Dynamics and Control of Oscillatory Bioreactors

TL;DR

This paper reviews oscillatory behaviors in bioreactors, exploring their mechanisms, impacts on process control, and proposing strategies and configurations to suppress undesirable oscillations for improved industrial bioprocessing.

Contribution

It offers a comprehensive overview of oscillatory dynamics in bioreactors, including mechanisms, control strategies, and novel process configurations to mitigate oscillations.

Findings

Oscillations arise from predator-prey dynamics, substrate inhibition, and cell synchrony.

Oscillatory behavior can negatively affect product quality and process stability.

Proposed alternative configurations can bypass oscillation mechanisms.

Abstract

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.