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. 2020 Aug 17;42(3):323–339. doi: 10.1038/s41401-020-0494-3

Table 1.

Comparison of high-resolution imaging techniques for applications in molecular and cell biology.

Characteristics Atomic force microscopy (AFM) Super-resolution optical microscopy (STED, PALM, and STORM) Scanning electron microscopy (SEM) Transmission electron microscopy (TEM)
Spatial resolution 1–50 nm 20–50 nm 2–10 nm 0.2–10 nm
Specimen preparations Living samples immobilized on support Fluorescent labeling Dehydrated and gilded samples on metal stubs Dehydrated or vitrified samples on grids
Advantages Topographical imaging and mechanical measurements under native conditions without pretreatments (e.g., fixation, lysis, labeling, or staining) Observing three-dimensional cellular structures and molecular activities in life processes with high spatiotemporal resolution Imaging surfaces of tissues, cells, and interfaces at nanometer resolution Visualizing atomic structures of proteins and molecular-resolution structures within cells
Limitations Restricted to the surface of samples and cannot access subsurface structures Fluorescent labeling possibly affects the cellular and molecular behaviors No life processes No life processes

Information compiled from Refs. [30, 31].