Conventionally, light and electron microscopy are seldom used in the study of the same biospecimen. Light microscopy allows for dynamic observations of biological processes with great temporal resolution. The spatial resolution of light microscopes, however, is restricted to 200-300 nm. In contrast, electron microscopy allows users to gain very high resolution but only captures a snapshot of static biological structures. Correlative Light and Electron Microscopy (CLEM) thus provides an extremely powerful combination of the advantages of these two techniques to directly link cell structures and dynamics.

The success of CLEM imposes unique demands at light and electron microscopy levels. In order to facilitate the precise identification of corresponding features in EM, users must perform the light microscopy at the hihest possible resolution and allow for the fast cessation of dynamic cellular processes at the end of the light microscopic observation.

The Cell Imaging Facility provides the necessary means for users to follow the dynamics of a living cell by time-lapse imaging and subsequently analyze the same cell by EM.

Platinum replica TEM is consist of three major steps: (a) detergent extraction, (b) chemical fixation, (b) critical point drying. In the replica EM technique, the contrast is created by shadowing of the three-dimensional samples with metal. The preservation of 3D structures is the major concern during EM processing, especially during drying. The main source of problems is the surface tension at the liquid-gas interface, which will destroy fragile macromolecular structures if the interface passes through the sample. Critical point drying is a simple and reliable technique, which circumvents this problem and preserves the complicated 3D biological structure. See figure 1.