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Electron Microscopy

Single Particle Analysis

Single particle analysis electron microscopy offers cryo-EM structural biology at near-atomic resolution.


What is single particle analysis?

Single particle analysis is an increasingly popular cryo-electron microscopy (cryo-EM) technique that allows you to investigate biomolecules at near-atomic resolutions, unraveling dynamic biological processes and the structure of biomolecular complexes/assemblies. 

In single particle analysis, purified proteins or protein complexes are suspended in amorphous (vitreous) ice through rapid plunge freezing, which preserve the samples’ native structures. Transmission electron microscopy (TEM) is then used to collect numerous 2D snapshots of the samples. As the proteins are oriented randomly within the ice, these images show the sample at various angles, and can be recombined into a high-resolution 3D reconstruction of the sample.

Learn more about the single particle analysis workflow ›

Single particle analysis electron microscopy benefits

One of the primary challenges with investigating dynamic biological processes is the inherent complexity of biological machinery. Traditional structural biology techniques have struggled with large and/or dynamic protein systems, requiring indirect observation or the study of fragments. Luckily, single particle analysis has emerged as a well-suited approach for the direct determination of native function and dynamics in complex biological systems.

Single particle analysis can validate your biochemistry work by showing the molecular details that underlie the interactions between proteins, small molecules, and post-translational modifications in large and dynamic protein systems at near-native conditions. These molecular details can reveal the mechanisms by which complex biological systems contribute to human health and disease. Single particle analysis is particularly suited for the study of membrane proteins, protein complexes, and macromolecular machines such as viruses, ribosomes, and proteasomes.

For example, the human GABAA (gamma-aminobutyric acid type A) receptor is a small membrane protein and ligand-gated chloride-ion channel that mediates inhibitory neurotransmission. GABAA receptors are important therapeutic targets as they impact a variety of important signaling pathways. Due to GABAA's conformational flexibility, traditional methods have been unable to reveal its molecular mechanism of action. Single particle analysis, however, has enabled researchers to see the molecular details of this important receptor, and how they underpin its allosteric modulation.

Getting started in cryo-EM single particle analysis

Our team is here to help you get started with cryo-EM, so that you too can integrate single particle analysis into your structural biology research. Follow the links below to see how we support you throughout the entire process, from initial advice and planning, to financing, to personal application-specialist support. 

Multi-level support at every stage

You can rely on our expertise to support both your investment and your research endeavors. Our highly knowledgeable cryo-EM application specialists can assist with everything from sample preparation to data processing. Rest assured when you trust your long-term ongoing support to a cryo-EM leader currently supporting 100+ systems worldwide.

Learn more ›

Advice for planning and building

Control costs and limit laboratory downtime by relying on our advanced expertise of lab infrastructure. Thermo Fisher Scientific offers the expertise you need to precisely plan every aspect of your laboratory, helping to reduce building costs, while optimizing your laboratory for the best results.

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Flexible options to get you in the game

We provide a variety of ways to meet your financial needs, from assistance with grants to leasing and financing options. Our experts are well versed in the unique procurement requirements of universities, governments, industry and research labs.

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Resources

Structure-guided design of SARS-CoV-2 antivirals

Register to watch our recorded webinar from Dr. Quan Wang of ShanghaiTech University and Dr. Renhong Yan of Westlake University on new cryo-EM studies of the structural basis of key molecular processes including RNA replication/transcription and receptor recognition.

Register now

Determining protein and small molecule structures with Microcrystal Electron Diffraction.

Structure-guided design of SARS-CoV-2 antivirals

Register to watch our recorded webinar from Dr. Quan Wang of ShanghaiTech University and Dr. Renhong Yan of Westlake University on new cryo-EM studies of the structural basis of key molecular processes including RNA replication/transcription and receptor recognition.

Register now

Determining protein and small molecule structures with Microcrystal Electron Diffraction.

Applications

Structural biology research

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

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

Drug Discovery

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

Neurodegeneration Research

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.


Samples


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.

Learn more ›


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.

Learn more ›


Products

Style Sheet for Instrument Cards Original
Thermo Scientific Krios G4 Cryo transmission electron microscope (TEM)

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
Thermo Scientific Glacios 2 Cryo-Transmission Electron Microscope

Glacios 2 Cryo-TEM

  • High-resolution structure determination tool (<3Å)
  • Unparalleled ease-of-use through AI-enhanced automation
  • Flexible modes of operation standard: SPA, tomography, MicroED
Thermo Scientific Tundra Cryo transmission electron microscope (TEM)

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
Thermo Scientific Talos Arctia transmission electron microscope (TEM)

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
Thermo Scientific Vitrobot vitrification sample system

Vitrobot System

  • Fully automated sample vitrification
  • Blotting device
  • Semi-automated grid transfer
  • High sample throughput
Thermo Scientific Selectris and Selectris X cryo electron microscopy imaging filters

Selectris and Selectris X Imaging Filters

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

Falcon 4i Detector

  • High throughput for more images per hour
  • Unsurpassed imaging quality with high DQE
  • Lossless data compression with EER
Thermo Scientific EPU Software for single particle analysis

Smart EPU Software

  • Microscope-embedded solution for single particle acquisition
  • Optimized for high-throughput particle collection, providing real-time image analysis
  • Includes components for scheduling, data acquisition, and decision algorithms
Thermo Scientific Smart EPU Software with Embedded CryoSPARC Live

Embedded CryoSPARC Live

  • Real-time, multidimensional feedback on sample quality and instrument settings
  • Adjust imaging and processing based on real-time information
  • Fully integrated with Smart EPU Software

EM Services for Single Particle Analysis

  • Empower your users so they can work with confidence
  • Keep step-by-step workflow guidance at your fingertips
  • Get set up for success with Workflow Validation

Contact us

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