Optimization of stirred animal cell bioreactor based on CFD-PBM

Abstract Stirred bioreactor has been widely used in biopharmaceutical field, and it is particularly important to understand the culture environment of animal cells in stirred bioreactor. This study, utilizing Computational Fluid Dynamics (CFD) in conjunction with the Population Balance Model (PBM), explores the effect of various operational conditions and impeller combinations (downward-pumping elephant ear impeller (EED) combined with a concave disc turbine impeller (CBDT), dual downward-pumping elephant ear impellers (EED-EED), and a combination of downward-pumping (EED) and upward-pumping (EEU) elephant ear impellers) on bioreactor performance, with the goal of developing a stirred bioreactor suited for animal cell culture. The findings reveal that increasing the stirring rate significantly enhances fluid circulation within the bioreactor, leading to an increase in gas holdup. Enhanced stirring rate and aeration not only facilitate bubble dispersion but also result in a significantly higher gas holdup in the lower part of the bioreactor compared to the upper part. Moreover, higher stirring rate also lead to larger bubble diameters. At the highest stirring rate, the maximum hydrodynamic stress in the bioreactor reaches 16 Pa, while the Kolmogorov length scale is smaller at high stirring rate. The EED-EEU demonstrates effective gas dispersion with uniform bubble distribution and minimal hydrodynamic stress; the EED-EED combination, while offering the best bubble dispersion, is associated with larger bubble diameters and higher hydrodynamic stress.