Experimental Validation of a Cascade Control Strategy for Continuously Perfused Animal Cell Cultures

Abstract

This paper is dedicated to the experimental validation of a cascade control strategy for simultaneously regulating the glucose and biomass levels in continuously perfused HEK-293 cell cultures. The inner loop consists of a partial feedback linearization, which requires the estimation of the biomass specific growth rate and glucose uptake rate. This latter task is achieved by sliding mode observers, which do not require a priori process knowledge in the form of a process model. The linearized process is then regulated by the outer loop, including two classical PI controllers with autotuning. The four manipulated variables are a feed flow rate with low glucose concentration, another feed flow with a higher glucose content, a bleed flow, and a perfusion stream. The experimental results demonstrate the ability of the control strategy to reach and regulate the prescribed setpoints. The main advantage of the strategy is that it can be applied in a plug and play manner and shows satisfactory robustness. To the best of our knowledge, this is the first time that such a multivariable control strategy, together with sliding mode observers, is applied at the lab scale to an industrial process in the pharmaceutical sector.