We review the recent biomedical detection developments of scanning near-field optical microscopy (SNOM), focusing on scattering-type SNOM, atomic force microscope-based infrared spectroscopy, peak force infrared microscopy, and photo-induced force microscopy, which have the advantages of label-free, noninvasive, and specific spectral recognition. Considering the high water content of biological samples and the strong absorption of water by infrared waves, we divide the relevant research on these techniques into two categories: one based on a nonliquid environment and the other based on a liquid environment. In the nonliquid environment, the chemical composition and structural information of biomedical samples can be obtained with nanometer resolution. In the liquid environment, these techniques can be used to monitor the dynamic chemical reaction process and track the process of chemical composition and structural change of single molecules, which is conducive to exploring the development mechanism of physiological processes. We elaborate their experimental challenges, technical means, and actual cases for three microbiomedical samples (including biomacromolecules, cells, and tissues). We also discuss the prospects and challenges for their development. Our work lays a foundation for the rational design and efficient use of near-field optical microscopy to explore the characteristics of microscopic biology.
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