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

Proteomics. 2018 Mar;18(5-6):e1700176. doi: 10.1002/pmic.201700176.


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.

Keywords: cryo-EM; microfluidics; negative stain; sample preparation; transmission electron microscopy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cryoelectron Microscopy / methods*
  • Humans
  • Imaging, Three-Dimensional / methods*
  • Microfluidics / methods
  • Microscopy, Electron, Transmission / methods*
  • Proteins / ultrastructure*
  • Proteomics / methods*
  • Specimen Handling


  • Proteins