| Summary: | Scale down models have been successfully developed and applied to the investigation of the effects of both dissolved oxygen and pH gradients, consequent of large scales of operation, on the biological performance of a culture of Bacillus subtilis. The strain used produces acetoin and butanediol as metabolites, and has been used as a model culture for mixing studies due to the unusual sensitivity of its product distribution to oxygen supply. It is a useful biological indicator of bioreactor performance. In addition, the sensitivity of metabolite production rates to pH has been exploited. Experiments using two different scale down models (two inter-connected stirred tanks and a stirred tank connected to a plug flow reactor) have been performed with the aim of simulating incomplete mixing with respect to oxygen supply. The effects of mean circulation time and the relative volumes of the compartments containing high and low dissolved oxygen concentrations, both in the ranges realistic of those found at large scales of operation, have been studied. For a given configuration, the biological response of the culture was consistent with the mixing conditions imposed. Similar trends (although significantly different in magnitude) in the biological performance of the culture in the two scale down models were found. Differences in performance between the two configurations have been explained in terms of the flow characteristics and oxygen availability in each system. The results presented also highlight the importance of the choice of the scale down model when studying the impact of large scale inhomogeneities on micro-organisms. The study shows that significant changes in biological performance are likely to occur upon scale up of this fermentation due to circulation of cells through oxygen deprived regions. These scale down experiments also indicate that both decreasing the mean circulation time and increasing the size of the well mixed impeller region should improve performance at the large scale. pH inhomogeneities can also occur in large scale fermenters near the addition point of acid or base for pH control as a consequence of poor bulk mixing. Frequent exposure of cells to such regions may affect microbial metabolism. Scale down experiments, under identical nonlimiting conditions of oxygen supply, have been used to simulate this phenomenon. It is shown that the effects of localised pH deviations from the bulk value on the biological performance of micro-organisms cannot be ignored for mixing times in bioreactors exceeding 60 seconds. Such effects of pH do not affect the growth of the culture. However, significant changes in product formation can be measured. Such scale down analysis may result in a better understanding of the effects of the physical environment on the biological performance of micro-organisms at different scales of operation, and help to produce a more rational approach to the design of bioreactors.
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