A coupled population balance model and CFD approach for the simulation of mixing issues in lab‐scale and industrial bioreactors

Lab‐scale (70 L) and industrial scale (70 m 3 ) aerated fermenters are simulated using a commercial computational fluid dynamics code. The model combines an Euler‐Euler approach for the two‐phase flow, a population balance model for biological adaptation to concentration gradients, and a kinetic model for biological reactions. Scale‐up at constant volumetric mass transfer coefficient is performed, leading to concentration gradients at the large scale. The results show that for a given concentration field and a given circulation time t c , the population (physiological) state depends on the characteristic time of biological adaptation T a . The population specific growth rate (T a ≫t c ) is found independent of the spatial location and closely related to the volume average concentration. Oppositely, the population specific uptake rate (T a ∼t c ) is spatially heterogeneous. The resulting local disequilibria between the uptake rate and the growth rate provide an explanation for the decreased performances of poorly macromixed industrial bioreactors.