An experimental assessment of robust control and estimation of acetate concentration in Escherichia coli BL21(DE3) fed-batch cultures

Avoiding acetate accumulation is a major challenge in Escherichia coli fed-batch cultures, since it leads to an inhibition of the cell respiratory capacity. A closed-loop regulation ensuring a low acetate concentration offers a practical solution to maintain the cultures near the optimal operating conditions. In this work, a robust Generic Model Controller (GMC) is designed and implemented to regulate the acetate concentration in E. coli BL21 (DE3) fed-batch cultures. To compensate for model mismatch, disturbances, and measurement noise, a robust design using the LMI formalism is achieved, considering robustness and transient performance requirements. Since the acetate concentration is not available for on-line measurement, an Unscented Kalman Filter (UKF) is also designed and implemented to estimate the acetate concentration based on an on-line biomass measurement. The proposed GMC-UKF strategy is validated through simulation runs and experimental tests at lab-scale. The control strategy shows good performance in regulating the non-measured acetate concentration. The estimation of this latter signal from the biomass measurement is performed accurately by the UKF. •Acetate accumulation causes growth inhibition in Escherichia coli fed-batch cultures.•Closed-loop regulation ensures a low acetate concentration and improves productivity.•A robust control and estimation strategy of the acetate concentration is presented.•The proposed strategy performance is validated through numerical simulations.•Experimental validation on a lab-scale fed-batch fermentation of E. coli BL21(DE3).