复合传感模式光电子鼻的构建及其对肺癌相关VOCs的检测研究

Through analyzing the results from theoretical model and experiments, we will reveal the principle that Ag+ interacts with aldehydes in a solution of sodium hydroxide. Based on optimized processing and hydrogel, a paper-based platform is fabricated to selectively respond to aldehydes. Additionally, different structures of enzyme-inorganic hybrid nanoflowers(HNFs) are prepared by changing the categories and concentrations of cationic. With the latest characterization methods like transmission electron microscope (TEM), X-ray diffraction (XRD) and electron spin resonance (ESR), the physicochemical nature of HNFs including crystal structure and surface electronic structure will be investigated. Combining the theoretical simulation with the results above, we attempt to illuminate the effect of categories and concentrations of cationic on formation of HNFs by ascertaining the adsorption sites, forming and morphology of nanocrystalline on the surface of enzyme. Sensitive dyes and nanomaterials are picked out based on the signal strength, response time, stability of composites when they respond to lung cancer-related VOCs. As a result, we can obtain a high-efficiency protocol for modification of sensitive dyes with nanomaterials. On basis of the researches above, a new type of electronic nose (e-nose) paper chip is constructed. The improvements of multiple sensing modes and functionalization with nanomaterials on sensing performance of the e-nose are carefully evaluated. Finally,we will find out the relationship among the preparation conditions, materials microstructure and performance of lung cancer-related VOCs sensing, which provides a theoretical and practical reference for the construction of high-performance e-nose.

采用理论计算与实验相结合的方法，探明强碱存在下Ag+与醛基的反应机理。基于工艺优化和凝胶改性，构建醛类特异敏感的纸基平台。通过调节阳离子种类和浓度、孵育时间和温度等参数，制备不同形貌结构的酶-无机杂化纳米花。采用透射电镜、X射线衍射、ESR等现代表征方法，研究纳米花的晶体结构、表面电子结构等物理化学性质。结合模拟计算，明晰无机纳米晶在酶蛋白表面的附着位点、生长方式和形态，探明阳离子种类和浓度对杂化纳米花生长机理的影响规律。以信号强度、响应时间、稳定性、抗温湿度干扰能力为评价指标，系统筛选敏感染料和纳米材料，针对肺癌VOCs标记物提出高效的改性方案。综合上述研究，构建新型电子鼻芯片，系统评价复合传感模式和纳米材料改性对电子鼻传感性能的提升效益，阐明敏感材料制备工艺-微观结构-肺癌VOCs传感性能之间的关系，为高性能电子鼻构建提供理论和实验参考。

本项目基于“纳米功能化”和“大类特异性设计”的联合策略，拟构建复合模式光电子鼻，并提升其呼气VOCs响应性能。具体采用理论计算和实验验证，表明强碱存在下Ag+与醛基的反应体系下，溶液中的OH-首先攻击C-OH基团上的正电性碳原子，并形成中间体，能量计算表明该过程是有利的，且成为整个反应的决速步骤。所形成的CH-(OH)2将进一步解离氢原子到溶液环境中。羰基碳的电性越正，反应就越易进行，为生化传感应用提供了理论支撑。其次，通过调节工艺参数，制备了不同形貌结构的酶-无机杂化纳米花。并采用现代表征技术，研究纳米花的物理化学性质及工艺影响规律。蛋白质浓度与金属离子浓度之比（摩尔比）决定了纳米花表面的枝晶生长结果，比值越低，表面枝晶越多越薄，纳米花整体表现为花状；比值越高，表面枝晶越少，纳米花整体趋于球状。酸碱度可改变蛋白质表面双电层结构，从而促进或抑制溶液中金属离子在蛋白质表面的配位锚定。搅拌过程和温度参数是典型的动力学参数，决定了纳米花的生长速度。金属离子种类对杂化纳米花的形貌影响巨大，但影响机制尚不明确。上述影响机制为纳米花，乃至纳米材料的可控制备提供了理论参考，有利于针对性构建高效传感方法。结合上述研究，成功构建了复合传感模式光电子鼻，并系统评价了其对肺癌呼气VOCs的传感性能。该电子鼻在4分钟内准确识别了低浓度VOCs，识别准确率和特异性分别大于95%和94.7%。相比于单纯的指示剂阵列，在可视化响应，灵敏度和识别准确率上分别提升了29.7%，64.7%和 5.3%。湿度稳定性、时间稳定性、以及重现性均表现优异。结果表明，“纳米功能化 + 大类特异性”的设计策略是提升电子鼻传感性能的正确且有效的途径之一，为高性能电子鼻构建提供理论和实验参考，实质性推动电子鼻呼气分析技术向实际临床应用迈进，更好地服务于个性化精准医疗。