Large-Eddy Simulations of microcarrier exposure to potentially damaging eddies inside mini-bioreactors

Mechanically stirred vessels equipped with rotating impellers generate heterogeneous transitional or turbulent flows. However, some cells as animal or human mesenchymal stem cells (hMSC) adhered on microcarriers, are reputed sensitive to hydromechanical stresses arising from stirring. Many publications, especially using Computational Fluid Dynamics, characterize spatial fields of velocity and turbulence inside bioreactors but the exposure frequency to these stresses is never taken into account in the case of animal cell culture bioreactor description. To fill this gap, this study used both CFD Reynolds-Averaged and Large-Eddy Simulations to characterize the hydrodynamics inside 250 mL mini-bioreactors, which is a relevant volume for hMSC cultures. Five impeller geometries were studied. From the velocity and turbulence fields calculated, an energy dissipation/circulation function, related to both frequency and intensity of potentially damaging hydrodynamic events for the cells, was determined for various operating conditions. Based on the simulation results, the marine propeller operating in up-pumping mode seems to be the most adapted condition, since it exhibits a low frequency of exposure to an acceptable intensity of the turbulent dissipation rate. From a general point of view, the new methodology proposed should be used in the future to screen the most adapted bioreactor geometry to biological constraints.