Integrating Biocatalysis with Viscous Deep Eutectic Solvents in Lab‐On‐A‐Chip Microreactors

Abstract

The combination of deep eutectic solvents (DESs, ChCl/glycerol 1 : 2) with buffer (up to 15 % v/v) leads to solvent mixtures that exert viscosities below 25 mPa s−1 at 45 °C while keeping their non‐aqueous nature. This enables the setup of efficient enzymatic esterifications, which can also be applied in different continuous systems. Following those premises, the use of microreactors in biocatalytic reactions was explored using (low‐viscous) DES‐buffer media, showing that reactions could be performed efficiently. Under non‐optimized conditions, the microreactor devices led to specific productivities considerably higher than those observed in the batch reactor (14 vs. 0.24 mgproduct min−1 mgbiocat−1) at the same enzyme loadings and conversion of 6 % (to assure a fair comparison). Looking beyond, the combination of several microchannels (e. g., in scale‐out fashion) with DES‐water media may lead to powerful, sustainable, and efficient tools for industrial synthesis.

Development of 3D Printed Enzymatic Microreactors for Lipase-Catalyzed Reactions in Deep Eutectic Solvent-Based Media

“…DESs are usually produced by using inexpensive quaternary ammonium salts such as choline chloride, millions of tons of which are produced every year, combined with HBDs from renewable sources such as sugars, amino acids, alcohols, and process wastes such as glycerol, depending on the desired application [16]. In addition to the concept of reaction media, research is moving toward the 2-in-1 concept in which the DES simultaneously acts as the reaction medium and the substrate pool, one (or both) of its components being the substrate of the biotransformation reaction, thus promoting the sustainability of the system [16][17][18][19][20].…”

“…As a biocatalyst, lipase from Candida antarctica B was used, one of the first enzymes exploited in DES-based processes and widely studied for its diverse biotechnological applications [26]. The incorporation of DESs into continuous biocatalytic processes in microreactor systems has been recently exerted by experts in the field of the application of DESs in biocatalysis [18,27]. More specifically, it has been proposed that the employment of DESs as alternative solvents in microfluidic bioprocesses renders these systems sustainable and highly efficient [27].…”

Sustainable Setups for the Biocatalytic Production and Scale-Up of Panthenyl Monoacyl Esters under Solvent-Free Conditions

“… 28 In such a study, the increase from 0.5 to 100 mmol of the overall mass improved not only the yield but also the selectivity and reaction rate, achieving the maximum conversion in just 30 min at 40 °C, being related to a better mixing because of an enhanced transfer of the ultrasonic waves to the core of the mixture. Alternatively, to improve the mass transfer of the reaction species, other authors working on biocatalysis with viscous DESs in lab-on-a-chip flow microreactors 27 reported the addition of a small amount of water to reduce the viscosity of the reaction system. However, water may have a detrimental effect on the yield of the reversible esterification reactions that becomes more evident in these batch setups.…”

“…The addition of water can partially reduce the DES viscosity, enabling their use even under flow conditions. For instance, it has been reported how the addition of water (up to 15% v/v) on DESs based on choline chloride/glycerol (1/2) leads to solvent mixtures with viscosities below 25 mPa·s that enable efficient enzymatic reactions in flow microreactor devices . In any case, it is highly important to remove the water from the enzyme microenvironment for this solvent-free approach because this byproduct can shift the reversible equilibria toward the hydrolysis of the product with a detrimental impact on the final yield (see Figure A). , Alternatively, different approaches can be used to improve the mass transfer overcoming the viscosity issues.…”

Tyrosinase Magnetic Cross-Linked Enzyme Aggregates: Biocatalytic Study in Deep Eutectic Solvent Aqueous Solutions

“…The use of DESs in biocatalysis offers additional advantages, as by choosing the appropriate solvent, a wide range of substrates can be solubilized [ 5 , 12 ]. Furthermore, a DES can act both as reaction medium and as substrate, leading to optimized yields [ 13 , 14 , 15 ]. For example, Candida rugosa lipase has been used for the esterification of (-)-menthol with fatty acids in a solvent-free system, as menthol was the HBA of the DES and each fatty acid was the HBD [ 16 ].…”