Tetrahedral DNA Nanostructure-Engineered Paper-Based Sensor with an Enhanced Antifouling Ability for...

Herein, a newly designed two-in-one tetrahedral DNA (TDN) nanostructure with an antifouling surface and backbone-rigidified interfacial tracks was developed for highly sensitive and selective detection of miRNA-182-5p. The well-regulated TDN tracks were assembled onto the surface of the TiO₂/MIL-125-NH₂-functionalized paper electrode, which efficiently avoided the obstacle of DNA strand tangling and decreased the probability of suspension during the walking process, thus greatly promoting the moving efficiency of DNA walkers. More interestingly, the TDN-modified sensing interfaces demonstrated incomparable antifouling ability against protein samples and interfering miRNAs due to the strong hydrophilic capacity and special molecular conformations, which addressed the dilemma of low sensitivity from traditional antifouling coating strategies. As a proof of concept, the designed bifunctional tetrahedron-modified paper-based photoelectrochemical sensor was successfully used to quantify miRNA-182-5p with a low detection limit of 0.09 fM and high specificity and was validated for monitoring of miRNA-182-5p in real samples. This TDN-engineered biointerface could be used as a universal platform for tracking various targets by substituting the biorecognition events, providing great promise for bioanalysis and clinical diagnosis.