Development of a Computational Fluid Dynamics Model for Scaling-up Ambr Bioreactors

It is known that process scaling-up has always been a challenge in biopharmaceutical and food industry. In recent years, newly emerging microscale bioreactors like Ambr15 and Ambr250 have attracted significant attention for that they can provide high throughput and accelerate upstream process development. In this work, we developed the first multiphase Computational Fluid Dynamics (CFD) model for an in-depth characterization of Ambr bioreactor systems. A number of advanced computational methods, including Reynolds stress turbulence model, population balance model, multiple reference frame (MRF), sliding mesh (SM) and user defined functions (UDFs), were integrated for the first time to systematically study the gas-liquid mixing in Ambr250 bioreactor. We provided detailed comparison between MRF and SM method, demonstrated the limitation of MRF for predicting bubble distribution in asymmetric reactors. Characteristics of hydrodynamics, mass transfer, turbulent dissipation and bubble size distribution were predicted from our CFD models and validated by existing experimental data for a variety of operating conditions for both the Ambr15 and Ambr250 bioreactors. The predicted k(L)a value ranges are 0.18-7.90 h(-1) and 2.15-11.52 h(-1) for Ambr250 and Ambr15, respectively. This work thus provides a superior framework for the computational modeling of microscale stirred bioreactors.