及早发现并准确检测特异性显著的生物标志物，是精准诊断，乃至精准医疗的关键。包括阿尔茨海默病(AD)在内的许多疾病临床诊断，依赖于单一生物标志物检测，往往特异性和准确度都不尽如人意。为此，本申请项目提出基于多生物标志物（长短不同的A-beta多肽、t-tau、p-tau等），或单一生物标志物区分多形态(如p-tau区分不同磷酸化点位)全息分析的AD诊断思路，设计构建适用于临床的、超灵敏、智能型诊断分析方法。拟参照医学研究结果，以前期构建的石墨烯基质免疫竞争荧光传感器为单元，引入分子逻辑门原理，设计研发以多重生物标志物含量为输入信号的，具有“单输入-单输出YES型”、“双输入-单输出OR型”、“双输入-单输出INHIBIT型”三种逻辑运算功能的荧光传感体系，实现多重生物标志物的超灵敏同步分析，探索AD病临床检验智能快捷诊断新方法，也为大数据时代临床检验数据网络化、远程诊断，提供接口。

Finding and accurate detection of biomarkers with significant specificity, are crucial to accurate diagnosis, and the precondition for precision medicine. Currently, clinical diagnosis of many diseases, including Alzheimer's disease (AD), relies on a single biomarker detection, its specificity and accuracy are often not satisfactory. In this application project, a new strategy for AD diagnosis has been suggested based on a comprehensive analysis of multiple biomarkers (different A-beta peptides, t-tau, p-tau, etc.), or a holographic analysis of a single biomarker with different conformations (e.g., distinguishing different phosphorylation site of p-tau). A novel analytical method suitable for clinical conditions is designed over the early development of graphene fluorescent bio-sensors based on the principle of immune competition, combined with the principle of molecular logic gate. With reference to medical data, fluorescent biosensors with three different logic gate, i) single input and single output, logic YES, ii) double input and single output, logic OR, iii) double input and single output, logic INHIBIT, are ready to build, in order to realize diagnosis of Alzheimer disease through joint analysis of multiple biomarkers. Implementation of this project will provide new ideas for AD accurate diagnosis technology, and an interface for data network of clinical test , remote diagnosis in the big data era.