Herein, a G-quadruplex-enriched DNA nanonetwork (GDN) self-assembled via Y-modules was designed to construct an ultrasensitive electrochemical biosensing platform with low background for the detection of mucin 1 related to cancers. The single-stranded DNA (ssDNA) S1 converted from target mucin 1 could hybridize with ssDNA S2 and ssDNA S3 with split G-quadruplex fragments at ends to form Y-modules and self-assemble into a GDN, which can capture abundant electroactive substance hemin for a significant electrochemical signal. Impressively, compared with conventional G-quadruplex nanowires with low loading capacity and poor structural stability, the GDN assembled by Y-modules was able to load more signaling probes and obtain a more stable structure for the support of G-quadruplexes, thereby outputting a stronger and more stable electrochemical signal. Moreover, a complete G-quadruplex assembled from two split G-quadruplex effectively reduced the background signal and thus improved the signal-to-noise ratio for the sensitive detection of mucin 1. As a result, the constructed electrochemical biosensor based on GDN achieved ultrasensitive detection of target mucin 1 with a detection limit down to 0.15 fg mL−1 and was successfully applied to analyze mucin 1 in human serum samples, exhibiting great potential for protein biomarker analysis and clinical diagnosis of diseases.

中文翻译：

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一种基于 G 四链体富集 DNA 纳米网络的高效低背景信号放大策略，用于粘蛋白 1 的超灵敏电化学检测


在此，设计了通过 Y 模块自组装的 G 四链体富集 DNA 纳米网络 （GDN），以构建一个低背景的超灵敏电化学生物传感平台，用于检测与癌症相关的粘蛋白 1。由靶粘蛋白 1 转化的单链 DNA （ssDNA） S1 可与 ssDNA S2 和 ssDNA S3 杂交，末端分裂的 G-四链体片段形成 Y 模块并自组装成 GDN，可以捕获丰富的电活性物质血红素，从而获得显著的电化学信号。令人印象深刻的是，与负载能力低、结构稳定性差的传统 G-四链体纳米线相比，由 Y 模块组装的 GDN 能够加载更多的信号探针并获得更稳定的结构来支持 G-四链体，从而输出更强、更稳定的电化学信号。此外，由两个分裂的 G-四链体组装的完整 G 四链体有效地降低了背景信号，从而提高了灵敏检测粘蛋白 1 的信噪比。结果，基于 GDN 构建的电化学生物传感器实现了对目标粘蛋白 1 的超灵敏检测，检测限低至 0.15 fg mL-1，并成功应用于分析人血清样品中的粘蛋白 1，在蛋白质生物标志物分析和疾病临床诊断方面表现出巨大潜力。