A smart DNA tweezer for universal proximity assay and logic building

Abstract

A smart DNA tweezer was constructed for universal proximity assay and logic building. In this tweezer, the set strand was designed as recognition module, and the ends of two motifs were ingeniously designed as toehold domain (TD) and branch migration domain (BMD). As the recognition of set strand and target, the set strand could be dismantled from the tweezer, resulting in a proximity binding of TD and BMD. Then, the proximal TD and BMD could initiate the dynamic assembly of two complementary hairpins, yeilding a long double-stranded polymer with multiple G-quadruplexes. By inserting fluorescent dye, enhanced fluorescent response could be observed. Universal and sensitive assay of miRNA and thrombin were achieved by altering the sequence of set strand. The corresponding detection limits were 9.4 fM and 0.35 pM. Moreover, quantitative analysis of miRNA in clinical serum sample was also performed, suggesting the feasibility of this proximity assay in clinical application. What’s more, based on the proposed DNA tweezer, a Boolean logic operation platform was fabricated, and systematic logic operations were also achieved. Therefore, this work provided a reliable strategy for universal proximity assay and logic operation, which could be further used in biomedical research and clinical diagnosis.