微流控SERS及其在生物医学应用的研究进展

微流控芯片以其对微量样品的精确操控能力而引起特别关注,表面增强拉曼光谱(SERS)作为一种超灵敏的光谱检测技术近年来在痕量检测上应用广泛。微流控芯片与SERS相结合的系统可对微量生物样品进行无损、快速、高灵敏度且高通量的检测分析,在生物医学领域有巨大的应用潜力,是当前的研究热点之一。本文介绍了微流控SERS系统近年的发展情况,包括微流控芯片的制作加工和流体操控,以及微流控芯片中SERS基底的集成;并重点介绍了近年来SERS微流控芯片系统在生物医学上的应用,如生物分子的检测、细胞分析、药物监测和筛选、疾病诊断,以及在环境和食品健康安全方面的检测应用。     

微流控等离子体:新型过程强化技术

作为一种新型高效的过程强化技术,微流控等离子体具备微流控及等离子体技术优势,能够提高反应过程的均一性及稳定性,控制反应接触界面,在增加活性物质的密度的同时避免物种的快速猝灭。介绍了微流控等离子体中的活性组分及相应的表征手段,归纳了几种反应器结构并对比了优缺点。系统阐述了微流控等离子体过程强化技术在化学合成、表面改性、材料制备、污染物检测和生物医学领域中的应用,并立足于当前研究现状对该技术的发展趋势进行讨论与展望。     

微流控光学器件与系统的研究进展

微流控技术作为微全分析系统的关键与核心,一直是MEMS领域中的一个研究重点。随着微流控技术水平的不断提高以及与其它学科的不断渗透与融合,近年来已经涌现出一批令人注目的研究热点,其中微流控光学器件就是其典型代表。微流控技术与光学器件的融合,为传统光学器件的微型化、阵列化、低成本化以及高精度控制提供了可能。叙述了一些基于微流控技术的可变焦光透镜、显示器件、光开关、以及可调光纤光栅等新型光学器件的近期研究成果和应用背景。     

仿生微流控的发展与应用

仿生微流控技术将仿生结构设计应用到微流体装置中,具有很强的学科交叉性.本文提出了通过仿生手段突破微流控的技术瓶颈,从而提高微流控器件的抗污染性能,告别单一功能的微流控系统应用的局限性,实现微尺度下通道的智能化及动态环境变化下的高适应性等.本文提出了仿生微流控的概念,重点介绍了仿生微流控在器件抗污染、器件智能化、生物学和医药方面的最新研究进展,从仿生设计导入应用前景,并探讨了所涉及的物理问题和关键技术,以期为智能微流控芯片的设计开发和应用提供新思路,并为软物质的开发应用、多功能型智能化仿生器件的设计、制备及应用提供参考.     

声学微结构的微流控声场的改进与优化*

受限于加工工艺,目前多数的声表面波微流控芯片,主要依靠普通的直通道调节细胞流速,从而控制微球在通道中的排列。但其形成的声场通常无法满足低能量、多功能的微流控需要。本文在普通声表面波微流控芯片的基础上,分别在频域和时域内构建声学微结构,并改变微结构阵列中铜柱间距,模拟仿真了微流控芯片输出端的电势,发现其输出端电压得到了明显的改善。当输入电信号频率在0-30MHz时,输出端电势增加约0.25V;在0-1000ns内,输出端电势增加0.015V左右;进而可以探索开发性价比更高的声波微流控芯片,针对病理检测等所存在的问题进行分析优化,提出新的细胞分离等技术。     

基于微流控技术的水的太赫兹吸收特性研究

很多生物大分子的特征振动模式和转动模式都位于太赫兹波段范围内,且太赫兹波的低电子能特性使其在实验过程中不会对待测样品造成破坏,所以可以采用太赫兹技术来鉴别生物样品。在许多研究中,生物样品都是溶液状态,溶液中水和其他分子之间的相互作用涉及很多生物现象,所以研究水的太赫兹特性就显得至关重要。众所周知,水分子是十分常见的极性分子,分子间氢键会与太赫兹波发生强烈的相互作用,从而使得水对太赫兹波有很强的吸收作用,导致利用太赫兹技术研究水溶液中生物样品的动态特性变得相当困难。为了解决这一难题,可以引入微流控技术。微流控技术以能精确操控微尺度流体而著称,其沟道深度可以达到50μm甚至更小。由于微流控技术减小了太赫兹波在流体中的传播距离,从而极大地减小了水对太赫兹波的吸收。本研究采用对太赫兹波具有高透过率的Zeonor 1420R材料制成了夹心式微流控芯片,芯片上微沟道的长度、宽度和深度分别为3 cm,4 mm和50 μm,太赫兹探测区的直径为3 mm。在制作微流控芯片时,利用厚度为50μm的强黏性双面胶代替传统夹心式微流控芯片中的聚二甲基硅氧烷(PDMS)薄膜,使微流控芯片在加热过程中不再有漏液现象。另外,设计了一个温控系统,它由加热片、温度传感器和温控仪构成,该温控系统能够以0.1 ℃的精度控制温度。利用该系统对微流控芯片中的去离子水进行加热,从20～90 ℃每隔5 ℃进行一次太赫兹透射测量,通过对实验数据的分析,发现随着温度升高,水的太赫兹透过率不断减小,说明水对太赫兹波的吸收随着温度的升高而变大。此结果为未来在不同环境温度下利用微流控技术研究液态样品的太赫兹吸收特性提供了先决条件,为未来太赫兹的应用与发展提供技术支持。     

磁致旋光增强效应与微量样品旋光检测方法

微流控光学检测系统的微型化和集成化是微流控技术的发展趋势,微量液体物质的旋光检测也是微流控光学技术的重要研究课题之一.分析了内含磁致旋光介质的旋光反射腔的偏光特性,理论预言这种旋光反射腔具有旋光增强效应,在此基础上提出了微量样品的旋光增强检测方法和器件设计原理.研究结果表明,该方法可以在小光程限制条件下显著提高磁旋光介质的检测灵敏度.在不考虑样品吸收的情况下.旋光增强法与普通消光法的检测灵敏度之比的极限约为78.5.该方法可以应用于微流控系统的旋光检测以及实现磁旋光仪器的小型化和微型化.     

微流控芯片流道特征超声C扫描分析*

微流控芯片流道宽度处于微米尺度,存在特征辨识困难的问题。该文选取两种具有不同流道宽度和布局的典型微流控芯片,采用超声C扫描技术进行流道特征成像。利用标称中心频率15 MHz、10 MHz和5 MHz聚焦探头实施水浸C扫描检测,并分析中心频率、焦斑直径、扫描步进等关键参数对流道表征的影响。实验结果表明,对于流道宽度200 μm的微流控芯片,当探头中心频率不低于10 MHz,扫描步进不超过0.1 mm时,成像分辨力和流道表征效果最佳,且流道中心间距测量误差不超过5%。同时,超声C扫描图像可以反映流道宽度变化,辨识发生堵塞的微流控芯片。     

磁场在微流控芯片中颗粒分离的发展和应用

<正>一、流控芯片技术与磁分离在过去的20年里,随着微纳米先进制造水平的提高,微流控技术作为微电机系统(microelectromechanical systems或MEMS)的一个重要分支,也得到了前所未有的快速发展。微流控(Microfluidics)是指在微尺度条件下(通常在微尺度管道网络内)对流体(体积在10~(-12)到10~(-6) L之间)进行精确操控所涉     

基于动态显微成像的红细胞多角度形态学分析方法

提出一种结合显微镜和微流控芯片技术的红细胞多角度形态学分析方法,实现了红细胞的动态显微成像,用于红细胞多角度形态学的测量与分析。利用微流控芯片的缩/扩结构使红细胞在特定位置产生旋转或翻转;利用MATLAB对采集到的视频图像进行分帧处理,通过灰度调整、中值滤波、形态学处理、质心法、目标物识别、动态跟踪等算法处理后,实现对血细胞的有效识别与准确的分类、计数;对分类结果进行多角度形态学分析,并对不同形态红细胞进行最大直径的测量。通过对单细胞多帧关联图像的分析,验证方法的准确性;并利用红细胞多角度形态学分析方法,对糖尿病患者血液及正常人血液进行实验。结果表明,糖尿病患者红细胞相比于正常人红细胞,其平均最大直径及分布宽度均增大。微流控芯片结合图像处理的方法可以实现糖尿病患者与正常人红细胞高通量检测及多角度分析,为其他类型样本细胞多角度形态学测量提供新方法。     

Microfluidic laser embedded in glass by three-dimensional femtosecond laser microprocessing

Microfluidic dye lasers three-dimensionally embedded in glass have been fabricated for what is believed to be the first time by integrating micro-optical and microfluidic components by use of a femtosecond laser. By pumping the microfluidic laser, in which the microfluidic chamber was filled with the laser dye Rhodamine 6G dissolved in ethanol, with a frequency-doubled Nd:yttrium aluminum garnet laser, lasing action was confirmed by analysis of the emission spectra at different pump powers. In addition, by arranging two microfluidic chambers serially in the glass, we built a microfluidic twin laser that produces an array of two simultaneous laser emissions with one pump laser.     

Electrophoresis Poly(Dimethylsiloxane)/Glass Chips with Integrated Active Cooling for Quantification of Amino Acids

Abstract

The objective of this work was to develop and characterize a poly(dimethylsiloxane) device with an integrated active cooling function able to carry out capillary electrophoresis separations. Polymer-based microdevices are indispensable to recent advances in biomedical analysis. In particular, they have been applied to many microfluidic platforms owing to their low cost, ease of fabrication, and versatility in preparing complex microstructures. However, when applied to capillary electrophoresis separations, polymer microfluidic structures present an inherent disadvantage compared to glass and Si structures; they have a lower thermal conductivity than glass and Si. Although miniaturized devices allow operation at high electric fields, they face separation efficiency limitations due to Joule heating. There is, therefore, a strong need of developing capillary electrophoresis microfluidic structures with active cooling in order to operate at a higher electric field and potentially increase separation efficiency in these microdevices. A poly(dimethylsiloxane)/glass hybrid microfluidic capillary electrophoresis system is presented, where Joule heating was minimized by using an integrated active cooling function. Two poly(dimethylsiloxane) slabs with embedded microfluidic structures were irreversibly sealed on both sides of a thin glass slide. The top poly(dimethylsiloxane) slab was used to carry out capillary electrophoresis separations, whereas the bottom poly(dimethylsiloxane) slab was employed to cool down the buffer solution used during the capillary electrophoresis separation. As demonstrated on current versus voltage plots and on capillary electrophoresis electropherograms, capillary electrophoresis separation was able to be operated at a higher electric field when using the cooling function. The cooling rate was adjustable by varying the flow rate and the initial temperature of the liquid flowing in the cooling microfluidic structure.     

Preparation of nanoparticles by continuous-flow microfluidics

We review a variety of micro- and nanoparticle formulations produced with microfluidic methods. A diverse variety of approaches to generate microscale and nanoscale particles has been reported. Here we emphasize the use of microfluidics, specifically microfluidic systems that operate in a continuous flow mode, thereby allowing continuous generation of desired particle formulations. The generation of semiconductor quantum dots, metal colloids, emulsions, and liposomes is considered. To emphasize the potential benefits of the continuous-flow microfluidic methodology for nanoparticle generation, preliminary data on the size distribution of liposomes formed using the microfluidic approach is compared to the traditional bulk alcohol injection method.     

聚甲基丙烯酸甲酯(PMMA)微流控芯片DNA分析系统的研制

生物分析是微流控芯片分析最具进一步发展及商品化前景的分支领域之一.报道了基于聚甲基丙烯酸甲酯(PMMA)微流控芯片DNA分析系统的研制.采用简易热压法自制的PMMA芯片,以小型光纤式激光诱导荧光为检测器,以四触点可切换1 800 V高压电源为电驱动系统,以2%羟乙基纤维素(HEC)为筛分介质,通过用于DNA分析的TO-PRO-3荧光染料和激光诱导荧光检测器670 nm截止滤光片的选择,构建了微流控芯片DNA分析系统.芯片凝胶电泳分离ψX174-HaeⅢRF DNA片段,以603 bp片段计算理论塔板数n为1.14×10~6·m~-1,271/281 bp的分离度R为1.2.建立的PMMA微流控芯片DNA分析系统具有制作和运行成本低,芯片可重复使用,分析重现性好等特点.该研究可用于制作微型化便携式DNA分析仪,应用于临床诊断、疾病筛查等领域.     

Multimode interference devices for focusing in microfluidic channels

Low-cost, compact, automated optical microsystems for chemical analysis, such as microflow cytometers for identification of individual biological cells, require monolithically integrated microlenses for focusing in microfluidic channels, to enable high-resolution scattering and fluorescence measurements. The multimode interference device (MMI), which makes use of self-imaging in multimode waveguides, is shown to be a simple and effective alternative to the microlens for microflow cytometry. The MMIs have been designed, realized, and integrated with microfluidic channels in a silica-based glass waveguide material system. Focal spot sizes of 2.4 μm for MMIs have been measured at foci as far as 43.7 μm into the microfluidic channel.     

微流控制备单分散微米级SiO2微球

采用软模板法制备出了聚二甲基硅氧烷微流控装置。利用该装置讨论了正硅酸乙酯和氨水的用量分别对反应体系凝胶化时间的影响,确定了制备SiO2微球的优化反应体系,即二甲基乙酰胺、正硅酸乙酯和氨水的体积比为8∶4∶1,实验所需的反应温度为60 ℃。实验发现:在微流体通道中,分散相的流速越大,粒径越大;连续相流速越大,粒径越小。因此,通过控制微流控装置中分散相和连续相的流速制备了粒径40~220 m的单分散SiO2微球,并对其形貌进行表征。光学显微镜和粒径分析均表明所制备的SiO2微球球形度高,单分散性好。     

Investigating passive immunodiffusion reactions in the channels of a microfluidic device

The passive immunodiffusion reaction in a microfluidic system is investigated via the interaction between fluorescein human albumin conjugate and monoclonal antibodies. The topology of a microfluidic device suitable for this reaction was designed, and the device was fabricated using LIGA technology. A system for transitioning from the macro- to the microlevel is developed and produced. The dissociation constants and specificity of interaction in complexes formed as a result of the reaction between fluorescein human albumin conjugates and monoclonal antibodies are determined. The results from our study reveal that systems based on combinations of passive immunodiffusion reactions and microfluidic technologies are applicable for detecting antigens and antibodies in the analyzed fluids.     

Microfluidic sample preparation for elemental analysis in liquid samples using micro X‐ray fluorescence spectrometry

The integration of microfluidic devices with micro X‐ray fluorescence (micro‐XRF) spectrometry offers a new approach for the direct characterization of liquid materials. A sample presentation method based on use of small volumes (<5 µl) of liquid contained in an XRF‐compatible device has been developed. In this feasibility study, a prototype chip was constructed, and its suitability for XRF analysis of liquids was evaluated, along with that of a commercially produced microfluidic device. Each of the chips had an analytical chamber which contained approximately 1 µl of sample when the device was filled using a pipette. The performance of the chips was assessed using micro‐XRF and high resolution monochromatic wavelength dispersive X‐ray fluorescence, a method that provides highly selective and sensitive detection of actinides. The intended application of the device developed in this study is for measurement of Pu in spent nuclear fuel. Aqueous solutions and a synthetic spent fuel matrix were used to evaluate the devices. Sr, which has its Kα line energy close to the Pu Lα line at 14.2 keV, was utilized as a surrogate for Pu because of reduced handling risks. Between and within chip repeatability were studied, along with linearity of response and accuracy. The limit of detection for Sr determination in the chip is estimated at 5 ng/µl (ppm). This work demonstrates the applicability of microfluidic sample preparation to liquid characterization by XRF, and provides a basis for further development of this approach for elemental analysis within a range of sample types. Copyright © 2014 John Wiley & Sons, Ltd.     

Towards a programmable magnetic bead microarray in a microfluidic channel

A new hybrid magnetic bead separator that combines an external magnetic field with 175 μm thick current lines buried in the back side of a silicon wafer is presented. A microfluidic channel was etched into the front side of the wafer. The large cross-section of the current lines makes it possible to use larger currents and obtain forces of longer range than from thin current lines at a given power limit. Guiding of magnetic beads in the hybrid magnetic separator and the construction of a programmable microarray of magnetic beads in the microfluidic channel by hydrodynamic focusing is presented.