Conscious coupling: The challenges and opportunities of cascading enzymatic microreactors

The continuous production of high value or difficult to synthesize products is of increasing interest to the pharmaceutical industry. Cascading reaction systems have already been employed for chemical synthesis with great success, allowing a quick change in reaction conditions and addition of new reactants as well as removal of side products. A cascading system can remove the need for isolating unstable intermediates, increasing the yield of a synthetic pathway. Based on the success for chemical synthesis, the question arises how cascading systems could be beneficial to chemo-enzymatic or biocatalytic synthesis. Microreactors, with their rapid mass and heat transfer, small reaction volumes and short diffusion pathways, are promising tools for the development of such processes. In this mini-review, the authors provide an overview of recent examples of cascaded microreactors. Special attention will be paid to how microreactors are combined and the challenges as well as opportunities that arise from such combinations. Selected chemical reaction cascades will be used to illustrate this concept, before the discussion is widened to include chemo-enzymatic and multi-enzyme cascades. The authors also present the state of the art of online and at-line monitoring for enzymatic microreactor cascades. Finally, the authors review work-up and purification steps and their integration with microreactor cascades, highlighting the potential and the challenges of integrated cascades

Stable Immobilization of Size-Controlled Bimetallic Nanoparticles in Photonic Crystal Fiber Microreactor

© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. The possibility of immobilizing ex situ-synthesized colloidal bimetallic nanoparticles (NPs) of well-defined characteristics inside hollow core photonic crystal fiber (HC-PCF) microreactors is demonstrated. With the developed method, PtNi clusters remain strongly attached to the fiber core and can be used as active catalysts for the hydrogenation of an azobenzene dye. The study revealed that optical transmission exhibits a size-dependent behavior, i.e., smaller NPs bring in less optical signal loss. Sufficient light transmission was achieved for all particle sizes. Furthermore, with these catalytic PCF microreactors, kinetic data can be obtained with a much lower amount of precious metals compared to a conventional batch reactor, opening a new pathway for in situ catalyst screening

Green process intensification using microreactor technology for the synthesis of biobased chemicals and fuels

Microreactor technology as an important means of process intensification has opened vast opportunities for green and sustainable chemical synthesis. Over the past decade, a promising research direction has been seen in the utilization of microreactors for intensifying catalytic biomass conversion. This Perspective provides a concise overview on green process intensification in microreactors for the synthesis of value-added chemicals and fuels from biomass. The focus is laid on process intensification merits of microreactor technology, its alignment with green chemistry and green engineering principles, typical application examples for manufacturing biobased chemicals and fuels including the synthesis of furanic platform chemicals and their derivatives from mono- and disaccharides, liquid-phase oxidation and hydrogenation of lignocellulosic biomass derivatives, and biodiesel synthesis. Finally, an outlook is provided for future research directions, including among others solid (catalyst, feed and product) handling strategies, process integration in cascades or one microreactor, expanding biomass transformation database, photocatalysis and use of novel solvents in microflow

In situ decolorization monitoring of textile dyes for an optimized UV-LED/TiO2 reactor

Heterogeneous photocatalysis, using photocatalysts in suspension to eliminate diverse contaminants, including textile wastewater, has several advantages. Nevertheless, current absorbance and decolorization measurements imply sample acquisition by extraction at a fixed rate with consequent photocatalyst removal. This study presents online monitoring for the decolorization of six azo dyes, Orange PX-2R (OP2), Remazol Black B133 (RB), Procion Crimson H-EXL (PC), Procion Navy H-EXL (PN), Procion Blue H-EXL (PB), and Procion Yellow H-EXL (PY), analyzing the spectrum measured in situ by using the light scattering provided by the photocatalyst in suspension. The results obtained have corroborated the feasibility of obtaining absorbance and decolorization measurements, avoiding disturbances in the process due to a decrease in the volume in the reactor.Peer ReviewedPostprint (published version

Bioprocess microfluidics: applying microfluidic devices for bioprocessing

Scale-down approaches have long been applied in bioprocessing to resolve scale-up problems. Miniaturized bioreactors have thrived as a tool to obtain process relevant data during early-stage process development. Microfluidic devices are an attractive alternative in bioprocessing development due to the high degree of control over process variables afforded by the laminar flow, and the possibility to reduce time and cost factors. Data quality obtained with these devices is high when integrated with sensing technology and is invaluable for scale-translation and to assess the economical viability of bioprocesses. Microfluidic devices as upstream process development tools have been developed in the area of small molecules, therapeutic proteins, and cellular therapies. More recently, they have also been applied to mimic downstream unit operations

Nanoscale Electrochemical Sensing and Processing in Microreactors

In this review, we summarize recent advances in nanoscale electrochemistry, including the use of nanoparticles, carbon nanomaterials, and nanowires. Exciting developments are reported for nanoscale redox cycling devices, which can chemically amplify signal readout. We also discuss promising high-frequency techniques such as nanocapacitive CMOS sensor arrays or heterodyning. In addition, we review electrochemical microreactors for use in (drug) synthesis, biocatalysis, water treatment, or to electrochemically degrade urea for use in a portable artificial kidney. Electrochemical microreactors are also used in combination with mass spectrometry, e.g., to study the mimicry of drug metabolism or to allow electrochemical protein digestion. The review concludes with an outlook on future perspectives in both nanoscale electrochemical sensing and electrochemical microreactors. For sensors, we see a future in wearables and the Internet of Things. In microreactors, a future goal is to monitor the electrochemical conversions more precisely or ultimately in situ by combining other spectroscopic techniques

In-situ monitoring of photocatalytic reactions in optofluidic microreactors

To advance the state-of-the-art technology in photocatalysis, there is a growing need to develop optically efficient microreactors that allow rapid changes in reaction conditions for catalyst screening. In addition, such microreactors should offer strong light-matter interactions for the in-situ spectroscopic detection of chemical species. Motivated by these challenges, this thesis marries the fields of fibre-based optofluidics and photocatalysis to generate scientific insights into how promising new photocatalysts behave. Novel types of optical fibre were optimised and characterised for liquid phase spectroscopy on sub-microlitre samples; these fibres included kagomé-style and single-ring hollow-core photonic crystal fibres (HC-PCFs). New kinetic insights were obtained into the photoactivity of carbon nanodots (CDs) through systematic screening of a wide range of reaction conditions within kagomé-style HC-PCF microreactors. Spectrokinetic insights across twenty-nine reaction conditions were studied with a cumulative sample volume of < 1.5 mL, using viologen species as indicators of electron transfer from CDs. First, amorphous and graphitic CDs were benchmarked against the well-known photocatalyst [Ru(bpy)3]2+. This study was then extended to replace the viologen indicator with hydrogen-evolving cobaloxime electrocatalysts, to probe catalytic intermediate states. To give further insight into the electron transfer from carbon nanodots to viologens, transient absorption spectroscopy was then performed to probe changes on timescales of 1 nanosecond to 1 millisecond. Finally, a new ultralow volume fibre-based fluorescence spectroscopy method was realised. As a proof of principle, the photoredox catalyst 4CzIPN was combined with the fluorescence quenchers tetrabutylammonium azide and cyclohexylamine. The extracted bimolecular Stern-Volmer quenching coefficients were compared with conventional fluorimeter-based approaches, which were taken on much larger sample volumes. This thesis provides a foundation for developing continuous-flow photocatalytic screening systems based on HC-PCFs, which minimise the consumption of precious reagents

Manipulation of gas-liquid-liquid systems in continuous flow microreactors for efficient reaction processes

Gas-liquid-liquid flow in microreactors holds great potential towards process intensification of operation in multiphase systems, particularly by a precise control over the three-phase contact patterns and the associated mass transfer enhancement. This work reviews the manipulation of gas-liquid-liquid three-phase flow in microreactors for carrying out efficient reaction processes, including gas-liquid-liquid reactions with catalysts residing in either liquid phase, coupling of a gas-liquid reaction with the liquid-liquid extraction, inert gas assisted liquid-liquid reactions and particle synthesis under three-phase flow. Microreactors are shown to be able to provide well-defined flow patterns and enhanced gas-liquid/liquid-liquid mass transfer rates towards the optimized system performance. The interplay between hydrodynamics and mass transfer, as well as its influence on the overall microreactor system performance is discussed. Meanwhile, future perspectives regarding the scale-up of gas-liquid-liquid microreactors in order to meet the industrial needs and their potential applications especially in biobased chemicals and fuels synthesis are further addressed