Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, P. R. China.
Henan Joint International Research Laboratory of Green Construction of Functional Molecules and Their Bioanalytical Applications, College of Chemistry, Zhengzhou University, Zhengzhou 450001, P. R. China.
Anal Chem. 2022 Aug 16;94(32):11416-11424. doi: 10.1021/acs.analchem.2c02541. Epub 2022 Aug 5.
Herein, an ultrasensitive and versatile electrochemical biosensor was developed through the target-controlled capture and release of signal probe-loaded DNA nanotube for the ultrasensitive detection of two different types of cancer-related biomarkers, microRNA-21 (miRNA-21) and glutathione (GSH). In this system, target 1 (miRNA-21) first triggered duplex-specific nuclease (DSN)-assisted recycle amplification to generate numerous disulfide-linked DNA strands (DL), which could effectively capture DNA nanotube to immobilize methylene blue (MB) to produce remarkable electrochemical signals and achieve the ultrasensitive detection of miRNA-21 with a detection limit down to 32.6 aM. Furthermore, in the presence of target 2 (GSH), the electrochemical signal was significantly reduced by a thiol-disulfide bond exchange reaction on DL to release MB-immobilized DNA nanotubes away from the sensing interface, which enabled the sensitive analysis of GSH with a detection limit of 0.379 nM. Impressively, this strategy could achieve ultrasensitive detection of different types of biomarkers to prominently lessen false-positive responses from the current sensing methods toward a single biomarker or the same type of biomarker and remarkably heighten the accuracy and precision of early cancer diagnosis. Meanwhile, the proposed electrochemical biosensor made it possible to realize the regenerative analysis of targets over four times without extra fuel, which could conspicuously improve the analytical efficiency compared with that of traditional biosensing assays. As a result, this study might open up novel insights to design a versatile and multifunctional sensing platform and encourage deeper exploration for detecting different types of biomarkers in the fields of early disease diagnosis and biochemical research.
在此，通过目标控制捕获和释放负载信号探针的 DNA 纳米管，开发了一种超灵敏且多功能的电化学生物传感器，用于超灵敏检测两种不同类型的癌症相关生物标志物，即 microRNA-21（miRNA-21）和谷胱甘肽（GSH）。在该系统中，靶标 1（miRNA-21）首先触发双链特异性核酸酶（DSN）辅助的循环扩增以产生大量的二硫键连接的 DNA 链（DL），其可以有效捕获 DNA 纳米管以固定亚甲基蓝（MB），从而产生显著的电化学信号，并实现对 miRNA-21 的超灵敏检测，检测限低至 32.6 aM。此外，在存在靶标 2（GSH）的情况下，通过 DL 上的硫醇-二硫键交换反应，电化学信号显著降低，从而使 MB 固定的 DNA 纳米管从传感界面释放，这使得可以通过检测限为 0.379 nM 的 GSH 的灵敏分析。令人印象深刻的是，该策略可以实现对不同类型生物标志物的超灵敏检测，显著减少当前传感方法对单个生物标志物或同一类型生物标志物的假阳性反应，并显著提高早期癌症诊断的准确性和精密度。同时，所提出的电化学生物传感器可以实现无需额外燃料即可对目标进行四次以上的再生分析，这与传统生物传感测定相比，可以显著提高分析效率。因此，这项研究可能为设计多功能传感平台开辟新的思路，并鼓励在早期疾病诊断和生化研究领域深入探索检测不同类型的生物标志物。
