Fixation: Negative Staining

Negative staining is a contrasting technique in electron microscopy. Biological samples do not strongly scatter electrons and break down under the electron beam. Therefore samples are embedded with heavy metals, in order to generate stability and contrast.

Using negative staining one can quickly preserve e.g. proteins, viruses and lipid vesicles to check their overall structure and concentration.

Negative staining is done by drying the sample on a carbon support film in the presence of a heavy metal salt solution, like e.g. Uranium, Lead, Molybdenum or Tungsten. The salts dry around the protein or virus particles and generate a reversed or negative contrast.

Negative staining is fast and easy to use specimen preparation technique that is commonly used as a first step in TEM. It is commonly used to identify particles in a suspension and have an initial view on what they look like.

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