Dynamic optimization of bioreactors using probabilistic tendency models and Bayesian active learning

Due to the complexity of metabolic regulation, first-principles models of bioreactor dynamics typically have built-in errors (structural and parametric uncertainty) which give rise to the need for obtaining relevant data through experimental design in modeling for optimization. A run-to-run optimization strategy which integrates imperfect models with Bayesian active learning is proposed. Parameter distributions in a probabilistic model of bioreactor performance are re-estimated using data from experiments designed for maximizing information and performance. The proposed Bayesian decision-theoretic approach resorts to probabilistic tendency models that explicitly characterize their levels of confidence. Bootstrapping of parameter distributions is used to represent parametric uncertainty as histograms. The Bajpai & Reuss bioreactor model for penicillin production validated with industrial data is used as a representative case study. Run-to-run convergence to an improved policy is fast despite significant modeling errors as long as data are used to revise iteratively posterior distributions of the most influencing model parameters.

► Model-based design of experiments for run-to-run optimization with imperfect models. ► Bayesian optimal design of experiments in modeling for optimization. ► Active learning to trade-off information gain with performance improvement in biasing data gathering. ► Fast scale-up of operating policies for innovative bioprocesses.