Production of high sensitive blood test systems using carbon nanotube biosensor

本课题致力于将碳纳米管的电学性质、固体表面固定化技术和生物技术相结合，研制出能够快速、高灵敏度地检测分子相互作用的装置。作为其应用，我们尝试建立了高灵敏度的人体血液检测系统，尤其是病原病毒检测系统。(1)化学气相沉积法制备碳纳米管场效应管。为了提高碳纳米管生物传感器的工艺产率，使传感器的电学性能更加均匀，我们对碳纳米管生物传感器的制备工艺进行了优化。(I)通过使用各种金属多层膜作为催化剂来控制碳纳米管的密度；(Ii)通过热化学气相沉积条件来控制碳纳米管的密度；(Iii)通过优化催化剂尺寸来控制桥接碳纳米管的数量；(Iv)安装电子束沉积系统的负载锁定室；(V)改进Pr…的提离更多的电极图案化，(Vi)碳纳米管生物传感器自动测量系统的引入，(Vii)金属碳纳米管的选择性击穿。(2)碳纳米管自组装膜固定化制备碳纳米管FET器件。在玻璃衬底上的源、漏电极位置制备了3-氨基丙基三乙氧基硅烷(APS)的溶胶凝胶层，然后将SWCNT分散体固定，用酸和过氧化氢的混合物处理后，在盖板玻璃上制备了纳米管FET器件。用上述方法制备的器件中约有60%表现出FET特性。该器件可以重复性地检测pH，通过对碳纳米管表面的修饰可以作为免疫传感器使用，尽管它的灵敏度低于CVD法。(3)检测乙肝病毒表面抗原(HBs抗原)为了制备检测乙肝病毒表面抗原的碳纳米管生物传感器，将抗HBs抗体固定在碳纳米管的反面，放在硅片的一侧。HBS表面抗原的重复性测定范围为10fg/ml~100pg/ml，加入终浓度为5%的人血清对CNT生物传感器的灵敏度和准确度无影响。较少

In this project, it has been aimed at the development of the device which can quickly detect the molecular interacton with high sensitivity, by combining the electric properties of carbon nanotubes, immobilization technology of the solid surface, and biotechnology. As an application of it, we tried to build the high sensitive test systems for human blood, especially the detection system of pathogenic viruses.(1) Fabrication of CNT-FET by chemical vapor deposition (CVD) method. In order to improve the process yield of the CNT biosensor and to uniform the electric property of the sensor, we optimized the fabrication process of the CNT biosensor. (i) Controlling the density of CNTs by using variety of metal multilayer films as catalysts, (ii) Controlling the density of CNTs with thermal CVD condition, (iii) Controlling a number of bridging CNTs by optimization of the catalyst dimension, (iv) Installation of the load lock chamber for EB deposition system, (v) Improvement in the lift-off pr … More ocess of the electrode patterning, (vi) Introduction of the automatic measurement system for the CNT biosensor, (vii) Selective breakdown of metallic CNTs. By these optimized processes, the yield ratio of conducting sensor and FET sensor improved 12.5 times and 5.2 times respectively.(2) Fabrication of CNT-FET by CNT immobilization through self-assedmbled membrane A nanotube FET device was fabricated on a cover glass after fabricationg a sol-gel layer of 3-aminopropyltriethoxysilane (APS) at the planned site of source and drain electrodes on the glass substrate, and after subsequent immobilizing SWCNT dispersion, which is treated using a mixture of acids and hydroxyperoxide. About 60% of the devices made by the above method showed a FET property. This devices, which can reproducibly detect pH, is applicable for use as a immunosensor through modification of the CNT surface, although it showed lower sensitivity compared to that fabricated by the CVD method.(3) Detection of Hepatitis B virus surface antigen (HBs antigen) To prepare the CNT-biosensor for detection of Hepatitis B virus surface antigen, anti-HBs antibodiy was immobilized on the reverse side of CNT put on the one side of silicon wafer. HBs surface antigen was reproducibly able to measure ranging from 10 fg/ ml to 100 pg/ml. Additon of human serum at final concentration of 5% to analyte had no effect to the measurement of the CNT-biosensor in respect to its sensitivity and accuracy. Less