微流控二维电泳芯片的电压控制优化

基于微流控二维电泳芯片(2D-EMC)的流路特点,建立等效电阻模型,以便给出各端电压的合理取值范围,成功实现微流控芯片二维电泳分离.经实验测定各微通道电阻,在各端电压合理取值范围内,通过电流测量调整(优化)电压,得到了一组优化的电压控制方案,在化学发光-2D-EMC系统中成功实现了精氨酸和甘氨酸衍生物的二维分离.本方法显著减小了实现微流控芯片二维电泳分离的实验次数.     

3D打印微流控芯片技术研究进展

近年来,微流控技术在生命科学和医学诊断等领域得到广泛的应用,显示出了其在检测速度、精度以及试剂损耗等方面相比传统方法的显著优势.然而,使用从半导体加工技术继承而来的微加工技术制作微流控芯片具有比较高的资金和技术门槛,在一定程度上阻碍了微流控技术的推广和应用.近年来随着3D打印技术的兴起,越来越多的研究者尝试使用3D打印技术加工微流控芯片.相比于传统的微加工技术,3D打印微流控芯片技术显示出了其设计加工快速、材料适应性广、成本低廉等优势.本文针对近年来国内外在3D打印微流控芯片领域的最新进展进行了综述,着重介绍了采用微立体光刻、熔融沉积成型以及喷墨打印等3D打印技术加工制作微流控芯片的方法,以及这些微流控芯片在分析化学、生命科学、医学诊断等领域的应用,并对3D打印微流控芯片技术未来的发展进行了展望.     

微流控芯片上的免疫分析

近20年来,随着微流控芯片加工技术的不断发展,微流控分析已从一个概念发展为当前世界上最前沿的科技领域之一,微流控芯片上免疫分析的方法研究也取得重要进展。这些芯片包含传输流体的微通道和免疫分析程序中部分或全部的必要组件。微流控技术用于免疫分析在减少试剂用量、缩短分析时间、自动化等方面提高了分析性能。本文综述了微流控芯片上免疫分析的发展、分类,并评述了各类微流控免疫分析芯片的性能及优缺点。     

微流控液滴技术及其在生物医学分析中的应用进展

微流控芯片微滴技术作为一种基于微流控芯片的操控微小体积液体的新技术,以分散的微滴单元作为微反应器,它大大强化了微流控芯片的高灵敏度、低消耗、高通量和自动化等优点,受到日益广泛的重视,并在物理学、化学和生物学等领域中显示出巨大的应用潜力。文章叙述了微流控微滴领域的最新进展,对新的微滴生成技术及操控技术进行介绍,最后阐述了微滴技术在生物医学分析中的最新研究进展。     

基于流体动力单细胞高效捕获的微流控芯片结构研究进展

单细胞分析对于重大疾病的早期诊断及治疗、药物筛选和生理病理过程的研究具有重要意义。微流控芯片能够精确控制单细胞的微环境,实时监测单细胞的行为,已成为单细胞分析的强大工具。单细胞捕获是单细胞分析的重要步骤。目前已报道了多种微流控芯片用于单细胞捕获的方法,其中基于流体动力的微流控芯片单细胞捕获方法具有操作方便、单细胞捕获效率高等优点,受到研究人员的广泛关注及使用。为了全面了解基于流体动力的微流控芯片单细胞捕获方法的研究现状,掌握单细胞高效捕获的微流控芯片结构设计,实现单细胞精准快速分析,本文综述了基于流体动力的单细胞高效捕获（>70%）原理及微流控芯片结构,根据结构设计不同分为微井结构、微柱结构和旁路通道结构,介绍了单细胞高效捕获的微流控芯片优化过程,总结了微流控芯片的材质、结构特点及单细胞捕获效率等,对不同单细胞捕获结构的优势及不足进行了分析。最后,对基于流体动力的微流控芯片单细胞捕获方法的发展趋势进行了展望。     

微流控芯片检测技术进展

介绍了目前微流控芯片应用的3种主要检测手段:质谱检测器、电化学检测器和光学检测器。微流控芯片是微全分析系统(μ-TAS)中最活跃的领域和发展前沿。人们在微流控芯片的研究中已经取得了很大的进展,研制出了多种微型化、集成化的芯片,而与微流控芯片配套的高灵敏度微型检测系统更是研制的热点。     

微流控芯片上细胞培养与分析方法研究进展

微流控芯片以其强大的微流体和微小物质控制能力成为研究单细胞、细胞群落乃至生物组织的重要手段。在本篇综述中,我们将以微流控芯片上细胞体外培养模型的建立为主,对近几年来重要的研究工作加以评述,全面地介绍微流控技术在细胞生命科学研究中应用的优势和未来发展方向,具体包括微流控芯片的细胞操控能力、细胞培养微环境的构建以及芯片联用检测手段,希望为从事这一领域研究工作的读者提供一些新的思路。     

微流控系统在生化分析领域的新应用

微流控芯片是近年来新兴的研究领域,它由微米级别的微通道及辅助器件构成,并且有着低试剂消耗量、响应时间短、高精度、高灵敏度、高集成度和独特的微观物理现象等特性。微流控芯片的独特优势为生物样品的处理与分析、生物模拟、药物传递和多组分分析等领域提供了前所未有的机会。为获得理想、完善的微流控平台,还需进一步挖掘微流控芯片的潜在应用。本文回顾了微流控芯片在生化分析领域中的新应用,分析了其优劣势与存在的挑战,并预测了微流控芯片未来可能的发展趋势,指出了微流控芯片"走出实验室"投入实际应用的可能。     

小型化智能微进样器的研究及其在微流控芯片中的应用

介绍了小型化智能微进样器的原理,讨论了宏观试样与微流控芯片的接口技术及其在微流控芯片应用的可能性.     

微流控芯片微孔膜液-液萃取系统

微流控芯片(Microfluidic chip)是微全分析系统(MTAS)研究中最为活跃的领域和发展前沿,在仪器微型化方面展现出很多优点^[1].Kitamori等^[2,3]根据多相层流无膜扩散分离技术建立了芯片上的微流控液-液萃取分离系统,对芯片上的液-液萃取方法进行了系统的研究.     

Microfluidic chip for fast nucleic acid hybridization

The design and experimental verification of a fast nucleic acid hybridization microchip using the fluidic velocity and strain rate effects was conducted. This hybridization chip was able to increase the hybridization signal 6-fold, reduce non-specific target-probe binding and background noise within 30 min, as compared to conventional hybridization methods, which may take from 4 h to overnight. Excellent correlation between experimental results and simulation analysis was obtained in this study. A detailed study of a newly designed microfluidic chip for enhancing hybridization was conducted. Three different designs of devices were fabricated and tested. Two different lengths of targets, 25-mer oligonucleotide and 1.4 kb ssDNA, were tested in this study. The hybridization efficiency can be improved by introducing velocity and extensional strain rate to the sample. This study demonstrates that the signal in the proposed method exhibits intensities 6-fold higher than those in static conditions. The necessary time for the hybridization process can be reduced from overnight to 30 min using the methods developed in this study. Experimental results also show that the strain rate provides stronger effect on hybridization than that of velocity. Combining hybridization with microfluidic concepts of velocity and strain rate effects may provide additional specificity and efficiency in nucleic acid detection and genomic study. This microfluidic hybridization chip can provide potential application in genomic study.     

Green microfluidic devices made of corn proteins

An alternative green microfluidic device made of zein, a prolamin of corn, can be utilized as a disposable environmentally friendly microchip especially in agriculture applications. Using standard soft lithography and stereo lithography techniques, we fabricated thin zein films with microfluidic chambers and channels. These were bonded to both a glass slide and another zein film. The zein film with microfluidic features bonds irreversibly with other surfaces by vapor-deposition of ethanol to create an adhesive layer resulting in very little or no trapped air and small shape distortion. Zein-zein and zein-glass microfluidic devices demonstrated sufficient strength to facilitate fluid flow in a complex microfluidic design that showed no leakage under high hydraulic pressure. Zein-glass microfluidic devices with serpentine mixing design showed successful fluid manipulation as a concentration gradient of Rhodamine B solution was generated. The ease of fabrication and bonding and the flexibility and moldability of zein offer attractive possibilities for microfluidic device design and manufacturing. These devices can include several unit operations with mixing being one of the most commonly used. The zein-based microfluidic devices, made entirely from a biopolymer from agricultural origin, offer alternative environmentally friendly material choices that are less dependent on limited petroleum based polymer resources.     

Rapid fabrication of microfluidic devices in poly(dimethylsiloxane) by photocopying

A very simple and fast method for the fabrication of poly(dimethylsiloxane) (PDMS) microfluidic devices is introduced. By using a photocopying machine to make a master on transparency instead of using lithographic equipment and photoresist, the fabrication process is greatly simplified and speeded up, requiring less than 1.5 h from design to device. Through SEM characterization, any micro-channel network with a width greater than 50 microm and a depth in the range of 8-14 microm can be made by this method. After sealing to a Pyrex glass plate with micromachined platinum electrodes, a microfluidic device was made and the device was tested in FIA mode with on-chip conductometric detection without using either high voltage or other pumping methods.     

Simple and cheap microfluidic devices for the preparation of monodisperse emulsions

Droplet microfluidics, which can generate monodisperse droplets or bubbles in unlimited numbers, at high speed and with complex structures, have been extensively investigated in chemical and biological fields. However, most current methods for fabricating microfluidic devices, such as glass etching, soft lithography in polydimethylsiloxane (PDMS) or assembly of glass capillaries, are usually either expensive or complicated. Here we report the fabrication of simple and cheap microfluidic devices based on patterned coverslips and microscope glass slides. The advantages of our approach for fabricating microfluidic devices lie in a simple process, inexpensive processing equipment and economical laboratory supplies. The fabricated microfluidic devices feature a flexible design of microchannels, easy spatial patterning of surface wettability, and good chemical compatibility and optical properties. We demonstrate their utilities for generation of monodisperse single and double emulsions with highly controllable flexibility.     

A review on continuous-flow microfluidic PCR in droplets: Advances,challenges and future

Significant advances have been made in developing microfluidic polymerase chain reaction (PCR) devices in the last two decades. More recently, microfluidic microdroplet technology has been exploited to perform PCR in droplets because of its unique features. For example, it can prevent crossover contamination and PCR inhibition, is suitable for single-cell and single-molecule analyses, and has the potential for system integration and automation. This review will therefore focus on recent developments on droplet-based continuous-flow microfluidic PCR, and the major research challenges. This paper will also discuss a new way of on-chip flow control and a rational design simulation tool, which are required to underpin fully integrated and automated droplet-based microfluidic systems. We will conclude with a scientific speculation of future autonomous scientific discoveries enabled by microfluidic microdroplet technologies.     

Rapid method for design and fabrication of passive micromixers in microfluidic devices using a direct-printing process

We developed a facile and rapid one-step technique for design and fabrication of passive micromixers in microfluidic devices using a direct-printing process. A laser printing mechanism was dexterously adopted to pattern the microchannels with different gray levels using vector graphic software. With the present method, periodically ordered specific bas-relief microstructures can be easily fabricated on transparencies by a simple printing process. The size and shape of the resultant microstructures are determined by the gray level of the graphic software and the resolution of the laser printer. Patterns of specific bas-relief microstructures on the floor of a channel act as obstacles in the flow path for advection mixing, which can be used as efficient mixing elements. The mixing effect of the resultant micromixer in microfluidic devices was evaluated using CCD fluorescence spectroscopy. We found that the mixing performance depends strongly on the gray level values. Under optimal conditions, fast passive mixing with our periodic ordered patterns in microfluidic devices has been achieved at the very early stages of the laminar flow. In addition, fabrication of micromixers using the present versatile technique requires less than an hour. The present method is promising for fabrication of micromixers in microfluidic devices at low cost and without complicated devices and environment, providing a simple solution to mixing problems in the micro-total-analysis-systems field.     

Numerical simulation of polymerization in interdigital multilamination micromixers

Free radical polymerization in microfluidic devices modeled with the help of numerical simulations is discussed. The simulation method used allows the simultaneous solvation of partial differential equations resulting from the hydrodynamics, thermal and mass transfer (convection, diffusion and chemical reaction). Three microfluidic devices are modeled, two interdigital multilamination micromixers respectively with a large and short focusing section, and a simple T-junction followed by a microtube reactor together considered as a bilamination micromixer with a large focusing section. The simulations show that in spite of the heat released by the polymerization reaction, the thermal transfer in such microfluidic devices is high enough to ensure isothermal conditions. Moreover, for low radial Peclet number, microfluidic devices with a large focusing section can achieve better control over the polymerization than a laboratory scale reactor as the polydispersity index obtained is very close to the theoretical limiting value. As the characteristic dimension of the microfluidic device increases, i.e. for high radial Peclet number, the reactive medium cannot be fully homogenized by the diffusion transport before leaving the system resulting in a high polydispersity index and a loss in the control of the polymerization.     

Polymer microfabrication technologies for microfluidic systems

Polymers have assumed the leading role as substrate materials for microfluidic devices in recent years. They offer a broad range of material parameters as well as material and surface chemical properties which enable microscopic design features that cannot be realised by any other class of materials. A similar range of fabrication technologies exist to generate microfluidic devices from these materials. This review will introduce the currently relevant microfabrication technologies such as replication methods like hot embossing, injection molding, microthermoforming and casting as well as photodefining methods like lithography and laser ablation for microfluidic systems and discuss academic and industrial considerations for their use. A section on back-end processing completes the overview.     

Design and fabrication of chemically robust three-dimensional microfluidic valves

A current problem in microfluidics is that poly(dimethylsiloxane) (PDMS), used to fabricate many microfluidic devices, is not compatible with most organic solvents. Fluorinated compounds are more chemically robust than PDMS but, historically, it has been nearly impossible to construct valves out of them by multilayer soft lithography (MSL) due to the difficulty of bonding layers made of "non-stick" fluoropolymers necessary to create traditional microfluidic valves. With our new three-dimensional (3D) valve design we can fabricate microfluidic devices from fluorinated compounds in a single monolithic layer that is resistant to most organic solvents with minimal swelling. This paper describes the design and development of 3D microfluidic valves by molding of a perfluoropolyether, termed Sifel, onto printed wax molds. The fabrication of Sifel-based microfluidic devices using this technique has great potential in chemical synthesis and analysis.     

Microfluidic depletion of endothelial cells, smooth muscle cells, and fibroblasts from heterogeneous suspensions

Interactions between ligands and cell surface receptors can be exploited to design adhesion-based microfluidic cell separation systems. When ligands are immobilized on the microfluidic channel surfaces, the resulting cell capture devices offer the typical advantages of small sample volumes and low cost associated with microfluidic systems, with the added benefit of not requiring complex fabrication schemes or extensive operational infrastructure. Cell-ligand interactions can range from highly specific to highly non-specific. This paper describes the design of an adhesion-based microfluidic separation system that takes advantage of both types of interactions. A 3-stage system of microfluidic devices coated with the tetrapeptides arg-glu-asp-val (REDV), val-ala-pro-gly (VAPG), and arg-gly-asp-ser (RGDS) is utilized to deplete a heterogeneous suspension containing endothelial cells, smooth muscle cells, and fibroblasts. The ligand-coated channels together with a large surface area allow effective depletion of all three cell types in a stagewise manner.