Adaptive fuzzy control of mammalian cell culture in fed-batch reactor for production of an antithrombin III variant

摘要

An adaptive fuzzy controller was developed to control the glucose and glutamine concentrations in the reactor constant at the desired level. It was applied to antithrombin III production from a recombinant BHK anchorage-dependent cell line performed in a fed-batch reactor on-line connected with an HPLC system. From six experiments with various set points, it was found that ammonia had a determining effect on productivity and its production was increased by an increase of glutamine or decrease of glucose set point concentrations. A combination of low glutamine with high glucose concentration was more efficient in maximizing the cell concentration and protein productivity.