Gas–liquid mass-transfer modeling in industrial-scale bioreactors: A standardized framework and critical assessment

Gas transfer often limits large-scale bioprocesses, demanding robust models for design, scale-up, and scale-down. This study establishes a standardized computational framework for gas–liquid mass-transfer modeling in industrial-scale bioreactors, integrating and evaluating the main sub-models governing kLa prediction — bubble dynamics, interfacial area, drag laws, and turbulence closures — within CFD simulations of a 134m3 bubble column and a 96m3 Rushton-impeller stirred tank. A systematic sensitivity analysis reveals that bubble size modeling (including pressure and coalescence corrections) and drag law selection are the dominant parameters controlling gas holdup and interfacial area, while kL correlations and bubble-induced turbulence models exert secondary but non-negligible influence on local extremes of kLa. Among tested formulations, the Grace–Simonnet drag law, hybrid (Higbie–Lamont–Scott) kL approach, and variable single-bubble-size model offered the best trade-off between physical realism and computational cost. The results are consolidated into a decision chart that ranks sub-model relevance and guides model selection based on reactor type and turbulence regime. This framework provides decision-ready guidance for reliable, scale-consistent CFD modeling of gas–liquid mass transfer in large-scale bioreactors.