Course Coordinator: 
Matthias Wolf
Electron Microscopy

An introduction to transmission electron microscopy techniques and applications in biology.  Learn important concepts of the physics of image formation and analysis, which require a basic level of mathematics. Learn about sample handling, contrast enhancement, alignment, and image processing.  Read and analyze relevant scientific papers and discuss jointly during student presentations. Practical demonstrations and hands-on exercises provide an opportunity to comprehend the concepts by experimenting with commonly-used image processing software. An emphasis will be given to highlighting common properties between diffraction and image data and how to take advantage of tools from both techniques during the final image processing projects.

This course provides an intro into electron microscopy techniques and applications in biology. Participants will obtain the background knowledge for critical reading of current literature and will be exposed to practical exercises in image processing.
Course Content: 
  1. History of the TEM / Design of a TEM - Lecture
  2. Design of a TEM (cont’d) -  Lecture
  3. Design of a TEM (cont’d) -  Lecture
  4. Demonstration of a TEM - Demo
  5. Math refresher / Electron waves - Lecture
  6. Fourier transforms - Lecture
  7. Intro to image processing software in SBGRID - Practical
  8. Image alignment - Practical
  9. Contrast formation and transfer -  Lecture
  10. Image recording and sampling - Student presentation
  11. Applications in biology - Lecture
  12. Preparation of biological samples -  Demo
  13. Low-dose cryo-EM - Student presentation
  14. 2D crystallography - Student presentation
  15. Overview of the single particle technique -  Lecture
  16. Review of theory - Lecture
  17. Electron tomography (guest lecture) - Lecture
  18. Physical limits to cryo-EM - Student presentation
  19. Particle picking -  Practical
  20. Classification techniques -  Student presentation
  21. 3D reconstruction - Student presentation
  22. Image processing project 1 - Practical
  23. Resolution-limiting factors -  Student presentation
  24. Refinement and sources of artifacts -  Student presentation
  25. Image processing project 2 - Practical
  26. A sampling of original literature - Discussion
Course Type: 
Participation 30%; Presentation, 30%; Practical Exercises 40%
Text Book: 
  • Three-Dimensional Electron Microscopy of Macromolecular Assemblies, 2 edn, by J Frank (2006) Oxford University Press
  • Transmission Electron Microscopy: A Textbook for Materials Science (4-vol set), by Williams and Carter (2009) Springer
Reference Book: 
  • Introduction to Fourier Optics, 3 edn, by J Goodman (2004) Roberts & Co.
  • Transmission Electron Microscopy: Physics of Image Formation and Microanalysis, 4th edn, by L. Reimer (1997) Springer
Prior Knowledge: 
Undergraduate mathematics.