Dynamics and Control of Oscillatory Bioreactors

Bioreactors are widely used in many industries to generate a range of products using various host cells e.g., yeast, insect, and mammalian cells. Depending on the process, product, and host cell, some bioreactors exhibit sustained periodic behavior in key process variables such as metabolite concentrations, biomass, and product titer. Such dynamical behavior can arise from different mechanisms, including predator-prey dynamics, substrate inhibition, and cell sub-population synchrony. Oscillatory dynamical behavior is undesirable as it can impact downstream processes, especially in a continuous operation, and can make process operations and product quality control more challenging. This article provides an overview of oscillatory dynamics. The mechanisms that give rise to the oscillations and process control strategies for suppressing the oscillations are discussed, while providing insights that go beyond past studies. Alternative process configurations are proposed for bypassing the mechanisms that generate oscillations.Comment: Submitted to Biotechnology Progress, ICB V Special Issue (invited). Pavan Inguva and Krystian Ganko contributed equally to this work. Corresponding author: Richard D. Braat

Mechanistic modeling to predict titers and infected cells in the two-stage continuous production of a viral vaccine

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