Rational Fermentation Scaleup: Response of Metabolic Kinetics to Hydrodynamic Variability
Members: Iowa State University, Cargill, Geno
Project dates: 2022 - 2025
Computational fluid dynamic (CFD) modeling is used widely in the petroleum and chemicals industry for visualizing and predicting the behavior of fluids at large and small scales. CFD has great potential to aid in the commercialization and scale-up of bioprocesses by studying phase interactions in fermentation processes and identifying possible challenges that the microorganism could face in commercial-scale fermentation. But incorporating biological reactions into existing models is challenging due to slower metabolic reaction times when compared to fluid dynamics, as well as changing kinetics and oxygen sensitivity.
Through experimental testing and simulations, CFD experts at ISU partnered with Geno and Cargill to model and validate production of citramalate – a precursor used to make protective plexiglass – in stirred tank and bubble column reactors. Researchers evaluated factors including gas holdup, sparger configuration, agitation speed, and gas flow rate. The modeling effort in this project led to the formulation of a validated model for gas-liquid flows in bubble columns. Researchers successfully simulated bubble column fermenters both at the pilot- and production-scale, demonstrating the use of computation fluid dynamics to predict the scale-up of fermenters. Members can use this model and freely-available CFD simulation software to investigate the behavior of their fermenters of specific interest.
This unique project brought together academia with large and small businesses to solve problems facing the bioindustrial manufacturing industry at large, including risks related to fermentation scale-up. Researchers developed scaledown tools, guidelines, and best practices through simulation of manufacturing-scale fermentation processes in computational models and laboratory equipment. These approaches – which are translatable to different microbial strains and processes – will save money and time while improving success rates for users. A detailed whitepaper is available through the BioMADE Member Portal.
In this report, members can find resources on how CFD can support risk‑reduction in scale‑up and information on the capabilities and data infrastructure needed for broader industrial adoption, featuring an example analysis of a uniformly sparged bubble column evaluated at 0.5 m³ and 500 m³
Funding source: U.S. Department of Defense
