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Table 2 Comparison of high-resolution imaging techniques in molecular and cell biology [171]

From: Application of atomic force microscopy in cancer research

Technique/feature Atomic force microscopy Super-resolution microscopy (STED, PALM, STORM) Transmission electron microscopy Scanning election microscopy
Resolution ≤ 1 nm–50 nm 20–50 nm 0.2–10 nm 2–10 nm
Sample preparation and environment Sample on support; physiological (buffer solution, temperature, CO2) Fluorescence labelling; physiological (buffer solution, temperature, CO2) Sample on grid; dehydrated (negative stain); vitrified (cryo-electron microscopy) Freeze/critical point drying and metal shadowing
Artefacts Tip, force, scanning Bleaching, toxicity Dehydration, ice crystal formation, beam damage Dehydration, metal shadowing, beam damage
Advantages Imaging under native conditions; no staining, labelling, or fixation necessary; high signal-to-noise ratio; assessment of multiple physical, chemical, and biological parameters Access to three-dimensional cellular structures; high spatiotemporal resolution; monitoring biomolecular processes in life cells Solves atomic structures of proteins; conformational snapshot of proteins and complexes; molecular resolution of structures within the cell Imaging surfaces of tissues, cells, and interfaces as nanometer-scale resolution
Limitation Restricted to surfaces Imaging restricted to fluorescence labels No life processes No life processes
  1. STED stimulated emission depletion, PALM photo activated localization microscopy, STORM stochastic optical reconstruction microscopy