核酸突变是人类基因序列中最常见的变异，由于很多核酸点突变与疾病有着重要关联甚至是检验某些疾病的直接检验指标，基因点突变分析无论在理论研究还是临床实际检验分析中都有着重要意义，若能实现低丰度DNA点突变准确检测，尤其对重大疾病的早期诊断和预防至关重要。但至今国际上尚缺少能完全保障特异性并兼具高灵敏、低成本、高通量的核酸点突变检测方法。因此研究准确、快速、高灵敏、高通量且适用于临床的核酸点突变分析方法非常重要。本课题综合应用基因组扩增技术、纳米磁分离技术、微孔板分析技术以及ddNTP的仅单碱基延伸功能，通过荧光双脱氧核苷酸(ddNTP)在金包铁核壳纳米磁性颗粒表面对点突变位点多次循环单碱基延伸，不需杂交识别，而且显著放大点突变信息，从而实现低拷贝数DNA点突变信息的高特异性、高灵敏和高通量分析。也可为研究具有自主知识产权的临床大规模分子诊断高端系统提供方法学支撑。

Nucleic acid mutation is one of the variation which takes place and is observed very frequently. Owing to many single nucleic acid mutations are closely associated with diseases and even are checked for diagnosis, detection of single nucleic acid mutations is of important significance in both research and clinic assay. It is very promising to detect the single nucleic acid mutations in very low copies with high specificity, high sensitivity and high accuracy, which should benefit people to get the clue of diseases at their very early stage. With the combination of genomic amplification, separation by mean of magnetic nanoparticles, micro-well assay and the single base extention feature of the ddNTP, this research is focused on the multiplex single base extention at the surface of Fe@Au magnetic nanoparticles by recycling the single base extention step. By means of this approach, the single point mutation information is amplified significantly and can be detected without hybridization and, therefore, the mutation with very few copies can be checked with high specificity, high sensitivity and high-throughput. Which can also contribute to the clinic diagnosis.