POLONA ŽNIDARŠIC-PLAZL
University of Ljubljana, Faculty of Chemistry and Chemical Technology, Aškerceva 5, 1000, Ljubljana, Slovenia. 

Abstract

Implementation of biocatalytic reactions in chemical processes is often hampered by poor solubility of organic compounds in water, as well as with low biocatalyst stability and/or near-equilibrium reactions, preventing high final yields. The use of non-aqueous solvents can substantially improve the applicability of biocatalysts for organic synthesis by offering substantially higher substrate and product solubility along with the possibility for in situ product removal in two-liquid phase systems, among others. Miniaturization and continuous-flow processing is gaining importance also in biocatalytic processes, especially when mass transport across phase boundaries is included. This review gives an insight into enzymatic microreactors utilizing either dissolved catalysts within various two-liquid phase systems, or immobilized enzymes employing non-aqueous media, namely ionic liquids and organic solvents. Benefits and drawbacks of parallel and segmented liquid-liquid flows within microfluidic systems, as well as of packed bed mezzo- or microscale reactors utilizing non-aqueous media for biocatalytic reactions are highlighted.

INTRODUCTION
Several evidences on the advantages of microreactor technology, such as substantially improved heat and mass transfer, better process control and safety, lower consumption of chemicals and time during process development stages, the possibility to perform reactions not feasible in conventional systems, as well as conceptually different approach to increase the capacity by numbering up instead of tedious scale-up have gradually changed the paradigm of chemical engineering (1, 2). Various classes of chemical reactions have already been performed in microchannels offering also more control over selectivity and suppression of by-product formation. Microfluidic-based continuous processing nowadays represents an excellent complement to traditional batch reactors in fine chemicals and pharma industry including drug discovery and development (3-6). There are evidences about approximately 50 companies which approached or entered industrial productions based on microreactor technology (3 and refs therein). The motivation for industrial application of microstructured devices is mainly related to safety and apparatus costs, as well as to process intensi ...