论文标题:应用于生物医学检测的MEMS器件的制造
Fabrication of MEMS Devices Used in Biomedical Detection
论文作者
论文导师 朱纪军；Simon S.Ang,论文学位 硕士,论文专业 生物医学工程
论文单位 东南大学,点击次数 196,论文页数 69页File Size3187K
2006-05-20论文网 http://www.lw23.com/lunwen_720167/
MEMS; Microfluidic; PDMS; Microelectrodes; LTCC; Blood separation
随着MEMS(Micro Electro-Mechanical System,微机电系统)制造技术的不断发展,生物医学与其之间的联系越来越紧密,自上世纪90年代初提出uTAS(Micro Total Analysis System,微全分析系统)之后,各种各样的微流控芯片、微反应器、微电极、微分离器等便大量涌现,广泛应用于药物检测、环境监测、基因分析等诸多领域中,并且由于其试剂消耗量少、检测效率高、环境污染小、体积小、易于携带等优点,在生物医学、化学、环境工程等领域受到越来越多的重视。本课题旨在利用MEMS制造工艺研制出应用于化学发光以及荧光检测的微流控芯片,应用于电化学检测的圆盘电极阵列,以及应用于血液分离的LTCC(Low Temperature Cofired Ceramics,低温共烧陶瓷)微器件。为光学检测、电化学检测以及血液分离提供适合的微反应环境,逐步实现在线检测以及芯片实验室的功能。 应用于化学发光以及荧光检测的微流控芯片以苏打玻璃作为基底,通过匀胶、曝光、显影、刻蚀等一系列工序在玻璃表面制作出微通道,将氧等离子体处理之后的PDMS(Polydimethylsiloxane,聚二甲基硅氧烷)与基底进行共价键结合来实现PDMS胶体对微通道的密封,从而完成微流控芯片的制作。文中详细介绍了微流控芯片制作的各个步骤,分析了各工艺参数对性能的影响,并与利用阳极键合技术与软刻蚀技术制造的微流控芯片进行了优缺点的比较。通过测试表明经过氧等离子体处理之后的PDMS能够与玻璃基底形成强度极高的共价键键合,其键合强度已大于PDMS的本体强度,在测试过程中未发生因微通道内液体压力过大而产生的渗漏现象以及PDMS在键合过程中堵塞微通道的现象,为化学发光和荧光检测提供了良好的微反应环境。 应用于电化学检测的圆盘电极阵列采用苏打玻璃作为基底,通过匀胶、曝光、显影、溅射等一系列工序在晶圆上制造了两种直径不同的能够应用于不同检测要求的微电极阵列。文中详细介绍了电极制作的各个步骤,分析了各工艺参数对电极性能的影响。通过自组装单分子膜技术将肠毒素C的单克隆抗体固定在圆盘电极表面,分别在含有抗原与不含抗原的缓冲液中,利用电化学循环伏安法分析了氧化还原探针Fe (CN)_6~(3-/4-)与电极表面自组装单分子膜N-乙酰半胱氨酸之间的反应关系,以及抗原与抗体之间的反应关系。从测试结果可以看出,该电极阵列具有检测时间短、响应灵敏度高、操作简单等优点,可用于对其表面所修饰的单分子膜的分析,也可用于对抗原抗体反应做出分析。 应用于血液分离的微器件以低温共烧陶瓷带作为制造材料,由垂直结构的微加速器与水平结构的离心分离器结合而成,利用经过加速之后的血液在流过微圆弧通道时所产生的离心力来实现对血液中血细胞的分离。文中介绍了利用ANSYS软件对分离模型进行流体仿真的方法,介绍了利用冲孔、迭片、切割、烧结等工艺对十层LTCC进行加工制作的方法,分析了不同工艺参数对芯片性能的影响,尤其对任意尺寸的微孔与微通道的制作进行了比较详细的分析。利用此分离器件对全血做血液分离测试,表明该器件能够对血细胞尤其是白细胞起到一定程度的分离作用,实现了对血液的初步分离。
As MEMS (Micro Electro-Mechanical Systems) technology progresses rapidly, the synergism between MEMS and biomedical technology becomes closer than ever before. When the uTAS (Micro Total Analysis System) was introduced in the last two decades, many microfluidic chips, microelectrodes, and microreactors are being studied for drug detection, environment detection, gene analysis etc. Due to its small volume, low pollution, low consumable and good portability, uTAS plays a very important role in biomedical, biochemical, environment engineering fields. In this dissertation, microfluidic chips used in chemiluminescence and fluorescence detection, microelectrodes used in electrochemical detection, and blood separation chips based on LTCC layers were fabricated using MEMS Fabrication Process. These microchips are useful for many biomedical and biochemical detections and enable real-time lab-on-a-chip applications. Microfluidic chips were fabricated on soda-lime glass. After photoresist application, UV light exposure, developer and wet chemical etching, the micro-channels are fabricated on the glass substrate. After an oxygen plasma treatment on the PDMS and glass substrate, the PDMS layer can form a good seal on the micro-channels. This thesis discusses the process parameters in detail and compared to the process such as anodic-bonding and soft-etch process. The test results show that the PDMS can seal the glass substrates with the micro-channels tightly after the oxygen plasma process. There is no fluid leakage when a high-pressurized fluid flows through these micro-channels. Microelectrodes were fabricated on the soda-lime glass. The electrodes arrays were fabricated using a process sequence of photoresist applications, UV light exposure, developing, gold sputtering, patterning, and etching. Two types of microelectrodes with different diameters were fabricated using this process. In this thesis, the fabrication processes are discussed. N-acetylcysteine was first assembled on microelectrodes’surface to form a self-assemble monolayer, and then the modified microelectrodes were activated by EDC and NHS, monoclonal antibody enterotoxin C was immobilized on the self-assemble monolayer to form the amperometric immuno-biosensors in the end to to detect the enterotoxin C antigen. Cyclic voltammetry is used to investigate the electrochemical behaviors of Fe (CN)6~(3-/4-)on the SAM modified microelectrodes and the electrochemical behaviors between the antigen and antibody. From the test results, we can see the microelectrodes arrays have some good characteristics such as low detection time, high sensitivity and easier operation ways. They can be used to do the electrochemical research of the self-assemble monolayer and they can also be used to do the qualitative assay about the reaction with antigen with antibody. The blood micro-separators were fabricated using a low-temperature co-fired ceramic (LTCC) technology. The separator includes several vertical micro-jets and horizontal distributors. Separation efficiency of different blood cells depends on the centrifugal force created when the blood passes through the bent micro-channels. ANSYS software was used to simulate the flowing of blood in the separator. The LTCC fabrication process involves punching, lamination process, cutting and sintering processes. These processes are discussed in the thesis. The tests show that the LTCC blood separation can separate the white blood cells better than the red blood cells and the micro separator can be used to make the Preliminary separation.
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