微流控芯片检测技术进展

对近年来用于微流控芯片的光学检测(包括荧光、吸收光度和电化学发光检测等)、电化学检测(电导检测、电位检测及安培检测)的发展和其他一些检测方法的研究成果进行了综述,随着微加工技术的不断发展,高速多通道检测以及集成多种方法的高通用性微流控检测芯片都将成为未来的研究热点。     

玻璃微流控芯片的制作

玻璃微流控芯片的研究在近十年得到了重视 ,但是多数研究基于 7740玻璃制作 ,由于基材需要抛光以及涂覆掩蔽层 ,价格昂贵 .作者研究了一种在商品化的SODA LIME玻璃 (掩蔽层为厚度 14 5± 15nm的Cr和 5 75±2 5nm的光刻胶S10 8)上制作微流控芯片的方法 ,减少了对掩蔽层溅射设备的需求 ,降低了生产成本并缩短了生产周期 .采用照相制版的方法制作沟道宽度为 5 0 μm的掩模 ;光刻后根据沟道深度要求选择腐蚀液湿法腐蚀沟道 ;优化超声钻孔仪的电流参数制作直径 3mm的储液池 ,清洗后采用热键合对芯片进行封接 ;最后在有效分离长度为3 5mm的芯片上实现多组分样品分离 ,采用激光诱导荧光获得检测信息     

PMMA微流控检测芯片的设计与制作

设计并制作了一种PMMA（polymethyl methacrylate）材料的微流控检测芯片,将外界气体驱动液体用于实际水样的分析和检测．利用精密加工的方法加工出芯片的整体尺寸为86mm×60mm×4．5mm．采用溶胶-凝胶的改性方法对微通道管路进行亲水处理,正硅酸乙酯的水解缩合生成了一层溶胶．凝胶覆盖在PMMA表面,从而大大提高了亲水性．在室温下对芯片进行键合,溶剂为二氯乙烷和无水乙醇按1：1混合的混合液．该方法避免了微通道的坍塌,有效防止了堵塞．实验证明,芯片接触紧密,且冲击强度能够满足要求．同时,芯片上集成了多个阀．阀膜选用0．5mm厚的硅胶膜,采用硅橡胶做黏合剂     

集成电化学检测三电极体系微流控芯片的研制

本文介绍了一种在单个PMMA衬底上集成Ag-Pt-Pt两种材料微电极的方法。PMMA是一种聚合物材料,而在聚合物材料上集成两种材料电极的微流控芯片制作,需集成不同材料的电极。电化学检测常采用三电极体系,且这三个电极往往是由不同材料组成的。工作电极和对电极一般采用贵金属材料。本文研究了一种在PMMA衬底上集成Pt-Pt-Ag三电极体系的微流控芯片方法。利用可逆键合法,将集成Pt-Pt-Ag三电极体系的PMMA衬底与一片带有检测池的PDMS盖片键合到一起,研制出了一种电化学检测微流控芯片。     

集成一次性微流控芯片的便携式荧光检测系统

本文研究了一种新型的生物化学分析系统,该系统包括便携式荧光检测仪和带光纤的微流控芯片．采用基于MEMS技术的微泵将待测物与荧光试剂的混合物导入微流控芯片,采用PMT检测受激发产生的荧光,荧光强度与待测物浓度成一定比例．激发光则通过光纤将光源LED光信号导入微沟道中．随着液体在微沟道中的流动,可连续分析和检测不同的样品．该系统检测1～1000μg／L浓度的荧光素具有0．966的相关系数．基于荧光猝灭原理,该系统还可检测浓度为5ng／μL的硝基化合物．该生化分析系统除具有便携式和一次性微流控芯片优点外,还具有成本低．试剂、样品消耗量少,且分析时间短等优点该系统能实现现场检测,可应用于临床诊断、环境检测及生物战剂检测等领域     

模板电解法快速制作玻璃微流控芯片

玻璃微流控芯片在许多领域已经得到较广泛的应用,但目前的加工需要繁琐的步骤及昂贵的设备进行图形转移及金属牺牲层开窗口.本文提出一种快速制作金属牺牲层图形窗口以用于玻璃微流控芯片加工的方法.以CO2激光直写加工PET膜模板,微细电解加工玻璃基片上的铬/金牺牲层快速获得窗口,湿法腐蚀及热键合制作玻璃微流控芯片.结果表明该法可在10秒内开窗口,电解加工过程使用的模板厚度、电解液组成及施加的压力与电压对窗口的质量都有显著影响.加工的微通道宽度为145μm,边缘整齐,宽度均匀,相对标准偏差为3.72%,深度μm,底部平整度高,并成功用于氨基酸混合液的芯片毛细管电泳分离.同时使用该方法加工的金微电极阵列,电极宽度为100μm,最小间距可达100μm.     

微流控芯片模具非平面微电铸技术

研究了微流控芯片中大线距/线宽比条件下的UV-LIGA制作工艺.针对微电铸的要求,优化了大面积SU8曝光的工艺;通过计算机模拟分析和实验验证手段,提出了一种非平面微电铸方法,有效的解决了大线距/线宽比条件下的UV-LIGA工艺,为微流控器件的批量化制作成奠定了坚实的基础.     

PDMS微流控电泳芯片的快速制备

采用Protel软件绘制微流控沟道的形状,利用电路板制作技术加工出模具.该芯片由PDMS基片和PDMS盖片组成,微流控沟道位于基片上,深度和宽度分别为75μm和100μm,由盖片对其进行密封.考察了有绝缘漆模具和无绝缘漆模具制作的芯片的电泳分离情况.在所制作的PDMS微流控电泳芯片上对用异硫氰酸酯荧光素标记的氨基酸进行了电泳分离,当信噪比S/N=3时,最小检测浓度达到0.8×10-11mol/L.     

微流控芯片微沟道的超声压印制作

作为一种新型聚合物微结构成形方法,超声波压印具有成形速度快和基片整体变形小的特点,但是微结构在较大面积成形时存在均匀性较差的问题．本文面向微流控芯片中微沟道的超声波压印成形,通过设计正交实验和有限元仿真研究的方法,分析了超声压印工艺参数对微流控芯片成形质量和均匀性的影响原因及规律．结果表明,可以通过优化超声波压印压力、振幅和超声波作用时间提高压印均匀性．其中超声波压印压力对成形精度和均匀性的影响最大．采用优化后的工艺参数进行实验,在48mm×32mm面积的PMMA微流控芯片基片上成形了微沟道,微沟道的复制精度优于95．6％．片上3点的均匀性为98．0％．     

Processing of immiscible metallic alloys by rheomixing process

Abstract

Mixing immiscible alloys has been a long standing challenge to both materials scientists and processing engineers. Despite great efforts made worldwide, including extensive space experiments, no casting techniques so far can produce the desirable fine and uniform dispersed microstructure. Based on extensive experience in mixing immiscible organic liquids offered by the polymer processing community, the authors have successfully developed a rheomixing process for mixing immiscible alloys. The rheomixing process utilises first the intensive shear stress-strain field offered by a twin screw extruder to create a fine homogeneous liquid dispersion within the miscibility gap and then the viscous force offered by a semisolid slurry at a temperature below the monotectic temperature is used to counterbalance the gravitational force and the Marangoni effect. A laboratory scale rheomixer has been designed and constructed to realise this two step mixing strategy. The Ga–Pb and Zn–Pb systems were selected to demonstrate the principles of rheomixing. The experimental results showed that the rheomixing process developed is capable of creating a fine and uniform microstructure from immiscible alloys. This paper describes the rheomixing process in detail and the preliminary experimental results on rheomixing in the Ga–Pb and Zn–Pb systems are discussed.     

Implementation of vibrational phase contrast coherent anti-Stokes Raman scattering microscopy

Detection of molecules using vibrational resonances in the fingerprint region for narrowband coherent anti-Stokes Raman scattering (CARS) is challenging. The spectrum is highly congested resulting in a large background and a reduced specificity. Recently we introduced vibrational phase contrast CARS (VPC-CARS) microscopy as a technique capable of detecting both the amplitude and phase of the CARS signal, providing background-free images and high specificity. In this paper we present a new implementation of VPC-CARS based on a third-order cascaded phase-preserving chain, where the CARS signal is generated at a single (constant) wavelength independent of the vibrational frequency that is addressed. This implementation will simplify the detection side considerably.     

Temperature-controlled confocal Raman microscopy to detect phase transitions in phospholipid vesicles

Optical-trapping confocal Raman microscopy enhances the capabilities of traditional Raman spectroscopy for the analysis of small particles by significantly reducing the sampling volume and minimizing background signal from the particle surroundings. Chemical composition and structural information can be obtained from optically trapped particles in aqueous solution without the need for labeling or extensive sample preparation. In this work, the challenges of measuring temperature dependent changes in suspended particles are addressed with the development of a small-volume, thermally conductive sample cell attached to a temperature-controlled microscope stage. To demonstrate its function, the gel to liquid-crystalline phase transitions of optically trapped lipid vesicles, composed of pure 1,2-ditridecanoyl-sn-glycero-3-phosphocholine (DTPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), were detected by changes in Raman spectra of the lipid bilayer. The Raman scattering data were found to correlate well with differential scanning calorimetry (DSC) results.     

The Raman spectra of high modulus polyethylene fibres by Raman microscopy

Raman-microscopy has been used to analyse a series of high modulus polyethylene fibres. The high degree of orientation within the material means that upon 90° rotation of the samples and/or polarisation analyser, marked variations in band intensities occur throughout the spectra. Measurements of the 1131 : 1064 cm–1 band intensity ratio of the fibres are made and related to their Young's modulus. This relationship is useful in morphological studies of polyethylene fibres.     

二元不互溶Cu-Ta体系非晶相的形成

利用X射线衍射(XRD)、高分辨透射电子显微术(HRTEM)和X射线能谱(EDS)研究了共溅射Cu-Ta薄膜中非晶相的形成.结果表明,共溅射Cu-Ta薄膜为非晶相,但是其中存在着纳米尺度的Cu晶粒和富Cu的非晶纳米颗粒,即存在纳米尺度的相分离.正的混合热是导致Cu-Ta二元不互溶体系非晶态薄膜相分离的本质原因.     

Raman microscopy study of basic aluminum sulfate Part II Raman microscopy at 77 K

The tridecameric aluminum polymer [AlO₄Al₁₂(OH)₂₄(H₂O)₁₂]⁷⁺ was prepared by forced hydrolysis of Al³⁺ up to an OH/Al molar ratio of 2.2. Upon addition of sulfate the tridecamer crystallised as the monoclinic basic aluminum sulfate Na_0.1[AlO₄Al₁₂(OH)₂₄(H₂O)₁₂](SO₄)_3.55. These crystals have been studied using Raman microscopy at 300 and 77 K and compared to Na₂SO₄·xH₂O and Al₂(SO₄)₃·xH₂O. The Raman spectrum of basic aluminum sulfate is dominated by two broad bands, which are assigned to the ₂ and ₄SO₄ ^2– triplets at 446, 459 and 496 cm^–1 and 572, 614 and 630 cm^–1. The ₁ is observed as a single band at 990 cm^–1, partly overlapped by the ₃ triplet at 979, 1009 and 1053 cm^–1 of the sulfate group in the Al₁₃ sulfate structure. Furthermore the band at 726 cm^–1 is assigned to an Al–O mode of the polymerised Al–O–Al bonds in the Al₁₃ Keggin structure. For the first time the OH-stretching region of the basic aluminum sulfate has been reported. The 77 K spectrum shows the presence of 3 crystal water bands at 3035, 3138 and 3256 cm^–1 accompanied by 3 Al–H₂O bands at 3354, 3418 and 3498 cm^–1 and 4 Al-OH bands at 3533, 3584, 3671 and 3697 cm^–1.     

Single-pollen analysis by laser-induced breakdown spectroscopy and Raman microscopy

The application of laser-induced breakdown spectroscopy to the analysis of single biological microparticles (bioaerosols) is described, exemplified here for a range of pollens. Spectra were recorded by exposure of the pollen to a single laser pulse from a Nd:YAG laser (lambda = 1064 nm, Ep approximately 30 mJ). The intensities of the single-pulse laser-induced breakdown spectra fluctuated dramatically, but an internal signal calibration procedure was applied that referenced elemental line intensities to the carbon matrix of the sample (represented by molecular bands of CN and C2). This procedure allowed us to determine relative element concentration distributions for the different types of pollen. These pollens exhibited some distinct concentration variations, for both major and minor (trace) elements in the biomatrix, through which ultimately individual pollens might be identified and classified. The same pollen samples were also analyzed by Raman microscopy, which provided molecular compositional data (even with spatial resolution). These data allowed us to distinguish between biological and nonbiological specimens and to obtain additional classification information for the various pollen families, complementing the laser-induced breakdown spectroscopy measurement data.     

Probing chirality of a lipid tubular by confocal Raman microscopy

The chiral phospholipids 1,2-bis-(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC8,9 PC) can self assemble into lipid nanotubules. This hollow cylindrical supramolecular structure shows promise in a number of biotechnological applications. The mechanism of lipid tubule formation was initiated by assembling of lipid bilayer sheets from amphiphilic solution. Upon cooling, small ribbons were detached from the sheets and rolled up into helical tubules. The lipid tubules obtained were 0.6-0.8 microm in diameter and approximately 50 microm in length. Raman spectra of individual polymerized lipid tubules were measured by focused laser excitation of 532 nm leading to intense and reproducible Raman spectra. The chirality of lipid tubules was investigated by atomic force microscopy (AFM) and confocal Raman microscopy. We report the Raman mapping images revealing helical tubular profiles of C=C stretching and C[triple bond]C stretching of lipid tubules. Circular dichroism property of lipid tubules has also been probed with a 532 nm laser.     

Detection of drug-membrane interactions in individual phospholipid vesicles by confocal Raman microscopy

Optical-trapping confocal Raman microscopy is developed as a method to study the interactions of drugs or other compounds with the membranes of individual phospholipid vesicles. This technique allows membrane disorder, permeability, and drug localization to be assessed without the need for labeling of the membrane or the compounds of interest. We have applied this technique to study the interactions of two nonsteroidal antiinflammatory drugs, salicylate and ibuprofen, with vesicles prepared from 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). The results show that both salicylate and ibuprofen increase membrane disorder, as determined from increases in the Raman scattering from gauche conformers in the phospholipid acyl chains. By monitoring the Raman scattering of the drug molecules in optically trapped DMPC vesicles, the membrane permeability and partitioning of the drugs could be determined; the spatial distributions of the drugs were also measured by scanning the laser focus through surface-adhered 1,2-dipalmitoyl-sn-glycero-3-phosphocholine vesicles, producing a profile of the vesicle and its contents. Though the membrane is permeable to both drugs, ibuprofen preferentially accumulates in the membrane, whereas salicylate does not. The measured ibuprofen accumulation agrees quantitatively with the water/octanol partition coefficient of the drug and the estimated volume of the lipid membrane. The results suggest that ibuprofen localizes in the hydrophobic acyl chain region of the membrane, whereas salicylate weakly associates with the phospholipid headgroups.