What is the principle behind tissue fixation?

"Fixation" is a process of stabilization important for anatomical study of biological tissue. To achieve this goal, one must arrest the decomposition caused by tissue enzymes and decay; it is usually desirable also to harden the tissue for convenient handling. The two basic approaches involve physical methods (rapid heating or quick-freezing) and/or chemical methods. Nearly all chemical methods were originally developed for the leather tanning industry, which faces similar problems.

The most widely-used chemical fixative is 4% formaldehyde gas dissolved in water or buffer. This (moderately toxic) agent rapidly penetrates tissue and (more slowly) denatures proteins, arresting enzymatic degradation. It also cross-links proteins, leading to tissue hardening. Glutaraldehyde, a di-aldehyde which cross-links very effectively, is often used for electron microscopy. A wide range of other chemical fixatives are sometimes used, including organic chemicals like tannic acid, picric acid, and absolute alcohol, and (highly toxic) inorganic fixatives like potassium dichromate, mercuric chloride, and osmium tetroxide. Their mechanisms of action are poorly-understood, but generally involve denaturation of protein.