(208a) In silico Design of a Commercial-Scale Bioreactor for Optimum Oxygen Transport Using Computational Fluid Dynamics (CFD)

In this work, a holistic in silico bioreactor model is employed to optimize oxygen mass transfer and homogeneity in a novel commercial scale stirred tank bioreactor using multiphase Computational Fluid Dynamics coupled with a Population Balance Model (CFD–PBM). The bubble population is represented by the Method of Moments (MOM) to account for bubble size distribution including breakup and coalescence of the bubbles. Hydrodynamics and species transport equations are solved to obtain oxygen mass transfer and its transport through the simulated cell culture media, and it includes a cellular oxygen uptake rate derived from a metabolic model of cell culture. The mass transfer coefficient is obtained using a combination of literature turbulent based theories and comparisons against experimental data for mass transfer (kla) measurements based on dissolved oxygen (DO) in the commercial scale bioreactor. The model is validated by comparing the numerically predicted kla values and the experimental data. The validated model is then applied to investigate kla and DO heterogeneities in the commercial bioreactor, in addition to oxygen transport performance optimal design. The model is used to iterate the underlying design more than 20 times, by running in excess of 200 simulations in a matter of weeks.