New Publication | SERS for Viral Diagnostics—Now Open Access

We are excited to share that our Chemical Reviews article, “Surface-Enhanced Raman Spectroscopy for Viral Diagnostics: Principles, Strategies, Clinical Challenges, and Future Directions,” is now open access and freely available to readers worldwide under a Creative Commons Attribution 4.0 (CC BY 4.0) license.

Rapid and reliable viral diagnostics are essential for managing seasonal infections, emerging pathogens, and future outbreaks. Although nucleic acid amplification and antigen-based assays remain central to clinical testing, there is a continuing need for diagnostic technologies that can provide rapid detection, high molecular specificity, multiplexing capability, and compatibility with portable or point-of-care platforms.

Surface-enhanced Raman spectroscopy (SERS) offers a promising pathway toward these goals by combining the molecular fingerprinting capability of Raman spectroscopy with the strong signal enhancement produced by plasmonic nanostructures. However, translating SERS from laboratory demonstrations into reliable clinical diagnostic tools requires more than achieving a low detection limit. Reproducible substrates, effective sample preparation, robust data analysis, standardized validation, and clinically meaningful performance evaluation are all critical.

What This Review Covers

This review provides a comprehensive and critical examination of SERS-based viral diagnostics, connecting fundamental principles, assay strategies, technological developments, and clinical translation.

Principles and sensing mechanisms

• Fundamental concepts underlying Raman scattering and SERS enhancement

• Roles of plasmonic nanostructures, electromagnetic hotspots, surface chemistry, and molecular interactions

• Relationships among substrate design, signal enhancement, spectral reproducibility, and diagnostic performance

Viral targets and detection strategies

• Detection of intact viral particles, viral nucleic acids, proteins, antigens, and host-response biomarkers

• Label-free approaches that use the intrinsic molecular fingerprints of viral samples

• Label-based assays employing Raman reporters, recognition probes, and encoded nanotags

• Strategies for sensitive, selective, and multiplexed virus detection

Integrated diagnostic technologies

• Combination of SERS with sample enrichment, molecular recognition, microfluidics, and portable Raman instrumentation

• Use of chemometrics, machine learning, and deep learning to interpret complex spectra and distinguish closely related viral signatures

• Opportunities for quantitative analysis, multi-virus detection, and rapid point-of-care testing

Clinical challenges and future directions

• Biological matrix interference, spectral variability, and nonspecific adsorption

• Substrate-to-substrate and instrument-to-instrument reproducibility

• Limitations in sample size, independent validation, and comparison with clinical reference methods

• Need for standardized protocols, shared spectral databases, rigorous blind testing, and multicenter clinical studies

• Future opportunities involving automated sample processing, artificial intelligence, portable instrumentation, and deployable diagnostic systems

Why This Matters

The future of SERS-based viral diagnostics depends on moving beyond isolated demonstrations of sensitivity toward complete and clinically validated diagnostic workflows.

This review emphasizes that successful translation requires the coordinated development of plasmonic substrates, surface chemistry, sample preparation, Raman instrumentation, spectral analysis, and clinical validation. By organizing these elements within a unified framework, we aim to help researchers evaluate current progress more critically and identify the steps needed to transform SERS from a powerful laboratory technique into a reliable tool for clinical diagnostics, public-health surveillance, and outbreak preparedness.

Making the article open access allows researchers, clinicians, students, and technology developers around the world to freely explore this rapidly advancing field.

Publication Information

Yanjun Yang and Yiping Zhao, “Surface-Enhanced Raman Spectroscopy for Viral Diagnostics: Principles, Strategies, Clinical Challenges, and Future Directions,” Chemical Reviews (2026).https://doi.org/10.1021/acs.chemrev.6c00201

Access: Open access under the CC BY 4.0 license.