Modeling heterogeneity in large-scale bioreactors using the method of moments with a truncated normal distribution

Abstract

Large-scale bioreactors in industrial bioprocesses pose challenges due to extracellular concentration gradients and intracellular heterogeneity. This study introduces a novel approach integrating the method of moments with truncated normal distributions (MM-TND) to model intracellular heterogeneity while maintaining computational feasibility compared to continuum simulations. The MM-TND framework reconstructs intracellular state distributions while respecting physical constraints, which previous methods could not ensure. Validation against experimental data confirms that MM-TND effectively captures microbial population dynamics, particularly in large-scale systems where convection and metabolic adaptation timescales are comparable. The results underscore the importance of intracellular heterogeneity in bioprocess modeling and highlight computational advantages of the MM-TND approach. This approach offers valuable insights into microbial behavior under industrially relevant conditions.