New Insights from Locally Resolved Hydrodynamics in Stirred Cell Culture Reactors

Abstract

The link between hydrodynamics and biological process behavior of antibody-producing mammalian cell cultures is still not fully understood. Common methods to describe dependencies refer mostly to averaged hydrodynamic parameters obtained for individual cultivation systems. In this study, cellular effects and locally resolved hydrodynamics were investigated for impellers with different spatial hydrodynamics. Therefore, the hydrodynamics, mainly flow velocity, shear rate and power input, in a single- and a three-impeller bioreactor setup were analyzed by means of CFD simulations, and cultivation experiments with antibody-producing Chinese hamster ovary (CHO) cells were performed at various agitation rates in both reactor setups. Within the three-impeller bioreactor setup, cells could be cultivated successfully at much higher agitation rates as in the single-impeller bioreactor, probably due to a more uniform flow pattern. It could be shown that this different behavior cannot be linked to parameters commonly used to describe shear effects on cells such as the mean energy dissipation rate or the Kolmogorov length scale, even if this concept is extended by locally resolved hydrodynamic parameters. Alternatively, the hydrodynamic heterogeneity was statistically quantified by means of variance coefficients of the hydrodynamic parameters fluid velocity, shear rate, and energy dissipation rate. The calculated variance coefficients of all hydrodynamic parameters were higher in the setup with three impellers than in the single impeller setup, which might explain the rather stable process behavior in multiple impeller systems due to the reduced hydrodynamic heterogeneity. Such comprehensive insights lead to a deeper understanding of the bioprocess.