Abstract
Scanning electron microscopy of wet tissue, wet SEM (WETSEMTM), is a new technology that permits ultrastructural examination of fully hydrated biological samples. This review provides a description of this innovative achievement in relation to its reported and potential applications in pathology and toxicology. Possessing LM, SEM and TEM functionality, wet SEM provides a resolution that enables visualizing common ultrastructural targets of disease and toxicity, such as mitochondria and the cytoskeleton. Additionally, this confluence of multiple microscopic modalities allows for a continuous spectrum of inspection options for all structural aspects of cells and tissues. Broad overviews of the sample surface smoothly interdigitate with a detailed scrutiny of the cell interior. Elemental microanalysis and immuno-gold labeling are also possible with the wet SEM, which facilitates diagnostic applications and structural-functional correlations. Importantly, all these options are possible on the same sample during a single scoping session using one instrument. Since hydrated material is being directly examined, there is no need for embedment and microtome sectioning, so that preparation time is minimal. With such a rapid preparation phase and multifaceted inspection options, wet SEM appears particularly advantageous for the multi-arm design of drug development and safety studies. Naturally, as in any new form of microscopy, limitations exist that should be appreciated, and the image repertoire will need to be defined so that the most suitable and practical applications can be identified. Within its niche, wet SEM is likely to serve as a uniquely useful tool in pathological investigation.
