Cryogenic Transmission Electron Microscopy for Direct Observation of Polymer and Small-Molecule Materials and Structures in Solution

The application of cryogenic transmission electron microscopy (cryo-TEM) in the study of molecular self-assembly of amphiphilic macromolecules, lipid/surfactants, peptides, and other hybrid material systems is quickly growing in popularity as a standard characterization technique. Cryo-TEM allows the direct visualization of nanostructures and microstructures embedded in a thin film of vitrified solvent at liquid nitrogen temperature. This direct observation technique provides precise measurements on particle size and shape on the nanoscale and can serve as a complementary method for unambiguous interpretation of structural information obtained by model-dependent X-ray and neutron scattering and light scattering. This review covers research results over the past several years using cryo-TEM to image interesting solution-state structures in molecular and materials research areas except biology where cryo-TEM has been extensively used to image biological assemblies and particles such as membranes and viruses, respectively. Some results that discuss particularly effective use of cryo-TEM for characterization of solute-state materials are highlighted.