DNA is a building block of life; surface-enhanced Raman spectroscopy (SERS) has been broadly applied in the detection of biomolecules but there are challenges in obtaining high-quality DNA SERS signals under non-destructive conditions. Here, we developed a novel label-free approach for DNA detection based on SERS, in which the Au@AgNPs core–shell structure was selected as the enhancement substrate, which not only solved the problem of the weak enhancement effect of gold nanoparticles but also overcame the disadvantage of the inhomogeneous shapes of silver nanoparticles, thereby improving the sensitivity and reproducibility of the SERS signals of DNA molecules. The method obtained SERS signals for four DNA bases (A, C, G, and T) without destroying the structure, then further detected and qualified different specific structures of DNA molecules. These results promote the application of SERS technology in the field of biomolecular detection.
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