Electron Microscopy
This course provides an introduction 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.
Upon successful completion of this course, students will be able to:
Explain the theoretical principles underlying transmission electron microscopy (TEM), including instrument design and the physics of image formation.
Apply foundational mathematical concepts—such as Fourier transforms—to analyze diffraction and image data in biological contexts.
Operate image processing software to perform key tasks such as image alignment, particle picking, classification, and 3D reconstruction.
Integrate knowledge of diffraction and imaging techniques to enhance the interpretation and processing of electron microscopy data.
Critically read and evaluate scientific literature related to TEM, demonstrating the ability to synthesize complex information and contribute to scholarly discussions.
Prepare and deliver effective presentations on selected TEM topics, showing clarity, depth, and engagement with current research.
Assess the limitations and artifacts in cryo-EM and other TEM techniques, and propose strategies to improve image quality and resolution.
The course is designed as a mix of introductions into selected topics in the theory of transmission electron microscopy followed by practical demonstrations and hands-on exercises, which provide an opportunity to comprehend the concepts by experimenting with commonly-used image processing software. Students will be required to read and digest scientific papers for a subset of lecture topics on their own, which will subsequently be discussed jointly during student presentations with the goal to immerse them into the subject without passive consumption. The lectures cover several important concepts of the physics of image formation and analysis, which require a basic level of mathematics. 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.
History of the TEM / Design of a TEM Lecture
Design of a TEM (cont’d) Lecture
Design of a TEM (cont’d) Lecture
Demonstration of a TEM Demo
Math refresher / Electron waves Lecture
Fourier transforms Lecture
Intro to image processing software in SBGRID Practical
Image alignment Practical
Contrast formation and transfer Lecture
Image recording and sampling Student presentation
Applications in biology Lecture
Preparation of biological samples Demo
Low-dose cryo-EM Student presentation
2D crystallography Student presentation
Overview of the single particle technique Lecture
Review of theory Lecture
Electron tomography (guest lecture) Lecture
Physical limits to cryo-EM Student presentation
Particle picking Practical
Classification techniques Student presentation
3D reconstruction Student presentation
Image processing project 1 Practical
Resolution-limiting factors Student presentation
Refinement and sources of artifacts Student presentation
Image processing project 2 Practical
A sampling of original literature Discussion
Participation 30%; Presentation, 30%; Practical Exercises 30%.
Undergraduate mathematics.
Transmission Electron Microscopy: A Textbook for Materials Science (4-vol set), by Williams and Carter (2009) Springer
Three-Dimensional Electron Microscopy of Macromolecular Assemblies, 2 edn, by J Frank (2006) Oxford University Press
Transmission Electron Microscopy: Physics of Image Formation and Microanalysis, 4th edn, by L. Reimer (1997) Springer
Introduction to Fourier Optics, 3 edn, by J Goodman (2004) Roberts & Co.