(734g) Structurally Optimized Microbioreactors: A Design Example for Immobilized Yeast Cultivations

During the last decade there has been a clear interest in using microfluidic systems for cultivation of microorganisms. This works exploits the increased design flexibility offered by microsystems for optimizing the operation of a microbioreactor. In this optimization project, the production of a recombinant protein in a continuous culture of immobilized Saccharomyces cerevisiae was used as a case study. A topology optimization methodology [1] was applied in order to obtain the spatial distribution of immobilized yeast that maximizes protein concentration at the outlet. Although yeast is typically cultivated as a suspension, immobilized S. cerevisiae has been successfully used in continuous and stable cultivations [2]. In the chosen case study, a population of yeast grows at steady state on a carrier and is partially released into the flow phase forming a suspended population. A plasmid-encoded recombinant protein is produced when yeast consumes glucose. However, at high glucose concentrations, respiration becomes limiting and glucose is preferably fermented to ethanol. Furthermore, when glucose is depleted, ethanol is consumed and its oxidation leads to further production of the protein. These events were translated into a mathematical model based on two models available in the literature describing the growth of a brewing yeast biofilm [2] and an aerobic culture of a recombinant yeast [3], respectively and the model was incorporated into the topology optimization routine. The maximum local protein production rate was set as the optimization target, which results in a maximization of the protein concentration at the reactor outlet. In order to benchmark the optimized solutions obtained for various feed concentrations, protein concentrations at the optimized reactor outlet were compared to the corresponding concentrations obtained for reactors where the immobilized biomass was homogeneously distributed. For a glucose feed concentration of 0.1 g/L, an increase of nearly 10 fold was observed for the optimized yeast distribution.

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