Characterizing the Effect of Volume on Hydrodynamics of Plant Cell Suspensions Using CFD Modeling.

Biomass productivities in shake flasks are often not reproduced in bioreactors for plant cell cultures due to change in hydrodynamics. Considering shake flask biomass productivity as benchmark, this study employs shake flask geometries as a model system to understand hydrodynamic changes with volume and identify suitable scale-up criteria for plant cell cultivations, with minimal cost and time, given their slow growth time, using computational fluid dynamics (CFD) and experiments. Cultivation of Viola odorata cells in increasing flask volumes (100-3000 mL) revealed no significant change in biomass productivity. CFD analysis indicated that volumetric oxygen mass transfer coefficient (kLa), increased up to 1000 mL and then decreased, due to saturation of energy dissipation rates (kL is a function of energy dissipation rates) and decreasing interfacial area. The unaffected biomass concentration, despite decreased kLa, suggests that kLa may not be a significant scale-up parameter. Instead, maintaining a constant shear environment, indicated by power per unit volume saturation at higher volumes, was proposed as a suitable scale-up parameter for V. odorata cell cultivation in bioreactors. Moreover, the decrease in velocity difference between fluid layers with increased flask volume, indicated that minimizing velocity gradients in bioreactors could help achieve shake flask biomass productivity.