Combined Metabolic and Cell Population Modeling for Yeast Bioreactor Control

Several investigators recently have explored the use of cell population balance equation (PBE) models for the design of biochemical reactor control strategies. A major disadvantage of the PBE modeling approach is that the incorporation of intracellular reactions needed to accurately describe cellular processes leads to substantial computational difficulties. We investigate an alternative modeling technique in which the cell population is constructed from an ensemble of individual cell models. The average value or the number distribution of any intracellular property captured by the cell model can be computed from ensemble simulation data. To illustrate the basic procedure, a single cell model of yeast glycolytic oscillations is used to construct large cell ensembles for the investigation of cell population synchronization. The potential use of cell ensemble models for bioreactor controller design are discussed.