What is a cryo-electron microscope?
A cryo-electron microscope is generally a transmission electron microscope (TEM) specifically designed to maintain cryogenic temperatures within the sample chamber. Compared to traditional TEMs, cryo-electron microscopes also feature a suite of automation and sample-handling technology, increasing ease of use and ensuring that the maximum amount of high-quality data can be collected for each sample. Cryo-electron microscopy (cryo-EM) samples can maintain cryogenic conditions for as long as 72 hours within the Krios Cryo-TEM and up to 24 hours within the Glacios or Tundra Cryo-TEM, allowing researchers to collect all the data they need to produce as high-quality a reconstruction as possible.
How does cryo-EM work?
Cryo-EM cools samples to cryogenic temperatures so quickly that it prevents water molecules from crystalizing, preserving the native sample structure. Once frozen, a range of EM techniques can be used to visualize the specimen in 3D at a variety of resolutions—including near-atomic resolution—allowing scientists to gain deeper, more comprehensive insights than previously possible.
Why choose cryo-EM?
Life scientists interested in understanding proteins and protein complexes face numerous challenges. Proteins are biologically complex, and many are notoriously tough to examine using traditional methods like crystallography and nuclear magnetic resonance (NMR).
With cryo-EM, researchers can observe proteins in all their complex conformations, structures, and modified forms and can look at multiple protein conformations in a single sample. Cryo-EM eliminates the need for crystals, resolves concerns around purity and heterogeneity, and the 3D protein structures produced allow scientists to investigate protein function inside the cell, which is critical to understanding how they work, their role in disease, and how they’ll respond to therapies. Cryo-EM has become the go-to method for scientists around the world, generating breakthroughs in research for infectious disease, neurodegenerative disease, and cancer among others.
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Learn more about cryo-EM
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Curious about getting started with cryo-EM? Our ebook walks new users through the single-particle analysis workflow, offers practical paths to access, and highlights several interesting case studies, including the SARS-CoV-2 spike glycoprotein.
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Life science electron microscopy techniques
Basic life processes start in the cell. To understand how they function and respond to disease or genetic variations, life scientists engage in cellular and structural biology research. Cellular biology explores individual cells and the ways in which they are organized into organs and tissues. Structural biologists delve deep into sub-cellular components, organelles and macromolecular structures. Electron microscopy (EM) is capable of providing insight at all these scales and more, revealing even atomic-level structural details for a range of biomolecules.
Explore electron microscopy and cryo-EM techniques for the life sciences with our interactive module
Structural Biology Research
Cryo-electron microscopy enables the structural analysis of challenging biological targets such as large complexes, flexible species and membrane protein.
Infectious Disease Research
Cryo-EM techniques enable multiscale observations of 3D biological structures in their near-native states, informing faster, more efficient development of therapeutics.
Drug Discovery
Learn how to take advantage of rational drug design for many major drug target classes, leading to best-in-class drugs.
Plant Biology Research
Fundamental plant biology research is enabled by cryo electron microscopy, which provides information on proteins (with single particle analysis), to their cellular context (with tomography), all the way up to the overall structure of the plant (large volume analysis).
Pathology Research
Transmission electron microscopy (TEM) is used when the nature of the disease cannot be established via alternative methods. With nano-biological imaging, TEM provides accurate and reliable insight for certain pathologies.
Cancer Research
In cancer research, potential protein-level therapeutic targets are still largely unexplored due to their inherent complexity. See how cryo-EM is used for the structural analysis of cancer-related membrane proteins and macromolecular complexes.
Neurodegenerative Disease Research
Cryo-EM can determine the structural features of protein aggregates implicated in neurodegenerative diseases, allowing scientists to address how they form, interact with the cellular environment, and alter brain function.
Single Particle Analysis
Single particle analysis (SPA) is a cryo-electron microscopy technique that enables structural characterization at near-atomic resolutions, unraveling dynamic biological processes and the structure of biomolecular complexes/assemblies.
Cryo-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 and also explains why the method has such an enormous potential for cell biology. Cryo-ET can bridge the gap between light microscopy and near-atomic-resolution techniques like single-particle analysis.
MicroED
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.
Large Volume Analysis
A novel serial block-face imaging (SBFI) solution that combines multi-energy deconvolution scanning electron microscopy (MED-SEM) with in situ sectioning. Automation and ease-of-use functions provide isotropic resolution for large volume samples.
Integrative Structural Biology
To understand protein function, you need complex and structure information beyond individual proteins. Integrative structural biology combines mass spectrometry and cryo EM for the determination of large dynamic complex structure.
Cryo-EM Sample Preparation
Successful protein preparation lies at the base of any successful structural biology technique. For cryo-electron microscopy, a wide range of solutions is required to achieve the highest sample quality before freezing of the specimen on the EM grid.
Single Particle Analysis
Single particle analysis (SPA) is a cryo-electron microscopy technique that enables structural characterization at near-atomic resolutions, unraveling dynamic biological processes and the structure of biomolecular complexes/assemblies.
Cryo-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 and also explains why the method has such an enormous potential for cell biology. Cryo-ET can bridge the gap between light microscopy and near-atomic-resolution techniques like single-particle analysis.
MicroED
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.
Large Volume Analysis
A novel serial block-face imaging (SBFI) solution that combines multi-energy deconvolution scanning electron microscopy (MED-SEM) with in situ sectioning. Automation and ease-of-use functions provide isotropic resolution for large volume samples.
Integrative Structural Biology
To understand protein function, you need complex and structure information beyond individual proteins. Integrative structural biology combines mass spectrometry and cryo EM for the determination of large dynamic complex structure.
Cryo-EM Sample Preparation
Successful protein preparation lies at the base of any successful structural biology technique. For cryo-electron microscopy, a wide range of solutions is required to achieve the highest sample quality before freezing of the specimen on the EM grid.
Proteins Analysis
Cryo-electron microscopy provides near-atomic resolution 3D protein structure. It can determine structural information for complexes and crystallization-resistant samples, as well as vital cellular context.
Biopharmaceutical Research
Structural drug discovery is enabled by cryo-electron microscopy, as the method provides near-atomic-resolution detail for small molecules and protein biologics in their fully hydrated state.
Virus Analysis
Cryo-EM enables the 3D structural visualization of virus particles, and the antigen-antibody interface, at near-atomic resolutions. A virus’s inherent structural symmetry makes it the ideal target for cryo-EM analysis.
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