(727d) Hybrid Agent-Based Framework Towards Virtual Cell Culture Bioreactors

Manufacturing complex therapeutic proteins requires unique operational conditions and highly specialized process knowledge to obtain consistent product quality and productivity. Optimization and control of these processes are challenging due to complexity involved in the interactions between mammalian cell metabolism and the bioreactor environment. These interactions become even more critical for large-scale bioreactors where cellular and fluid phases are heterogeneous.

Understanding hydrodynamic influence on culture viability and productivity is crucial. Mammalian cells are highly sensitive to shear stress and its damaging effect. In order to reduce the shear exposure of cell, mammalian bioreactors often operate with low agitation speeds that may cause further increase in the presence of spatial gradients and mass transfer limitations. This in term may further impact cell cycle of the individual cells, leading to sub-optimal growth.

Due to the complexity and heterogeneity involved in the culture environment, conventional mechanistic modeling efforts are often incomplete when used to describe the interactions of cell physiology and environmental conditions. Hybrid computational models provide a better approach for studying mammalian cell culture bioreactor processes where environmental factors and cellular interactions may be coupled. Agent-based modeling is a natural choice to account for the heterogeneity in the cell population where agents (cells) take action based on changing dynamics of their immediate vicinity. These models provide more realistic description of process when coupled with computational fluid dynamics (CFD) models. An ABM was previously developed to simulate individual mammalian cell behavior and its cell cycle regulation in response to dynamic bioreactor conditions (Bayrak et al., 2015). In the current study, this model has been further developed and combined with a CFD model to account for the mass transport of nutrients and oxygen and shear stress on individual cells.

Reference

Bayrak, E. S., Wang, T., Cinar, A. & Undey, C. Computational Modeling Of Fed-Batch Cell Culture Bioreactor: Hybrid Agent-Based Approach.  International Symposium On Advance Control Of Chemical Processes, June 7-10 2015 Canada.