Surface-enhanced Raman spectroscopy for label-free cancer liquid biopsy - from fundamentals to clinical analysis of biofluid

Sep 22, 2026

Cancer’s high morbidity and mortality make early, accurate diagnosis a priority, since metastasis drives most cancer deaths. This review synthesizes recent progress in label-free SERS-based cancer diagnostics enabled by liquid biopsy and its rich metabolic information. It summarizes SERS fundamentals, substrate fabrication strategies, and spectral analysis methods, then details applications using blood, urine, saliva, and sweat, concluding with key challenges and future directions.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages22

Reading Time55 min

AccessFree to download

Introduction

Cancer diagnosis needs and liquid biopsy

SERS principles and enhancement mechanisms

Fundamentals of label-free SERS for liquid biopsy

Substrate fabrication and spectral analysis

Applications in clinical biofluids

Blood, urine, saliva, and sweat

Challenges and future directions

TYPE Review PUBLISHED 12 January 2026 DOI 10.3389/fchem.2025.1696979 OPEN ACCESS EDITED BY Zhanjun Yang, Yangzhou University, China REVIEWED BY Beenish Rahat, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NIH), United States Yue Cao, Nanjing University of Posts and Telecommunications, China En Han, Jiangsu University, China *CORRESPONDENCE Zhibin Wang, [zb.wang@siat.ac.cn](zb.wang@siat.ac.cn) †These authors have contributed equally to this work RECEIVED 07 September 2025 REVISED 08 December 2025 ACCEPTED 15 December 2025 PUBLISHED 12 January 2026 CITATION Chen M, Zhao M, Cai Y, Zhang Q, Peng Z, Li Q and Wang Z (2026) Surface-enhanced Raman spectroscopy for label-free cancer liquid biopsy: from fundamentals to clinical analysis of biofluid. Front. Chem. 13:1696979 . doi: 10.3389/fchem.2025.1696979 COPYRIGHT © 2026 Chen, Zhao, Cai, Zhang, Peng, Li and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Surface-enhanced Raman spectroscopy for label-free cancer liquid biopsy: from fundamentals to clinical analysis of biofluid Ming Chen 1†, Mingjun Zhao 1†, Yue Cai 1, Qiong Zhang 1, Zhenzhen Peng 1, Qiwen Li 1 and Zhibin Wang 2,3* 1Department of Nuclear Medicine, The First Hospital of Lanzhou University, Lanzhou, Gansu, China, 2Department of Bipharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Shenzhen University of Advanced Technology, Shenzhen, China, 3Center for Cancer Immunotherapy of Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China Cancer remains one of the major public health problems due to its high morbidity and mortality globally. Because metastasis is the major cause of cancer death, developing new approaches for early diagnosis is of paramount importance in this context. Surface-enhanced Raman scattering (SERS) has emerged as a cutting-edge analytical technique. SERS features an exceptional sensitivity and specificity, enabling rapid non-destructive detection of trace-level samples. Therefore, SERS technology is widely used across medical disciplines, particularly in cancer diagnosis for early-stage and non-invasive diagnostic evaluation. Using liquid biopsy with rich metabolic information, SERS has facilitated the identification, analysis, and progression monitoring of various cancers. In this review, we systematically summarize recent advances in labelfree SERS-based cancer diagnostics. We first outline the fundamental principles of SERS, key substrate fabrication methodologies, and essential spectral analysis techniques. We then highlight the applications of label-free SERS in liquid biopsy using various biofluids, including blood, urine, saliva, and sweat. Finally, we discuss current challenges and future directions in this rapidly evolving field. KEYWORDS cancer, clinical biofluids, deep learning, label-free detection, liquid biopsy, SERS 1 Introduction Cancer is a life-threatening disease characterized by uncontrolled tumor growth and high lethality, making early and accurate diagnosis a paramount challenge in modern medicine (Attwaters, 2023). The advent of precision medicine has dramatically changed the landscape of cancer treatment, yet current diagnostic approaches remain imperfect (Moutinho, 2023) . These methods are primarily categorized into histopathological examination (e.g., tissue biopsy) and imaging-based techniques (e.g., CT, MRI, PET)(Billimoria and Bhatt, 2023; Lu et al., 2021; Pickhardt, 2022) . Although tiss

FAQs

Why is early cancer diagnosis important in this review?

The review emphasizes that metastasis is a major cause of cancer death, so early detection is critical for improving outcomes.

What makes SERS suitable for label-free detection of cancer biomarkers?

SERS provides exceptional sensitivity and specificity, enabling rapid, non-destructive analysis of trace-level samples using minimal volumes, supported by electromagnetic and chemical enhancement mechanisms.

Which biofluids are discussed for liquid biopsy applications?

The review highlights label-free SERS applications using multiple clinical biofluids including blood, urine, saliva, and sweat.

Sep 22, 2026

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