{"title":"Deciphering cellular heterogeneity: Breakthroughs and prospects of single-cell-level SERS analysis in precision medicine","authors":"Biqing Chen, Jiayin Gao, Haizhu Sun, Yan Liu, Yinghan Zhao, Xiaohong Qiu","doi":"10.1016/j.ymeth.2025.09.002","DOIUrl":null,"url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":390,"journal":{"name":"Methods","volume":"244 ","pages":"Pages 7-29"},"PeriodicalIF":4.3000,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Methods","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1046202325001938","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
Methods focuses on rapidly developing techniques in the experimental biological and medical sciences.
Each topical issue, organized by a guest editor who is an expert in the area covered, consists solely of invited quality articles by specialist authors, many of them reviews. Issues are devoted to specific technical approaches with emphasis on clear detailed descriptions of protocols that allow them to be reproduced easily. The background information provided enables researchers to understand the principles underlying the methods; other helpful sections include comparisons of alternative methods giving the advantages and disadvantages of particular methods, guidance on avoiding potential pitfalls, and suggestions for troubleshooting.