Microfluorometric and ENG'G Analyses of Immobilized Recom- binant Cell Systems

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Genetically engineered cells hold promise for production of a wide range of biologically important compounds under relatively mild and controllable bioreactor conditions. The immobilization of genetically engineered cells is now being considered more frequently in industry, as this configuration allows the presence of a high concentration of the biological catalyst (the cells), and thus holds promise for high volumetric production rates. The proposed research will apply the technique of scanning microfluorimetry to immobilized cell populations for the first time in order to answer the following questions: Does immobilization increase recombinant plasmid stability in succeeding generations? Does immobilization influence plasmid copy number, product formation rates, and cell metabolism? Can the measured biological rates be described with an extended version of a structured biochemical engineering model for recombinant cell metabolism, previously developed by one of the investigators for chemostat and other uniform environments? A novel high resolution fluorescence microscope will be used to examine genetically engineered bacterial cells grown to very high concentrations. The results from this research will allow design of more efficient reactors to take advantage of the many fundamental discoveries which the new biotechnology has produced. The present engineering research will assist the pace of commercialization of processes based on these novel biological systems, by providing quantitative observation of these cells under commercially realistic conditions.