Extractive fermentation (or in situ product removal (ISPR)) is an operational method used to combat product inhibition in fermentations. To achieve ISPR, different separation techniques, modes of operation and physical reactor configurations have been proposed. However, the relative paucity of industrial application necessitates continued investigation into reactor systems. This article outlines a bioreactor designed to facilitate in situ product extraction and recovery, through adapting the reaction volume to include a settler and solvent extraction and recycle section. This semipartition bioreactor is proposed as a new mode of operation for continuous liquid-liquid extractive fermentation. The design is demonstrated as a modified bench-top fermentation vessel, initially analysed in terms of fluid dynamic studies, in a model two-liquid phase system. A continuous abiotic simulation of lactic acid (LA) fermentation is then demonstrated. The results show that mixing in the main reaction vessel is unaffected by the inserted settling zone, and that the size of the settling tube effects the maximum volumetric removal rate. In these tests the largest settling tube gave a potential continuous volumetric removal rate of 7.63 ml/min; sufficiently large to allow for continuous product extraction even in a highly productive fermentation. To demonstrate the applicability of the developed reactor, an abiotic simulation of a LA fermentation was performed. LA was added to reactor continuously at a rate of 33ml/h, while continuous in situ extraction removed the LA using 15% trioctylamine in oleyl alcohol. The reactor showed stable LA concentration of 1 g/L, with the balance of the LA successfully extracted and recovered using back extraction. This study demonstrates a potentially useful physical configuration for continuous in situ extraction.
Bioprocesses can be hampered by product concentrations within a fermentation leading to product‐inhibition, and reductions in yield and productivity. This limitation impacts operational considerations, process economics, and viability, and, ultimately, whether a technology is industrially viable. One approach to circumventing these concerns is in situ extraction of products. In this way, the organism is no longer exposed to the inhibitory product, and fermentation can proceed, often at improved rates. Significant advances in this field have been made in recent years, however, they are for the most part siloed into sub‐fields (focusing on the product extracted, or the method of extraction). This review considers in situ extraction more holistically in terms of i) the separation methodology, ii) the mode of reactor operation, and iii) the physical reactor configuration. The summary hopes to give insight into promising areas for research and potentially spark ideas for novel in situ extractive processes.
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