Electron Microscopy: How We Work

Collaborating to Advance Your Science

Electron microscopy allows researchers to visualize the morphological effects of biological, genetic, and physical perturbations by diving into tissues and cells. Images collected on our microscopes can resolve details smaller than dust particles. Scanning electron microscopy reveals the surfaces of samples while transmission electron microscopy uncovers cells’ inner workings. Cryogenic electron microscopy allows investigators to determine biomolecular structures at near-atomic resolutions.

Cryo-EM is an exciting and quickly advancing field of structural biology that can answer a variety of questions about protein form and function. These insights can inform applications ranging from structure-based drug design to mutational analysis. Cryo-EM also captures dynamic movements of large protein complexes and molecular machines that cannot be visualized using other structural biology techniques.

To support users, we have equipped the facility with state-of-the art instruments for EM specimen processing and data collection. These include two cryogenic TEMs and one SEM on which users can request to be trained to independence. Additionally, we have live-processing software and temporary data storage for the large datasets generated by cryo-EM. Assisted image analysis for TEM and SEM data can be found through the Cellular Imaging shared resource.

Our team has over 50 years of combined experience in the highly specialized techniques necessary to prepare samples for SEM and TEM. We also empower users to produce their own cryo-EM samples and images to help reveal the structure and function of large proteins. Expert staff members are available to provide guidance at every step, from experimental design to data analysis.

Researchers working on a computer
Melody Campbell (right) discuss data collection parameters at the Glacios microscope control desk. Photo by Robert Hood / Fred Hutch News Service

Single-Particle Electron Microscopy Workflow

Electron microscopy projects begin and end in users’ own labs. Our staff members are available to consult at every step of the experimental process, from sample preparation to image analysis. We also train users in the experimental steps conducted within the Electron Microscopy facility, including grid generation, microscope use, and data collection and analysis. Below is an example of a typical cryo-EM workflow.

Workflow for developing a PDX model from a patient donation Workflow for developing a PDX model from a patient donation Workflow for developing a PDX model from a patient donation