(69f) Integrated Modeling of Bioreactors and Cell Growth to Evaluate Large-Scale Production of Cultivated Meat Cells

Large-scale commercialization of cultivated meat as an alternative protein source has the potential to help meet the growing global demand for meat in a more sustainable manner than an increase in conventional meat production alone. To be commercially viable, the animal cells for cultivated meat will have to be grown at an order of magnitude larger scale than has been previously accomplished in biopharma, likely using bioreactors on the order of 200,000 L. Experiments at that scale are prohibitively expensive, but computational modeling provides a faster and more cost-effective way of identifying what major factors will affect animal cell growth at these large scales. To develop these predictive models, we have applied computational fluid dynamics to model the hydrodynamics of a variety of bioreactor configurations. We have built CFD models using OpenFOAM to simulate multiphase aerated flow in stirred tank reactors. After first verifying reasonable agreement between the CFD models and hydrodynamic data obtained at smaller scales, we apply the model to larger scales and to different geometries and operating conditions. We also couple the CFD models with cell growth models based on appropriate animal cell types to identify which aspects of bioreactor design and operation are most likely to impact cell viability and proliferation at large scale. We will discuss our predictions of the impact of impeller geometry and configuration, air flow rate, and bioreactor geometry on shear forces, mixing, oxygen transfer, and dissolved carbon dioxide concentration at increasing scale.