Raman Spectroscopy in Cellular and Molecular Biology

Raman spectroscopy is a vibrational spectroscopic technique that probes molecular bonds via inelastic scattering of monochromatic light, providing non-invasive, label-free analysis of biomolecules in situ. Advances in laser technology, detector sensitivity and computational analysis have elevated the method to subcellular resolution, enabling dynamic mapping of proteins, lipids, nucleic acids and small-molecule metabolites. Variants such as stimulated Raman scattering microscopy offer orders-of-magnitude improvements in imaging speed and sensitivity, facilitating real-time chemical imaging of live cells, tissues and three-dimensional cultures. The fusion of Raman data with machine-learning algorithms has spawned a new discipline—often dubbed “Ramanomics”—that supports high-content phenotyping for fundamental studies of organelle composition, cellular metabolism and differentiation. Globally, these capabilities underpin applications ranging from disease diagnostics and therapeutic monitoring to quality control in biomanufacturing and regenerative medicine.

Research from Nature Portfolio

Recent studies have demonstrated the power of Raman micro-spectroscopy to detect and spatially map accumulated metabolites within living cells and tissues. In one study, the technique distinguished fumarate hydratase–deficient cells from normal counterparts by measuring fumarate concentration directly in mitochondria, cytoplasm and nuclei, and was further applied to classify enzyme-loss status in a mouse kidney model without tissue disruption. Another foundational contribution introduced quantitative volumetric Raman imaging (qVRI) for three-dimensional cell cultures. By applying a computational framework to deconvolute volumetric Raman datasets into discrete biomolecular channels—proteins, lipids, nucleic acids and cytoskeletal elements—researchers achieved unprecedented visualisation and quantification of subcellular structures in pluripotent stem cells, monocytes, macrophages and mesenchymal stem cells embedded in biomimetic hydrogels.

Raman Spectroscopy in Cellular and Molecular Biology publication trend

The graph below shows the total number of articles in raman spectroscopy in cellular and molecular biology across all publications each year (not limited to Nature Index journals).

Technical terms

Raman spectroscopy: A non-destructive optical technique based on inelastic scattering of light, producing a spectrum of vibrational fingerprints characteristic of molecular bonds.

Stimulated Raman scattering (SRS): A coherent Raman imaging modality in which two laser beams induce and amplify vibrational signals, enabling rapid, high-contrast chemical imaging.

Quantitative volumetric Raman imaging (qVRI): A computational method for decomposing three-dimensional Raman datasets into quantitative maps of discrete biomolecular constituents within cell cultures.

Label-free imaging: An imaging approach that relies on intrinsic molecular signals for contrast and specificity, eliminating the need for external fluorescent or enzymatic tags.

References

1. Advances in Raman spectroscopy and imaging for biomedical research. Advances in Optics and Photonics (2023).
2. Raman micro-spectroscopy reveals the spatial distribution of fumarate in cells and tissues. Nature Communications (2024).
3. Quantitative volumetric Raman imaging of three dimensional cell cultures. Nature Communications (2017).
4. Raman Spectroscopy in Cellular and Tissue Aging Research. Aging Cell (2025).
5. Vibrational spectroscopy identifies myocardial chemical modifications in heart failure with preserved ejection fraction. Journal of Translational Medicine (2023).
6. Raman spectroscopy and regenerative medicine: a review. npj Regenerative Medicine (2017).
7. In situ Characterisation of Living Cells by Raman Spectroscopy. Journal of Spectroscopy (2002).