Proteins serve as the primary molecular machinery of life, maintaining the functional order of our cells. As their structure informs their function, accurate determination of structural information is the basis of biological insights for any number of physiological, pharmaceutical, and biomaterial advances.

Cryo-electron microscopy (cryo-EM) is an established method for the determination of 3D structural information for a wide range of biomolecules, including proteins and protein complexes.
Until recently, proteins had to be crystallized to reconstruct and visualize them with X-ray crystallography. This information came with several stipulations; crystallization is time consuming and can typically only work on single purified protein (monomers or dimers); additionally, some proteins do not crystallize. Finally, the structure has to be determined outside of the cellular environment, removing vital contextual information.

Cryo-EM, which is comprised of several applications like single particle analysis (SPA), cryo-electron tomography (cryoET), and micro electron diffraction (MicroED), has revolutionized the study of proteins, their complexes, and their dynamics.

  • Single particle analysis (SPA)Images and analyzes small (<250kDa) and intermediate sized proteins (>250kDa) as well as large protein complexes with high throughput and high resolution.
  • Cryo tomography (cryoET)Ideal for the analysis of cellular components and fractions at intermediate resolutions. It provides cellular context to the macromolecular structures determined with single particle analysis.
  • Micro electron diffraction (MicroED)Suited for structural determination of small sub-750-nm protein crystals, a unique class of crystals that cannot be analyzed by traditional X-ray crystallography.
GABA receptor protein within a lipid nanodisk, generated with cryo electron microscopy.
3D reconstructions of the GABA receptor membrane protein in a nanodisk, bound to the drug Ro-15-4513. Displayed resolution is 2.75 Å. Data collected on a Krios Cryo-TEM with the Falcon 4 Detector. Images Courtesy of Simonas Masiulis, Radu Aricescu, MRC-LMB Cambridge and Evgenia Pechnikova, Abhay Kotecha, Thermo Fisher Scientific.
Granulin protomer structure generated by micro electron diffraction.
Granulin protomer (29 kDa) structure generated by cryo electron microscopy (MicroED) with atomic-resolution detail visible.
Electron Microscopy

Protein Electron Microscopy

Protein cryo-EM analysis for near-atomic structural insight.



Applications

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Structural Biology Research

Cryo-electron microscopy enables the structural analysis of challenging biological targets such as large complexes, flexible species and membrane protein.

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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.

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Drug Discovery

Learn how to take advantage of rational drug design for many more major drug target classes, leading to best-in-class drugs.


Techniques

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.

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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.

Learn more ›

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.

Learn more ›

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.

Learn more ›

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.

Learn more ›

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.

Learn more ›

Products

Style Sheet for Instrument Cards Original

Krios Rx Cryo-TEM

  • Industry leading productivity and ease of use
  • Fixed 300 kV voltage for SPA only
  • Pharma-dedicated service package for guaranteed reliability

Krios G4 Cryo-TEM

  • Improved ergonomics
  • Fits more easily into new and existing labs
  • Maximized productivity and automation
  • Best image quality for high-resolution 3D reconstruction

Glacios Cryo-TEM

  • Flexible Accelerating Voltage 80-200 kV
  • Industry-leading Autoloader for cryogenic sample manipulation
  • Small footprint
  • Enhanced ease-of-use

Tundra Cryo-TEM

  • Structural information at biologically relevant resolution
  • Space efficient and cost effective
  • Easy, iterative sample optimization
  • Unique AI algorithms for streamlined data collection

Talos Arctica TEM

  • Increased data acquisition speed
  • High data with robotic sample handling & automated loading
  • Unattended platform operation and automated data acquisition
  • Low cost of ownership with remote diagnostics and preventive service

Talos F200C TEM

  • Flexible EDS analysis reveals chemical information
  • High-contrast, high-quality TEM and STEM imaging
  • Ceta 16 Mpixel CMOS camera provides large field of view and high read-out speed

Talos L120C TEM

  • Increased stability
  • 4k × 4K Ceta CMOS camera
  • TEM magnification range from 25–650 kX
  • Flexible EDS analysis reveals chemical information

Aquilos 2 Cryo-FIB

  • Automation enables production of multiple lamellas
  • Target and extract your structure of interest with lift-out nano-manipulator
  • 3D visualization for high-resolution tomography

Vitrobot System

  • Fully Automated Sample vitrification
  • Blotting Device
  • Semi-Automated Grid Transfer
  • High Sample Throughput

Selectris and Selectris X Imaging Filters

  • Designed for high stability and atomic resolution imaging
  • Straightforward operation
  • Paired with the latest generation Thermo Scientific Falcon 4 Direct Electron Detector

Ceta-D Camera

  • Optimum performance at any high tension (20–300 kV)
  • Compatible with post-column filters and spectrometers
  • Movie acquisition for dynamic studies

Falcon 4 Detector

  • Leading detective quantum efficiency
  • 10x shorter exposure time than its predecessor
  • Fully embedded in Thermo Scientific software
  • Built in data management

Tomography 5
Software

  • Automated multi-site batch tomography
  • Automatic cassette mapping
  • Dose symmetric tilt scheme for optimal electron dose
  • Fully integrated with Selectris Imaging Filters

Maps Software

  • Acquire high resolution images over large areas
  • Easily find regions of interest
  • Automate image acquisition process
  • Correlate data from different sources

Auto Slice and View 4.0 Software

  • Automated serial sectioning for DualBeam
  • Multi-modal data acquisition (SEM, EDS, EBSD)
  • On-the-fly editing capabilities
  • Edge based cut placement

Inspect 3D Software

  • Image processing tools and filters for cross-correlation
  • Feature tracking for image alignment
  • Algebraic reconstruction technique for iterative projection comparison

Amira Software
Life Sciences

  • Import and process image data
  • Auto-segmentation, object separation, labeling
  • Analyze and quantify with automated statistics
  • Create images, animations and videos

EPU 2 Software

  • Microscope-embedded solution for single particle acquisition
  • Optimized for high-throughput particle collection
  • Compatible with film, CCD cameras, and direct electron detectors

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