Raman Spectroscopy Techniques in Biological Applications

Raman spectroscopy has emerged as a versatile, non-destructive, label-free technique for probing the molecular composition of biological matter. By measuring inelastic scattering of monochromatic light, it yields a unique vibrational fingerprint of biomolecules such as proteins, lipids, nucleic acids and metabolites. Recent advances span from single-cell analysis and tissue imaging to in vivo diagnostics, driven by improvements in instrument design, data processing and probe technologies. Miniaturised spectrometers are enabling point-of-care devices and integration into portable platforms, while surface-enhanced Raman scattering (SERS) probes extend detection sensitivity down to low picomolar concentrations. Time-gated and shifted-excitation approaches effectively reject fluorescence background, broadening applicability to complex biological samples. High-throughput spectral preprocessing methods, including self-supervised learning pipelines, automate baseline correction and noise removal, thereby standardising data across instruments and laboratories. Hyperspectral Raman imaging, often combined with machine-learning classifiers, has proven powerful for tumour margin delineation, microbial identification and metabolic profiling. Quantitative studies in the near-infrared have established detection depths in tissue and refined calibration models for in vivo monitoring. Together, these developments position Raman spectroscopy as a cornerstone of precision medicine, facilitating label-free molecular diagnostics, real-time surgical guidance and fundamental studies of biomolecular dynamics.

Research from Nature Portfolio

A recent study demonstrated centimetre-scale miniaturisation of a Raman spectrometer using inexpensive laser diodes, densely packed optics and uncooled sensors, achieving research-grade performance with 7 cm⁻¹ resolution across 400–4 000 cm⁻¹. This compact design enabled in vivo skin measurements, sub-micrometre chemical mapping, quantitative quantification of methanol in beverages, SERS mapping of an anticancer drug and bacterial identification, all at low power consumption. The work highlights the potential to embed Raman modules into smartphones and medical devices, democratising access and supporting point-of-care molecular diagnostics.

Raman Spectroscopy Techniques in Biological Applications publication trend

The graph below shows the total number of articles in raman spectroscopy techniques in biological applications across all publications each year (not limited to Nature Index journals).

Technical terms

Raman scattering: Inelastic scattering of monochromatic light by molecular vibrations, yielding a spectrum of discrete frequency shifts characteristic of chemical bonds.

Surface-enhanced Raman scattering (SERS): Enhancement of Raman signals by several orders of magnitude via plasmonic nanostructures, enabling detection of low-concentration analytes.

Time-gated Raman spectroscopy: A fluorescence-rejection method synchronising short laser pulses with fast detectors to collect Raman photons before longer-lived fluorescence emission.

Self-supervised learning: A computational strategy wherein algorithms autonomously learn data representations without manual labelling, here used to correct and denoise Raman spectra.

References

1. RSPSSL: A novel high-fidelity Raman spectral preprocessing scheme to enhance biomedical applications and chemical resolution visualization. Light: Science & Applications (2024).
2. Optics miniaturization strategy for demanding Raman spectroscopy applications. Nature Communications (2024).
3. Direct and quantitative assessments of near-infrared light attenuation and spectroscopic detection depth in biological tissues using surface-enhanced Raman scattering. Med-X (2023).
4. Time-gated Raman spectroscopy a review. Measurement Science and Technology (2020).