Probing control of fed-batch cultivations: analysis and tuning

Production of various proteins can today be made using genetically modified Escherichia coli bacteria. In cultivations of E. coli it is important to a void accumulation of the by-product acetate. Formation of acetate occurs wh en the specific glucose uptake exceeds a critical value and can be avoided by a proper feeding strategy. A difficulty is that the critical glucose upt ake often is poorly known and even time varying. We here analyze an approac h for control of glucose feeding that enables feeding at the critical gluco se uptake without prior information. The key idea is to superimpose a probi ng 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 o f this paper is to derive guidelines for tuning of the probing controller. A sufficient condition for stability is presented. By introducing proportio nal and proportional-integral control action it is possible to improve perf ormance with an unchanged stability guarantee. This also gives a possibilit y to maintain a minimum specified distance to the critical glucose uptake w here acetate formation starts. (C) 2001 Elsevier Science Ltd. All rights re served.