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

Beichen Zhao; Xueliang Li; Wanqiang Sun; Juntao Qian; Jin Liu; Minjie Gao; Xin Guan; Zhenwu Ma; Jianghua Li

LAPSE

Living Archive for Process Systems Engineering

LAPSE:2023.35291

Published Article

LAPSE:2023.35291

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

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

April 28, 2023

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.

Record ID

LAPSE:2023.35291

Keywords

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

Subject

Modelling and Simulations

Suggested Citation

Zhao B, Li X, Sun W, Qian J, Liu J, Gao M, Guan X, Ma Z, Li J. BioDT: An Integrated Digital-Twin-Based Framework for Intelligent Biomanufacturing. (2023). LAPSE:2023.35291

Author Affiliations

Zhao B: Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, China; Science Center for Future Foods, Jiangnan University, Wuxi 214122, China
Li X: Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, China; Science Center for Future Foods, Jiangnan University, Wuxi 214122, China; T&J Bioengineering (Shanghai) Co., Ltd., Shanghai 201611, China
Sun W: Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, China; Science Center for Future Foods, Jiangnan University, Wuxi 214122, China
Qian J: T&J Bioengineering (Shanghai) Co., Ltd., Shanghai 201611, China
Liu J: T&J Bioengineering (Shanghai) Co., Ltd., Shanghai 201611, China
Gao M: Key Laboratory of Carbohydrate Chemistry and Biotechnology of Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China
Guan X: Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, China; Science Center for Future Foods, Jiangnan University, Wuxi 214122, China [ORCID]
Ma Z: College of Mechanical Engineering, Suzhou University of Science and Technology, Suzhou 215009, China
Li J: Science Center for Future Foods, Jiangnan University, Wuxi 214122, China; Key Laboratory of Carbohydrate Chemistry and Biotechnology of Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China

Journal Name

Processes

Volume

11

Issue

4

First Page

1213

Year

2023

Publication Date

2023-04-14