对肌酐、尿酸具有智能光学响应的金纳米粒子研究

Gold nanoparticle (AuNP) exhibits unique surface plasmon resonances that are the collective oscillations from conduction electrons under light irradiation. Such resonance is susceptible to several parameters like particle size and shape, inter-particle distance, and local dielectric environment of nanoparticles. The plasmon band of AuNP (13 nm) in water media is centered around 520 nm, while aggregated AuNP solution shows obvious red-to-blue color changes with blue-shifted absorption bond in range of 600-700 nm, which possess 1000-fold greater absorption extinction coefficient than common organic dyes. We found that the mercury ion could induce the aggregation of AuNP functionalized by creatinine and uric acid in urine with obvious red-to-blue color changes. In this study, the active sites of creatinine, uric acid and ions on the surface of AuNP as well as their molecular configuration optimization would be explored, based on the supramolecular chemistry on the surface of AuNP. And following quantitative colorimetric response of creatinine and uric acid would be achieved by the synergy among molecules, ions, and nanoparticles. Therefore, creatinine and uric acid kits are presented for fast, sensitive, convenient and lowcost colorimetric monitoring of creatinine and uric acid for patients with kidney disease at home. In China, the nephritic patients reach about 100 million, and contents of creatinine and uric acid in human body are most important index for the kidney function and renal disease diagnosis. The result in this study can provide qualitative and quantitative determination by colorimetric changes for uric acid and creatinine content with cost as low as 0.1 Yuan per time, which shows important significance in theory and practical.

金纳米粒子具有独特的表面等离子共振光学特性，其溶液颜色对微环境极为敏感，分散状态的金纳米粒子(13 nm)水溶液呈红色（吸收峰520 nm），而聚集状态的水溶液为蓝色（吸收峰600-700 nm），其摩尔消光系数ε为普通染料的1000倍。申请人发现，汞离子可以诱导肌酐和尿酸修饰的金纳米粒子聚集，伴随溶液由红到蓝的颜色变化。本项目拟从这一发现出发，研究肌酐和尿酸与不同具有氢键、主客体和配位作用的含氮化合物、过渡金属离子等，在溶液中与金纳米粒子的作用规律和之间的协同超分子作用规律，构建对肌酐和尿酸的定量颜色变化响应的超分子体系，制成简便、廉价的试剂盒，用于慢性肾病患者的家庭自我监控。目前我国肾病患者约有1亿人，尿液中肌酐和尿酸的含量是肾功能的关键指标。通过超分子体系颜色响应的调控，可望使这种裸眼颜色变化检测实现定性和定量化，单次使用成本可望控制在0.1元左右，具有重要理论和实际意义。

本研究工作主要以具有独特的表面等离子共振光学特性的金纳米粒子为研究平台，以分子间氢键、配位络合等超分子作用为手段，以肌酸酐、尿酸等生化小分子及金属离子为刺激源，实现了金纳米粒子的多尺度调控，并表现为吸收光谱的红移及肉眼可见的颜色变化。完成了1）肌酐、尿酸等分子在AuNP 表面的作用位点；2）金属离子在体系内的分子协同机制；和3）AuNP响应体系控制等关键难点的研究。通过筛选，得到了肌酐、尿酸参与协同配位络合体系，组装AuNP比色传感器，实现了人体体液（血清、尿液等）中肌酐、尿酸的选择性定性/定量比色识别。目前本项目所涉及的肌酸酐和尿酸的试剂盒正处于试制阶段，并以慢性肾病患者家庭自我肌酐等生化指标监测为目标，致力于方便、廉价、可靠的金粒子裸眼检测试剂盒规模化应用基础研究。本项目按照申请书中年度研究计划开展研究，顺利完成预期研究目标。此外，在完成目标物肌酸酐等生化小分子的选择性定量识别后，在本基金的支持下我们还开展了相关的重要小分子及金属离子的定量比色识别研究工作。共计以第一作者或通讯作者发表了7篇SCI、EI收录论文：1) Small, 2015, 11, 4104-4110; 2) Sensor and Actuators, B: Chemical 2015, 212, 481-486；3) Industrial and Engineering Chemistry Research 2015, 54, 12011-12016；4) Industrial and Engineering Chemistry Research 2016, 55, 12334-12340；5) Sensor and Actuators, B: Chemical 2017, 248, 318-323；6) Nanoscale 2017, 9, 19139-19144； 7) Sensor and Actuators, B: Chemical 2018, 255, 808-813；并申请了两项发明专利CN 106353270 A 20170125和CN 106053451 A 20161026。在本课题研究期间，共计在与本课题相关的国际会议上发表口头报告3次（含两次邀请报告），以及国内会议口头报告4次。共计培养博士生1人、硕士生3人（毕业2人）。