What is an advantage of primary aldehyde fixation compared with osmium tetroxide?

• A. Better penetration is obtained than with osmium.
• B. It renders lipids insoluble.
• C. It may remain in fixative indefinitely.
• D. It cannot be used for light microscopy.

Answer: (A)

Penetration of fixatives into tissue is a key factor in preparing samples for electron microscopy. Primary aldehyde fixatives, such as glutaraldehyde and formaldehyde, are small molecules that diffuse rapidly into tissue and crosslink proteins, giving quick and relatively uniform initial stabilization. Osmium tetroxide is larger and diffuses more slowly, and its main role is fixing lipids and adding membrane contrast, not rapid penetration. Because aldehydes penetrate more readily than osmium, they provide better overall penetration as the initial fixation step. The other statements don’t describe this advantage: lipids are not insolubilized by aldehydes (osmium fixes lipids better), and aldehyde fixation can be compatible with light microscopy.