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金纳米粒子增强光纤生物传感器重复性和特异性研究
李凯伟
学位类型博士
导师宣明
2014-07
学位授予单位中国科学院大学
学位专业机械制造及其自动化
摘要在过去的十年中生物传感技术发展迅速,各种高灵敏度传感方法和器件不断涌现,然而高灵敏度也导致其易受非特异性因素干扰,从而影响了生物传感的实用化进程。本文针对双锥型光纤生物传感器的原理、制作工艺、灵敏度增强、金纳米粒子标记等技术开展了深入细致的理论和实验研究,揭示了双锥光纤无标生物传感器重复性差的内在原因,提出了可同时获得该传感器高灵敏度、重复性和特异性的方法。 (1)通过研究微纳光纤的传导特性,特别是纳米粒子在光纤消逝场中的散射和吸收特性,建立了微纳米粒子在微纳光纤消逝场中功率损耗的理论模型,证明了采用纳米光纤可实现单个金、银纳米粒子以及细菌的检测,并通过50nm的金纳米粒子的单粒子探测实验对其进行了验证; (2)通过系列实验和仿真分析研究,揭示了双锥型光纤无标生物传感器高灵敏度和高重复性之间的矛盾。研究表明,其高灵敏度得益于锥腰中的模式干涉,但模式干涉所引起的光纤对折射率的不规则震荡又导致了传感器的重复性较差;该发现对从根本上解决高灵敏光纤消逝场生物传感的实用化问题有重要意义; (3)研究了金纳米粒子对光纤传感器的折射率灵敏度及其生物探测灵敏度增强效应;相比传统的光纤LSPR传感器,本文构造的金纳米粒子修饰的微纳光纤LSPR传感器,具有单模传输和表面场增强特性,对折射率灵敏度达到,对亲和素检出限达到1pg/mL;由于该传感器具有在测试范围内的较好的线性,因此也具有较好重复性;该方法较成功地解决了光纤传感器灵敏度和重复性间的矛盾; (4)采用金纳米粒子标记方法对双锥型光纤传感器的特异性、灵敏度及重复使用特性进行了研究,实现了对癌症标志物AFP血清样品的高灵敏度检测,检出限达到2ng/mL,最小解离再生次数可达9次。
其他摘要Biosensing technology has advanced rapidly and dramatically in the last decade and various highly sensitive sensing methods and devices are constantly emerging. However, high sensitivity also makes these devices vulnerable to nonspecific interferences, which hindered the application process for biosensors. In this dissertation, biconical optical fiber sensors were systematically studied in the aspect of sensing mechanism, manufacturing technology, sensitive enhancement, and labeling technique. The underlying mechanism of poor reproducibility for biconical optical fiber sensors was revealed and several methods to enhance the sensitivity, reproducibility and specificity were proposed.(1) By combining the optical guiding property of optical micro/nanofibers and the scattering and absorbance property of nanospheres, a model for calculating the optical losses caused by nano spheres in the evanescent field of an optical fiber was built. Theoretical calculations suggested the possibility of single particle detection for gold nanoparticles, silver nanoparticles and bacterial using optical nanofibers. Single gold nanoparticles of 40 were detected using a 500 nm thick nanofiber in experiments, which demonstrated the reliability of the model.(2) The underlying contradiction between sensitivity and reproducibility were revealed through systematically experimental and simulation studies. The study shows that the high sensitivity is mainly caused by the modes coupling and this in turn caused the poor reusability of biconical fiber biosensors. This finding is of great importance for promoting the application process of highly sensitive optical fiber biosensors. (3) The enhanced sensitivity of optical micro/nanofiber sensors modified with gold nanoparticles for refractive index detection and biodetection was carefully studied both theoretically and experimentally. By introducing gold nanoparticles to the surface of optical micro/nanofibers, the sensitivity and reproducibility can be greatly improved. A RI sensitivity of 20 ΔA/RIU and detection limit of 1 pg/mL was archived in the experiments.(4) The selectivity enchantment of using gold nanoparticles as labels for optical microfiber biosensors was evaluated. This sensor utilizes both the unique optical property of ultrathin optical microfibers and the strong optical absorption property of gold nanoparticles. Bio-functionalized gold nanoparticles are used as signal amplifiers in a sandwich assay to enhance both sensitivity and selectivity. In immunoassay, AFP was detected in bovine serum with limits of detection of 2 ng/mL. This biosensor can be regenerated for 9 times.
语种中文
文献类型学位论文
条目标识符http://ir.ciomp.ac.cn/handle/181722/41427
专题中科院长春光机所知识产出
推荐引用方式
GB/T 7714
李凯伟. 金纳米粒子增强光纤生物传感器重复性和特异性研究[D]. 中国科学院大学,2014.
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