结构型微纳光纤长周期光栅免疫传感器机理与实现研究

Biosensor technologies have become a point of attraction of many researchers and investors for detection in biomedical and clinical diagnostic or Point of Care Testing, driven by the needs of rapid and low cost testing. Among these biosening methods, high-capability fiber-optic immunosensors possessing relatively low cost, and convenience, are commonly regarded as alternatives to traditional immunological methods for the analysis of biomolecules. Indeed, fiber evanescent wave as a transduction approach is based on measurable slight refractive index changes at the interface between the optical fiber device and the surrounding media, deriving from the binding reaction of immobilizing substrates with molecular analytes in near proximity of the interface. Therefore, the sensitivity of the sensor has become a major bottleneck restricting the further development of the fiber optic biosensor. In this case, we propose a novel high-sensitivity immunosensor employing microfiber long-period grating. This sensor, based on structural microfiber long-period grating with high refractive index sensitivity, is aiming to promote the spectral precision through the construction of interferometer and laser structure, and to achieve fiber surface modification by coating nano-porous thin film. The complex interaction mechanism between evanescent field and immunoreaction will be investigated and determined in our work, as well as the dominated factors which affect the immunosensitivity, not only to achieve the ultrahigh sensitivity of immunosensor, but also to offer substantial research foundation in future fiber-optic immunosensor exploitation in application ranging from life science to clinical treatment.

生物医学和即时诊断领域对快速、低成本新型检测技术的需求，驱动着生物传感器技术的研究兴趣和投资热情。光纤免疫传感器由于其低成本和方便性等特性，已经成为生物传感器研究的重要方向。光纤倏逝波免疫传感器是通过检测生物分子免疫识别过程所引起的微小变化而实现传感的，传感器的灵敏度成为制约光纤生物传感器进一步发展的主要瓶颈。在此背景下，本项目提出一种新型微纳光纤长周期光栅免疫传感器。传感器以高折射率灵敏度结构型微纳光纤长周期光栅为基础，通过构建干涉仪和激光器实现光谱精细度提升，以纳米多孔薄膜包覆实现光纤表面改性优化。最终，通过全面阐释各因素变化的作用机制，明确影响传感灵敏度的决定性因素，实现高灵敏度免疫传感器，为未来光纤免疫传感器在临床等领域展开应用提供研究基础。

健康问题已成为影响人类生存与发展的重要问题。面向人类健康监测和疾病检测的早发现、早诊断、早治疗应用需求，发展高灵敏度、高精度、高特异性、低成本、简单快速的新型生物医学传感器是健康监测和疾病检测以及智慧医疗的发展方向。.本项目面向生物医学检测需求，提出一种新型微纳光纤长周期光栅免疫传感器。传感器以微纳光纤长周期光栅为基础，通过倏逝场增强和色散调控实现传感器折射率敏感性提升；以结构型微纳光纤长周期光栅构建干涉仪和激光器，实现光谱精细度提升；以纳米多孔薄膜作为界面改性材料，增加了比表面积，为生物识别元件提供更大的装配空间，提升表面适应性和能动性；最终研究实现高灵敏度的光纤免疫传感器。.经过三年的研究，（1）已实现高阶衍射微纳光纤长周期光栅研制，光栅周期扩大到300-1000μm，光谱对比度达到25dB。实验测得光栅的折射率为2012.6nm/RIU、温度灵敏度为7.6pm/℃，和应变灵敏度为-10.6pm/με。基于色散拐点增敏技术，将微纳光纤传感器折射率灵敏度提高到10000nm/RIU。（2）利用结构型微纳光纤长周期光栅的多端口特性，构建了环形耦合的单光栅干涉仪，将光栅光谱3dB带宽降低了20倍。进一步利用缠绕光纤输出端口的带通滤波特性构建环形腔光纤激光器，将长周期光栅谱精细化，并实现了范围达到28nm的激光输出光谱的调节。（3）实现了光纤表面ZIF-8三维纳米多孔薄膜和聚多巴胺分子印迹薄膜的可控制备，使光纤界面具备了尺寸筛选能力和特异识别能力。（4）实现了对前列腺癌标志物PSA的检测，检测极限达到9.9ng/ml。结合ELISA技术，实现了对IL-6的检测，检测极限达到了9.75pg/mL。结合聚多巴胺分子印迹薄膜，实现了对C-反应蛋白的检测，检测极限达到了10−9ng/mL，较传统ELISA技术提升了8个量级。超高灵敏度光纤免疫传感器的实现，为肿瘤疾病早期诊断提供了可行的科学手段，具有重要的科学意义。