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+旨在继续在SPP 2170第一阶段资助的多相流研究所（IMS）和生物化学工程研究所（IBVT）之间的成功合作，通过在高水平的成熟度和应用上推进其新开发的技术。扩大/缩小规模的主题是当前呼吁的一个重要支柱，仍然以生产IgG-1抗体的中国卵巢（CHO）细胞的应用为中心和展示。利用IMS对12000 L生物反应器的独特访问，成功研究了在线颗粒跟踪的关键问题，提供了第一批生命线数据，允许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。基于此，IBVT开发了一个全新的多室生物反应器（SMCB）概念，从而为哺乳动物细胞生物过程的规模缩小生物反应器设计了新的模型驱动设计。CHOLife+通过强化拉格朗日传感器粒子（LSP）的粒子跟踪和12000 L规模的流体动力学建模进一步推进了这一概念。IMS和IBVT的研究活动与IMS大规模确定的特定隔室混合时间τi和体积Vi交织在一起，并用作IBVT SMCB的设计指南。所得SMCB将用于CHO细胞的湿实验室试验，从而实现细胞反应的数据驱动建模。在此基础上，通过与颗粒生命线耦合的单向模型，在SMCB和大尺度上预测应变性能。

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.