A Microfluidic Toolbox for the Development of In-Situ Product Removal Strategies in Biocatalysis

Abstract

A microfluidic toolbox for accelerated development of biocatalytic processes has great potential. This is especially the case for the development of advanced biocatalytic process concepts, where reactors and product separation methods are closely linked together to intensify the process performance, e.g., by the use of in-situ product removal (ISPR). This review provides a general overview of currently available tools in a microfluidic toolbox and how this toolbox can be applied to the development of advanced biocatalytic process concepts. Emphasis is placed on describing the possibilities and advantages of the microfluidic toolbox that are difficult to achieve with conventional batch-processbased technologies. Application of this microfluidic toolbox will potentially make it possible to intensify biocatalytic reactions and thereby facilitate the development towards novel and advanced biocatalytic processes, which in many cases have proven too difficult in conventional batch equipment.

An Immobilized Enzyme Reactor for Spatiotemporal Control over Reaction Products

“…Our example ensures a more efficient transfer of the intermediate to the second enzyme. Further, microfluidic devices have a large surface‐to‐volume ratio and small length scales that allow for fast mass transfer, which can serve to remove inhibitory products and reduce product inhibition of the enzymes …”

“…Compartmentalization provides many advantages over traditional batch processes because multiple reaction steps can be individually interrogated and optimized . Recent work has demonstrated strategies to sequentially organize two or more enzymes on solid supports for performing multistep transformations .…”

Removal of benzaldehyde from a water/ethanol mixture by applying scavenging techniques

“…Applications of adsorption techniques [5], such as usage of activated carbon [6,7], alumina [8], and titanium [9] are very well-known already and have great applications in the petrochemical industry. The application of ex situ and in situ product removal technologies [10], such as pervaporation, has shown great advantages in fermentation processes [11]. Furthermore, an application of reactive extraction with amines has achieved great results with various aromatic and aliphatic carbonyl compounds [12].…”

Development of in situ product removal strategies in biocatalysis applying scaled‐down unit operations

“…Therefore, the aim of this work is to transfer that knowledge base and scale-down concepts to biocatalysis, in order to establish a scaled-down experimental platform that can assist the development of novel and robust biocatalytic processes. For example, modular scaled-down unit operations enable compartmentalization of different process steps, which is not possible to the same extent with conventional batch based technologies (Heintz et al, 2016). Furthermore, combining scaled-down unit operations in a plug-and-play manner enables easy, robust, and flexible experimentation with the possibility of automated operation.…”

“…Despite this, such strategies often fail to reach industrial implementation, for example, due to increased process complexity (Stark and von Stockar, 2003;Van Hecke et al, 2014). Furthermore, it is frequently difficult to test complex ISPR process options with conventional batch based technologies, since it is difficult to compartmentalize and link multiple process steps at the same time (Heintz et al, 2016). Therefore, we demonstrated herein how combining modular scaled-down unit operations in a plug-and-play manner provides an experimental platform for developing ISPR options, where upstream and downstream process steps can be linked, compartmentalized, and tested in combination.…”