BioDT: An Integrated Digital-Twin-Based Framework for Intelligent Biomanufacturing

作     者：Zhao, Beichen Li, Xueliang Sun, Wanqiang Qian, Juntao Liu, Jin Gao, Minjie Guan, Xin Ma, Zhenwu Li, Jianghua 

作者机构：Jiangnan Univ Key Lab Ind Biotechnol Minist Educ Wuxi 214122 Peoples R China Jiangnan Univ Sci Ctr Future Foods Wuxi 214122 Peoples R China T&J Bioengn Shanghai Co Ltd Shanghai 201611 Peoples R China Jiangnan Univ Sch Biotechnol Key Lab Carbohydrate Chem & Biotechnol Minist Educ Wuxi 214122 Peoples R China Suzhou Univ Sci & Technol Coll Mech Engn Suzhou 215009 Peoples R China 

出 版 物：《PROCESSES》 (Process.)

年 卷 期：2023年第11卷第4期

页      面：1213页

核心收录：

基　　金：National Key R&D Program of China [2021YFC2101100] Innovative Research Groups Project of the National Natural Science Foundation of China [SNZJU-SIAS-0013] Starry Night Science Fund of Zhejiang University Shanghai Institute for Advanced Study 32021005 

主　　题：digital twin advanced process control process analytical technology Chinese hamster ovary (CHO) cells soft-sensor 3D-printing open-source software 

摘      要：The field of industrial biotechnology has shown an increasing interest in adopting digital twins for improving process productivity and management efficiency. Despite its potential benefits, digital-twin-based biomanufacturing has not been fully implemented. As a preliminary undertaking, we developed an open-source digital twin framework for cell culture. The core models of the digital twin were coded in C++ and compiled as a reusable Python library. A web-based, cloud-native HMI application that links the physical and virtual systems was developed. A microbioreactor digital twin system was implemented using the framework as a proof of concept. The system features a 3D-printed rocking platform that is customized to fit T25 flasks, enabling automated rocking rate and angle control and in-place optical cell density measurement. The digital twin was validated using Chinese Hamster Ovary (CHO) cells and was found to be able to predict the changes in cell density, glucose consumption, lactic acid production, and oxygen uptake rate (OUR). Finally, we performed a case study to demonstrate the system s practical applicability in Advanced Process Control (APC) by constructing real-time glucose and lactic acid soft sensors, which are in turn used to alert the operator for manual media change or for automated feeding.