适于疾病诊断的微型化光声检测系统研制

Miniaturized analytical instruments play an important role in the rapid detection of disease markers and diagnosis. The conventional optical measuring instruments have high requirements on sample morphology, matrix and optical properties, and have great limitations on the detection of living samples. This project aims to develop a miniature photoacoustic instrumentation for disease diagnosis. As the photoacoustic signal directly depends on the light energy absorbed by sample, without reflected light and scattered light interference, it is suitable for the detection of disease markers in living system. For the photoacoustic detection sensitivity, selectivity and other bottlenecks, we try to resolve them by the employments of dual-wavelength detection, target labeling, signal enhancement/amplification and online analytical techniques, from the view of system firmware, detection methods, real samples and other aspects. The miniature photoacoustic instrumentation can be applied to the rapid detection of disease markers in breath gas, body fluid, tissue and other living systems, and provides a multi-mode detection method based on photoacoustic signal and a cellphone control mode. The fulfillment of this project will lay the foundation for the development of miniaturized photoacoustic detection and related sample pretreatment techniques, and provide a new technical tool for the rapid detection of disease markers as well as theoretical basis, experimental methods and basic data for disease diagnosis.

微型化分析仪器在疾病标志物的快速检测与诊治应用中发挥着重要作用。传统的光学检测仪器对样品形态、基质、光学性质都有较高的要求，对于生命样品检测有很大局限性。本项目拟构建适于疾病诊断的微型化光声检测系统。由于光声信号直接取决于样品所吸收的光能，不受反射光、散射光干扰，适于生命体系中疾病标志物的分析检测。针对光声检测灵敏度、选择性等瓶颈问题，将分别从系统固件、检测方法、实际样品等角度出发，结合双波长检测技术、靶向标记技术、信号增强/放大技术和在线分析技术，予以解决。该微型化光声检测系统可应用于呼吸气、体液、组织等生命体系中疾病标志物的快速检测，并提供基于光声信号的多模式检测方式和手机操控方式。该项目的完成将为微型化光声检测技术和相关样品预处理技术发展奠定基础，为疾病标志物的快速检测提供新的技术手段，以及为疾病诊断提供理论依据、实验方法和基础数据。

为了不断适应现场检测和实时监测的分析需求，分析仪器不仅需要高灵敏度、精密度和分析速度，更不断朝着微型化和集成化的方向发展。本项目构建了可用于多种形态样品定量分析的基于气体-传声器模式的光声装置，并系统考察优化了光声池设计，为疾病标志物的即时检测提供了微型化检测系统；使用金纳米棒作为光声信号增强探针和适配体作为特异性识别元件，提升了光声检测的灵敏度和选择性；以体液和皮肤等生物样品为研究对象，建立了一系列与人类生命健康相关的葡萄糖、尿酸、凝血酶、碱性磷酸酶和pH等疾病标志物的光声即时检测方法，克服了传统光学方法对复杂生命样品检测的局限性；结合便携式滤纸及凝胶试纸条，采用手机APP作为信号接收端，集成微型化的光声检测系统，并拓展了光声分析方法在食品安全领域的应用。本项目研究成果为开发微型化和集成化的光声装置提供了新途径，为疾病标志物的快速检测提供了新技术手段，并为疾病治疗过程实时监测提供了方法学基础。