液滴微流控的集成化放大方法研究进展

相比于传统乳化方法,液滴微流控技术可以在微通道内可控制备单分散液滴模板用于合成各种功能微球,被广泛应用于生物、医疗、制药、环境等领域。由于单个液滴制备微流控单元的产量低,液滴微流控的集成化放大成为了液滴微流控技术面向工业应用的技术难点。本文综述了近年来液滴微流控集成化放大方法的研究进展,重点介绍了不同类型液滴制备微流控单元集成化放大的研究进展,包括基于剪切力形成液滴、基于界面张力形成液滴和基于被动分裂形成液滴的液滴制备微流控单元的集成化放大方法。     

微通道内卫星液滴生成机理与惯性分离机制

由于非线性动态特征，液液界面破裂过程常伴随卫星液滴的产生，对基于液滴的微流体技术生产液滴的均一性和精准化目标提出了挑战。阐释了微流体界面失稳的复杂动力学特征，剖析了界面失稳的影响因素，并分析了伴随界面失稳而产生的卫星液滴的现象与原理。结合惯性微流体新概念，总结了卫星液滴的惯性分离机制。展望了卫星液滴生成-惯性微流体分离一体化及其并行化数目放大的构想。相关工作的开展，有利于实现微流体技术生产单分散性液滴的精准化目标，为微流体与复杂流体相关的界面动力学行为与调控夯实基础。     

液液微分散及其用于标准颗粒制备的研究进展

液液分散与液滴生成是化工生产最典型的多尺度动态过程之一，针对该类过程的精准控制是化工研究的难点与重点。近年来，伴随机械微加工与流体微量输运技术的快速兴起，基于微米尺度作用的微化工技术在液液分散与液滴生成的调控中展现出了显著优势，成为化工研究的前沿方向。本文针对近年来在微分散基本规律、微分散动态界面现象与微分散标准颗粒材料等领域的研究进展进行综述：围绕微分散基本规律，介绍了微尺度液滴破碎的主导作用力、液液微分散流型及微分散数值模拟方法；围绕微分散动态界面现象，分析了动态界面张力的变化规律及其影响因素；围绕微分散标准颗粒制备，简述了微分散颗粒制备的主流技术及其适用范围。同时，针对相关领域的发展方向进行了展望。     

微通道并行模块化设计制造及规模化制备功能材料

液滴微流控技术可控制备功能微粒材料目前一直局限于实验室规模产量,制约着规模化的产业应用。本文基于微通道并行概念,以数量放大为基本原则,设计了八通道并行的微流控放大模块,模块由位于不同平面的两相流体的分配功能区和液滴制备功能区构建组合而成。借助激光雕刻技术以PMMA作为基板材料进行加工制造,实现了规模化制备均匀液滴的目的。同时研究了流速控制对各个通道液滴制备过程的影响,分析了微通道阵列由于流体分配关键问题所产生的放大效应。两种通道阵列形式对比实验表明,环形阵列制备出液滴的均匀性比线性阵列提高近42.4%,主要得益于完全对称的环形阵列减小了结构性因素对流体分配性能的影响。并借助环形并行模块平台大规模制备了具有广阔应用前景的壳聚糖微球,平均粒径为540.59μm,CV值为2.73%,并行放大模块在提升产量的同时确保了微球的高单分散性。     

微通道内液滴/气泡破裂动力学分析

微化学工程与技术是现代化学工程学科的前沿领域。微通道内液滴及气泡破裂动力学是决定多相过程并行微通道数目放大的基础与难点。破裂流型转换条件、界面动力学和尺寸调控等三方面是微通道内液滴与气泡破裂动力学的主要研究对象。讨论了对称微通道、非对称微通道、多级微通道、旁路微通道、含有障碍物的微通道内气泡和液滴破裂行为及影响因素,指出了目前微尺度下气泡与液滴破裂行为相关研究工作存在的不足,并对该领域未来的发展进行了展望。     

微通道内气-液两相流及并行放大的研究进展

微化工技术从基础研究到工业应用的关键步骤是过程放大。为了实现产品的高通量、易控制和连续生产,微化工过程的研究主要集中于单通道内多相流的稳定性和微通道的并行放大。对单微通道内气液两相流的流型及其对传质的影响进行了综述,阐明了微通道内气液两相流的流动稳定性和传质高效性。同时,综述了微化工技术的应用现状,证明了微化工技术在工业化应用中的潜力。此外,综述了对称并行放大和非对称并行放大2种基本并行放大方式的研究进展,对其中的流体分布及其对传质的影响进行了总结。最后,对未来的研究方向进行了展望。     

微通道内气泡和液滴自组织行为的研究进展

微流体技术良好的可控性为制备高通量的单分散性气泡或液滴提供了新的途径，气泡和液滴的流动行为因在材料领域具有较大的应用前景而受到关注。综述了近年来微通道内气泡和液滴自组织行为的研究进展。气泡或液滴自组织晶格具有周期性的流动特征，自组织行为受分散相体积分数、液滴或气泡尺寸、聚并效应和通道构型的影响。展望了气泡和液滴自组织行为研究过程中待解决的关键科学问题，为进一步的模拟和实验研究提供了参考。     

液-液两相流体黏度对微通道内流型的影响

为了研究流体黏度对液-液两相流流型的影响，采用实验和数值模拟相结合的方法,研究十字型微通道内液-液两相流流型变化。结果表明，当两相流体系中存在高黏度流体时，会加剧两相界面的不稳定性，两相流流型极易向不规则流和环状流转换，且当连续相流体黏度较高时，液滴的形状更易为子弹流。通过引入毛细数和韦伯数，提出两相流流型转换关系。当连续相流体和分散相流体分别由水平通道和垂直通道流入时，通过合理调节两相流体流速，可在微通道下游实现大小液滴的融合。这一方式将为高黏度流体流动操控提供新思路，通过控制两相流速，可以实现不依赖于复杂微通道结构的液滴被动融合。     

液滴流微反应器的基础研究及其应用

综述了近些年来快速发展的液滴微流控技术, 回顾了微流控系统中液滴的基本行为, 如液滴的生成、运动、聚并和分裂等研究进展, 重点探讨微液滴作为反应器其内部的流动、传质和反应过程, 以及液滴流微反应器已有的和潜在的重要应用价值。通过精确调控液滴在微尺度上的行为(产生、聚并与分裂、内部的混合与反应等), 使单个液滴成为新型受限空间内的微型间歇反应器, 而微通道内的液滴流进而形成了若干间歇反应器构成的连续流反应器新型式。除了微流控技术普遍具有的微小尺寸效应带来传质传热强化、易于放大等优势外, 液滴流微反应器还具有诸如避免试剂交叉污染、液滴内部可控混合、易于独立调控、便于高通量筛选或者制备等独特特点, 使得其在功能材料制备、化学合成以及生物化工方面有着广泛的应用。     

微胶囊的微流体数字化技术制备方法及实验装置

提出了一种新的基于微流体数字化技术的单分散微胶囊制备方法。该方法通过对微喷嘴施加小幅可控的脉冲惯性力，完成对微胶囊材料的小份分割、数字化传输及喷射。使用该方法进行了海藻酸钠对芝麻油微胶囊化的实验。制备过程中，每个驱动脉冲喷射出一颗微胶囊乳化液液滴。制备的节拍既可以是连续的，也可以是编码的，因此可以对制备过程进行有效的控制。通过改变微喷嘴内径可以制备出微米级系列尺寸的规整化的微胶囊，微胶囊粒径分布窄。     

Synthesis of crystals and particles by crystallization and polymerization in droplet-based microfluidic devices

The recent advances in crystallization and polymerization assisted by droplet-based microfluidics to synthesize micro-particles and micro-crystals are reviewed in this paper. Droplet-based microfluidic devices are powerful tools to execute some precise controls and operations on the flow inside microchannels by adjusting fluid dynamics parameters to produce monodisperse emulsions or multiple-emulsions of various materials. Major features of this technique are producing particles of monodispersity to control the shape of particles in a new level, and to generate droplets of diverse materials including aqueous solutions, gels and polymers. Numerous microfluidic devices have been employed to generate monodisperse droplets of range from nm to μm, such as T junctions, flow-focusing devices and co-flow or cross-flow capillaries. These discrete, independently controllable droplets are ideal microreactors to be manipulated in the channels to synthesize the nanocrystals, protein crystals, polymer particles and microcapsules. The generated monodisperse particles or crystals are to meet different technical demands in many fields, such as crystal engineering, encapsulation and drug delivery systems. Microfluidic devices are promising tools in the synthesis of micron polymer particles that have diverse applications such as the photonic materials, ion-exchange and chromatography columns, and field-responsive rheological fluids. Processes assisted by microfluidic devices are able to produce the polymer particles (including Janus particles) with precise control over their sizes, size distribution, morphology and compositions. The technology of microfluidics has also been employed to generate core-shell microcapsules and solid microgels with precise controlled sizes and inner structures. The chosen “smart” materials are sensitive to an external stimulus such as the change of the pH, electric field and temperature. These complex particles are also able to be functionalized by encapsulating nanoparticles of special functions and by attaching some special groups like targeting ligands. The nucleation kinetics of some crystals like KNO₃ was investigated in different microfluidic devices. Because of the elimination of the interactions among crystallites in bulk systems, using independent droplets may help to measure the nucleation rate more accurately. In structural biology, the droplets produced in microfluidic devices provide ideal platforms for protein crystallization on the nanoliter scale. Therefore, they become one of the promising tools to screen the optimal conditions of protein crystallization.     

Synthesis of crystals and particles by crystallization and polymerization in droplet-based microfluidic devices

The recent advances in crystallization and polymerization assisted by droplet-based microfluidics to synthesize micro-particles and micro-crystals are reviewed in this paper. Droplet-based microfluidic devices are powerful tools to execute some precise controls and operations on the flow inside microchannels by adjusting fluid dynamics parameters to produce monodisperse emulsions or multiple-emulsions of various materials. Major features of this technique are producing particles of monodispersity to control the shape of particles in a new level, and to generate droplets of diverse materials including aqueous solutions, gels and polymers. Numerous microfluidic devices have been employed to generate monodisperse droplets of range from nm to μm, such as T junctions, flow-focusing devices and co-flow or cross-flow capillaries. These discrete, independently controllable droplets are ideal microreactors to be manipulated in the channels to synthesize the nanocrystals, protein crystals, polymer particles and microcapsules. The generated monodisperse particles or crystals are to meet different technical demands in many fields, such as crystal engineering, encapsulation and drug delivery systems. Microfluidic devices are promising tools in the synthesis of micron polymer particles that have diverse applications such as the photonic materials, ion-exchange and chromatography columns, and field-responsive rheological fluids. Processes assisted by microfluidic devices are able to produce the polymer particles (including Janus particles) with precise control over their sizes, size distribution, morphology and compositions. The technology of micro-fluidics has also been employed to generate core-shell microcapsules and solid microgels with precise controlled sizes and inner structures. The chosen “smart” materials are sensitive to an external stimulus such as the change of the pH, electric field and temperature. These complex particles are also able to be functionalized by encapsulating nanoparticles of special functions and by attaching some special groups like targeting ligands. The nucleation kinetics of some crystals like KNO₃ was investigated in different microfluidic devices. Because of the elimination of the interactions among crystallites in bulk systems, using independent droplets may help to measure the nucleation rate more accurately. In structural biology, the droplets produced in microfluidic devices provide ideal platforms for protein crystallization on the nanoliter scale. Therefore, they become one of the promising tools to screen the optimal conditions of protein crystallization.     

Recent developments in scale-up of microfluidic emulsion generation via parallelization

Microfluidics affords precise control over the flow of multiphasic fluids in micron-scale channels. By manipulating the viscous and surface tension forces present in multiphasic flows in microfluidic channels, it is possible to produce highly uniform emulsion droplets one at a time. Monodisperse droplets generated based on microfluidics are useful templates for producing uniform microcapsules and microparticles for encapsulation and delivery of active ingredients as well as living cells. Also, droplet microfluidics have been extensively exploited as a means to enable highthroughput biological screening and assays. Despite the promise droplet-based microfluidics hold for a wide range of applications, low production rate (<<10mL/hour) of emulsion droplets has been a major hindrance to widespread utilization at the industrial and commercial scale. Several reports have recently shown that one way to overcome this challenge and enable mass production of microfluidic droplets is to parallelize droplet generation, by incorporating a large number of droplet generation units (N>>100) and networks of fluid channels that distribute fluid to each of these generators onto a single chip. To parallelize droplet generation and, at the same time, maintain high uniformity of emulsion droplets, several considerations have to be made including the design of channel geometries to ensure even distribution of fluids to each droplet generator, methods for large-scale and uniform fabrication of microchannels, device materials for mechanically robust operation to withstand high-pressure injection, and development of commercially feasible fabrication techniques for three-dimensional microfluidic devices. We highlight some of the recent advances in the mass production of highly uniform microfluidics droplets via parallelization and discuss outstanding issues.     

双重乳液的微流控制备进展

双重乳液是一种离散相液滴中还包裹着更小的液滴的高度结构化流体,单分散的在食品、化工、医疗等领域有着广泛的应用。微流控技术作为一门研究微尺度流体的新兴技术,已经成为制备优质双重乳液的首选。本文对被动式微流控技术进行了系统地综述,介绍了协流式、交叉流式、流动聚焦式微通道的结构及其乳化机理,展望了该项技术在微液滴制备方面的发展前景。在学科交叉应用的背景下,通过对微流控装置的改进与升级,可以克服常见微流控方法出现的双乳液生产效率低,不具备超薄壁结构等问题。此外,本文还讨论了微流控技术背景下双重乳液流型演化研究的进展,提出可以通过单乳液的研究基础,联系和发展双重乳液流型演化的完备理论体系。     

梳状并行微通道内液液分布规律研究

为了实现工业化应用,微反应器的并行放大已成为最有效的放大策略之一。在微反应器的放大过程中,相分布规律的研究是非常重要的。采用高速摄像仪研究了梳状并行微反应器的支通道间距和流量对液液两相分布的影响。当连续相和分散相流量Q_c及Q_d都较小时,不同支通道间距的微反应器内前方支通道的分散相含率较低,后方支通道的分散相含率较高,同时液滴长度的均匀性较差。随着Q_c与Q_d的增大,三种不同构型微反应器内分散相的体积相含率的数值分布逐渐趋于集中。在较高的两相流量下,支通道内液滴长度的均匀性显著提高,其变异系数小于0.15。在实验范围内,支通道间距S = 0.6 mm的微反应器中液滴尺寸均匀分布的操作范围最大。     

Untersuchungen zum Kristallisationsfouling in Mikrowärmeübertragern

The advantages of microstructure devices concerning heat and mass transfer are well known. However, the usage of microstructure devices in chemical industry is still limited today. A limitation for industrial application is the liability of microstructures to blocking due to impurity of the fluid or by unintended deposition (fouling) in the microchannels. Fouling can lead to a degradation of the heat transfer performance, to an increase of the pressure drop, to a change of the fluid distribution in the microstructures and to a shorter residence time of the fluid. In the framework of this research project a micro heat exchanger for fundamental experimental investigations on crystallization fouling of CaCO₃ in microchannels was developed and manufactured.     

Effect of microchannel structure on droplet size during crossflow microchannel emulsification

A monodispersed oil-in-water emulsion was continuously produced using a crossflow-type silicon microchannel plate in which a liquid flow path for the continuous phase was made, and on each side of the wall of the path, an array of regular-sized slits (microchannels) was precisely fabricated on a micrometer scale by photolithography. A flat glass plate was tightly attached to the microchannel plate to cover the top of the microchannels. Regular-sized oil (triolein) droplets were generated by pressing the oil through the microchannels into a continuous phase of 0.3 wt% aqueous sodium lauryl sulfate. The average size of the oil droplets was regulated within a range of 11.3 to 28.2 μm by changing the microchannel structural features such as the shape of the cross section and outlet, the equivalent diameter, and the length of the terrace, which is a flat area fabricated at the outlet of the microchannels. In every case, the droplet size distribution was narrow, and the geometric standard deviation was 1.03 or less.