Using computational fluid dynamics software to estimate circulation time distributions in bioreactors.

Nonideal mixing in many fermentation processes can lead to concentration gradients in nutrients, oxygen, and pH, among others. These gradients are likely to influence cellular behavior, growth, or yield of the fermentation process. Frequency of exposure to these gradients can be defined by the circulation time distribution (CTD). There are few examples of CTDs in the literature, and experimental determination of CTD is at best a challenging task. The goal in this study was to determine whether computational fluid dynamics (CFD) software (FLUENT 4 and MixSim) could be used to characterize the CTD in a single-impeller mixing tank. To accomplish this, CFD software was used to simulate flow fields in three different mixing tanks by meshing the tanks with a grid of elements and solving the Navier-Stokes equations using the kappa-epsilon turbulence model. Tracer particles were released from a reference zone within the simulated flow fields, particle trajectories were simulated for 30 s, and the time taken for these tracer particles to return to the reference zone was calculated. CTDs determined by experimental measurement, which showed distinct features (log-normal, bimodal, and unimodal), were compared with CTDs determined using CFD simulation. Reproducing the signal processing procedures used in each of the experiments, CFD simulations captured the characteristic features of the experimentally measured CTDs. The CFD data suggests new signal processing procedures that predict unimodal CTDs for all three tanks.