Ultrasensitive electrochemical biosensor for attomolar level detection of let 7a based on toehold mediated strand displacement reaction circuits and molecular beacon mediated circular strand displacement polymerization

Abstract

In this study, an ultrasensitive electrochemical miRNA biosensor based on toehold mediated strand displacement reaction circuits (SDRCs) and molecular beacon mediated isothermal circular strand displacement polymerization reaction (ICSDPR) has been proposed. During the SDRCs module, the cascade strand displacement reaction induces the recycling of the target let 7a and generation of a large amount of strand A (SA). The SA recognition opens the hairpin capture probe immobilized on the gold electrode, thus, varying the distance between the redox molecules and electrode surface. The primer mediated ICSDPR is observed to further generate a large amount of SA, thus, leading to a reduction in the signal. Considering these merits, the proposed method is observed to exhibit a log-linear linearity from 10 aM to 100 pM and ultrahigh sensitivity towards let 7a down to 6.2 aM, with a capability of distinguishing the let 7a family members, thereby, providing a new electrochemical route for early cancer screening.

Keywords: Circular strand displacement circuits; Electrochemical biosensor; Isothermal circular strand displacement polymerization reaction; Molecular beacons; Non-coding RNA marker.