An oxygen-uptake-rate-based estimator of the specific growth rate in Escherichia coli BL21 strains cultivation processes

The cell cultivation process in a bioreactor is a high-value manufacturing process that requires excessive monitoring and control compatibility. The specific cell growth rate is a crucial parameter that describes the online quality of the cultivation process. Most methods and algorithms developed for online estimations of the specific growth rate controls in batch and fed-batch microbial cultivation processes rely on biomass growth models. In this paper, we present a soft sensor – a specific growth rate estimator that does not require a particular bioprocess model. The approach for online estimation of the specific growth rate is based on an online measurement of the oxygen uptake rate. The feasibility of the estimator developed in this study was determined in two ways. First, we used numerical simulations on a virtual platform, where the cell culture processes were theoretically modeled. Next, we performed experimental validation based on laboratory-scale (7, 12, 15 L) bioreactor experiments with three different Escherichia coli BL21 cell strains.