Direct Electron 1 article published in JoVE Biochemistry Advancing High-Resolution Imaging of Virus Assemblies in Liquid and Ice Liza-Anastasia DiCecco*1,2, Samantha Berry*1, G. M. Jonaid*1,3, Maria J. Solares1,4, Liam Kaylor1,4, Jennifer L. Gray5, Carol Bator6, William J. Dearnaley1, Michael Spilman7, Madeline J. Dressel-Dukes8, Kathryn Grandfield2, Sarah M. McDonald Esstman9, Deborah F. Kelly1,5,6 1Department of Biomedical Engineering, Pennsylvania State University, 2Department of Materials Science and Engineering, McMaster University, 3Bioinformatics and Genomics Graduate Program, Huck Institutes of the Life Sciences, Pennsylvania State University, 4Molecular, Cellular, and Integrative Biosciences Graduate Program, Huck Institutes of the Life Sciences, Pennsylvania State University, 5Materials Research Institute, Pennsylvania State University, 6Huck Institutes of the Life Sciences, Pennsylvania State University, 7Applications team, Direct Electron, 8Application Scientist, Protochips, Inc., 9Department of Biology, Wake Forest University Here protocols are described to prepare virus assemblies suitable for liquid-EM and cryo-EM analysis at the nanoscale using transmission electron microscopy.