CHOLife+: Multiscale experimental analysis and simulation of lifelines in bioreactors to study their impact on the cultivation performance of Chinese Hamster Ovary (CHO) cells

CHOLife：对生物反应器中的生命线进行多尺度实验分析和模拟，以研究其对中国仓鼠卵巢（CHO）细胞培养性能的影响

• 批准号: 427899833
• 负责人: Professor Dr.-Ing. Michael Schlüter
• 金额: --
• 依托单位: Institut für Bioverfahrenstechnik (IBVT)
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/427899833?language=en
• 关键词: CHOLife+; Multiscale; experimental; analysis; simulation

CHOLife+ aims to continue the successful collaboration between the teams at the Institutes of Multiphase Flows (IMS) and Biochemical Engineering (IBVT) funded during the first phase of SPP2170 by advancing their newly developed technologies on a high level of maturity and application. The topic of scaling up/down, a vital pillar of the current call, is still centered and show-cased by the application of Chinese Hamster Ovary (CHO) cells producing IgG-1 antibodies. Exploiting the unique access to a 12000 L bioreactor at IMS the crucial question of at-line particle tracking was successfully investigated providing first-of-its-kind lifeline data that allow a most valuable comparison between hydrodynamic simulation and wet-lab measurements. Thereupon, the fundamentally renewed concept of a single multi-compartment bioreactor (SMCB) was developed at IBVT leading to the novel model driven design of a scale-down bioreactor for mammalian cell bioprocesses.CHOLife+ advances this concept further by intensified particle tracking of Lagrangian sensor particles (LSP) and hydrodynamic modelling in the 12000L scale. Intrinsically, research activities at IMS and IBVT are intertwined by the compartment-specific mixing times τi and volumes Vi that are identified in large-scale at IMS and that are used as design guideline for the SMCB at IBVT. Resulting SMCBs will be used for wet-lab tests with CHO cells enabling data-driven modeling of cellular response. Thereupon, strain performance will be predicted in SMCB and in large scale by uni-directional model coupling with particle lifelines.

CHOLife+的目标是继续在SPP2170第一阶段资助的多相流研究所（IMS）和生化工程研究所（IBVT）的团队之间的成功合作，通过推进他们在高成熟度和应用水平上开发的新技术。放大/缩小的主题是当前呼吁的一个重要支柱，仍然以中国仓鼠卵巢（CHO）细胞产生IgG-1抗体的应用为中心和展示。利用IMS 12000 L生物反应器的独特通道，成功研究了近线粒子跟踪的关键问题，提供了同类首个生命线数据，可以在流体动力学模拟和湿实验室测量之间进行最有价值的比较。因此，IBVT从根本上更新了单一多室生物反应器（SMCB）的概念，从而导致了哺乳动物细胞生物过程的新型模型驱动生物反应器的设计。CHOLife+通过加强拉格朗日传感器粒子（LSP）的粒子跟踪和12000L尺度的流体动力学建模，进一步推进了这一概念。从本质上讲，IMS和IBVT的研究活动与特定隔间的混合时间τi和体积Vi交织在一起，这些时间τi和体积Vi是IMS大规模确定的，并用作IBVT SMCB的设计准则。由此产生的smcb将用于CHO细胞的湿实验室测试，从而实现细胞反应的数据驱动建模。在此基础上，将单向模态与颗粒生命线相耦合，预测单向模态在SMCB和大尺度下的应变性能。