Deciphering cellular heterogeneity: Breakthroughs and prospects of single-cell-level SERS analysis in precision...

Single-cell surface-enhanced Raman scattering (SERS) has emerged as a powerful tool for precision medicine owing to its label-free detection, ultrasensitivity, and unique molecular fingerprinting. Unlike conventional bulk analysis, it enables detailed characterization of cellular heterogeneity, with particular promise in circulating tumor cell (CTC) identification, tumor microenvironment (TME) metabolic profiling, subcellular imaging, and drug sensitivity assessment. Coupled with microfluidic droplet systems, SERS supports high-throughput single-cell analysis and multiparametric screening, while integration with complementary modalities such as fluorescence microscopy and mass spectrometry enhances temporal and spatial resolution for monitoring live cells. Despite hurdles in nanoprobe safety, complex spectral interpretation, and clinical translation, advances in AI-driven data processing (e.g., convolutional neural networks) and miniaturized devices are accelerating progress toward intraoperative guidance, improved liquid biopsy, and primary healthcare adoption. Looking ahead, its applications in single-cell metabolomics, exosome studies, and microbial detection hold promise for uncovering disease mechanisms and fostering personalized diagnostics and therapeutics.