Direct-imaging cryo-electron microscopy combined with CCD cameras provide a powerful tool for studying macromolecular assemblies in the 2 to 300 nm range, which form in biological systems, biomedical solutions, surfactants, microemulsions and a host of other diverse systems. The CCD cameras are especially advantageous for identifying rare assemblies, studying specific assembly details (figures A and B) and transient structures forming during dynamic processes and phase transformations (figures C-E). This setup is also beneficial for exploring coexistence of structures and studying highly radiation-sensitive systems such as oil-continuous solutions. Information on internal ordering is also readily obtained (figure A).
Continuous CCD application at low dose conditions provides numerous significant advantages over classical imaging on photographic plates. First, it allows a preview of the exact area to be recorded (search and focus modes), concentration on specific interesting features and adjustment of microscope parameters for optimal imaging (focus mode), at very low exposures and with minimal radiation damage.