Tip-Enhanced Raman Imaging of Single-Stranded DNA with Single Base Resolution

Area of Science:

• Nanotechnology
• Spectroscopy
• Biophysics

Background:

• Tip-enhanced Raman scattering (TERS) offers high-resolution chemical imaging and sensing at the single-molecule level.
• Gap-mode TERS, utilizing a silver tip and gold substrate, has shown potential for resolving structures below 1 nm.

Purpose of the Study:

• To demonstrate subnanometer spatial resolution using TERS for direct nucleic acid sequencing.
• To validate TERS for analyzing the structure and sequence of single-stranded DNA (ssDNA).

Main Methods:

• Direct sequencing of phage ssDNA (M13mp18) using TERS with a silver tip on a gold substrate.
• Deposition strategy to stretch ssDNA and expose nucleobases for tip interaction.
• Scanning the TERS tip along the ssDNA at 0.5 nm intervals to collect spectral data.

Main Results:

• Achieved spatial resolution below 1 nm for ssDNA analysis.
• Successfully demonstrated real-time profiling of ssDNA configuration.
• Obtained unique TERS signals from monomeric units of biopolymers.

Conclusions:

• TERS can achieve subnanometer resolution for direct nucleic acid sequencing.
• The technique is extendable to high-resolution imaging of diverse nanostructures.
• TERS holds promise for direct sequencing of other biopolymers like RNA, polysaccharides, and polypeptides.