Miniaturizing EM Sample Preparation: Opportunities, Challenges, and "Visual Proteomics"

作者:Arnold Stefan A; Muller Shirley A; Schmidli Claudio; Syntychaki Anastasia; Rima Luca; Chami Mohamed; Stahlberg Henning; Goldie Kenneth N; Braun Thomas
来源:Proteomics, 2018, 18(5-6): 1700176.
DOI:10.1002/pmic.201700176

摘要

This review compares and discusses conventional versus miniaturized specimen preparation methods for transmission electron microscopy (TEM). The progress brought by direct electron detector cameras, software developments and automation have transformed transmission cryo-electron microscopy (cryo-EM) and made it an invaluable high-resolution structural analysis tool. In contrast, EM specimen preparation has seen very little progress in the last decades and is now one of the main bottlenecks in cryo-EM. Here, we discuss the challenges faced by specimen preparation for single particle EM, highlight current developments, and show the opportunities resulting from the advanced miniaturized and microfluidic sample grid preparation methods described, such as visual proteomics and time-resolved cryo-EM studies.