纳流控芯片的微加工技术及其应用*

纳流控学和纳流控芯片应用于化学和生化分析的研究近年来取得了长足的发展。纳流控的基础和应用研究以纳流控芯片的研制为基础,而纳流控新品的制备需依靠微纳加工技术。本文着重介绍目前已经建立的纳流控芯片加工技术,包括掩膜加工法、牺牲层技术、模具加工法、化学-机械抛光法、机械拉伸技术以及其他的加工技术。此外,还简单介绍了纳流控芯片在试样预处理以及生化分析中的应用。     

制造玻璃微流控芯片的简易加工技术

报道了在普通化学实验室中设计和加工玻璃微流控芯片的方法。用Adobe Illustrator 8.0软件微流控片图形，通过高分辨率激光照排机在照相底片上制得光刻掩模。用商品匀胶铬板表面的145nm Cr/570nm Az-1805光胶层作为保护层，在50℃刻蚀液（1mol/L HF 1mol/L NaF)中，刻蚀速度为2μm/min。通过彻底洗净加工好的玻璃基片，提高了芯片热键合的质量和成品率。制得的芯片已成功地用于氨基酸分离和PCR扩增。     

模板法合成纳米通道在微流控系统中的应用

纳流控芯片作为研究单分子水平上分子行为的一种新工具,人们期待纳流控在生物技术等领域有更广泛的应用.纳米结构的制作,作为纳流控芯片应用的前提之一,正逐渐引起人们的重视.本文综述了近几年来纳流控芯片中模板法制作纳米结构的研究进展,主要是以氧化铝膜,多孔硅,以及其它一些带有纳米通道的物质为模板,制作纳米结构应用于纳流控生化分析.     

电泳芯片微通道中分子传递效率的比较研究

选用聚二甲基硅氧烷为电泳芯片材料,比较了同步辐射和紫外光刻蚀技术制作的芯片微通道内样品的分子分散特性.研究结果表明,采用同步辐射刻蚀技术制作的微通道具有更好的分子传递效率.根据扫描电子显微镜的表征结果初步推断,可能与通道的内表面的粗糙度有关.进一步的色谱保留分析证实了该假设的可靠性.     

玻璃微流控芯片廉价快速制作方法的研究

研究了一种玻璃微流控芯片的快速、低成本制作工艺和方法. 该方法采用商品化的显微载玻片(soda-lime玻璃)作为芯片基质材料, 利用AZ 4620光刻胶代替传统工艺中的溅射金属层或多晶硅/氮化硅层作为玻璃刻蚀的掩膜层, 同时利用一种紫外光学胶键合方法代替传统熔融键合方法实现芯片的键合, 整个工艺对玻璃基质材料要求低, 普通微流控芯片(深度小于50 μm)制作流程仅需约3.5 h, 可降低制作成本, 缩短制作周期. 还系统地研究了光刻胶厚度、光刻胶硬烘时间和玻璃腐蚀液配比对玻璃微流控芯片制作的影响, 获得了优化的工艺参数.     

聚二甲基硅氧烷/玻璃微流控芯片永久性粘合方法及其微通道表面改性研究及其应用

近年来,聚二甲基桂氧烷[Poly(dimethylsilloxane),PDMS]基质微流控芯片因其透光性能好,价格便宜,加工容易,适合大规模生产,成为微全分析系统(Micro total analysis system,μ-TAS)发展的一个热点^[1].PDMS易于复制微通道形状,且具有较高的保真度,省去了玻璃芯片刻蚀的复杂过程;而玻璃具有易于集成功能单元,散热性能好的优点,PDMS-玻璃杂合微流控芯片同时结合了PDMS和玻璃的优点,具有良好的发展前景^[2].     

自制玻璃微流控芯片及其基本性能考察

20世纪90年代初,自Manz等首次提出微全分析系统的概念以来,各种不同材料和功能的微流控芯片不断问世,其中应用得最多的是玻璃、石英及聚合物3种材料．玻璃和石英芯片因具有优异的电渗、光学和表面性质,其刻蚀加工技术和表面改性的化学方法均比较成熟,且传统毛细管电泳中各种成熟的分离方法可直接应用到玻璃芯片的制作中,因此在微全分析系统研究中具有十分重要的地位．     

微流控纸芯片的加工技术及其应用

微流控纸芯片是一种新兴的微流控分析技术平台,具有成本低、加工简易、使用和携带方便等优点,在临床诊断、食品质量控制和环境监测等应用领域具有很大的应用前景,近年来,引起广大科学工作者极大的兴趣。本文着重介绍目前文献相继报道的各种纸芯片加工技术,包括紫外光刻、蜡印、等离子体处理、喷墨打印、喷墨溶剂刻蚀、绘图、柔印和激光光刻等技术。此外,还介绍了微流控纸芯片分析中的检测方法及其应用。     

微流控芯片技术在生命科学研究中的应用

微流控芯片最初起源于分析化学领域,是一种采用精细加工技术,在数平方厘米的基片,制作出微通道网络结构及其它功能单元,以实现集微量样品制备、进样、反应、分离及检测于一体的快速、高效、低耗的微型分析实验装置.随着微电子及微机械制作技术的不断进步,近年来微流控芯片技术发展迅猛,并开始在化学、生命科学及医学器件等领域发挥重要作用.本文首先简单介绍了微流控芯片制作材料和工艺,然后主要阐述了其在蛋白质分离、免疫分析、DNA分析和测序、细胞培养及检测等方面的应用进展.     

聚合酶链式反应微流控芯片的准分子激光制备和应用研究

摘要采用价格便宜的聚甲基丙烯酸甲酯(PMMA)代替价格昂贵的硅或玻璃作为聚合酶链式反应(PCR)微流控芯片的基片材料,采用柔性大且自动化程度高的准分子激光微加工方法代替加工工艺复杂的光刻化学腐蚀方法,在19 kV和18 mm/min的优化加工参数下,在48 mm×67 mm×1 mm的PMMA基片上制备出20个循环的PCR微流控芯片. 芯片微通道横截面呈梯形,底面光滑. 微通道宽104 μm,深56 μm,长2 060 mm,加工耗时约110 min. 该芯片和相同尺寸的盖片在160 N和105 ℃条件下通过热压经20 min键合在一起,键合强度为0.85 MPa. 键合后的芯片和温控系统集成在一起,采用比例积分微分(PID)方法得到的控温精度为±0.2 ℃,采用红外热像仪得到的相邻温区间的温度梯度分别为16.5和22.2 ℃,最后利用该芯片在对170 bp的DNA片段实现了体外扩增.     

Electric field control and analyte transport in Si/SiO2 fluidic nanochannels

This article presents an analysis of the electric field distribution and current transport in fluidic nanochannels fabricated by etching of a silicon chip. The channels were overcoated by a SiO2 layer. The analysis accounts for the current leaks across the SiO2 layer into the channel walls. Suitable voltage biasing of the Si substrate allows eliminating of the leaks or using them to modify the potential distribution of the fluid. Shaping the potential in the fluid can be utilized for solute focusing and separations in fluidic nanochannels.     

Multi-layer microfluidic glass chips for microanalytical applications

A new, versatile architecture is presented for microfluidic devices made entirely from glass, for use with reagents which would prove highly corrosive for silicon. Chips consist of three layers of glass wafers bonded together by fusion bonding. On the inside wafer faces a network of microfluidic channels is created by photolithography and wet chemical etching. Low dead-volume fluidic connections between the layers are fabricated by spark-assisted etching (SAE), a computer numerical controlled (CNC)-like machining technique new to microfluidic system fabrication. This method is also used to form a vertical, long path-length, optical cuvette through the middle wafer for optical absorbance detection of low-concentration compounds. Advantages of this technique compared with other, more standard, methods are discussed. When the new glass-based device for flow-injection analysis of ammonia was compared with our first-generation chips based on silicon micromachining, concentration sensitivity was higher, because of the longer path-length of the optical cuvette. The dependence of dispersion on velocity profile and on channel cross-sectional geometry is discussed. The rapid implementation of the devices for an organic synthesis reaction, the Wittig reaction, is also briefly described.     

一种可逆键合电泳微芯片的制作及在蛋白质分离中的应用

阐述了一种可逆键合电泳微芯片的制作方法, 以及电泳微芯片在蛋白质分离、临床尿蛋白检测方面的应用. 用标准光刻腐蚀技术在石英基片上腐蚀泳道, 清洗腐蚀好的基片和盖片后, 在真空条件下实现键合. 此种方法键合制作的电泳微芯片可重复键合使用, 制得的电泳微芯片成功地用于标准蛋白质分离以及临床尿蛋白分析.     

Simple and rapid methods for the fabrication of polymeric and glass chips for using in analytical chemistry

This paper describes simple and rapid methods for the fabrication of glass and polymeric chips for routine analytical applications. The methods are easily interfaced to the general laboratory environment and do not require special clean room facilities or expensive instruments. Glass microchips were fabricated by etching with HF solution. Microfluidic channels were designed with CAD program and transferred onto a sheet of commercial polymeric self-adhesive (PSA) film by a cutter plotter. The PSA film was used as a mask for etching process. The etching rate was about 7 μm min⁻¹. A cover glass plate was sealed on the top of etched substrate by using polycellulose (cellophane). Polymeric microchips were fabricated by sawing with a jigsaw. Commercial polycarbonate (PC) was used as a substrate and two iron sheets were used as leader masks. While this restricts us to the fabrication of straight channels, it is however, much faster and less complicated than the other methods. The chip comprised three polymeric plates and the channels were created in the middle plate. Thermal bonding was used to bond three layers of the microfluidic chip. With this method, we could achieve simple channels with the width of about 200 μm. The channel depth depends on the polymeric plate thickness. Fabricated channels were accurate without any sinuosity or sideshow.     

All-silica nanofluidic devices for DNA-analysis fabricated by imprint of sol-gel silica with silicon stamp

We present a simple and cheap method for fabrication of silica nanofluidic devices for single-molecule studies. By imprinting sol-gel materials with a multi-level stamp comprising micro- and nanofeatures, channels of different depth are produced in a single process step. Calcination of the imprinted hybrid sol-gel material produces purely inorganic silica, which has very low autofluorescence and can be fusion bonded to a glass lid. Compared to top-down processing of fused silica or silicon substrates, imprint of sol-gel silica enables fabrication of high-quality nanofluidic devices without expensive high-vacuum lithography and etching techniques. The applicability of the fabricated device for single-molecule studies is demonstrated by measuring the extension of DNA molecules of different lengths confined in the nanochannels.     

Multiphase flow in microfluidic systems --control and applications of droplets and interfaces

Micro- and nanotechnology can provide us with many tools for the production, study and detection of colloidal and interfacial systems. In multiphase flow in micro- and nanochannels several immiscible fluids will be separated from each other by flexible fluidic interfaces. The multiphase coexistence and the small-volume confinement provide many attractive characteristics. Multiphase flow in microfluidic systems shows a complicated behavior but has many practical uses compared to a single-phase flow. In this paper, we discuss the methods of controlling multiphase flow to generate either micro- or nano-droplets (or bubbles) or stable stratified interfaces between fluidic phases. Furthermore, applications of the droplets and interfaces in microchannels are summarized.     

1-D nanochannels fabricated in polyimide

A simple method using spin-deposition and sacrificial layer etching is used to fabricate all-polyimide nanochannels (100 and 500 nm channel height). Channels are characterized using spontaneous capillary filling with water, ethanol and isopropanol, and with electroosmotic flow. The channels can be produced with simple cleanroom equipment, namely spinning and metal deposition facilities. Polyimide is an excellent material for micro- and nanofluidic channels due to its favourable electrical and mechanical properties and its biocompatibility.     

集成铜电极的聚甲基丙烯酸甲脂电泳芯片的制作

在聚甲基丙烯酸甲脂(PMMA)上溅射金属Cu，然后利用光刻、湿法腐蚀的办法制出铜电极。与另一片含有微沟道的PMMA基片热键合，制成集成铜电极的电泳芯片。在电极制作过程中，对Cu表面上覆盖的正性光刻胶的前、后烘烤温度及时间进行了研究。对Cu腐蚀液的选择及其浓度的确定进行了分析。首次提出采用二次曝光的办法去除铜电极表面的光刻胶。为了证明该种方法的可行性，在制作的一种集成铜电极的PMMA芯片上，进行了循环伏安及动态伏安实验，采用安培法对葡萄糖溶液的电泳分析进行检测。     

TiO_2纳米多孔薄膜漏模光波导共振传感器研究小分子的光谱灵敏度

在玻璃基片上溅射约50nm厚的金膜,在掺有P123聚合物的TiO2胶体溶液中浸渍提拉基片,经高温热处理后获得厚度约为210nm的TiO2纳米多孔薄膜。以此双层膜为漏模光波导芯片,并结合卤钨灯光源、CCD光谱仪、棱镜耦合器以及流动测试槽构建了基于Kretschmann结构的光谱测量式漏模光波导共振传感器。以非吸附型蔗糖水溶液为折射率液体,测试了传感器的折射率灵敏度。结果表明,在给定溶液折射率范围(1.3330～1.3557)内,漏模光波导共振波长随着折射率的升高而线形增大。以离子型表面活性剂和溴百里酚蓝为小分子吸附质,考察了传感器对小分子吸附的响应特性。结果表明,与只有一层金膜的SPR传感器相比,多孔薄膜漏模传感器对小分子吸附质的灵敏度大幅提高,这由于小分子在TiO2多孔薄膜导波层内的大量吸附。