Model predictive control and moving horizon estimation for adaptive optimal bolus feeding in high-throughput cultivation of \textit{E. coli}

Abstract: We discuss the application of a nonlinear model predictive control (MPC) and a moving horizon estimation (MHE) to achieve an optimal operation of \textit{E. coli} fed-batch cultivations with intermittent bolus feeding. 24 parallel experiments were considered in a high-throughput microbioreactor platform at a 10 mL scale. The robotic island in question can run up to 48 fed-batch processes in parallel with automated liquid handling and online and at-line analytics. The implementation of the model-based monitoring and control framework reveals that there are mainly three challenges that need to be addressed; First, the inputs are given in an instantaneous pulsed form by bolus injections, second, online and at-line measurement frequencies are severely imbalanced, and third, optimization for the distinctive multiple reactors can be either parallelized or integrated. We address these challenges by incorporating the concept of impulsive control systems, formulating multi-rate MHE with identifiability analysis, and suggesting criteria for deciding the reactor configuration. In this study, we present the key elements and background theory of the implementation with \textit{in silico} simulations for bacterial fed-batch cultivation.