Raman spectroscopy is a powerful analytical technique for identifying molecular vibrations, but its spatial resolution is limited by the diffraction of light to approximately half the wavelength, typically around 300–500 nm for visible light. Tip-enhanced Raman spectroscopy (TERS) overcomes this limitation by combining atomic force microscopy (AFM) with Raman spectroscopy, leveraging plasmonic effects at a sharp metallic tip to achieve sub-10 nm spatial resolution. This breakthrough enables the chemical mapping of surfaces at the single-molecule level, making TERS indispensable for studying nanomaterials, molecular monolayers, and heterogeneous interfaces.

The core of TERS lies in the integration of AFM and Raman spectroscopy. In a typical setup, a laser is focused onto a sample surface through either an upright or inverted microscope configuration. A plasmonic AFM tip, often made of gold or silver due to their strong plasmonic response in the visible and near-infrared range, is positioned at the laser focal point. When the tip approaches the sample surface, localized surface plasmons are excited at the tip apex, creating an intense electromagnetic field known as the "hot spot." This field enhances the Raman scattering signal from molecules located directly beneath the tip, while suppressing contributions from regions further away. The AFM component provides precise topographical control, allowing simultaneous mapping of surface morphology and chemical composition.

The plasmonic tip is critical to TERS performance. Optimal tips must exhibit high electromagnetic field enhancement, mechanical stability, and reproducibility. Gold-coated silicon or silicon nitride tips are commonly used due to their balance between plasmonic activity and durability. The tip apex radius must be below 20 nm to achieve sufficient field confinement, with sharper tips providing higher resolution. Additionally, the tip material and geometry must be tailored to the excitation laser wavelength to maximize plasmon resonance. For example, silver tips are preferred for visible light excitation, while gold tips perform better in the near-infrared range. Recent advances in tip fabrication, such as focused ion beam milling and electron beam-induced deposition, have enabled the production of tips with controlled nanostructures, further improving enhancement factors.

TERS achieves spatial resolutions below 10 nm, far surpassing conventional Raman microscopy. This capability has been demonstrated in studies of molecular monolayers, where individual molecules can be distinguished within densely packed assemblies. For instance, TERS has resolved the vibrational signatures of thiol monolayers on gold surfaces with 5 nm resolution, revealing heterogeneity in molecular orientation and packing density. In another example, graphene edges and defects were mapped with 3 nm precision, providing insights into localized strain and doping effects. Such high-resolution chemical imaging is invaluable for understanding surface reactions, catalysis, and nanomaterial interfaces.

Despite its advantages, TERS faces challenges in signal interpretation. The enhanced Raman signal is highly sensitive to tip-sample distance, requiring stable feedback control to maintain optimal enhancement. Variations in tip geometry or contamination can lead to inconsistent signal intensities, complicating quantitative analysis. Additionally, the plasmonic enhancement mechanism can alter the relative intensities of Raman peaks compared to conventional spectra, necessitating careful calibration. Background signals from the tip itself or far-field contributions must also be subtracted to isolate the near-field response. Advanced data processing techniques, including multivariate analysis and machine learning, are increasingly employed to address these challenges.

Compared to other nanoscale characterization techniques in the taxonomy, TERS offers unique advantages. AFM alone provides topographical information but lacks chemical specificity. SEM can achieve nanometer-scale imaging but requires conductive samples and offers limited molecular information. In contrast, TERS combines the spatial resolution of AFM with the chemical specificity of Raman spectroscopy, enabling correlative analysis of structure and composition. However, TERS is more complex to implement than standalone AFM or SEM, requiring precise alignment of optical and scanning probe components. It also has a smaller field of view compared to electron microscopy techniques.

TERS has been applied to diverse systems, including two-dimensional materials, biological membranes, and catalytic surfaces. In one study, TERS mapped the distribution of amyloid fibrils at the single-filament level, identifying structural variations linked to disease progression. In catalysis, TERS has resolved active sites on bimetallic nanoparticles, revealing how local composition influences reactivity. These applications highlight the technique's ability to bridge the gap between nanoscale structure and molecular function.

Future developments in TERS aim to improve tip reliability, enhance signal-to-noise ratios, and expand compatibility with a wider range of materials. Integration with other techniques, such as time-resolved spectroscopy or electrochemical AFM, could further broaden its applications. As nanomaterial research progresses toward increasingly complex systems, TERS will remain a critical tool for uncovering chemical details at the smallest scales.

In summary, TERS represents a significant advancement in nanoscale spectroscopy, breaking the diffraction limit to provide unparalleled chemical imaging capabilities. Its combination of AFM and Raman spectroscopy, coupled with plasmonic enhancement, enables investigations of molecular monolayers, defects, and interfaces with nanometer precision. While challenges in signal interpretation and instrumentation persist, ongoing innovations continue to solidify TERS as a cornerstone of nanoscience research.