Negative-stain electron microscopy Created 2026-10-20 Updated 2026-11-05
Negative-stain electron microscopy makes a small specimen visible by surrounding it with an electron-scattering stain. Regions containing more stain scatter more electrons out of the accepted transmitted beam, so the specimen can appear relatively bright against a darker background in bright-field transmission electron microscopy.
A typical preparation deposits a dilute sample onto a supported grid, removes excess liquid, applies stain and removes excess stain before examination in a transmission electron microscope.[ref]
Negative Staining by Harvard Medical School. Grid preparation, washing and staining protocol
The resulting outline is useful for checking particle size, aggregation and gross shape. Drying, flattening and stain distribution can change the appearance, so an apparent cavity or fine boundary need not reproduce the hydrated specimen's structure.