Surface-Enhanced Raman Spectroscopy Applications in Biomedical Imaging and Diagnostics

Surface-enhanced Raman spectroscopy (SERS) leverages the intense electromagnetic fields generated at the surface of plasmonic nanomaterials to amplify the fingerprint-like vibrational signals of biomolecules by orders of magnitude. This ultrasensitive optical technique enables non-invasive, multiplexed detection of chemical and biological targets in complex environments, offering unique advantages over fluorescence such as minimal photobleaching, narrow spectral bands and high spatial resolution. In biomedical imaging, SERS nanoprobes coated or encoded with Raman reporter molecules can be targeted to tissues or circulating markers, facilitating in vivo visualisation of tumours, vasculature and metabolic activity. In diagnostics, SERS-based assays support liquid biopsy through the quantitative detection of circulating tumour cells, nucleic acids and exosomes at trace concentrations. Recent advances in nanoprobe design, substrate-free enhancement strategies and instrumentation have propelled SERS towards clinical translation, addressing challenges of biocompatibility, penetration depth and real-time measurement. As a result, SERS is emerging as a versatile platform for early disease detection, intraoperative guidance and theranostic interventions, with global significance across oncology, infectious disease and personalised medicine.

Research from Nature Portfolio

Recent studies have shown that self-stacking small-molecule nanoprobes can achieve substrate-free enhancement by forming ordered charge-transfer assemblies, yielding signal intensities over a thousand times greater than conventional gold-based SERS tags and enabling deep-tissue imaging of blood and lymphatic vessels. Work on ultrabright gap-enhanced Raman tags has demonstrated the fabrication of core–shell nanoparticles with interior nanogaps and petal-like shells, achieving single-particle sensitivity and high-speed cellular and lymph node imaging under low laser power. Foundational research into fluorescence-Raman bimodal nanoprobes has illustrated how DNA-guided assembly of dual-mode reporters can combine rapid fluorescence guidance with highly specific Raman verification, enabling real-time tumour margin delineation and subsequent photothermal therapy with attomolar detection limits.

Surface-Enhanced Raman Spectroscopy Applications in Biomedical Imaging and Diagnostics publication trend

The graph below shows the total number of articles in surface-enhanced raman spectroscopy applications in biomedical imaging and diagnostics across all publications each year (not limited to Nature Index journals).

Technical terms

Surface-Enhanced Raman Spectroscopy (SERS): A technique that enhances Raman scattering signals of molecules adsorbed on or near plasmonic nanostructures by exploiting localised surface plasmon resonances.

Nanoprobe: A nanoparticle functionalised with targeting ligands and Raman reporter molecules for selective detection and imaging of biological targets.

Plasmonic nanomaterial: A material, typically composed of gold or silver, that supports collective oscillations of conduction electrons to amplify electromagnetic fields at its surface.

Raman reporter molecule: A chemical compound with a strong, characteristic Raman spectrum used to encode nanoprobes for multiplexed detection.

Liquid biopsy: A minimally invasive diagnostic approach that analyses biomarkers, such as circulating tumour DNA or cells, in body fluids rather than tissue samples.

Photothermal ablation: A therapeutic modality in which light-absorbing agents generate heat under laser irradiation to selectively destroy diseased tissue.

References

1. Self-stacked small molecules for ultrasensitive, substrate-free Raman imaging in vivo. Nature Biotechnology (2024).
2. Ultrabright gap-enhanced Raman tags for high-speed bioimaging. Nature Communications (2019).
3. DNA-enabled rational design of fluorescence-Raman bimodal nanoprobes for cancer imaging and therapy. Nature Communications (2019).
4. Optical nanomaterial-based detection of biomarkers in liquid biopsy. Journal of Hematology & Oncology (2024).
5. Design and Synthesis of SERS Materials for In Vivo Molecular Imaging and Biosensing. Advanced Science (2023).
6. Intraoperative Assessment and Photothermal Ablation of the Tumor Margins Using Gold Nanoparticles. Advanced Science (2021).