Editorial: Insights in Raman microscopy for bio-imaging applications

Currently, Raman microscopy, a highly specific technique, has become an increasingly useful tool for studying biological systems because it provides chemical information with little or no labeling (Verduijn et al., 2025). Recent progress has also made this technique faster, more sensitive, and more practical for bioimaging (Munoz-Bolanos et al., 2025), with applications ranging from pharmacological to nanotoxicological studies (Ghosh et al., 2025).

The four papers collected in this Research Topic highlight progress in the field from several important perspectives. Together, they cover intracellular imaging of anticancer copper complexes and identification of its possible targets, rapid identification of toxigenic Clostridioides difficile in stool samples, surface-enhanced Raman scattering (SERS) detection of breast cancer biomarkers in liquid biopsy, and a broad review of stimulated Raman scattering (SRS) microscopy.

The study by Marin et al. shows how Raman imaging can be used to examine both where a metallodrug goes in the cell, and what it does after uptake (Marin et al.). The authors designed a dual-purpose assembly composed of gold nanoparticles, a Raman reporter, 5,5′-dithiobis-(2-nitrobenzoic acid) (DTNB), and oxindolimine-copper (II) complexes. By combining conventional Raman imaging at 532 nm with SERS imaging at 785 nm, they mapped both cellular composition and probe localization in living HeLa cells. The treatment of the cells with the studied copper complexes provided lipidic distribution images that were different from those obtained in reference cells, indicating that the metallodrugs significantly interact with lipids. Their results point to marked effects in the nucleus as well as in lipid-rich regions. They also found no evidence of water entry into the cells, suggesting that membrane rupture was not the main effect. This work is important because it connects intracellular speciation with biochemical response in the same experiment.

Ling et al. extend single-cell Raman spectroscopy toward clinical diagnostics by identifying toxin-producing C. difficile in stool samples (Ling et al.). The authors constructed one reference spectral database for common intestinal bacteria and C. difficile, and a second database to distinguish toxin-producing from non-toxin-producing strains. They then tested the approach on raw clinical specimens rather than cultured isolates alone. This makes the study especially relevant to practice. Their results show that Raman fingerprints, when combined with statistical and machine-learning models, can support rapid identification of this bacterium, and also help distinguish toxigenic from non-toxigenic strains. This distinction matters because its pathogenicity depends on toxin production.

Liu et al. review recent progress in using SERS to detect breast cancer biomarkers in liquid biopsy (Liu et al.). The paper covers exosomes, circulating tumor cells, miRNA, proteins, and related targets. The review also discusses practical factors that affect SERS detection, including substrate design, Raman tags, enrichment and isolation strategies, microfluidics, and data analysis. One strength of this review is that it presents SERS not only as a sensitive readout, but as part of a broader diagnostic workflow. The review also makes clear that reproducibility, multiplexing, and standardization remain central issues for the translation of SERS-based assays to clinical use.

The review by Lu places the collection in a wider methodological context by examining stimulated Raman scattering (SRS) microscopy from fundamentals to applications (Lu). The article covers the basic theory, instrument design, single-band and hyperspectral imaging, Raman and SRS probes, recent laser and detection advances, endoscopic implementations, and emerging quantum-enhanced SRS technologies. It also surveys applications in metabolic imaging, drug and metabolite tracking, stimulated Raman histology (SRH), and AI-assisted tissue analysis. Within this Research Topic, the review helps show how SRS complements spontaneous Raman and SERS by offering fast, label-free chemical imaging with strong potential for biological and medical studies.

Taken together, these four papers point to several directions that are shaping Raman bioimaging today. One is the move from simple detection toward mechanistic and functional questions. Another is the growing integration of spectroscopy with nanoparticles, advanced instrumentation, and computation. A third is the steady push toward clinical use, whether in liquid biopsy, infection diagnosis, or rapid tissue analysis. These are encouraging developments, but they also highlight continuing needs in reproducibility, standardized workflows, and reliable analysis in complex biological samples.

While this Research Topic includes a small number of papers, it captures a useful range of current work in Raman microscopy for bioimaging applications. The collection brings together spontaneous Raman, single-cell Raman spectroscopy, SERS, and SRS. Further, it connects methodological development with problems in crucial areas such as cancer biology, infectious disease, and biomedical imaging. We hope these contributions encourage further exchanges among spectroscopists, chemists, biologists, engineers, and clinicians, and help advance Raman imaging as a practical tool for studying living systems. We thank all authors and reviewers who have contributed to this Research Topic.

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Footnotes

Edited and reviewed by: Gustavo F. S. Andrade, Juiz de Fora Federal University, Brazil