. 种子细胞生理状态 (生长阶段) 和N-1 perfusion rate.
- 分析了细胞生理参数,包括活性氧物种,细胞周期阶段和氧气吸收率.
- 在台式生物反应器中使用双系统研究了空气化策略.
主要成果:
- 呈指数增长阶段的种子细胞与高的N-1 perfusion rate导致了更高的可活细胞密度和生产中的标位.
- 这些最佳的种子细胞表现出较低的活性氧物种,更高的G1/S相比率和更高的氧气吸收率 (OUR).
- 与单个 sparger 系统相比,双 sparger 透气系统实现了最终产量增加 110% (4.5 g/L).
结论:
- 种子细胞生理状态和N-1输液策略极大地影响uHSD-IFB的性能.
- 优化的通风,特别是使用双 sparger 系统,显著提高了最终产品的产量.
- 这些发现为设计高位uHSD-IFB过程提供了合理的基础.
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