Label-Free Detection of DNA Supramolecular Structure Formation by Surface-Enhanced Raman Spectroscopy.

The precise self-assembly of DNA molecules can be used to create nanoprecision supramolecular materials. However, the lack of methods to characterize such supramolecular materials limits their development. Surface-enhanced Raman spectroscopy (SERS) is widely used to detect the secondary structure of simple DNA molecules, but its application in the revealing of complex DNA supramolecular information remains challenging. Herein, we proposed a modified SERS-based platform able to provide structural information on DNA supramolecular materials. The silver nanoparticle-enhanced substrate uses acetonitrile as an internal standard and modifier, and calcium ions are used as an aggregating agent to induce the formation of stable "hotspots" of silver nanoparticles, where the base planes in DNA supramolecules are perpendicular to the surface of the substrate, obtaining enhanced Raman signals of base ring in both single-stranded DNA and DNA supramolecules for the first time. The structure of DNA supramolecules was efficiently characterized using this technique, showing the great application potential of this technique in the structural analysis of nucleic acids and their ligands.