The transfer of batch processes to continuous flow is a major driver for the application of microreactors. Here, we present a methodology for the transfer of (bio)chemical reactions in batch mode to two-phase continuous flow. For our purposes, the coiled flow inverter (CFI) is a promising reactor design providing enhanced heat and mass transfer, narrow residence time distribution, and rapid mixing. First, this methodology is used for current development of a droplet-based reaction screening system, which was first tested with a Paal−Knorr pyrrole synthesis as model reaction. The reaction was successfully performed in the automated screening system. The yields compared to the batch mode revealed enhanced mass transfer of the product into the continuous phase. Second, we investigated the biocatalyzed oxidation of ABTS by the enzyme laccase in a straight capillary for process development in a CFI. Because of its high flexibility regarding substrate specificity, laccase oxidizes many substrates with a colored product. Hence, an optical evaluation method for determination of reaction rate is used. We compare the Michaelis−Menten kinetic of the batch reaction and the continuous reaction in a capillary. The results show that the batch reaction can be mapped to the capillary setup. However, the capillary in continuous operation enables higher screening capacity of different reaction conditions and simple scale-up procedure.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Biocatalysis offers a broad spectrum of possible ecological and economic advantages over conventional chemical catalysis processes, e.g., lower energy consumption and high enantio selectivity. The focus of this work is on gas-liquid reactions. These are of great importance in the chemical and biochemical industry and subject of current research since they are often limited by mass transfer or show low selectivity. Different suitable biocatalytically gas-liquid reaction systems were tested in capillary reactor designs in order to obtain information about the interaction between reaction and fluid mechanics. Furthermore, an optical measuring method was established. The experiments were performed in batch mode in a glass beaker with a flow cuvette for UV/Vis measurement of product concentration.
Miniaturized bioreactors, such as the coiled flow inverter (CFI), offer several benefits within process development such as lower time and cost factors. In this study, we demonstrate continuous flow experiments in a CFI and transferred them to experiments in a batch reactor by using the oxygen transfer coefficient k L a as a key parameter. In order to simplify the parameter transfer and at the same time develop a basis for future data handling according to the FAIR data principles, an equipment and process ontology was developed for these examples.
In the course of the investigation of biocatalytic gas‐liquid reactions with color change in straight and coiled capillaries, a non‐invasive evaluation method is needed to determine reaction progress and selectivity. Correlations between hydrodynamics, mass transfer phenomena, and reaction kinetics are in the focus of our work. For this purpose, it is necessary to investigate the flow and evaluate the reaction progress without disturbing the flow. Digital image processing (DIP) is presented as a suitable optical evaluation method for reactions with color change in capillary reactor designs. The developed DIP program is independent from the capillary reactor design, applicable to differently colored systems, and can analyze up to three different species simultaneously.
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