An asymmetric double-strand displacement amplification strategy by a side-shifted hybrid chain reaction for the ultrasensitive detection of let-7a.

MicroRNA (miRNA) plays a crucial role in a great number of human cancers so that the detection of miRNA has been widely acknowledged as an effective strategy for the early discovery and diagnosis of cancer. Building upon conventional strand displacement amplification, the study was introduced a dual strand displacement process to enhance primer amplification efficiency. Additionally, we designed a lateral displacement assembly-based DNA nanostructure, expanding on traditional hairpin structures, and constructed a side-shifted hybrid chain reaction (SHCR) strategy for dual amplification of primer sequences. This approach yielded a three-way junction (3WJ) DNA nanostructure, providing optimal molecular recognition sites. The SHCR facilitated the assembly of fluorescent probes through a straightforward hybridization chain reaction. The target-triggered double strand displacement amplification (DSDA) exhibited high specificity for miRNA-let-7a with the rang from 50 fM to 50 nM, and the biosensor's limit of detection is 22 fM. Moreover, the sensor system performed exceptionally well in detecting real samples, such as cell lysates. Therefore, this work offers a novel strategy for early cancer screening.