Simulation of bioreactor flow environments for large-scale animal cell culture conditions relevant to cultivated meat production

Abstract

Cultivated meat has the potential to mitigate many detrimental effects of conventional meat production on land use and greenhouse gas emissions. However, to meet an increasing demand for sustainable protein sources and to achieve cost parity with conventionally grown meat, animal cells will likely be required to be produced in bioreactors at an order of magnitude larger scale than has been done so far. To help de-risk this scale up, simulations of plausible bioreactor configurations were performed at a series of scales ranging from 200 L to 200,000 L using computational fluid dynamics. Several different bubble drag models were compared, and the one that predicted the lowest mass transfer and highest shear was used in order to be conservative about the predicted cell environment. The distributions of shear stress, oxygen mass transfer coefficient, and Kolmogorov length scale were compared across the bioreactor scales, showing only minor changes with increasing scale. The case of a Rushton and pitched impeller was compared to a case with two Rushton impellers, and the latter was found to have higher mass transfer and only slightly higher shear for a given power input. This study provides a step towards predicting animal cell culture performance at the scales needed for sustainable cultivated meat production.