Real-time model correction using Kalman filter for Raman-controlled cell culture processes  

作　　者：Xiaoxiao Dong Zhuohong He Xu Yan Dong Gao Jingyu Jiao Yan Sun Haibin Wang Haibin Qu 

机构地区：[1]Pharmaceutical Informatics Institute,College of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310058,China [2]Hisun Biopharmaceutical Co.Ltd.,Hangzhou 311404,China

出　　处：《Chinese Journal of Chemical Engineering》2024年第6期251-260,共10页中国化学工程学报（英文版）

基　　金：supported by the Key Research and Development Program of Zhejiang Province,China(2023C03116).

摘　　要：Raman spectroscopy has found extensive use in monitoring and controlling cell culture processes.In this context,the prediction accuracy of Raman-based models is of paramount importance.However,models established with data from manually fed-batch cultures often exhibit poor performance in Raman-controlled cultures.Thus,there is a need for effective methods to rectify these models.The objective of this paper is to investigate the efficacy of Kalman filter(KF)algorithm in correcting Raman-based models during cell culture.Initially,partial least squares(PLS)models for different components were constructed using data from manually fed-batch cultures,and the predictive performance of these models was compared.Subsequently,various correction methods including the PLS-KF-KF method proposed in this study were employed to refine the PLS models.Finally,a case study involving the auto-control of glucose concentration demonstrated the application of optimal model correction method.The results indicated that the original PLS models exhibited differential performance between manually fed-batch cultures and Raman-controlled cultures.For glucose,the root mean square error of prediction(RMSEP)of manually fed-batch culture and Raman-controlled culture was 0.23 and 0.40 g·L^(-1).With the implementation of model correction methods,there was a significant improvement in model performance within Raman-controlled cultures.The RMSEP for glucose from updating-PLS,KF-PLS,and PLS-KF-KF was 0.38,0.36 and 0.17 g·L^(-1),respectively.Notably,the proposed PLS-KF-KF model correction method was found to be more effective and stable,playing a vital role in the automated nutrient feeding of cell cultures.

关 键 词：Raman spectroscopy Model correction Algorithm Model-predictive control BIOPROCESS 

分 类 号：O657.37[理学—分析化学] Q813.11[理学—化学]