Perspectives of heterogeneous process intensification in microreactors

Recent developments in microreactor technology basing on different types of heterogeneous reaction systems: phase transfer catalysis, biocatalysis, and synthesis of nanoparticles are reviewed. Special attention is focused on the intensification of processes in microreactors compared with traditional approaches, which makes microtechnique of great interest for industry.     

Continuous flow enzyme-catalyzed polymerization in a microreactor

Enzymes immobilized on solid supports are increasingly used for greener, more sustainable chemical transformation processes. Here, we used microreactors to study enzyme-catalyzed ring-opening polymerization of ε-caprolactone to polycaprolactone. A novel microreactor design enabled us to perform these heterogeneous reactions in continuous mode, in organic media, and at elevated temperatures. Using microreactors, we achieved faster polymerization and higher molecular mass compared to using batch reactors. While this study focused on polymerization reactions, it is evident that similar microreactor based platforms can readily be extended to other enzyme-based systems, for example, high-throughput screening of new enzymes and to precision measurements of new processes where continuous flow mode is preferred. This is the first reported demonstration of a solid supported enzyme-catalyzed polymerization reaction in continuous mode.     

Microwave-assisted organic synthesis in microstructured reactors

The coupling of microwave heating with microprocessing in continuous-flow reactors has been reviewed in various organic synthesis reactions. The fast growing field of microwave and microreactor technology has a significant impact on the development of fine chemicals industry. Both technologies offer not only the possibility of realizing many of the individual advantages integrated into one combined system, but also the potential of eliminating the major hurdle of a limited microwave penetration depth for large-scale chemical synthesis. Metal film-coated capillary microreactors allow creation of local hot spots to achieve temperatures far in excess of the solvent temperature, which accelerates chemical reactions under MW heating.     

Difluoro-and Trifluoromethylation of Electron-Deficient Alkenes in an Electrochemical Microreactor

Electrochemical microreactors, which have electrodes integrated into the flow path, can afford rapid and efficient electrochemical reactions without redox reagents due to the intrinsic properties of short diffusion distances. Taking advantage of electrochemical microreactors, Kolbe electrolysis of di-and trifluoroacetic acid in the presence of various electron-deficient alkenes was performed under constant current at continuous flow at room temperature. As a result, di-and trifluoromethylated compounds were effectively produced in either equal or higher yields than identical reactions under batch conditions previously reported by Uneyamas group. The strategy of using electrochemical microreactor technology is useful for an effective fluoromethylation of alkenes based on Kolbe electrolysis in significantly shortened reaction times.     

Bioproduction of Food Additives Hexanal and Hexanoic Acid in a Microreactor

Hexanal and hexanoic acid have number of applications in food and cosmetic industry because of their organoleptic characteristics. Problems like low yields, formation of unwanted by-products, and large quantities of waste in their traditional production processes are the reasons for developing new production methods. Biotransformation in a microreactor, as an alternative to classical synthesis processes, is being investigated. Because conditions in microreactors can be precisely controlled, the quality of the product and its purity can also be improved. Biocatalytic oxidation of hexanol to hexanal and hexanoic acid using suspended and immobilized permeabilized whole baker’s yeast cells and suspended and immobilized purified alcohol dehydrogenase (ADH) was investigated in this study. Three different methods for covalent immobilization of biocatalyst were analyzed, and the best method for biocatalyst attachment on microchannel wall was used in the production of hexanal and hexanoic acid.     

Enzyme-immobilized microfluidic process reactors

Microreaction technology, which is an interdisciplinary science and engineering area, has been the focus of different fields of research in the past few years. Several microreactors have been developed. Enzymes are a type of catalyst, which are useful in the production of substance in an environmentally friendly way, and they also have high potential for analytical applications. However, not many enzymatic processes have been commercialized, because of problems in stability of the enzymes, cost, and efficiency of the reactions. Thus, there have been demands for innovation in process engineering, particularly for enzymatic reactions, and microreaction devices represent important tools for the development of enzyme processes. In this review, we summarize the recent advances of microchannel reaction technologies especially for enzyme immobilized microreactors. We discuss the manufacturing process of microreaction devices and the advantages of microreactors compared to conventional reaction devices. Fundamental techniques for enzyme immobilized microreactors and important applications of this multidisciplinary technology are also included in our topics.     

Ionic-liquid supported oxidation reactions in a silicon-based microreactor

The combination of microfabrication and reaction engineering techniques has the potential to produce powerful microreactors. In a microreactor, aqueous buffers provide high electroosmatic mobility and no external pumping is required. While numerous reactions have been demonstrated to be highly efficient in microreactors, so far there has been no report on the epoxidation of cyclohexene in a microreactor. This is mainly due to the reduced solubility of cyclohexene in aqueous media. The greater volatility of cyclohexene leading to long reaction times is another reason. To improve the solubility of cyclohexene in the reaction buffer, a water soluble ionic-liquid 1-butyl-3-methylimidazolium tetrafluoroborate was used, also for the first time in microreactor work. In this letter, four different catalysts (i.e., manganese(II) and copper(II) complexes of Schiff and reduced Schiff bases) were synthesized and used for the oxidation reactions considered. The reactions were monitored by gas chromatography/mass spectrometry. The microreactor performance was evaluated by comparing with a conventional (batch scale) reaction. Catalytic activities and yields were found to be relatively high for the copper(II) complexes as compared with the conventional route.     

Microreactors as Tools for Synthetic Chemists—The Chemists' Round‐Bottomed Flask of the 21st Century?

Will microreactors replace the round‐bottomed flask to perform chemical reactions in the near future? Recent developments in the construction of microstructured reaction devices and their wide‐ranging applications in many different areas of chemistry suggest that they can have a significant impact on the way chemists conduct their experiments. Miniaturizing reactions offers many advantages for the synthetic organic chemist: high‐throughput scanning of reaction conditions, precise control of reaction variables, the use of small quantities of reagents, increased safety parameters, and ready scale‐up of synthetic procedures. A wide range of single‐ and multiphase reactions have now been performed in microfluidic‐based devices. Certainly, microreactors cannot be applied to all chemistries yet and microfluidic systems also have disadvantages. Limited reaction‐time range, high sensitivity to precipitating products, and new physical, chemical, and analytical challenges have to be overcome. This concept article presents an overview of microfluidic devices available for chemical synthesis and evaluates the potential of microreactor technology in organic synthesis.     

Indirect micromanipulation of single molecules in water-in-oil emulsion

Based on real-time observation and micromanipulation, analytical methods for single DNA molecules have been under development for some time. Precise manipulation, however, is still difficult because single molecules are too small for conventional techniques. We have developed a chemical reaction system that uses water droplets in oil as containers of materials. The water droplets can be manipulated by optical force. The manipulation of the water droplets permits the fusion of two selected droplets. This process corresponds to mixing of different samples. We designate this system as "w/o (water-in-oil emulsion) microreactor system", and each droplet can be thought of as a "microreactor". In this system, single molecules can be manipulated readily, as a molecule can be contained in a microm-sized microreactor. The microreactor utilizes extremely small quantities of samples, therefore, reactions are rapid, as diffusion times in the microreactor are very short. The manipulation technique of the microreactors based on optical force has been applied to induce fusion between microreactors loaded with DNA and YOYO, a fluorescent dye that binds to DNA. This fusion induced a rapid binding of YOYO.     

Thin Organic-Inorganic Anti-Fouling Hybrid-Films for Microreactor Components

Deposit formation and fouling in reactors for polymer production and processing especially in microreactors is a well-known phenomenon. Despite the flow and pressure loss optimized static mixers, fouling occurs on the surfaces of the mixer elements. To improve the performance of such parts even further, stainless steel substrates are coated with ultra-thin films which have low surface energy, good adhesion, and high durability. Perfluorinated organosilane (FOTS) films deposited via chemical vapor deposition (CVD) are compared with FOTS containing zirconium oxide sol-gel films regarding the prevention of deposit formation and fouling during polymerization processes in microreactors. Both film structures led to anti-adhesive properties of microreactor component surfaces during aqueous poly(vinylpyrrolidone) (PVP) synthesis. To determine the morphology and surface chemistry of the coatings, different characterization methods such as X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR) spectroscopy as well as microscopic methods such as field-emission scanning electron microscopy (FE-SEM) and atomic force microscopy (AFM) are applied. The surface free energy and wetting properties are analyzed by means of contact angle measurements. The application of thin film-coated mixing elements in a microreactor demonstrates a significant lowering in pressure increase caused by a reduced deposit formation.     

Development of a multireactor microfluidic system for the determination of DNA using real-time polymerase chain reaction

A microfluidic system that allowed us to perform the real-time polymerase chain reaction (PCR) in a glass-silicon microchip containing nine 250-nL microreactors was developed and studied. The resulting high heating/cooling rates of a PCR mixture in a microreactor allowed us to optimize the amplification mode (1 min/cycle). The silicon surface of microreactors was successfully passivated. The resulting analytical system allowed us to measure the PCR kinetic curves in chip microreactors at a DNA concentration of ～5 × 10⁴ copies per microreactor. It was found that, if the PCR is performed in a microchip with real-time detection using the optimized amplification mode, the result can be obtained 13–14 min after the onset of reaction.     

Direct synthesis of hydrogen peroxide in microreactors

Several studies concerning direct synthesis of hydrogen peroxide in microreactors are reviewed. Several types of microreactors have been applied. Their high surface area-to-volume ratio and small internal volume improve safety, which is required when operating with explosive gases. The tested microreactors represent capillary reactors and more sophisticated reactors with a special plate structure on which reaction channels have been machined. Both single- and multi-channel arrangements have been applied. The catalysts have been installed in the reactor in the form of powder or washcoat layer on the channel wall. Palladium and platinum on various support material, such as SiO₂, Al₂O₃ and C, have been tested. Water was the most common solvent, but also methanol, ethanol, and isopropanol have been used because of their better gas dissolving properties. In addition to solvents, chemicals, often called promoters, have been utilised to improve productivity. The most typical promoters were halide ions, such as Br^? and Cl^? and inorganic acids. Hydrogen peroxide has been produced successfully by several research groups. The highest reported mass fraction of hydrogen peroxide was 5 wt %.     

Flash chemistry: fast chemical synthesis by using microreactors

This concept article provides a brief outline of the concept of flash chemistry for carrying out extremely fast reactions in organic synthesis by using microreactors. Generation of highly reactive species is one of the key elements of flash chemistry. Another important element of flash chemistry is the control of extremely fast reactions to obtain the desired products selectively. Fast reactions are usually highly exothermic, and heat removal is an important factor in controlling such reactions. Heat transfer occurs very rapidly in microreactors by virtue of a large surface area per unit volume, making precise temperature control possible. Fast reactions often involve highly unstable intermediates, which decompose very quickly, making reaction control difficult. The residence time can be greatly reduced in microreactors, and this feature is quite effective in controlling such reactions. For extremely fast reactions, kinetics often cannot be used because of the lack of homogeneity of the reaction environment when they are conducted in conventional reactors such as flasks. Fast mixing using micromixers solves such problems. The concept of flash chemistry has been successfully applied to various organic reactions including a) highly exothermic reactions that are difficult to control in conventional reactors, b) reactions in which a reactive intermediate easily decomposes in conventional reactors, c) reactions in which undesired byproducts are produced in the subsequent reactions in conventional reactors, and d) reactions whose products easily decompose in conventional reactors. The concept of flash chemistry can be also applied to polymer synthesis. Cationic polymerization can be conducted with an excellent level of molecular-weight control and molecular-weight distribution control.     

纳米沸石修饰微通道反应器内固定化酶催化的水解反应动力学

通过在毛细管内层叠层组装纳米沸石并固定脂肪酶来构建纳米沸石修饰的固定化酶微反应器通道,将纳米沸石良好的生物相容性和高的酶固定能力与微反应器反应效率高、扩散传质快等优点相结合. 以对硝基苯棕榈酸酯的水解作为探针反应对该微反应器内固定化酶催化水解反应动力学进行了研究和计算,并与普通反应器内同样的反应进行比较. 通过对比米氏方程参数,证实在微反应器内酶催化水解反应效率可比普通反应器内提高3倍以上并可提高酶和反应底物的亲和能力.     

Monolith and coating enzymatic microreactors of L-asparaginase: kinetics study by MCE-LIF for potential application in acute lymphoblastic leukemia (ALL) treatment

The study of enzyme immobilization using an extracorporeal shunt system is essential to eliminate the side effects of L-asparaginase (L-Asnase; including hepatic toxicity, allergic reaction, pancreatitis, central nervous system toxicity and decreased synthesis of blood clotting factors) when it was applied as an anticancer drug given directly to patients by injection. Thus, the novel monolith and coating enzymatic reactors of L-asparaginase were provided in this assay and a microchip electrophoresis-laser induced fluorescence (MCE-LIF) method was set up for the enzyme kinetics study. The enzymatic reactors would be a promising in vitro therapeutic method in an extracorporeal shunt system for acute lymphoblastic leukemia (ALL) treatment. For the first time, L-asparaginase was covalently bound to the polymer monolith and coating in the capillary and the activity characteristics of these enzymatic microreactors have been probed by Michaelis-Menten kinetic constants. Meanwhile, the D,L-amino acids were chirally separated using microchip electrophoresis with a laser induced detector and D,L-aspartic acid (D,L-Asp) were tested for the L-asparaginase enzymatic reactor kinetics study. Furthermore, human serum adding with L-asparagine (L-Asn) as the sample was hydrolyzed by the enzymatic microreactors. The results demonstrated that the developed enzymatic microreactor of L-asparaginase would be a potential therapeutic protocol for ALL treatment.     

A novel method for determining residence time distribution in intricately structured microreactors

A precise characterisation of microreactors can be achieved by determining the residence time distribution as one of the most important flow characteristics. An approach specially designed for microreactor applications was developed, which employs a tracer 'injection' using the optical activation of a caged fluorescent dye. Furthermore, the effect of the laminar flow on the determination of the residence time distribution in microreactors has been taken into account during the measurements and their interpretation to fulfill the requirements of the so-called 'mixing-cup-problem' on the microscale. Residence time distributions for an intricately structured thin microreactor were determined for different velocities. The ideality of the stimulus signal generated by the newly introduced technique is demonstrated for an analytically well-defined straight channel and compared with a signal derived from deconvolution of non-ideal input signals.     

Effect of the microchannel plate design on the capacity of methanol steam reformers

Methanol steam reforming in microreactors is considered, and the effects of the microreactor geometry (cylindrical and rectangular) and microchannel plate (MCP) design on the hydrogen capacity of the microreactor is analyzed. The MCPs were made from aluminum foil, stainless steel, and foamed nickel by laser engraving, electrochemical etching, and pressing. The amount of catalyst powder (CuO/ZnO = 40: 60 mol/mol) fixed on one MCP was 0.04–2.5 g. The specific hydrogen capacity (U _w) of the cylindrical microreactor is more than 3 times as high as the U _w of the rectangular microreactor and is 6 times as high as the U _w of a conventional fixed-bed catalytic reactor. This gain in hydrogen capacity is due to the more efficient use of the catalyst in the microreactors. The MCP design, which determines the residence time of the reactants in the microreactor, also has a significant effect on the capacity of the microreactor.     

基于超亲水纳米通道的智能可控微反应器

对阳极氧化铝(Anodic Alumina Oxide, AAO)多孔膜进行低温空气等离子体处理得到超亲水纳米通道. 在此基础上引入油溶性铁磁流体(Ferrofluid), 通过调节外磁场的方向和强度构建出智能可控微反应器. 该智能微反应器具有多梯度门控、 高电流门控比、 长期循环稳定性的特点. 将其分别用于均相和非均相反应中, 采用荧光分光光度计和扫描电子显微镜等手段进行表征. 结果表明, 不同门控状态下反应产物具有不同的产量和结构, 在微反应器的可控反应方面具有良好的应用前景.     

Dense ceramic catalytic membranes and membrane reactors for energy and environmental applications

Catalytic membrane reactors which carry out separation and reaction in a single unit are expected to be a promising approach to achieve green and sustainable chemistry with less energy consumption and lower pollution. This article presents a review of the recent progress of dense ceramic catalytic membranes and membrane reactors, and their potential applications in energy and environmental areas. A basic knowledge of catalytic membranes and membrane reactors is first introduced briefly, followed by a short discussion on the membrane materials including their structures, composition and strategies for material development. The configuration of catalytic membranes, the design of membrane reaction processes and the high temperature sealing are also discussed. The performance of catalytic membrane reactors for energy and environmental applications are summarized and typical catalytic membrane reaction processes are presented and discussed. Finally, current challenges and difficulties related to the industrialization of dense ceramic membrane reactors are addressed and possible future research is also outlined.     

Green Effectively Enhanced Extraction to Produce Yttrium(III) in Slug Flow Microreactor

Process reinforcement research was carried out in Y‐junction slug flow microreactors under variable conditions, using EHEHPA (2‐ethylhexyl phosphonic acid mono‐2‐ethylhexyl) to extract yttrium(III) from hydrochloric acid solution. The influence of pH and flow rate on the extraction‐reaction efficiency, slug size, mass transfer performance was assessed. The experimental results showed that maximum extraction‐reaction efficiency of 91.85% can be achieved in the smallest microreactor (residence time is 11.25 s), which was significantly higher than traditional extraction requiring more than 10 min. The slug length tended to decrease with the increase of pH and flow rate. Volumetric mass transfer coefficients for the slug flow microreactors were found to be in the range of 1.39×10^?1—1.642 s^?1 that is several orders of magnitude higher as compared to traditional extractors, which testified the beneficial effects of Y‐junction slug flow microreactor. Significant mass transfer reinforcement has prompted the use of microreactor as a suitable alternative to traditional extractors, which can advantageously improve the economic and environmental development of mineral processing.