Stimuli-Responsive DNA Microcapsules for SERS Sensing of Trace MicroRNA

In this work, one stimuli-responsive DNA microcapsule was designed to combine duplex-specific nuclease (DSN) amplification strategy and surface-enhanced Raman spectroscopy (SERS) technology for sensitive detection of microRNA 155 (miRNA 155). First, toluidine blue (TB) as Raman dye and CaCO₃ as core templates co-precipitated to form TB@CaCO₃ composite. Then, DNA networks were layer by layer constructed with oligonucleotide layers cross-linked by linker ssDNA L to lock TB@CaCO₃ inside. In the presence of ethylenediaminetetraacetic acid, the core CaCO₃ would be dissolved to form TB-loading DNA microcapsule. With target miRNA 155-induced DSN signal amplification, a large amount of simulative target ssDNA D was obtained, which can completely complement with the linker L on the DNA networks, destroying the microcapsule to release TB and obtain a strong Raman signal. So by this smart design, a SERS platform was fabricated on the basis of the stimuli-responsive DNA microcapsule to detect miRNA 155 from 1 fM to 10 nM with a detection limit of 0.67 fM. In the present study, the programmable property and rapid response speed of DNA microcapsule, which helped in fabrication of a new potential biosensing technology for miRNA detection that is anticipated to be applied for clinical diagnosis.