Ultrasensitive electrochemical detection of miRNA coupling tetrahedral DNA modified gold nanoparticles tags and catalyzed hairpin assembly

Highlights: • An ultrasensitive electrochemical biosensor for the detection of miRNA is developed. • Tetrahedral DNA modified AuNPs tags are applied for signal enhancement. • The electrochemical method successfully distinguishes target miRNA from mismatched miRNAs. • The electrochemical method performs satisfactorily in clinical samples. MicroRNAs (miRNAs) play key regulatory roles in a number of biological processes, which act as critical biomarkers for clinical diagnosis. There are urgent needs to develop advanced tools for accurate and convenient analysis of miRNA in biological circumstances. In this study, an ultrasensitive electrochemical biosensor for miRNA assay is fabricated. Tetrahedral DNA modified gold nanoparticles tags are applied with optimized orientation, which are able to recruit a large number of electrochemical species for remarkable signal responses. Benefiting from the excellent amplification efficiency of the association of strand displacement amplification and catalyzed hairpin assembly, the established method shows ultrahigh sensitivity with the limit of detection as low as 10 aM. A wide linear range from 10⁻¹⁷ to 10⁻⁷ M is achieved. In addition, this method is capable to specifically discriminate interfering miRNAs with slightly different sequences. The successful assessment of miRNA levels in human serum samples also demonstrates good practical utility. Therefore, the proposed method has great potential to the applications of miRNA expression profiling and biological studies.