透明导电多孔光波导共振镜电化学传感器研究

This project aims to develop high-sensitivity, high-reliability and high-Q electrochemical resonant mirror sensors based on transparent conductive nanoporous optical waveguide electrodes,in order to meet the significant demand for advanced sensors for small biomolecule detection in the fields of biomedicine and point-of-care diagnostics. To realize this novel sensor, we will address the following main topics: (1) A variety of methods for preparing transparent conductive nanoporous films and for functionalizing their internal surfaces will be first tested and then the low-loss nanoporous waveguide electrodes will be fabricated using an appropriate technique; (2) An angle-adjustable and time-resolved broadband electrochemical resonant mirror sensor platform will be constructed, and both the sensor measurement methodology and the sensor data analysis algorithm will be researched; (3) The electrical and optical response properties of the electrochemical resonant mirror sensor to small biomolecule analytes such as amino acids and glucose will be investigated in detail; (4) On the basis of a combination of the simulation and experimental data, the sensing mechanism of the nanoporous waveguide electrode and the influences of their structural parameters on both the electrochemical and resonant mirror sensitivities as well as the correlation and mutual calibration of the two sensitivities will be deeply understood; (5) The nanoporous waveguide electrodes will be optimized for enhancing the guided-mode sensitivity to small biomolecules and simultaneously suppressing the evanescent-wave sensitivity to large biomolecules, consequently realizing such a resonant mirror sensor that is merely responsive to small biomolecules. We believe that the project implementation will lead to great original achievements on the electrical-optical hybrid nanostructured biosensors and will lay a foundation for developing novel advanced sensors for in situ, real-time and label-free detection of small biomolecules.

面向生物医学和临床诊断对生物小分子传感器的重大需求，立足于纳米光电传感器领域的国际前沿，结合前期工作，提出高灵敏度、高可靠性、高品质因子的纳米多孔光波导共振镜电化学传感器研究方案，研究透明导电多孔薄膜的可控制备与内表面修饰方法，研制低损耗多孔薄膜光波导电极，构建角度可调、时间分辨的宽光谱共振镜电化学联用测试平台，研究共振镜电化学联用检测方法与数据分析算法，测试传感器对氨基酸、葡萄糖等生物小分子的光/电响应特性，解明多孔光波导电极的光/电敏感机理，分析纳米孔结构参数对光/电灵敏度的影响规律，探索光/电灵敏度的相关性和光电互校准方法；从增强对生物小分子的导波光灵敏度，抑制对生物大分子的消逝波灵敏度的角度出发，优化多孔光波导电极结构，进而实现只对生物小分子敏感的共振镜传感器。通过本项目实施，在光电融合纳米生化传感器方面取得一批原创性成果，为研发原位实时非标记检测生物小分子的新型传感器奠定基础。

本项目旨在研制光电融合高灵敏度纳米多孔光波导共振传感器，用于探测小分子。本项目取得的主要成果包括：（1）基于Fresnel公式与光波导本征方程建立了共振镜传感器仿真平台，构建了波长检测型共振镜传感器系统，优化设计并制备了Glass/MgF2/PMMA 和Glass/MgF2/Ta2O5两种共振镜芯片，实验获得了共振镜表面单分子层的定向荧光和定向拉曼信号；（2）探索出一套可重复制备TiO2介孔薄膜光波导的溶胶-凝胶成膜工艺参数，制备出一系列孔隙率不同的TiO2介孔薄膜，实现了对水中Cr6+、Pb2+ 等重金属离子以及苯并芘、反油酸等化学小分子的直接探测。实验结果表明TiO2介孔薄膜光波导容许利用TE或TM导模进行原位检测，在相同入射角下TM导模的灵敏度高于TE导模，但两者的灵敏度均随着薄膜孔隙率的增大而增大；（3）提出了一种原位无损同步测定多孔膜厚度和孔隙率的方法，该方法利用Fresnel 公式结合Bruggeman等效介质近似方程，对实验测得的多个角度共振谱或波长共振谱进行仿真拟合，由此得出待测多孔膜的厚度和孔隙率；（4）对光波导消逝场激发与消逝场耦合定向拉曼散射特性进行了理论和实验研究，得出了在非Krestchmann结构下基底的近场耦合发射不利于表面增强拉曼探测的结论；（5）深入研究了多孔金膜SPR传感方法，通过对多孔金膜的功能化修饰，实现了对水中苯并芘的超灵敏免疫探测；利用聚四氟乙烯作为敏感膜，通过调控薄膜厚度，将SPR 消逝场约束于敏感膜内，制作出无参比SPR传感器，基于苯并芘分子在聚四氟乙烯膜内的可逆富集，实现了水中苯并芘的直接探测；（6）构建了电化学-共振光谱联合检测装置，原位分析了硫堇电聚合成膜过程，实现了基于TiO2介孔薄膜光波导对重金属离子的电化学/共振光谱双重灵敏度实时检测。.在项目执行期间，课题组发表相关SCI论文28篇，获得相关授权发明专利7项，在国内外学术会议上作邀请报告10次，获得国际学术会议优秀墙报奖一次，培养出博士后一名，博士四名，硕士五名，李金洋博士获中科院院长优秀奖并入选北京市优秀毕业生，陈晨博士获中科院朱李月华博士生奖。项目负责人祁志美入选中国仪器仪表学会传感器分会第五届理事会理事和OSA Senior Member，获ACS Awarded Membership，中科院优秀研究生指导教师和中科院朱李月华优秀教师奖。