基于功能化核酸的非标记光学传感新方法及其在超痕量肿瘤标志物检测中的应用研究

The project based on basic research of life sciences. In response to the requirement of new technologies for early diagnosis and early warning of country's major diseases, this project is aimed to develop new label-free, highly sensitive and specific homogenous optical biosensors based on functional nucleic acids, nanomaterials and tool enzymes signal amplification for detection of ultra-trace tumor markers. The main research content includes: (1) preparation and characterization of nanomaterials; (2) design and optimization of functional nucleic acid probes; (3) label-free optical sensor new methods based on functional nucleic acids, nanomaterials and tool enzymes signal amplification for different research objects; (4) mechanism research and methodological study; (5) the new methods were applied to the rapid detection of tumor markers in serum, urine, saliva, cell and other clinical samples, and evaluated the performance of the designed sensors. The project through a combination of functional nucleic acids, nanomaterials and tool enzymes signal amplification technology, the sensitivity and selectivity of the label-free optical sensors can significantly improved, this project can achieve ultra-trace tumor markers for early diagnosis and rapid detection, and provide theoretical basis and technical support for the early diagnosis of cancer, these methods also have positive significance for promoting the development of analytical chemistry, life science foundation research and biomedical sciences.

本项目立足生命科学的基础研究，面向国家重大疾病的早期诊断与预警新技术、新方法的战略需求，以光学传感中的分子识别机制为基础，将功能化核酸、纳米材料及工具酶信号放大进行巧妙结合，建立非标记、超灵敏、高特异性的均相光学传感新方法并用于超痕量肿瘤标志物的检测。主要研究内容包括：(1)纳米材料的制备与表征；(2)功能化核酸探针的构建与优化；(3)针对不同研究对象，建立基于功能化核酸、纳米材料和工具酶信号放大的一元或多元非标记光学传感新方法；(4)机理研究及方法学考察；(5)将所建立的新方法用于人血清、尿液、细胞等临床样本中肿瘤标志物的快速检测，并对所构建方法进行性能评价。通过结合功能化核酸、纳米材料和工具酶信号放大技术，解决非标记光学传感器的灵敏度和选择性等关键问题，为超痕量肿瘤标志物的快速灵敏检测和肿瘤疾病的早期诊断提供有力的理论依据和技术支持，积极推动分析化学、生命科学基础研究和生物医学的发展。

高灵敏、高选择性的分析方法的建立对于疾病的早期诊断起着至关重要的作用。本项目以光学传感中的分子识别机制为基础，利用功能化核酸（G-四连体、核酸适配体）、纳米材料（二氧化硅、银纳米簇、硫化钨纳米片、血红素功能化的二硫化钨纳米片、磁性氮化碳纳米片、纳米金等）、工具酶（聚合酶、切刻内切酶、外切酶）信号放大、DNA自组装技术构建了一系列灵敏度高、特异性好的光学传感新方法（化学发光、荧光、紫外），实现了抑癌基因p53、乙肝病毒DNA、生物素-链酶亲和素、双氧水、葡萄糖、鸟苷四磷酸等多种靶标的检测。并在方法学研究的基础上，将构建的新方法应用于细胞、血液等生物实际样本中相关活性物质的分析。以上方法的建立，可以为一些超痕量的肿瘤标志物的检测、疾病的早期诊断、预后治疗、病变过程跟踪和精准分析提供理论依据和技术支持，为新器件研制提供一些新思路。本项目标注的SCI论文有10篇，包括Biosensors and Bioelectronics、Chemical Communication、Journal of Materials Chemistry B等。