Surface-Enhanced Raman Spectroscopy for Detection of Bacterial Biological Warfare Agents: A Review

Abstract

Bacterial biological warfare agents (BBWAs) pose a severe global threat due to their high pathogenicity, rapid transmission, and potential for mass casualties. Conventional detection methods, such as culture-based identification and polymerase chain reaction (PCR), are hindered by limitations in time consumption, operational complexity, and adaptability to complex environments. Surface-enhanced Raman spectroscopy (SERS) has emerged as a transformative analytical tool, offering the simplicity of optical detection, molecular fingerprint specificity, and single-molecule sensitivity. This mini-review systematically reports recent advancements (2019–2024) in SERS-based technologies for BBWA detection, including label-free direct detection leveraging nanostructured substrates, antibody-reporter molecule labeling for enhanced specificity, immunomagnetic separation to address low-concentration samples, and microfluidic-SERS integration enabling portable on-site analysis. These innovations highlight SERS’s potential in biodefense, environmental monitoring, clinical diagnostics, and food safety. Recent breakthroughs in machine learning, particularly deep-learning-assisted spectral analysis, enhance multiplexed, real-time pathogen detection. Despite such progress, challenges persist in substrate consistency, signal stability, and field deployment. Emerging solutions, including atomic-scale substrate engineering, artificial intelligence (AI)-driven data interpretation, and hybrid enrichment-detection platforms, promise to bridge the gap between laboratory precision and adaptability to practical testing environments. By synthesizing advancements across interdisciplinary fields, this review underscores SERS’s evolving role as a rapid, ultrasensitive, and field-deployable tool for combating biosecurity threats, ultimately contributing to global health security frameworks.