Probing control of fed-batch cultivations: analysis and tuning

Abstract Production of various proteins can today be made using genetically modified Escherichia coli bacteria. In cultivations of E. coli it is important to avoid accumulation of the by-product acetate. Formation of acetate occurs when the specific glucose uptake exceeds a critical value and can be avoided by a proper feeding strategy. A difficulty is that the critical glucose uptake often is poorly known and even time varying. We here analyze an approach for control of glucose feeding that enables feeding at the critical glucose uptake without prior information. The key idea is to superimpose a probing signal to the feed rate in order to obtain information used to determine if the feed rate should be increased or decreased. The main contribution of this paper is to derive guidelines for tuning of the probing controller. A sufficient condition for stability is presented. By introducing proportional and proportional–integral control action it is possible to improve performance with an unchanged stability guarantee. This also gives a possibility to maintain a minimum specified distance to the critical glucose uptake where acetate formation starts.