Fig. 1. Principle of SERS
(a) Illustration of the collective oscillation of free electrons in metal nanoparticles upon excitation by an electromagnetic wave; (b) Chemical enhancement results from charge transfer resonance between signal molecules and metal nanostructures, which is usually weaker than electromagnetic enhancement

Fig. 2. SERS-based nucleic acid analysis using a label-free SERS approach (left) or SERS tags (right)
In label-free SERS, the spectroscopic signal results from analyte adsorption onto the SERS substrate, whereas in SERS tags-based specific recognition assays, the spectroscopic signal results from the reporter molecules on the SERS tags

Fig. 3. Scheme of SERS-based nucleic acid detection based on sandwich structure^[18]

Fig. 4. (A) Schematic illustration of the synthetic procedures of Raman dye-coded Au-RNNPs using DNA-modified AuNPs as templates (a) and Ag-HMSs using bacteria as template; (B) Schematic illustration of the multiplex SERS assay for triple-target miRNA detection; (C)SERS spectra of the nanoprobes obtained in the presence of (a) single and (b) multiple miRNA^[19]

Fig. 5. Scheme of SERS-based nucleic acid detection based on hairpin structure^[18]

Fig. 6. (a) Schematic illustration of the molecular beacons functionalized-SERS sensor for simultaneously measuring multiple miRNAs^[24]; (b) Detection scheme of the SERS “inverse Molecular Sentinel” nanoprobes^[25]

Fig. 7. Scheme of SERS-based nucleic acid detection based on the signal amplification of hybridization chain reaction^[26,27]

Table 1. Analysis of the label-free SERS approach and SERS tags-based nucleic acid assays

Table 2. Typical research about SERS used for detection on nucleic acids