The detection of single nucleotide polymorphisms (SNPs) is of great clinical significance to the diagnosis of various genetic diseases and cancers. In this work, the development of an ultrasensitive ratiometric electrochemical sensor for screening SNP with a significantly enhanced discrimination factor is reported. The ferrocene (Fc) and methylene blue (MB) dual-tagged triple helix complex (THC) probes are self-assembled on the gold electrode to construct the sensing interface. The addition of the mutant p53 gene causes the disassembly of the THC probes with the release of the Fc-tagged sequence and the folding of the MB-labeled sequence into a hairpin structure, causing the change in the current response ratio of MB to Fc for monitoring the mutant p53 gene. Such ratio is dramatically enhanced by the toehold-mediated displacement reaction-assisted target recycling amplification with the presence of an assistance hairpin sequence. With the significant signal amplification and the advantageous specificity of the THC probes, sub-femtomolar detection limit and a highly enhanced SNP discrimination factor for the mutant p53 gene can be obtained. Besides, the proof-of-demonstration application of the sensor for diluted real samples has been verified, offering such sensor new opportunities for monitoring various genetic related diseases.

中文翻译：

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通过放大比例传感器电化学筛选具有显着增强鉴别因子的单核苷酸多态性

单核苷酸多态性（SNPs）的检测对各种遗传疾病和癌症的诊断具有重要的临床意义。在这项工作中，报告了一种用于筛选 SNP 的超灵敏比率电化学传感器的开发，该传感器具有显着增强的鉴别因子。二茂铁 (Fc) 和亚甲蓝 (MB) 双标记三螺旋复合物 (THC) 探针在金电极上自组装以构建传感界面。突变 p53 基因的加入导致 THC 探针解体，释放 Fc 标记序列，MB 标记序列折叠成发夹结构，导致 MB 对 Fc 的电流响应比发生变化。监测突变 p53 基因。在辅助发夹序列的存在下，立足点介导的置换反应辅助目标再循环扩增显着提高了这种比率。由于 THC 探针的显着信号放大和有利的特异性，可以获得亚飞摩尔检测限和高度增强的突变 p53 基因 SNP 鉴别因子。此外，该传感器用于稀释真实样品的证明应用已经得到验证，为此类传感器监测各种遗传相关疾病提供了新的机会。可以获得亚飞摩尔检测限和高度增强的突变 p53 基因 SNP 鉴别因子。此外，该传感器用于稀释真实样品的证明应用已经得到验证，为此类传感器监测各种遗传相关疾病提供了新的机会。可以获得亚飞摩尔检测限和高度增强的突变 p53 基因 SNP 鉴别因子。此外，该传感器用于稀释真实样品的证明应用已经得到验证，为此类传感器监测各种遗传相关疾病提供了新的机会。