Tip-enhanced Raman spectroscopy: plasmid-free vs. plasmid-embedded DNA.

Tip-enhanced Raman spectroscopy (TERS) provides greatly enhanced Raman signals along with ultra-high lateral spatial resolutions and has been demonstrated to be a technique of choice to study a variety of biochemical specimens such as DNA and RNA at the single chain level. However, the sensitivity of TERS to demonstrate the influence of the nanoscale environment on DNA properties has not been investigated. Herein, we used a gap-mode TERS as an ultra-sensitive label-free technique to investigate the influence of the local plasmid on the DNA properties of a β2-adrenergic receptor (β2AR). Remarkable lateral spatial resolutions down to 8 nm were also acquired for the collected Raman signals under ambient conditions. This approach offers not only a tool to examine the influence of the local nanoscale environment surrounding the DNA structure, but also the localization of the majority of nucleic acid base(s) present in selected regions on the DNA strand.