Effective Dissolved Oxygen Control Strategy for High-Cell-Density Cultures

Abstract

Dissolved oxygen control is critical to ensure microorganisms' growth in high-cell-density cultures. Since biological oxygen consumption strongly depends on biomass concentration, high-cell-density cultures demand an increasing and continuous oxygen supply. This is a challenging control problem and one of the major limitations of this type of cultures. The aim of this paper is to provide a simple dissolved oxygen control strategy capable of achieving high biomass levels by manipulating three process variables: agitation, aeration and oxygenation. This strategy was developed using a split-range control scheme specially designed so that the controller action is linear with respect to the maximum transfer rate (kLa•DO*). The controller parameters were tuned through simulation and later implemented and validated in Escherichia coli fed-batch cultivations. The strategy presented here allowed reaching high biomass concentrations while maintaining oxygen concentration at an appropriate level. The implementation of this strategy in high-cell-density cultures will help improve the productivity of aerobic cultures.