大数据-模型混合驱动下生物过程优化与放大的新机遇与挑战  

New opportunities and challenges for hybrid data and model driven bioprocess optimization and scale-up

作　　者：王冠 田锡炜[1,2,3] 夏建业 储炬[1,2,3] 张嗣良 庄英萍[1,2,3] Guan Wang;Xiwei Tian;Jianye Xia;Ju Chu;Siliang Zhang;Yingping Zhuang(State Key Laboratory of Bioreactor Engineering,Shanghai 200237,China;School of Bioengineering,East China University of Science and Technology,Shanghai 200237,China;National Center of Bio-Engineering&Technology(Shanghai),Shanghai 200237,China)

机构地区：[1]生物反应器工程国家重点实验室,上海200237 [2]华东理工大学生物工程学院,上海200237 [3]国家生化工程技术研究中心(上海),上海200237

出　　处：《生物工程学报》2021年第3期1004-1016,共13页Chinese Journal of Biotechnology

基　　金：国家自然科学基金(Nos.31900073,21978085);上海市自然科学基金(No.19ZR1413600)资助。

摘　　要：当前,生物制造技术和产业是世界关注的热点。然而,生物过程优化与放大过程中普遍面临以下几个难题,包括:过程检测手段缺乏,难以满足关键指标参数的监控;细胞代谢认知匮乏,无法理性实现过程最优化调控;反应器环境差异大,导致逐级放大效率低下。文中针对以上亟待解决的关键问题,通过案例分析介绍发酵过程实时检测-动态调控-理性放大全链条关键技术创新。在未来,生物过程设计将以集成细胞生理学(时空多尺度细胞代谢模型)和流体动力学(CFD模型)的全生命周期模型为指导,推进计算机辅助设计与开发,加速生物过程实现大规模智能化生产,开启绿色生物制造新时代。Currently,biomanufacturing technology and industry are receiving worldwide attention.However,there are still great challenges on bioprocess optimization and scale-up,including:lacing the process detection methods,which makes it difficult to meet the requirement of monitoring of key indicators and parameters;poor understanding of cell metabolism,which arouses problems to rationally achieve process optimization and regulation;the reactor environment is very different across the scales,resulting in low efficiency of stepwise scale-up.Considering the above key issues that need to be resolved,here we summarize the key technological innovations of the whole chain of fermentation process,i.e.,real-time detection-dynamic regulation-rational scale-up,through case analysis.In the future,bioprocess design will be guided by a full lifecycle in-silico model integrating cellular physiology(spatiotemporal multiscale metabolic models)and fluid dynamics(CFD models).This will promote computer-aided design and development,accelerate the realization of large-scale intelligent production and serve to open a new era of green biomanufacturing.

关 键 词：新型传感器 动态调控 智能生物制造 理性放大 代谢模型 

分 类 号：TQ920.1[轻工技术与工程—发酵工程]