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. MRI (Metabolic Rate Index) is a dynamic Process Variable generated in real time by the system that describes the overall state of the metabolic environment of the process under observation. 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 expression phases for each feeding event<b>. </b>MRI data acquired by the system is used to construct an automatic feeding protocol that responds to changes in the media composition caused by the target organism’s consumption of limiting nutrients. The resulting automatic protocol maintains an optimum concentration of nutrients determined in real time in order to produce high quality, high yield product. Very little <i>a priori</i> knowledge is required to successfully use the technology. New protocols that describe application of the Ranger to multiple feeds and to continuous and perfusion systems will be described. 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.

Automatic bioreactor feeding: Moving forward with metabolic activity monitoring for nutrient feeding

251st National Meeting (2016)

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