Review analyzes scanning near-field optical microscopy capabilities in resolving molecular details in biological samples, suggesting future clinical applications.
Precision medicine requires tools that can resolve molecular information at the nanoscale, where many early biological and pathological changes arise. Scanning near-field optical microscopy (SNOM) combines molecular vibrational fingerprints with nanoscale spatial resolution, providing a unique platform for overcoming the diffraction limit of conventional optics and enabling in situ chemical characterization of biological samples. This paper systematically reviews the development of SNOM from near-field imaging to spectroscopic platforms such as nano-FTIR and AFM-IR, and summarizes the latest advances in ultrafast, liquid-phase, terahertz, and miniaturized systems. Focusing on representative studies involving proteins, nucleic acids, bacteria, viruses, extracellular vesicles, and cell-material interfaces, this paper discusses SNOM's ability to resolve molecular heterogeneity, structural transitions, and local biochemical interactions in near-natural environments. Additionally, the article analyzes the major challenges facing its clinical translation, including sample preparation, signal-to-noise ratio, measurement speed, quantitative analysis, and standardization, and explores its application potential in AI-assisted analysis, portability, and neuroscience. SNOM is expected to become a key technological platform bridging molecular diagnostics and nanobiological imaging.
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Deng et al. (2026) studied this question.
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