基于新型MXenes量子点和加速DNA反应放大策略的灵敏电致化学发光microRNA生物传感器的研究

The occurrence and development of many malignant tumors are closely related to the abnormal expression of microRNA. However, the content of some microRNAs in cells is too small to be detected. Therefore, in order to achieve accurate detection of microRNA in cells, this project intends to synthesize Mxenes quantum dots (QDs) with high luminous efficiency, good stability and excellent conductivity as novel electrochemiluminescence (ECL) materials, design accelerated DNA reaction as efficient target conversion and recycling strategy to construct sensitive ECL biosensor. The novel and functionalized Mxenes QDs are synthesized by etching combined with mechanical force-assisted liquid flaking and etching combined with hydrothermal method, respectively. Based on the DNA technologies of catalyzed hairpin assembly and toehold-mediated chain displacement, the accelerated DNA reaction strategies are fabricated by using multiplex footholds DNA double-stranded and DNA-functionalized supramolecular polymer as supporting material to immobilize DNA reactants and confine them in a localized space with high concentration. Thus, the obtained accelerated DNA reaction strategies can shorten the reaction time required for target conversion and improve the efficiency of target conversion. Through the research of this project, it is expected to provide new research ideas for the early diagnosis of malignant tumors, and further improve the efficiency of disease diagnosis and treatment.

诸多恶性肿瘤的发生和发展都与microRNA的异常表达密切相关，但是部分microRNA在细胞内的含量很小以致难以检测。为实现细胞内痕量microRNA的准确检测，本项目拟通过刻蚀-机械力辅助剥离法、刻蚀辅助剥离与水热相结合的方法制备导电性好、发光效率高、稳定性好的MXenes量子点作为新型电致化学发光材料；拟以催化发夹组装和toehold介导的链置换为DNA放大技术，根据目标microRNA的序列设计合理的DNA反应物，采用多足的DNA双链和DNA功能化的动态超分子聚合物作为支撑材料固载DNA反应物，使其在一定范围内保持高的局部浓度，得到加速的DNA反应，从而缩短目标物转换所需时间以及提高目标物转换的效率；以此构建灵敏度高、检测快速、稳定性好的电致化学发光microRNA生物传感器测试平台。通过本项目的研究，有望为恶性肿瘤的早期诊断提供新的研究思路，进一步提高疾病诊断与治疗效率。

本项目合成一系列具有高发光效率的电致化学发光材料（如N参杂的Ti3C2量子点、AuAg纳米簇、CNNS@NH2-MIL(Fe)纳米材料等），通过多种技术实现信号放大（如颗粒间DNA步行器、DNA四面体自组装三维基质和多种纳米材料催化等），构建了具有不同信号输出模式的超灵敏电致化学发光生物传感器，实现了多种疾病标志物（如心肌肌钙蛋白I（cTn-I）、 粘蛋白1（MUC-1）、谷胱甘肽（GSH）等）的检测。并将所制得的生物传感器初步应用到血清内相关目标物含量的灵敏监测。项目中提出的多种高效率发光材料的合成及多种信号放大策略为灵敏电致化学发光传感器的构建提供了新思路，也为拓宽电致化学发光技术提供了新思路。