面向肿瘤标志物检测的三维纳米传感器制备方法与特性研究

In allusion to demands for improving sensitivity and reducing detection time of microfluidic chips, In this proposal, we aimed at applying lower nanomaterials on Microfluidic system by self-assembly technology, to building a 3-demension(3D) nano-sensor with high sensitivity to typical tumor biomark or circulating tumor cells (CTCs), and research the detection features of this sensor, explore the detection techniques with miniaturization, fast and high sensitivity. The main research contents are described as follows: by building a 3D nano-structure in microfluidic chips through self-assembly technology and immobilized biological antibody molecules on it, research the structure-controllable preparation method for microfluidic chips combined with 3D nano-sensor. Research the response characteristic of electrochemical signal to different tumor biomark and CTCs, research and improve the basic performance index of the 3D photoelectric nano-sensor, construct detection model of the 3D nano-sensor. Then introduced more nano-materials into 3D nano-structure to build 3D hybrid nano-structure, and realized the structure-controllable preparation method for microfluidic chips combined with 3D hybrid nano-sensor, research the response characteristic of the sensor, used electrochemical and visual electrochemical luminescence (ECL) signal to realized the high-sensitive and visual rapid detection. This project provides a new strategy to improve the sensitivity of early cancer detection, and also lay the theoretical foundation for extension of the type of microfluidic chip and application range.

针对微流控芯片对提高灵敏度和检测速度的需求，本项目利用自组装技术将低维纳米材料引入微流控芯片内构建三维纳米结构，制备针对典型肿瘤标志物或循环肿瘤细胞的高灵敏度三维纳米光电传感器并研究该传感器的检测特性，探索高灵敏度、微型化的快速检测技术。项目主要研究内容涉及：通过在芯片内自组装构建三维纳米结构并在其表面固定生物抗体分子，研究三维纳米传感器的可控制备方法；研究三维纳米传感器电化学信号对不同肿瘤标记物和循环肿瘤细胞的响应特性，对传感器的基本指标进行研究和改进，并建立其检测模型，随后进一步将其他纳米材料引入以构建三维杂化纳米结构，完成三维杂化纳米传感器的可控制备，并研究其检测特性，利用电化学信号和电化学发光信号实现对典型肿瘤标志物和循环肿瘤细胞的高灵敏度及可视化快速检测。本项目为提高癌症早期检测的灵敏度提供了新的思路，对扩展微流控芯片的类型和应用范围奠定理论基础。

癌症的早期检测与诊断一直是近年来科研界的热门研究领域。在不断的尝试与探索中，研究者们利用物理、化学、生物等各个学科的方法与知识开发出了许多应用于癌症早期检测诊断的技术。本文是关于一种基于三维石墨烯气凝胶（3D GA）材料的微流控生物芯片的设计、制备与应用研究，通过使用该芯片电化学免疫检测手段对典型的肿瘤标志物与外泌体实行定量与定性检测实验，以证明其对于癌症早期检测诊断具有很高的应用价值。本文的主要内容包括以下三个方面：（1）提出了一种适用于电化学免疫检测的微流控生物芯片的设计思路与制备方法，并研究该芯片的电学与化学性能。（2）使用电化学阻抗法（EIS）对典型的肿瘤标志物(IgG, CEA, AFP)进行检测与分析，证明该芯片具有良好的检测灵敏度与选择性，以及较宽的线性响应区间与较低的检测限。（3）尝试了在该芯片中引入石墨烯金颗粒复合材料（AuNPs@GA）作为电极，探索不同的制备方法对芯片的电学与化学特性的影响。