在抗体分离过程中实现数字双胞胎用于动态控制对离子交换染色学样本变异的实现
Ce Shi1,2, Xu-Jun Chen1, Xue-Zhao Zhong1
1Process Development Downstream, Shanghai Engineering Research Center of Anti-tumor Biological Drugs, Shanghai Henlius Biotech, Inc., Shanghai, China.
Biotechnology and bioengineering
|January 17, 2024
概括
数字双胞胎 (DT) 增强了对样本变异的离子交换色谱 (IEC) 控制. 这种DT系统提高了产量,并提供了准确的,自动化的聚合,模仿真实世界的过程.
科学领域:
- 生物技术是生物技术.
- 化学工程是化学工程的重要组成部分.
- 过程控制 过程控制
背景情况:
- 离子交换色谱 (IEC) 对于分离生物分子至关重要.
- 由于样本的变化,IEC过程的动态控制具有挑战性.
- 数字双胞胎 (DT) 技术为流程优化提供了一种新的方法.
研究的目的:
- 开发和验证用于IEC收集窗口的动态控制的数字双胞胎.
- 为了提高IEC过程中的产量和精度,尽管样本变化.
- 为IEC建立一个强大的和自动化的聚合策略.
主要方法:
- 通过实验装配和验证 (RMSE 7.4%) 建立了一个精确的IEC机械模型.
- 开发了一个基于feedforward模型的控制数字双胞胎,集成模型,色谱系统和在线HPLC.
- 在不同的负载条件下验证了DT,样本变化>10%.
主要成果:
- 通过基于模型的梯度优化实现了70.0%的收益率,增加了11.2%.
- 与线下分析相比,DT证明了精确的控制,酸性变体比例和产量差异<2%.
- 在 >10%的样本变化下,DT显示出积极的预测性表现 (RMSE 11.7%),成功率>98%和平均收益率72.7%.
结论:
- 开发的数字双胞胎准确地模仿了现实世界的IEC场景.
- DT可以实现自动化,灵活的聚合,并提高流程的稳定性.
- 总结了在IEC中应用DT的详细方法.
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