Tip-Enhanced Raman Spectroscopy Techniques in Nanoscale Chemical Imaging

Tip-Enhanced Raman Spectroscopy (TERS) leverages a finely sharpened metallic probe to concentrate incident light into a plasmonic near-field at the apex of the tip, thereby amplifying Raman scattering from adjacent molecules or materials. By scanning this probe across a surface, it is possible to generate chemical maps with spatial resolution down to the nanometre or even sub-nanometre scale. Such capability overcomes the diffraction limit inherent to conventional optical microscopy and enables the direct visualisation of molecular structure, chemical composition and reaction intermediates under ambient or controlled environments. Advances in probe fabrication, combined with integration into Atomic Force Microscopy (AFM) and Scanning Tunnelling Microscopy (STM) platforms, have extended TERS applications into operando studies of catalytic processes, two-dimensional materials and biological assemblies. Recent developments include protocols for reliable TERS imaging across diverse samples, theoretical frameworks to explain sub-molecular resolution through local density changes, and multimodal measurements that correlate local electronic properties with chemical identity. These innovations position TERS as a versatile tool for exploring nanoscale phenomena in materials science, chemistry and life sciences, with global significance for sensor design, energy conversion and the elucidation of disease-related aggregates.

Research from Nature Portfolio

Recent studies have demonstrated the power of TERS for simultaneous chemical and electronic characterisation of two-dimensional materials. One investigation mapped the distribution of functional groups on graphene oxide modified with carboxyl moieties, achieving ≈10 nm spatial resolution while probing local Fermi level variations in situ. This in situ multi-parameter approach linked defect density to electronic behaviour under operational conditions, paving the way for nanoscale device diagnostics. In a complementary effort, high-resolution TERS was used to reveal sub-molecular density changes induced by confined plasmonic fields. This theoretical and experimental work showed that local rearrangements of molecular electron density govern the observed image contrast and selection rules, thereby providing a unified mechanism for sub-nanometre resolution. To support broader adoption, a detailed protocol for AFM-based TERS imaging was published, outlining procedures for preparing plasmonically active tips, aligning the optical configuration, performing chemical imaging in both air and liquid, and processing spectroscopic data. Together, these contributions have standardised best practices and deepened mechanistic understanding of TERS at its spatial limits.

Tip-Enhanced Raman Spectroscopy Techniques in Nanoscale Chemical Imaging publication trend

The graph below shows the total number of articles in tip-enhanced raman spectroscopy techniques in nanoscale chemical imaging across all publications each year (not limited to Nature Index journals).

Technical terms

Tip-Enhanced Raman Spectroscopy (TERS): A vibrational spectroscopy technique that uses a metallic nanoscale tip to amplify Raman scattering signals and achieve chemical imaging beyond the diffraction limit.

Plasmonic near-field: A highly confined electromagnetic field generated at a metal nanostructure by collective electron oscillations, which intensifies light–matter interactions at the nanoscale.

Enhancement factor: The ratio of Raman signal intensity obtained under near-field conditions to that from conventional far-field Raman measurements, quantifying signal amplification.

Atomic Force Microscopy (AFM): A scanning probe method that measures forces between a sharp tip and a sample to map topography and surface properties at nanometre resolution.

Scanning Tunnelling Microscopy (STM): A technique that images conductive surfaces by measuring electron tunnelling currents between a sharp tip and the sample, providing atomic-scale resolution.

Spatial resolution: The smallest lateral distance at which two separate features can be distinguished in an image or map.

References

1. Tip-enhanced Raman spectroscopy: principles and applications. EPJ Techniques and Instrumentation (2015).
2. In situ topographical chemical and electrical imaging of carboxyl graphene oxide at the nanoscale. Nature Communications (2018).
3. High-resolution tip-enhanced Raman scattering probes sub-molecular density changes. Nature Communications (2019).
4. Nanoscale chemical imaging using tip-enhanced Raman spectroscopy. Nature Protocols (2019).
5. Precise tracking of tip-induced structural variation at the single-chemical-bond limit. Light: Science & Applications (2023).
6. Chemical Imaging of RNA‐Tau Amyloid Fibrils at the Nanoscale Using Tip‐Enhanced Raman Spectroscopy. Angewandte Chemie International Edition (2023).
7. Visually constructing the chemical structure of a single molecule by scanning Raman picoscopy. National Science Review (2019).