Getting Started in Cryo-EM: The Dynamic Catalyst for Advancing Scientific Frontiers

March 28, 2024 3 min read

Getting Started in Cryo-EM: The Dynamic Catalyst for Advancing Scientific Frontiers


In the ever-evolving landscape of scientific exploration, Cryo-Electron Microscopy (Cryo-EM) stands as a beacon of innovation, offering unprecedented insights into the intricate world of molecular structures. By preserving specimens in their native state at cryogenic temperatures, Cryo-EM transcends traditional limitations, enabling researchers to visualize biomolecules with exquisite detail and fidelity. This transformative technology not only unveils the hidden complexities of life's building blocks but also fuels groundbreaking discoveries across diverse scientific disciplines.


What is Cryo-electron microscopy?

In Cryo-Electron Microscopy (Cryo-EM), specimens undergo rapid freezing (vitrification), preventing crystalline ice formation and maintaining their inherent state. Subsequently, a Transmission Electron Microscope (TEM) captures two-dimensional projections of the sample. By collecting numerous projections from various angles, these images are averaged and reconstructed into a comprehensive 3D model of the sample's structure. Leveraging state-of-the-art electron detectors and advanced image-processing software, Cryo-EM achieves high-resolution imaging akin to conventional structural techniques.

 "Cryo-EM is filling a gap that is typically unattainable by NMR and X-ray crystallography — allowing the visualization of cells, viruses, and molecular complexes."


Comparison between cryo-EM, X-ray crystallography, and NMR techniques

In comparison to X-ray crystallography and Nuclear Magnetic Resonance (NMR) techniques, Cryo-Electron Microscopy (Cryo-EM) offers distinct advantages. Unlike X-ray crystallography, Cryo-EM does not require crystallization of samples, allowing for the study of challenging molecules. Additionally, Cryo-EM surpasses NMR in its ability to visualize larger macromolecular complexes with greater precision. Moreover, Cryo-EM's capacity to analyze heterogeneous samples provides a significant edge over both X-ray crystallography and NMR, making it particularly valuable for structural studies of flexible or dynamic biomolecules. These attributes render Cryo-EM a versatile and powerful tool for elucidating the structures of complex biological systems, positioning it at the forefront of structural biology research.



Electron microscopy is the fastest growing technique, quickly becoming the second-most-prolific method.


Cryo-EM Workflows

Cryo-Electron Microscopy (Cryo-EM) workflows encompass two primary techniques: Single Particle Analysis and Microcrystal Electron Diffraction. These methodologies revolutionize structural biology by offering complementary approaches for elucidating the 3D structures of biological macromolecules.

Single particle analysis

Single particle analysis is a cryo-EM technique that enables structural characterization at near-atomic resolutions, unraveling dynamic biological processes and the structures of biomolecular complexes or assemblies.

Cryo-electron tomography

Cryo-electron tomography (cryo-ET) delivers both structural information about individual proteins as well as their spatial arrangements within the cell. This makes it a truly unique technique, with an enormous potential for cell biology. Cryo-ET can bridge the gap between light microscopy and near-atomic-resolution techniques like single-particle analysis.

Microcrystal electron diffraction

Microcrystal electron diffraction (MicroED) is an exciting new technique with applications in the structural determination of small molecules and protein. With this method, atomic details can be extracted from individual nanocrystals (<200 nm in size), even in a heterogeneous mixture.


SFR: Your Guide to Cryo-EM in Canada 

At Systems for Research (SFR) we are proud to lend a helping hand in delivering innovation and years of excellence to your doorstep every step of the way. Our partnership with Thermo Fisher Scientific, the pioneers in the Cryo-em industry is a testament to our promise of delivering the best, always. 

We have been collaborating with universities, industry, and health science institutions for over 30 years, to offer an array of cutting-edge scientific instrumentation and provide greater visibility into the molecular world.

Our in-house service team, a group of highly certified Thermo Fisher Scientific engineers, work to provide our clients with uninterrupted and on-going local support for their research needs.