Multi-Scale Modeling of Heterogeneities in Mammalian Cell Culture Processes

Conventionally cell cultures are modeled using either structured/unstructured average cell models to capture the intracellular processes or population balance models (PBM) to account for the cell cycle propagation. The former is based on average cell population behavior and cannot describe the heterogeneities within, whereas the latter cannot alone probe into the detailed phenomena of intracellular metabolism. In this work, a multiscale modeling approach is proposed to unify the understanding of intracellular metabolism and the probabilistic nature of intercellular heterogeneities arising because of cell cycle apportioning. As a first step, average culture dynamics are described using an unstructured model encompassing cell growth, cell death, nutrient consumption, metabolite, and protein production and their dependency on various environmental factors. The model parameter identification is performed on the data obtained from the batch Chinese Hamster Ovary (CHO) cell cultures in spinner flasks. Then, a o...