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Abstract:The multi-fixed-bed bioreactor "Multiferm" provides a downscaled system for the development of fixed-bed processes with immobilized microorganisms or cells. It consists of twelve single fixed-bed units that can be operated independently. Different bacterial strains, carriers used for immobilization, media or flow rates can be studied in one compact experimental set-up. Experiments can be run in parallel to allow for determination of experimental errors. In these studies several continuous cultivations were carried out with Lactobacillus delbrueckii ssp. bulgaricus using different dilution rates and culture durations as proof-ofconcept for the Multiferm. Parameters relevant for process design such as reproducibility of simultaneously performed cultures, optimal dilution rate and long-term performance were determined by means of volume specific lactate and biomass productivity. First indications on a reduced growth rate of the cells due to immobilization were found.

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Fixed-bed processes, where cells are immobilized within macroporous carriers, are a promising alternative to processes with suspended cells. A scale-up concept is presented in order to evaluate the performance as part of process design of fixed-bed processes. Therefore, Lactococcus lactis cultivation in chemostat and batch mode was compared to fixed bed cultures on three different scales, the smallest being the downscaled Multiferm with 10 mL fixed bed units, the second a 100 mL fixed-bed reactor and the third a pilot scale reactor with 1 L fixed bed volume. As expected, the volume specific lactate productivity of all cultivations was dependent on dilution rate. In suspension chemostat culture a maximum of 2.3 g·L -1 ·h -1 was reached. Due to cell retention in the fixed-beds, productivity increased up to 8.29 g·L -1 ·h -1 at a dilution rate of D = 1.16 h -1 (corresponding to 2.4·µ max ) on pilot scale. For all fixed bed cultures a common spline was obtained indicating a good scale-up performance.

Fixed-bed processes operated in perfusion, where cells are immobilized within macroporous carriers, are a promising alternative to processes with suspended microbial or mammalian cells. Their potential has been demonstrated for many purposes. Nevertheless, the number of industrial fixed-bed processes is quite small. To some extent, this is due to the lack of process development tools for fixed-bed processes. To fill this gap, a strategy was developed for the design and evaluation of relevant process parameters of fixed-bed processes. A scale-up concept is presented in order to evaluate the performance as part of process design of fixed-bed processes. This comprises fixed-bed reactors on three different scales, the smallest being the downscaled Multiferm with 10 mL fixed-bed units, the second a 100 mL fixed-bed reactor, and the third a pilot-scale reactor with 1 L fixed-bed volume. The performance of this concept will be discussed for fixed-bed cultures of lactic acid bacteria. Furthermore, a reaction kinetic model for the design of fixed-bed reactors will be presented.