Topology optimized microbioreactors.

This article presents the fusion of two hitherto unrelated fields--microbioreactors and topology optimization. The basis for this study is a rectangular microbioreactor with homogeneously distributed immobilized brewers yeast cells (Saccharomyces cerevisiae) that produce a recombinant protein. Topology optimization is then used to change the spatial distribution of cells in the reactor in order to optimize for maximal product flow out of the reactor. This distribution accounts for potentially negative effects of, for example, by-product inhibition. We show that the theoretical improvement in productivity is at least fivefold compared with the homogeneous reactor. The improvements obtained by applying topology optimization are largest where either nutrition is scarce or inhibition effects are pronounced.

Application of microbioreactors in fermentation process development: a review.

Biotechnology process development involves strain testing and improvement steps aimed at increasing yields and productivity. This necessitates the high-throughput screening of many potential strain candidates, a task currently mainly performed in shake flasks or microtiter plates. However, these methods have some drawbacks, such as the low data density (usually only end-point measurements) and the lack of control over cultivation conditions in standard shake flasks. Microbioreactors can offer the flexibility and controllability of bench-scale reactors and thus deliver results that are more comparable to large-scale fermentations, but with the additional advantages of small size, availability of online cultivation data and the potential for automation. Current microbioreactor technology is analyzed in this review paper, focusing on its industrial applicability, and directions for future research are presented.