Microreactor Technology Research Articles

"Snapshot" Trapping of Multiple Transient Azolyllithiums in Batch.

Recent developments in flow microreactor technology have allowed the use of transient organolithium compounds that cannot be realized in a batch reactor. However, trapping the transient aryllithiums in a "halogen dance" is still challenging. Herein is reported the trapping of such short-lived azolyllithiums in a batch reactor by developing a finely tuned in situ zincation using zinc halide diamine complexes. The reaction rate is controlled by the appropriate choice of diamine ligand. The reaction is operationally simple and can be performed at 0 °C with high reproducibility on a multigram scale. This method was applicable to a wide range of brominated azoles allowing deprotonative functionalization, which was used for the concise divergent syntheses of both constitutional isomers of biologically active azoles.

Concentration measurement of a mixture using an infrared transceiver

Microreaction technologies are employed in various applications like space propulsion, atomization, drug delivery and in lab-on-chip applications. Mixing index measurement in micro reactors is essential to assess the performance of the proposed micro mixer. A major roadblock in the design of a micromixer is its assessment and determination of mixing index during the operation due to the complex flow characteristics and mass transfer that occur during the mixing of fluids or reactants. Sensor design is thus vital in analyzing the performance of micro mixers during operation. Infrared sensing is a versatile flow visualization technique which has been effectively used previously to characterize two phase flows in conventional macro channels. The present work develops a robust multiphysics simulation framework and provides a comprehensive characterization of an infrared sensor to perform online assessment of micromixers during their operation. This study considers the case of an optimized passive micromixer described in several literatures and models the microfluidic mixing between silica nanoparticles and distilled water at various concentrations. Further coupling was done by applying the physics of ray optics to understand the performance of an infrared sensor. The variation in infrared sensor output with the mixing index is presented based on the multiphysics coupling. With this analysis, the characteristic output of an infrared sensor can be inferred for any practical microfluidic mixing and microreactor application, thus helping the instrumentation design for online performance assessment of micromixers.

Cyber security for microreactors in advanced energy systems

Demand for clean and resilient energy has led to new and advancing frontiers of energy development in nuclear technology, specifically in the development of microreactors. These miniaturised modular reactors are generally <20 megawatts thermal (MWt) or 10 megawatts electric (MWe) and offer new opportunities to meet energy needs in remote locations and mobile operations. As with the slightly larger small modular reactors (<300 MWe), microreactor development must demonstrate security and safety, as well as economic competitiveness, to be seen as potential opportunities for new applications. Current research focuses on passive safety features, capital costs, reliability, semi-autonomous or autonomous control, cyber informed design, digital twins and non-proliferation. This paper focuses specifically on microreactor cyber informed design and cyber risk. An overview of microreactor technology provides a basis for examining the cyber nuclear playing field, with an emphasis on the USA. Frameworks for evaluating cyber security threats, and thereby designing for them, are reviewed. Recommendations follow with ideas for future research.

Methane sulfonic acid ionic liquid extraction of gasoline desulfurization process and enhancement of microchannel technology

Methane sulfonic acid (MSA) was used as anion to synthesize a series of ionic liquids and its desulfurization performance was evaluated by extraction. The basic physical properties and structural properties of the ionic liquids were evaluated, and it was proved that the ionic liquids could be used and separated well in liquid–liquid extraction desulfurization (EDS) system. The liquid–liquid extraction desulfurization system was enhanced by microchannel technology. The effects of microchannel diameter, extraction temperature, residence time and extraction stage on extraction efficiency were discussed. In the microchannel extraction system, this extraction equilibrium time can be reduced to 60 s from more than 10–15 min or longer in the conventional intermittent extraction techniques, which effectively reduces the synthesis and production cost. This finding may provide some reference for the further study of the micro-reaction technology in the deep removal of sulfur compounds from gasoline by ionic liquid, and further optimize the operating conditions.

Research Progress on Microreactor Technology in Oxidation Reactions

In recent years, the development of the chemical industry has been moving in a green, safe and efficient direction. Oxidation reactions are one of the most important types of reactions and have key applications in food, medicine, cosmetics, and petrochemicals. However, the occurrence of the oxidation reaction is accompanied by a strong exothermic phenomenon, and improper control can easily lead to safety problems and even explosions. The realization of an environmentally friendly oxidation reaction is a key industrial milestone. The unique structural characteristics of microreactors result in good mass and heat transfer performance, precise control of the reaction temperature, reduced risk of explosion, improved safety production and selectivity of products. These unique advantages of the microreactor determine its significant application value in oxidation reactions. In this paper, the research progress of several typical oxidation reactions, including alkane oxidation, alcohol oxidation, aldosterone oxidation, aromatics oxidation and olefin oxidation combined with microreactors, is reviewed systematically.

Continuous flow asymmetric synthesis of chiral active pharmaceutical ingredients and their advanced intermediates.

Catalytic enantioselective transformations provide well-established and direct access to stereogenic synthons that are broadly distributed among active pharmaceutical ingredients (APIs). These reactions have been demonstrated to benefit considerably from the merits of continuous processing and microreactor technology. Over the past few years, continuous flow enantioselective catalysis has grown into a mature field and has found diverse applications in asymmetric synthesis of pharmaceutically active substances. The present review therefore surveys flow chemistry-based approaches for the synthesis of chiral APIs and their advanced stereogenic intermediates, covering the utilization of biocatalysis, organometallic catalysis and metal-free organocatalysis to introduce asymmetry in continuously operated systems. Single-step processes, interrupted multistep flow syntheses, combined batch/flow processes and uninterrupted one-flow syntheses are discussed herein.

A New Strategy for the Synthesis of Monomethylhydrazine Using the Raschig Process

A new strategy for the development of monomethylhydrazine (MMH) using the Raschig process is discussed in this publication. The determination of optimal conditions for the synthesis of MMH required the development of a kinetic model. In order to validate the results of the calculation, a device for synthesis under pressure (13 bar) by direct injection of the stoichiometric monochloramine, synthesized using microreactor technology, into monomethylamine (MMA) was developed. The experimental data, in accordance with the theoretical results of the kinetic model, make it possible to establish a new process for the synthesis of monomethylhydrazine.

Multi-Criteria Assessment of Continuous Manufacturing Reactor Technologies in Upstream Pharmaceutical Supply Chains

The COVID-19 pandemic highlighted vulnerabilities in upstream pharmaceutical supply chains (PSC) associated with the manufacture of essential active pharmaceutical ingredients (APIs). The need to develop health countermeasures provided new impetus to supporting advanced manufacturing technologies such as process intensification through continuous manufacturing (CM). Recent advanced manufacturing developments suggest potential advantages in adopting CM over traditional batch technologies. However, at an early stage of evaluation detailed quantitative information is limited, and selecting specific reactor technologies based on multiple, conflicting criteria is challenging. To address these early-stage manufacturing technology selection challenges, this paper applies an Analytical Hierarchy Process approach, integrating multiple managerial and engineering criteria. The analysis focuses on reactor technologies in upstream PSC manufacturing. Findings suggest that microreactor technologies outperform alternatives all things considered. However, PSC managerial considerations introduce nuances in specific therapeutic areas e.g., antivirals where a tension between complex chemistry and the need for flexibility in unit operations may favour batch manufacturing. For analgesics the need to exploit the existing manufacturing base whilst addressing inventory reduction favour technologies that incorporate elements of batch and CM. Research enriches previous conceptual frameworks predicated on volume-variety considerations, providing an empirical workflow for the multi-faceted evaluation of alternative CM reactor technologies in PSC.

Recent developments in microreactor technology for biocatalysis applications

Through the use of microfluidics technology, one can severely accelerate the development and optimization of biocatalytic processes. In this work, the authors present a comprehensive review of the recent advances in the field.

Engineering Research Progress of Electrochemical Microreaction Technology—A Novel Method for Electrosynthesis of Organic Chemicals

Electrochemical methods are environmentally friendly and have unique advantages in the synthesis of organic chemicals. However, their implementation is limited due to the complex transport problems posed by traditional electrochemical reactors. Recently, the application of microreaction technology in electrosynthesis studies has reduced the transport distance of ions and increased the specific surface area of electrodes, leading to efficient, successive, and easily scaled-up electrosynthesis technologies. In this review article, engineering advantages of using microchannels in electrosynthesis are discussed from process enhancement perspective. Flow patterns and mass transfer behaviors in recently reported electrochemical microreactors are analyzed, and prototypes for the reactor scale-up are reviewed. As a relatively new research area, many scientific rules and engineering features of electrosynthesis in microreactors require elucidation. Potential research foci, considered crucial for the development of novel electrosynthesis technology, are therefore proposed.

Electrowetting-on-dielectric (EWOD) digital microfluidic device for in-line workup in organic reactions: A critical step in the drug discovery work cycle

As microfluidic systems play important roles to advance chemical synthesis applications in pharmaceutical and life science fields, the demand for fully-automated chemical synthesis work cycles grows. A successful automation of chemical synthesis with high yields requires not only executing sequential steps of organic chemical reactions, but also simple and adaptive purification (i.e., workup) techniques in each step. Despite recent advances in microreactor technologies, seamlessly integrating reactions and work-up toward a fully-automated chemical synthesis platform is an unmet challenge. In this study, we have demonstrated an electrowetting-on-dielectric (EWOD) digital microfluidic device (DMF) as an efficient in-line work-up tool for organic chemical synthesis reactions. The model protocol performed on EWOD DMF involves an acid-base workup, liquid-liquid extraction (LLE), and in-line solvent-swap. Device operation parameters of each reactant and unit process have been optimized. This study manifests the capacity of an EWOD device to transform into a drug discovery platform, particularly by hosting synthetically important reactions that require complicated work-up sequences.

A comparative structural and photocatalytic study on SnO2 nanoparticles fabricated in batch reactor and microreactor

Controlling of scalability, agglomeration and monodispersity of nanoparticles are fundamental to be exploited in diverse application-based fields such as catalysis, sensing, drug delivery, bio-imaging etc. Currently fabrication of scalable, non-agglomerated and monodispersed nanoparticles by using continuous flow microreactor technology pay severe consideration as it offers a variety of advantages such as competent heat transfer and better intermixing of the reactants compare to the conventional batch reactor technology. In this contribution, we advance the prior art by introducing a straightforward, scalable, cost-effective and environmentally benign continuous flow microreactor synthetic approach for the fabrication of pristine SnO2 nanoparticles at a reasonably low reaction temperature and short reaction period. A PTFE (polytetrafluoroethylene)-based helical tubular microreactor is being exploited that comprises compact structure and offers enhanced heat and mass transport as well as better intermixing among the reactants. To discriminate this technique with the conventional batch reactor method herein SnO2 nanoparticles have been synthesized by using both techniques by maintain the identical reaction temperature and reaction time in both cases. Inherent crystal phases, lattice strain, lattice parameters and oxygen vacancies of the as-synthesized SnO2 nanoparticles have been investigated by using XRD/Rietveld analysis. High resolution (HR) -Transmission electron microscopy (TEM) is carried out to investigate the size, shape, crystallinity and agglomeration behaviour of the SnO2 nanoparticles fabricated by each method. SnO2 nanoparticles fabricated by microreactor technology demonstrate excellent activity in the degradation of methylene blue (MB) dye and good stability in response to irradiation. Results demonstrate that altering the synthetic technique amends both surface properties (extent of oxygen vacancies and defects at the surface) and optical band gaps and that these alterations are eventually reflected in the photocatalytic properties of the SnO2 nanoparticles.

Rapid degradation of refractory organic pollutants by continuous ozonation in a micro-packed bed reactor

Recently microreactor technology attracts attention due to the excellent multiphase mixing and enhanced mass transfer. Herein, a continuous ozonation system based on a micro-packed bed reactor (μPBR) was used to improve the dissolution rate of ozone and achieved a rapid and efficient degradation of refractory organic pollutants. The effects of liquid flow rate, gas flow rate, initial pH, initial O3 concentration and initial phenol concentration on the phenol and chemical oxygen demand (COD) removal efficiencies were also investigated. Experimental results showed that phenol and COD removal efficiencies under optimal conditions achieved 100.0% and 86.4%, respectively. Compared with large-scale reactors, the apparent reaction rate constant in μPBR increased by 1-2 orders of magnitude. In addition, some typical organic pollutants (including phenols, antibiotics and dyes) were treated by ozonation in μPBR. The removal efficiencies of these organic pollutants and COD achieved 100.0% and 70.2%–80.5% within 71 s, respectively. In this continuous treatment system, 100% of the unreacted ozone was converted to oxygen, which promoted the healthy development of aquatic ecosystems. Thus, this continuous system based on μPBR is a promising method in rapid and efficient treating refractory organic pollutants.

Additive Manufacturing of Functional Microarchitected Reactors for Energy, Environmental, and Biological Applications

The use of microreactors in the continuous fluidic system has been rapidly expanded over the past three decades. Developments in materials science and engineering have accelerated the advancement of the microreactor technology, enabling it to play a critical role in chemical, biological, and energy applications. The emerging paradigm of digital additive manufacturing broadens the range of the material flexibility, innovative structural design, and new functionality of the conventional microreactor system. The control of spatial arrangements with functional printable materials determines the mass transport and energy transfer within architected microreactors, which are significant for many emerging applications, including use in catalytic, biological, battery, or photochemical reactors. However, challenges such as lack of design based on multiphysics modeling and material validation are currently preventing the broader applications and impacts of functional microreactors conjugated with digital manufacturing beyond the laboratory scale. This review covers a state-of-the-art of research in the development of some of the most advanced digital manufactured functional microreactors. We then the outline major challenges in the field and provide our perspectives on future research and development directions.

Accelerating Heat-Initiated Radical Reactions of Organic Halides with Tin Hydride Using Flow Microreactor Technologies

AbstractWe herein report that flow microreactors can promote an efficiency of radical chain reactions. The chain reactions with a fast propagation step can be accelerated by virtue of an efficient heat-transfer character of the microreactors, whereas the yield of those reactions with a slow propagation step was increased by flow microreactors. Moreover, the yield was further increased by a sequential addition of the initiators, which was allowed by a flow-sequential-addition system.

Flow Photochemistry as a Tool in Organic Synthesis.

Photochemical transformations of molecular building blocks have become an important and widely recognized research field in the past decade. Detailed and deep understanding of novel photochemical catalysts and reaction concepts with visible light as the energy source has enabled a broad application portfolio for synthetic organic chemistry. In parallel, continuous‐flow chemistry and microreaction technology have become the basis for thinking and doing chemistry in a novel fashion with clear focus on improved process control for higher conversion and selectivity. As can be seen by the large number of scientific publications on flow photochemistry in the recent past, both research topics have found each other as exceptionally well‐suited counterparts with high synergy by combining chemistry and technology. This review will give an overview on selected reaction classes, which represent important photochemical transformations in synthetic organic chemistry, and which benefit from mild and defined process conditions by the transfer from batch to continuous‐flow mode.

Assessment of Critical Experiment Benchmark Applicability to a Large-Capacity HALEU Transportation Package Concept

This work presents an assessment of the applicability of existing benchmark critical experiments to the criticality safety code validation for a large-capacity high-assay low-enriched uranium (HALEU) transportation package concept. Numerous next-generation nuclear reactor designs require HALEU fuel, which is characterized by an enrichment between 5 and 20 wt% 235U. The U.S. Department of Energy (DOE) has proposed to recover and downblend highly enriched uranium from DOE-owned used nuclear fuel to accelerate the demonstration of commercially viable microreactor technologies. One element of the infrastructure needed to demonstrate HALEU-fueled reactors is the ability to safely transport enriched product to be used for fuel fabrication. There is uncertainty as to whether existing critical benchmark experiment data are sufficient to support criticality safety code validation for HALEU transportation applications. The anticipated chemical form of the HALEU in the proposed transportation concept is UO2 with 20 wt% 235U/U. The concept uses a combination of an existing transportation packaging design and a novel basket design, including borated aluminum flux traps. The basket provides space for 18 reusable, stainless steel canisters that contain the HALEU. In 10 CFR 71, normal conditions of transport (NCTs) and hypothetical accident conditions (HACs) are defined for fissile material transportation packages. NCT and HAC KENO-VI models of the transportation package were developed using the Standardized Computer Analyses for Licensing Evaluation (SCALE) 6.2.3 computer code package, and optimum moderation conditions were determined using the SCALE SAMPLER sequence. The SCALE Tools for Sensitivity and Uncertainty Analysis Methodology Implementation (TSUNAMI) sequences were then used to compare the neutronic characteristics of 1584 International Criticality Safety Benchmark Evaluation Project benchmark critical experiments with the NCT and HAC HALEU transportation models. The TSUNAMI integral correlation coefficient ck was the criterion used to rank neutronic similarity. Thirty-four experiments were identified as similar (ck ≥ 0.9) to the NCT model, and 55 experiments were identified as similar to the HAC model. Hundreds of experiments were also identified as at least marginally similar (ck ≥ 0.8) to both models. The results indicate that additional critical experiments are unlikely to be needed to support HALEU transportation criticality safety analyses for package concepts similar to the concept package analyzed.

Application of microreactor technology to dehydration of bio-ethanol

Dehydration and etherification of bio-ethanol was studied in a microreactor using γ-alumina, H-Beta-38 and Sn-Beta-38 as catalysts. An extensive series of kinetic experiments was carried out in the microreactor device operating at ambient pressure and temperatures 225–325 °C.The H-Beta-38 catalyst coated microplates exhibited the highest production rate of ethene. While the fresh H-Beta-38 catalyst allowed complete conversion of ethanol and 98% selectivity towards ethene, the catalyst deactivated significantly with time-on-stream. Diethyl ether was the dominating co-product, whereas trace amounts of acetaldehyde were detected in the experiments.Based on the kinetic studies, thermodynamic analysis and catalyst characterization results obtained with SEM-EDX, TEM, nitrogen physisorption, FTIR-Pyridine and white light confocal microscopy, a surface reaction mechanism was proposed. The fundamental hypothesis of the reaction mechanism was the co-existence of two kinds of active sites on the catalyst surface, namely the Brønsted sites promoting dehydration and the Lewis sites responsible for etherification. The Brønsted sites deactivate, whereas the Lewis sites are more stable, which leads to a shift of the product distribution during long-term experiments, from ethene to diethyl ether. The rate equations were implemented in the microreactor model. The kinetic and adsorption parameters included in the model were estimated by non-linear regression analysis. The experimental data were satisfactorily described by the proposed mechanism. The work demonstrated that microreactors are strong tools in the determination of catalytic kinetics and catalyst durability.

Two-phase flow and mass transfer in microchannels: A review from local mechanism to global models

Microreaction technology is preferential in process intensification and chemical synthesis, especially in multiphase applications. A thorough understanding of the hydrodynamics and mass transfer is the pre-requisite for implementing such applications. This review discusses the recent progress on the flow and mass transfer of two-phase systems in microchannels, in a multi-scale view from local mechanism to global behavior. The flow patterns, the formation of bubbles/droplets, and the manipulation of bubbles/droplets are presented and discussed in detail. The mass transfer aspects include the velocity profile and mixing inside droplets/slugs, as well as the interfacial mass transfer mechanism and simulative models. The aim of the review is to show directly the physical ingredients which determine the transport phenomena, help explain the observed behavior, and guide reactor design. To simplify the physical ingredients, the attention is focused on straight channels while phenomena in other channels (e.g., meandering channel) are neglected.

Characterization of the Mixing Performance of an Innovative Hepatic Sinusoids-Based Microreactor Using Villermaux-Dushman Protocol

Microreactor technology has drawn attention in many industrial applications, especially those that requires the use of low flow rates whereas the flow is considered to be stratified. At such low flow rates, the reactor performance is usually down especially if mass transfer occurs mainly by diffusion. In the present work, the mixing performance of a novel hepatic sinusoids-based microreactor has been investigated using Villermaux–Dushman protocol. The protocol is an iodide/iodate chemical test reaction that relies on testing the absorbance of the product at 352 nm as an indication of the formation of triiodide. The investigation is carried out at low flow rates ranges from 0.5 to 3 ml/min. The novel microreactor has proven to give satisfactory performance and is easy to be fabricated as it consists of a single layer. The absorbance of light ranges between 0.29 to 0.48 resulting on the creation of limited amount of triiodide ions. It is also noticed that the mixing performance of the reactor is nearly the same over the whole studied range of flow rate. The mixing quality is also determined using another system containing 200 ppm congo red aqueous solution and pure distilled water. About 94% to 96% mixing quality is achieved.