Composition-Tunable Hollow Au/Ag SERS Nanoprobes Coupled with Target-Catalyzed Hairpin Assembly for Triple-Amplification Detection of miRNA

Detecting disease-related biomarkers is of great significance for disease diagnosis and therapy. In this work, we develop an ultrasensitive surface-enhanced Raman scattering (SERS) biosensor for the detection of an acute myocardial infarction-related miRNA (miR-133a) using composition-adjustable hollow Ag/Au nanosphere-based SERS probes coupled with the target-catalyzed hairpin assembly (CHA) strategy. Bimetallic probes displaying high stability and a strong surface plasmon resonance effect were synthesized with a controllable ratio of silver and gold by a galvanic replacement method and then captured by a duplex linker produced in the CHA process to accomplish signal amplification. In this way, the target miR-133a can be detected in a wide linear range with a detection limit of 0.306 fM and high selectivity over other miRNAs expressed in human hearts. Practical applications in human blood samples reveal the strong anti-interference ability and ideal sensitivity of our developed sensing platform in physiological environments, benefiting its potential biomedical applications.