On-line control of feeding of medium components to attain high cell density

On line control coupled with an expert system was constructed for the control of a fed-batch culture with the aim of achieving a high cell density. During the cultivation, the expert system could monitor the extents of sufficiencies in the amounts of chemical elements in the medium every 10 min, and suggest a modification to the feeding control policy if the amount of a particular component was inadequate for cell growth. However, we often encounter such a kind of cultivations in which some particular carbon source such as glucose and ethanol should be controlled at low concentration in many culture processes, because the excess feeding might cause the growth inhibition by its own accumulation in the culture broth, or the biproduct accumulation like as lactate or acetate, unsuitable substances for smoothed growth. In this study, we developed an online control system based on production rules which managed the glucose feed rate from DO signal. The online control was carried out by the control computer connected with the other computer for expert system, because a relatively long time (several minutes) was needed for the inference of the expert system and the influence of the starvation of carbon source on the cell growth is not negligible even in several minutes. The on-line control system with expert system was applied to the production of cell mass of E. coli W3110 and the final cell concentration reached 137 g-dry cell weight/l.