SCI和EI收录∣中国化工学会会刊

Chinese Journal of Chemical Engineering ›› 2024, Vol. 74 ›› Issue (10): 22-30.DOI: 10.1016/j.cjche.2024.05.021

Previous Articles     Next Articles

Model-based risk assessment on dynamic control of twin-column continuous capture under feedstock variations

Yu Fan, Liang-Zhi Qiao, Shan-Jing Yao, Dong-Qiang Lin   

  1. Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Zhejiang Key Laboratory of Smart Biomaterials, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310058, China
  • Received:2024-04-04 Revised:2024-05-14 Accepted:2024-05-19 Online:2024-06-22 Published:2024-10-28
  • Contact: Dong-Qiang Lin,E-mail:lindq@zju.edu.cn
  • Supported by:
    This work was supported by the Zhejiang Key Science and Technology Project (2023C03116), National Natural Science Foundation of China (22078286) and National Key Research and Development Program of China (2021YFE0113300).

Model-based risk assessment on dynamic control of twin-column continuous capture under feedstock variations

Yu Fan, Liang-Zhi Qiao, Shan-Jing Yao, Dong-Qiang Lin   

  1. Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Zhejiang Key Laboratory of Smart Biomaterials, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310058, China
  • 通讯作者: Dong-Qiang Lin,E-mail:lindq@zju.edu.cn
  • 基金资助:
    This work was supported by the Zhejiang Key Science and Technology Project (2023C03116), National Natural Science Foundation of China (22078286) and National Key Research and Development Program of China (2021YFE0113300).

Abstract: Dynamic control is essential to guarantee the stable performance of continuous chromatography. AutoMAb dynamic control strategy has been developed to ensure a consistent protein load in twin-column CaptureSMB continuous capture by integrating the UV signal of breakthrough. In this study, the process risk of CaptureSMB continuous capture under AutoMAb control towards the feedstock variations was assessed by a mechanistic model developed by us. The effects of target protein and impurities under the variation range of ±10 mAU·min-1 on load amount, protein loss, process productivity, and resin capacity utilization were investigated. The results showed that the CaptureSMB process could be successfully controlled by AutoMAb towards increased or slightly decreased concentration of feedstock. However, the load process would be out of control with drastically decreased target protein or impurities, and the decreased impurities would lead to protein loss. It was found that AutoMAb control would cause 44.7% non-operational areas and 18.3% protein loss areas in the variation range of ±10 mAU·min-1. To improve the stability of the CaptureSMB process, a modified AutoMAb control that would stop the load procedure when the absolute value of the integral area reached the preset value, was proposed to reduce the risk of protein loss and the non-operational area.

Key words: Continuous chromatography, Process control, Feedstock variations, Mechanistic modeling, Purification

摘要: Dynamic control is essential to guarantee the stable performance of continuous chromatography. AutoMAb dynamic control strategy has been developed to ensure a consistent protein load in twin-column CaptureSMB continuous capture by integrating the UV signal of breakthrough. In this study, the process risk of CaptureSMB continuous capture under AutoMAb control towards the feedstock variations was assessed by a mechanistic model developed by us. The effects of target protein and impurities under the variation range of ±10 mAU·min-1 on load amount, protein loss, process productivity, and resin capacity utilization were investigated. The results showed that the CaptureSMB process could be successfully controlled by AutoMAb towards increased or slightly decreased concentration of feedstock. However, the load process would be out of control with drastically decreased target protein or impurities, and the decreased impurities would lead to protein loss. It was found that AutoMAb control would cause 44.7% non-operational areas and 18.3% protein loss areas in the variation range of ±10 mAU·min-1. To improve the stability of the CaptureSMB process, a modified AutoMAb control that would stop the load procedure when the absolute value of the integral area reached the preset value, was proposed to reduce the risk of protein loss and the non-operational area.

关键词: Continuous chromatography, Process control, Feedstock variations, Mechanistic modeling, Purification