Microscopy of whole cells in ice
Cryomicroscopy of frozen hydrated specimens makes it possible to visualize biological material in a condition that is close to its native state by avoiding chemical fixatives, dehydration or stain. In the past, cryoimaging using a conventional TEM has been limited to thin frozen suspensions of biological material or to thin cryosections of frozen cells and tissues. High voltage electron microscopes (HVEM) offer the advantage of improved penetration of thick samples by the electron beam and thus are suitable for imaging thick frozen samples. Here we describe a comparative method for studying the ultrastructure of freeze substituted, critical point dried cells and frozen hydratpd cells in the HVEM.