Surface-Enhanced Raman Spectroscopy for Cancer Biomarker Detection

Surface-Enhanced Raman Spectroscopy (SERS) has emerged as a transformative approach for the ultrasensitive detection of cancer biomarkers in bodily fluids. By exploiting the plasmonic properties of metallic nanostructures, SERS amplifies Raman signals from target molecules by orders of magnitude, enabling molecular fingerprinting at concentrations unattainable by conventional techniques. In a typical SERS-based assay, specific capture and detection elements—often antibodies or aptamers—are immobilised on nanostructured substrates or nanoparticles decorated with Raman reporter molecules. Binding of a biomarker induces a proximity-enhanced electromagnetic field that yields distinctive spectral patterns, facilitating both qualitative identification and quantitative analysis. This approach offers sensitivities down to the single-molecule level in some configurations and broad multiplexing capacity by employing distinct Raman reporters. Recent innovations in substrate fabrication, nanomaterial engineering and assay design have improved reproducibility and portability, paving the way for point-of-care diagnostics and real-time monitoring of tumour progression and therapeutic response. Integration with microfluidic platforms, advanced statistical methods for spectral deconvolution and dual-enhancement strategies further extends analytical performance, underscoring the global significance of SERS as a practical tool for early cancer detection and personalised medicine.

Research from Nature Portfolio

Recent studies have developed microfluidic SERS immunoassays capable of simultaneous quantification of multiple protein biomarkers in blood plasma. By integrating SERS-active nanostructures with antibody-conjugated Raman reporters within a microfluidic device, it has been possible to detect interleukins at picogram-per-millilitre concentrations with high specificity. Advanced statistical analyses, such as principal component analysis, have been employed to differentiate overlapping spectral signatures, achieving multiplexed detection of interleukin-6, interleukin-8 and interleukin-18 in a single run. This platform demonstrated significant improvements over standard immunoassays in terms of sensitivity, assay time and sample volume, illustrating the potential for translation into portable diagnostic devices for clinical applications.

Surface-Enhanced Raman Spectroscopy for Cancer Biomarker Detection publication trend

The graph below shows the total number of articles in surface-enhanced raman spectroscopy for cancer biomarker detection across all publications each year (not limited to Nature Index journals).

Technical terms

Surface-Enhanced Raman Spectroscopy (SERS): A technique that uses metallic nanostructures to greatly amplify Raman scattering signals from molecules adsorbed on or near their surfaces.

Cancer Biomarker: A biological molecule, such as a protein or nucleic acid, whose presence, concentration or structure indicates the existence or progression of cancer.

Nanostructured Substrate: A surface engineered at the nanoscale, often composed of metals like gold or silver, designed to support plasmonic enhancement of electromagnetic fields.

Sandwich Immunoassay: An assay format using two antibodies—a capture antibody immobilised on a substrate and a detection antibody labelled with a reporter—to bind a target antigen in a “sandwich” configuration for specific detection.

References

1. SERS-based Immunoassay in a Microfluidic System for the Multiplexed Recognition of Interleukins from Blood Plasma: Towards Picogram Detection. Scientific Reports (2017).
2. Comparison of Survivin Determination by Surface-Enhanced Fluorescence and Raman Spectroscopy on Nanostructured Silver Substrates. Biosensors (2024).
3. A sandwich SERS immunoassay platform based on a single-layer Au–Ag nanobox array substrate for simultaneous detection of SCCA and survivin in serum of patients with cervical lesions. RSC Advances (2021).
4. Recent Advances in Sandwich SERS Immunosensors for Cancer Detection. International Journal of Molecular Sciences (2022).
5. Dual-enhancement and dual-tag design for SERS-based sandwich immunoassays: evaluation of a metal–metal effect in 3D architecture. Microchimica Acta (2021).