Recent advances in automated nutrient feeding for fermentors - using MRI to monitor and control metabolic activity

A novel bioprocess control system and method for in-situ, real time, dynamic monitoring and control of nutrient feeding in upstream bioreactors and fermentors is described.  The system generates a dynamic, real time Process Variable, MRI (Metabolic Rate Index), that measures, tracks, and controls the overall state of the metabolic environment of the process.  MRI is highly sensitive to any molecular level perturbation in the process media, such as occurs when a biological process is fed nutrients and carbon sources and subsequently during the consumption and product expression phases for each feeding event.  MRI data acquired by the system automatically constructs an adaptive feeding protocol that responds to changes in the media composition caused by the target organism’s consumption of limiting nutrient(s) and maintains an optimum concentration of nutrients determined to produce high quality, high yield product. Minimal a priori knowledge is required to successfully adopt the technology. The system is applicable to all scales of operation from process development to commercial production and is compatible with SUBs. This technology is applicable in microbial, fungal, and mammalian cultures.  Examples of applications will be shown.