微反应器和微聚合反应器

微反应器是指容量仅为零点几μm^3或宽度为1μm左右的反应“容器”，反应在这个微小区域内有控地进行。以表面科学与微制造技术为核心，新型微反应器近年来发展很快。本文介绍五种微反应器，即反相胶束微反应器，聚合物微反应器，固体模板微反应器，微条纹反应器和微聚合反应器，以及它们在各高科技领域中的可能应用。     

微通道反应器在合成工艺改进中的应用研究进展

随着对低耗能、环保、连续化生产工艺的不断探索,微通道反应器极佳的传质传热性能、精确的反应条件控制及反应过程的安全性等优势引起了研究人员的广泛关注。本文就微通道反应器的研究进展及其在工艺参数优化、连续化合成中的应用进行综述,对反应器现存问题及解决方法进行分析,并对其未来发展进行展望。     

微通道反应器在合成反应中的应用

微流控学(microfluidics)是在微米级结构中操控纳升至皮升体积流体的技术与科学,是近10年来迅速崛起的新交叉学科.流体在微流控芯片微米级通道中,由于尺度效应导致了许多不同于宏观体系的特点,例如分子间扩散距离短、微通道的比表面积大、传热和传质速度快等,促进了微流控芯片在有机合成反应中的发展.本文总结了微通道反应器的特点、微通道反应器中常用的流体驱动技术和微通道中流体的混合技术.通过一系列在微流控芯片中进行的有机合成反应,包括液-液均相反应、催化反应、相转移反应和异常激烈的有机合成反应等,进一步说明了微通道反应器同时具有微量和连续流动的优点.微通道反应器的发展不但在合成路线的优化方面有重要意义,而且有助于相关化学工业过程的改进.     

基于烧结微纤多孔结构材料的微反应器中的苯硝化反应

基于烧结微纤结构材料发展了一种集微混合、反应和换热于一体的微反应器,以苯硝化为模型反应考察了该微反应器用于快速、强放热的液-液两相混合反应的效果.烧结微纤材料具有大的空隙率、三维开放孔结构和大的面积与体积比,有利于传质和传热,同时微纤三维网络具有微搅拌器的作用,有利于流体的微米尺度分割和快速混合.因此,苯硝化反应得以在很短的时间内高选择性地进行完全.在一定的操作条件下,苯转化率可以达到91.7%,硝基苯选择性高达99.4%.     

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.     

连续流微通道反应技术在合成黄酮类天然产物中的应用研究

本文采用连续流微通道反应技术,通过碘介导的二氢黄酮的氧化反应对黄酮类化合物半合成工艺进行了研究。首先选择黄酮类代表药物地奥司明为研究对象,通过连续流微通道反应器分别考察了在常压和背压条件下不同反应条件的影响,实现橙皮苷转化率98%,产品地奥司明收率90%。然后,采用连续流微通道反应完成了多种黄酮、黄酮醇和异黄酮类天然产物的合成。本文研究的黄酮类天然产物的连续流微通道反应工艺,不仅实现了与传统工艺相当的转化率和收率,而且反应时间从传统工艺的8~20小时缩短到2~3 min,反应过程更加安全、高效和快捷,同时拓展了连续流微通道反应技术在药物合成领域的应用范围。     

微通道反应器内"就地"合成沸石膜催化层及其性能

采用简单、新颖的沸石粒子引入方法,将NaX沸石晶种引入不锈钢微反应器的微通道内,并用流动法"就地"直接在微通道内通过沸石生长形成NaX沸石膜层,经铯离子交换处理成为CsNaX催化层,用苯甲醛和氰基乙酸乙酯的Knoevenagel缩合反应评价了该催化层的催化性能.结果表明,微通道内形成的沸石膜层连续,均匀,具有良好的催化功能.微反应器内缩合反应的结果明显优于传统反应器.     

微反应技术在均相反应中的应用

微反应技术是研究和开发新型化学过程的合适方法，能够精准控制混合时间和反应温度，获得高重复性结果，提高反应效率。微反应技术可应用于均相和多相反应体系，尤其适合处理高温、高压、强放热反应和易燃、易爆、有毒有害原料或中间体。本文总结了近年来微反应技术应用在不同均相反应中的研究，包括酸催化反应、光化学反应、不对称催化反应、其他液-液相及临界反应。提出了目前微反应技术在工程应用的主要问题和相关解决方案。模拟及研发新型微通道反应系统的关键在于统筹多尺度界面强化效果，结合其他使能技术避免潜在通道堵塞，通过破乳技术改善微界面反应条件，开发用于特殊复杂环境的新型复合通道材料，为今后微反应系统的工业化设计和优化提供参考。     

基于MCM-41微反应器的微波辅助合成新方法研究

采用微波辐射合成法合成了纳米介孔分子筛MCM-41作为微反应器.以苯并呋喃-2(3H)-酮的合成为实例,在甲苯介质中将邻羟基苯乙酸组装到MCM-41微反应器中,研究了溶液体系及微反应器中反应温度、反应时间及微波辐射时间对反应的影响.结果显示,在施加微波与不施加微波情况下,MCM-41微反应器中进行的反应较溶液体系中进行的反应产率提高了2～33与2～12倍.对于MCM-41微反应器中的反应,施加微波辐射后反应产率可进一步提高20%～100%.     

毛细管电泳柱端酶微反应器研究进展

微反应器是指使物理、化学、生化等反应在微小的空间内发生的装置。微反应器能减少试剂消耗和样品污染,且反应条件易于控制,特别适合于酶促反应分析,因而多为酶微反应器。微反应器与电泳联用时,可将毛细管柱端作为微反应器,集反应与分离于一根毛细管柱上,可实现反应与分离一次性完成。根据酶微反应器制备原理的不同进行分类,综述了近2年来毛细管电泳柱端酶微反应器的研究进展。     

电泳芯片结构和芯片电泳分离操作参数的模拟、优化和实验验证

选择了L-精氨酸和L-苯丙氨酸为分离样品体系,根据电泳实验提出样品基本参数,通过模拟计算考察了进样管道宽度和进样时间对进样方差的贡献;根据分离度与分离长度拟合曲线确定电泳芯片的有效分离长度;对化学发光柱后衍生管道施加的夹流电压进行了模拟优化,得出氨基酸体系分离分析的电泳芯片设计方案和操作参数为:进样管道宽度为分离管道宽度的1/2,简单进样充样时间应大于5 s,分离管道有效分离长度为30 mm,衍生夹流比1.0~1.6。根据模拟优化结果提出了电泳芯片设计方案,采用整体浇注法制作带有柱后衍生反应器的PDMS电泳芯片,按照模拟计算提出的电压操作参数实现了精氨酸和苯丙氨酸样品体系的准确进样、芯片电泳分离和柱后衍生化学发光检测。电泳过程模拟结果和实验结果相结合,考察了柱后衍生对样品谱带展宽的影响,简单进样过程样品泄露引起的谱峰拖尾现象,并讨论了夹流进样法对减小进样方差和抑制样品泄露的贡献。     

Optimization of Glycosylation Reactions in a Microreactor

Glycosylations are notoriously difficult reactions that require extensive optimization regarding the type of anomeric leaving group, solvent, reaction temperature, and reaction time. Described is the use of a silicon‐based microreactor to screen reaction conditions and to scale‐up synthetic procedures. For the first time, glycosyl phosphates were employed in a microreactor. The optimized reaction conditions were successfully transferred to a batch process.     

Product selectivity control induced by using liquid-liquid parallel laminar flow in a microreactor

Product selectivity control based on a liquid-liquid parallel laminar flow has been successfully demonstrated by using a microreactor. Our electrochemical microreactor system enables regioselective cross-coupling reaction of aldehyde with allylic chloride via chemoselective cathodic reduction of substrate by the combined use of suitable flow mode and corresponding cathode material. The formation of liquid-liquid parallel laminar flow in the microreactor was supported by the estimation of benzaldehyde diffusion coefficient and computational fluid dynamics simulation. The diffusion coefficient for benzaldehyde in Bu(4)NClO(4)-HMPA medium was determined to be 1.32 × 10(-7) cm(2) s(-1) by electrochemical measurements, and the flow simulation using this value revealed the formation of clear concentration gradient of benzaldehyde in the microreactor channel over a specific channel length. In addition, the necessity of the liquid-liquid parallel laminar flow was confirmed by flow mode experiments.     

PDMS-glass hybrid microreactor array with embedded temperature control device. Application to cell-free protein synthesis

A microreactor array was developed which enables high-throughput cell-free protein synthesis. The microreactor array is composed of a temperature control chip and a reaction chamber chip. The temperature control chip is a glass-made chip on which temperature control devices, heaters and temperature sensors, are fabricated with an ITO (indium tin oxide) resistive material. The reaction chamber chip is fabricated by micromolding of PDMS (polydimethylsiloxane), and is designed to have an array of reaction chambers and flow channels for liquid introduction. The microreactor array is assembled by placing the reaction chamber chip on the temperature control chip. The small thermal mass of the reaction chamber resulted in a short thermal time constant of 170 ms for heating and 3 s for cooling. The performance of the microreactor array was examined through the experiments of cell-free protein synthesis. By measuring the fluorescence emission from the products, it was confirmed that GFP (Green Fluorescent Protein) and BFP (Blue Fluorescent Protein) were successfully synthesized using Escherichia coli extract.     

Selective deprotection of trityl group on carbohydrate by microflow reaction inhibiting migration of acetyl group

The trityl group is an important and useful protecting group for primary hydroxy groups on carbohydrates. However, during deprotection, neighboring acetyl groups can easily migrate to the deprotected hydroxy groups. Hence, deprotection of trityl groups was optimized using a microreactor with regard to flow rate, reagent concentration, reaction time, and substrate concentration. The optimized microflow reaction conditions inhibited migration and could be applied to large-scale reactions and other substrates.     

Efficient photosensitized oxygenations in phase contact enhanced microreactors

A transparent dual-channel microreactor with highly enhanced contact area-to-volume ratio was fabricated for efficient photosensitized oxygenations. The dual-channel microreactor shielded with polyvinylsilazane (PVSZ) consisting of an upper channel for liquid flow and a lower channel for O(2) flow, allows sufficient phase contact along the parallel channels through a gas permeable PDMS membrane for maintaining the O(2) saturated solution. Under full exposure of reactants to light, the reactions in high concentration are completed in minutes rather than hours that it takes to complete in a batch reactor. Moreover, the scale-up process using the microreactor revealed higher productivity than the batch reactor, which would be valuable for the practical applications in a broad range of gas-liquid chemical reactions.     

Novel monolithic enzymatic microreactor based on single-enzyme nanoparticles for highly efficient proteolysis and its application in multidimensional liquid chromatography

In this work, a novel and facile monolithic enzymatic microreactor was prepared in the fused-silica capillary via a two-step procedure including surface acryloylation and in situ aqueous polymerization/immobilization to encapsulate a single enzyme, and its application to fast protein digestion through a direct matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (MALDI-TOF-MS) analysis was demonstrated. At first, vinyl groups on the protein surface were generated by a mild acryloylation with N-acryloxysuccinimide in alkali buffer. Then, acryloylated enzyme was encapsulated into polyacrylates by free-radical copolymerization with acrylamide as the monomer, N,N′-methylenebisacrylamide as the cross-linker, and N,N,N′,N′-tetramethylethylenediamine/ammonium persulfate as the initiator. Finally, polymers were immobilized onto the activated inner wall of capillaries via the reaction of vinyl groups. Capability of the enzyme-immobilized monolithic microreactor was demonstrated by myoglobin and bovine serum albumin as model proteins. The digestion products were characterized using MALDI-TOF-MS with sequence coverage of 94% and 29% observed. This microreactor was also applied to the analysis of fractions through two-dimensional separation of weak anion exchange/reversed-phase liquid chromatography of human liver extract. After a database search, 16 unique peptides corresponding to 3 proteins were identified when two RPLC fractions of human liver extract were digested by the microreactor. This opens a route for its future application in top–down proteomic analysis.     

Fabrication of a Flexible and Disposable Microreactor Using a Dry Film Photoresist

In this paper, we demonstrate that a low‐cost flexible microreactor can be manufactured using a dry film photoresist in conjunction with photolithographic and hot roll lamination techniques. A microfluidic flow path and sample reservoir patterns were prefabricated in a dry film photoresist tape using traditional photolithographic methods. This tape was sandwiched between two plastic films ‐ wells were prepouched on the cover film — that were bonded upon passage through a hot roll laminator. A simple Plexiglas reactor holder was designed and constructed to use in evaluating the flexible microchip reactor. We demonstrate a chemical synthesis of polyaniline that was performed with this polymeric microreactor using a hydrodynamic flow control system. The fabrication of this microreactor suggests that there is great potential for designing and prototyping disposable microscale reaction systems using dry film photoresist for a range of chemical and biochemical syntheses.     

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.