Ultrasensitive miR-451 Detection via DNAzyme-Mediated Etching with In Situ Single-Nanoparticle LSPR Monitoring

to produce reactive species capable of etching the silver shell of Au@Ag core-shell nanoparticles (Au@AgNPs) immobilized in the microfluidic chip, leading to a measurable LSPR redshift. By tracking the spectra of the same individual nanoparticles before and after etching, the platform minimized spatial sampling errors associated with conventional ensemble-based LSPR measurements. The proposed method achieved a limit of detection of 40.96 aM and a linear range from 100 aM to 100 pM, with high specificity toward nontarget and mismatched sequences. Its applicability was preliminarily evaluated in fetal bovine serum and further assessed in commercial human serum through spike-in recovery experiments, while RT-qPCR provided auxiliary verification of the concentration-dependent response trend. These results support the potential of this platform for ultrasensitive miRNA analysis in complex biological matrices.