A supervision and control tool based on artificial intelligence for high cell density cultivations

High cell density cultivations of recombinant E. coli have been increasingly used for the production of heterologous proteins. However, it is a challenge to maintain these cultivations within the desired conditions, given that some variables such as dissolved oxygen concentration (DOC) and feed flow rate are difficult to control. This paper describes the software SUPERSYS_HCDC, a tool developed to supervise fed-batch cultures of rE. coli with biomass concentrations up to 150 gDCW/L and cell productivities up to 9 gDCW.L-1.h-1. The tool includes automatic control of the DOC by integrated action of the stirrer speed as well as of the air and oxygen flow rates; automatic start-up of the feed flow of fresh medium (system based on a neural network committee); and automatic slowdown of feeding when oxygen consumption exceeds the maximum capacity of the oxygen supply.