Models for high cell density bioreactors must consider biomass volume fraction: Cell recycle example

Intrinsic models, which take into account biomass volume fraction, must be formulated for adequate simulation of high‐biomass‐density fermentations with cell recycle. Through comparison of corresponding intrinsic and non‐intrinsic models in dimensionless form, constraints for non‐intrinsic model usage in terms of biokinetic and fermenter operating parameters can be identified a priori. Analysis of a simple product‐inhibition model indicates that the non‐intrinsic approach is suitable only when the attainable biomass volume fraction in the fermentation broth is less than about 0.10. Inappropriate application of a non‐intrinsic model can lead to gross errors in calculated substrate and product concentrations, substrate conversion, and volumetric productivity.