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Miniaturizing EM Sample Preparation: Opportunities, Challenges, and “Visual Proteomics”
Author(s) -
Arnold Stefan A.,
Müller Shirley A.,
Schmidli Claudio,
Syntychaki Anastasia,
Rima Luca,
Chami Mohamed,
Stahlberg Henning,
Goldie Kenneth N.,
Braun Thomas
Publication year - 2018
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201700176
Subject(s) - cryo electron microscopy , sample preparation , nanotechnology , automation , computer science , single particle analysis , proteomics , sample (material) , microfluidics , materials science , chemistry , engineering , chromatography , mechanical engineering , biochemistry , aerosol , organic chemistry , gene
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.