高稳定性银膜表面等离子体共振成像传感器的空间结构与性能优化研究

Known for its advantage of label-free and real-time monitoring, surface plasmon resonance imaging (SPRi) has become a key technique of high-throughput screening in frontier of biological techniques, such as cancer immunotherapy and biologics. A silver SPRi sensor with a gold island film as nucleation center is widely studied recently due to its high stability, singal-noise ratio and capability of detecting large molecule, however, uncontinuity of the island film hinders further structure optimization and enhancement of sensing performances. Therefore, this project researches such optimization and enhancement step by step, aiming at characterizing spatial structure and optimizing multiple sensing performances of the sensor. Firstly, surface morphology and spatial structure are characterized to study effect of the nucleation center on the structure of the silver SPRi sensor. Secondly, spectroscopic ellipsometer data fitting and polynomial approaching methods are utilized to establish thickness-refractive index model of the gold and silver films. Finally, optimization of the sensing performances and stability is established based on multi-objective optimization algorithm and electrochemical method. Researches of this project have the potential of promoting development of highly stable and sensitive SPRi technique and innovations of biological techniques.

表面等离子体共振成像具有无标记、可实时检测等优点，已经成为癌症免疫治疗、生物制药等前沿领域里高通量筛选的关键技术。具有岛状金薄膜成核中心的银薄膜表面等离子体成像传感器以其强稳定性、高信号噪声比、可检测大尺寸分子的特点得到了行业的广泛关注，然而岛状金薄膜的非连续性为传感器的结构优化和检测性能提高带来了挑战。为解决上述问题，本项目从传感器的空间结构研究入手，首先综合采用多项表征手段和统计学方法探索岛状金薄膜改变传感器空间结构的机制。然后采用拟合光谱椭偏仪数据和多项式拟合方法优化等方式获得金、银薄膜的厚度-折射率模型。最后，基于多目标优化算法和电化学稳定性测量手段提出多项检测性能和稳定性同时优化的方法，实现了结构参数优化设计和提高检测性能的目标。本项目的研究成果对于推动高稳定性、高灵敏度的表面等离子体共振成像技术向前发展，促进生物技术的持续创新具有重要意义。

由于具有良好的检测灵敏度和信噪比，银膜表面等离子体共振成像传感芯片一直是表面检测分析领域的研究热点，但是稳定性差的缺点使其难以在实际应用中推广。为解决上述问题，课题申请人设计并实现了一种金岛型银膜表面等离子体共振成像传感芯片，使用寿命可达100天以上，然而存在空间结构缺乏表征，灵敏度难以有效优化等局限性，导致金岛层对银膜传感芯片的空间结构和物理、电化学性能的改变有何影响，以及传感芯片的稳定性机制有待研究。.本课题从截面和成分分析技术出发，研究金岛层银膜表面等离子体共振成像传感芯片的空间结构和表面形貌，通过拟合光谱椭偏仪数据建立各薄膜折射率-厚度模型，并通过同步优化吸收峰深度宽度比和倏逝波穿透深度得到各薄膜厚度的Pareto最优解集，采用循环伏安法测试具有上述薄膜厚度的传感芯片抗电化学腐蚀能力从而得到稳定性和灵敏度最优的薄膜厚度组合，最后通过测试薄膜粘附力、使用寿命和保存寿命，从而实现明确传感芯片稳定性机制、优化传感芯片结构参数的目的，为该芯片在检测分析领域的推广奠定理论基础。

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