ONLINE MONITORING OF PRODUCT CONCENTRATION BY FLOW-ELISA IN AN INTEGRATED FERMENTATION AND PURIFICATION PROCESS

Process integration involving fermentation with cell recycling, affinity adsorption to remove the product, and on-line process monitoring of the product were investigated. alpha-Amylase was produced in continuous and batch fermentations of Bacillus amyloliquefaciens with complete cell recycling, which was achieved using a membrane unit coupled to the fermenter. An affinity column of crosslinked starch was employed in the recycling loop to adsorb the alpha-amylase before the cell-free broth was recycled to the fermenter. The concentration of alpha-amylase in the cell-free broth prior to and after the affinity separation step was continuously registered using a flow-injection, immunochemical monitoring system. The different unit operations were integrated pair-wise, and eventually as a complete system. The complete feasibility of monitoring a macromolecular product on-line during a cultivation/adsorption process was also demonstrated.