Coupling Between Cell Kinetics and CFD to Establish Physio-Hydrodynamic Correlations in Various Stirred Culture Systems

Abstract

According to the recent increase of the culture volumes of industrial processes using animal cells, it becomes necessary to precisely study the reactor hydrodynamics. Indeed, scale-up rules have to integrate hydrodynamic stress distributions to be more reliable. The aim of our work was to establish new correlations between pertinent hydrodynamic parameters and cellular physiology data obtained by suspension cell cultures study. Global kinetic response of recombinant CHO cells to various agitation rates, in spinner flasks and in stirred tank reactors, were studied. Reactors hydrodynamics was described using Computational Fluid Dynamics (CFD) and validated by Laser Doppler Velocimetry (LDV). The results revealed, contrary to the commonly admitted idea, a beneficial effect of increased agitation rates on cell growth. Moreover, by coupling experimental and numerical results, original physio-hydrodynamic correlations were established for both cell culture systems. It is thus possible to propose an integrated and innovative method for reactor scale-up by using the Kolmogorov theory of turbulence and CFD simulations.