Imaging of self-assembled structures: interpretation of TEM and cryo-TEM images

The investigation of solution-borne nanostructures by transmission electron microscopy (TEM) is a frequently used analytical method in materials chemistry. In many cases, the preparation of the TEM sample involves drying and staining steps, and the collection of images leads to the interaction of the specimen with the electron beam. Both aspects call for cautious interpretation of the resulting electron micrographs. Alternatively, a near-native solvated state can be preserved by cryogenic vitrification and subsequent imaging by low-dose cryogenic TEM. In this Minireview, we provide a critical analysis of sample preparation, and more importantly, of the acquisition and interpretation of electron micrographs. This overview should provide a framework for the application of (cryo)-TEM as a powerful and reliable tool for the analysis of colloidal and self-assembled structures with nanoscopic dimensions.