Triple-Input Molecular AND Logic Gates for Sensitive Detection of Multiple miRNAs

Abnormal miRNA expressions are closely related to the occurrence and development of cancers. It is of great significance to monitor miRNA expression levels for early diagnosis and therapy of the diseases. This study presents two independent colorimetric strategies for simultaneously monitoring multiple miRNAs based on cross-linking or non-cross-linking aggregations of gold nanoparticles (AuNPs). By introducing a Y shaped DNA structure and two types of DNA modified AuNPs, a triple-input DNA AND logic gate is facilely developed with the cross-linking aggregation of AuNPs as the signal output. To improve the sensitivity and shorten reaction time, the logic gate is modified by further employing a three DNA strands formed duplex and hybridization chain reaction. Non-cross-linking aggregation of AuNPs is used to evaluate the concentration of initial miRNA inputs. This strategy does not require DNA modification of AuNPs and ultrahigh sensitivity is achieved with the amplification of hybridization chain reaction. The present work may provide powerful tools for multiple miRNAs diagnostics and inspire further development of DNA based logic gates.