Molecular Recognition-Modulated Hetero-Assembly of Nanostructures for Visualizable and Portable Detection of Circulating miRNAs

Biomolecular markers, particularly circulating microRNAs(miRNAs)play an important role in diagnosis, monitoring, and therapeutic interventionof cancers. However, existing detection strategies remain intricate,laborious, and far from being developed for point-of-care testing.Here, we report a portable colorimetric sensor that utilizes the hetero-assemblyof nanostructures driven by base pairing and recognition for directdetection of miRNAs. Following hybridization, two sizes of nanoparticlesmodified with single-strand DNA can be robustly assembled into heterostructureswith strong optical resonance, exhibiting distinct structure colors.Particularly, the large nanoparticles are first arranged into nanochainsto enhance scattering signals of small nanoparticles, which allowsfor sensitive detection and quantification of miRNAs without the requirementof target extraction, amplification, and fluorescent labels. Furthermore,we demonstrate the high specificity and single-base selectivity oftesting different miRNA samples, which shows great potential in thediagnosis, staging, and monitoring of cancers. These heterogeneousassembled nanostructures provide an opportunity to develop simple,fast, and convenient tools for miRNAs detection, which is suitablefor many scenarios, especially in low-resource setting.