Parth Shah, Satchit Nagpal, Dong Hun Kwak, Jung Ho Kim, J. Cho, Jun‐Woo Kim, Kosan Roh, Sang Min Park, Joseph Sang‐Il Kwon
Spatial gradients arising from incomplete mixing are a major challenge in large-scale fermenters, often leading to non-uniform substrate and oxygen availability, suppressed productivity, and economic inefficiencies. This study presents a dynamic compartment modeling framework, developed using an axisymmetric CFD model and integrated with a detailed kinetic model, to investigate the process-level impact of impeller configuration in a 525 m 3 industrial reactor. The compartment model evolves dynamically over time using discrete, quasi-steady CFD snapshots at multiple reactor volumes, enabling prediction of spatiotemporal distributions of biomass, substrates, product, and dissolved oxygen. The kinetic submodel includes dual-substrate Monod kinetics, product inhibition, and oxygen uptake. We apply this framework to evaluate two representative industrial impeller height configurations, previously identified by plant engineers as contributing to different productivity outcomes. Simulation results align with plant-scale trends, confirming that higher impeller placement improves axial circulation, increases k L a , and leads to a 7.5% higher product mass and a 4.5% higher volumetric productivity. Economic translation of these improvements indicates a projected cost reduction of approximately 5%–6% per ton of product. This study demonstrates a comparative analysis of different reactor designs and hydrodynamic conditions to assess their impact on bioreactor performance. By evaluating how variations in the flow field and oxygen transfer affect productivity, the study aims to identify conditions that lead to improved performance without applying formal optimization methods.