乳腺癌是世界上发病率较高的一类癌症，严重威胁我国女性的身心健康。乳腺癌的诊断与预后紧密相关，早发现、早诊断、早治疗是提高治愈率的关键。大型诊断设备无法满足常规化、大规模乳腺癌筛查，急需开发成本低、效率高、操作简便的非侵入式替代诊断技术。本项目在充分调研文献资料和总结课题组前期研究工作的基础上提出：联合检测多个miRNA形成指纹图谱可以提高临床血检诊断乳腺癌的准确性和特异性。拟完成如下开创性工作：a. 针对血液样本干扰组分多、靶标浓度低等问题，设计功能核酸/MOFs多级信号放大检测探针，用于提高miRNA即时检测的灵敏度、选择性和重复性; b.筛选高效的miRNA组合标志物形成指纹图谱，交叉响应、模式识别，避免因缺少统一性分子内标而造成的丰度测定差异和单个miRNA特异性差等关键性问题。本项目有望为智能化乳腺癌筛查研究提供新方法和新思路，为血液miRNA联合诊断多种癌症的新技术奠定基础。

Breast cancer (BC) is among the most common cancers worldwide, and continues to pose great health threat to Chinese women. As survival rate of BC is closely associated with its diagnostic state, early screening and diagnosis are thus considered as the key to improve treatment efficiency. Large equipment-based techniques can hardly meet the requirement of generalized large-scale diagnosis of BC, spurring cost-effective, highly efficient, operation-friendly and noninvasive detection alternatives. After comprehensive literature review and summary of our previous research work, we propose that combined analysis of multiple miRNAs to create fingerprints would potentially improve the accuracy and specificity of BC diagnosis by blood test. We plan to accomplish the following tasks: a. Design of high-performance bio-probes using functional nucleic acids and metal-organic frameworks (MOFs) to overcome problems like high interference and low target concentrations in blood, so as to realize good sensitivity, selectivity and reproducibility for in-site miRNA detection; b. Screening of efficient combined miRNA markers to form specific fingerprints to allow for cross-reactive pattern recognition. It will circumvent technical issues resulted from variation in abundance quantification due to the lack of reliable inner reference and low specificity with a single miRNA biomarker. Approval and execution of the project as-proposed will definitely open up new perspectives for automotive BC diagnosis, and promote the development of new methods and new ideas to screen and monitor multiple cancers by blood miRNA analysis.