Electron Microscopy

Drug Discovery Using Electron Microscopy

Drug discovery using cryo-electron microscopy for rational drug design of major drug targets.


As targets become more challenging, solving structures of your drug target molecules or biologics also becomes increasingly difficult. Structure-based drug design is not always a given, but cryo-electron microscopy (cryo-EM) is changing the paradigm. By adding cryo-EM to your portfolio of methods, all your projects can now be structure-enabled.

Whether you are a structural biologist or a medicinal chemist, cryo-EM allows you to visualize anything, from small to large molecules, at near-atomic resolution. With this level of detail, you can obtain time-critical insight for your particular drug discovery project.

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

Cryo-EM can help accelerate your drug design

Cryo-EM techniques, such as single-particle analysis (SPA) and micro-electron diffraction (microED), are designed to determine the structures of proteins and small molecules. Cryo-EM can overcome your toughest structural chemistry challenges and provide structural information for rational drug discovery.

Cryo-EM can visualize drug-target complexes at high resolution, giving you key insight into the interactions of small molecules or large macromolecular assemblies. By using single particle analysis, you can determine near-atomic level molecular structures, guiding compound design from hit to lead and beyond. Cryo-EM excels at exposing the structure of biologics as well, providing critical information for everything from therapeutic antibody epitope mapping to increasingly large biopharmaceuticals.

 

Single-particle analysis: no need for crystals

Single-particle analysis vitrification (rapid plunge freezing) allows you to sidestep crystallization while facilitating protein purification. Because single particle analysis does not require sample crystallization or even recombinant overproduction, it is an incredibly versatile method that is well-suited for a wide range of targets, particularly membrane proteins and large assemblies in their native state. Our single-particle analysis workflow combines cutting-edge hardware with dedicated automated sample screening software, allowing you to optimize your biochemistry and vitrification parameters before transferring your best samples to the cryo-transmission electron microscope (cryo-TEM) for the ultimate 3D structure analysis.

From protein sequence to structure

One of the greatest advantages of cryo-EM relative to conventional structural biology techniques is its ability to analyze large, complex and flexible structures. Often, these cannot be crystallized for X-ray crystallography (XRD) or are too large and complex for nuclear magnetic resonance (NMR) spectroscopy. These include many biologically important proteins, especially those with variable or flexible structures, such as membrane proteins. Our dedicated SPA workflow has been developed around our instruments to ensure a smooth pathway from sample preparation to image acquisition to data processing. This purpose-driven design can help a wider range of structural biology labs achieve faster time-to-data when determining the 3D structure of proteins and protein complexes at near-atomic resolution.

Explore the simplicity of our single particle analysis workflow ›

MicroED: structural chemistry with electrons

MicroED is a single crystal diffraction technique using electrons instead of X-rays. Because of the stronger interaction of electrons with much smaller crystals, you can obtain a solvable structure from mere nanocrystals of your compound. Studies have also shown the potential for impressive time-to-structure results of just a few hours. This opens unheard of avenues of structural characterization for natural products, precious ligands and metabolites. Not only that, but microED also makes polymorph identification possible.

Learn how microED helps accelerate time-to-structure results ›

 

 

Cryo-EM within your reach 

Getting started with cryo-EM

You have a partner! With our help, setting up a cryo-electron microscopy facility can be easier than you imagined. We will be with you every step of the way, from discussing flexible financing options, to building planning, to initial sample testing and installation. Our goal is to get you up and running as quickly and efficiently as possible. You can also take advantage of fee-for-service providers, cryo-EM training, and more.

Review our tailor-made cryo-EM SPA solution ›

Now-time-adopt-2

View the latest publications

It’s time to invest in cryo-EM today. Early cryo-EM adopters in the pharma industry already see its benefits. Find out why pharmaceutical leaders around the globe have invested in cryo-EM for drug discovery and learn how their motivations may align with your goals.

Read testimonials and publications ›

Setting-up-success_600x362

Setting up for ongoing success

From day one to year one and beyond, you can rely on our expertise to support your investment and research. Our highly knowledgeable cryo-EM application specialists can assist with everything from sample preparation to data processing. Our Cryo-EM University combines online instruction with practical training to transform your lab personnel into a qualified team of cryo-electron microscopists. You can rely on us, a cryo-EM leader currently supporting more than 100 systems worldwide, for long term ongoing support.

Learn about our cryo-EM support expertise ›

Planning_600x362-4

Planning and building advice

We are experts in creating cryo-EM labs. Supporting more than 100 high-end cryo-EM facilities around the world, we offer unparalleled knowledge and expertise. We will perform a site survey to make sure your site meets all room readiness requirements (including vibrations, magnetic fields, temperature stability, and humidity control) prior to installation. We will provide advice on IT infrastructure and resources required to handle big data, environmental conditions needed for the facility, and we will help you to determine what auxiliary lab equipment you might need. Our expertise and support are designed to get you up and running quickly.

Learn more from our in-depth planning guide ›

adoption-financial-600x362

Financial resources

We provide a variety of ways to meet your financial needs, including assistance with leasing and financing options. Avoid unexpected expenses by letting us help you properly plan for building and/or remodeling, determine IT infrastructure expenditures and operational costs, including personnel needs, power consumption, and data storage.

Review available financing options ›

CardEMUniversity_600x362

Increase your cryo-EM knowledge

Your lab personnel can quickly turn into cryo-EM experts by watching our online Cryo-EM University videos and with practical training from our dedicated application specialists. This exciting free course, created in collaboration with Professor Grant Jensen of Caltech University, combines online instruction with practical training to transform your personnel into cryo-electron microscopists. Learn a range of cryo-EM essentials, including step-by-step single particle analysis (SPA) instructions, expert demonstrations, and theoretical lessons, all available at your pace, wherever you want.

Enroll in Cryo-EM University ›

cryo-em-workflow-app-600x362

Cryo-EM? We have an app for that.

Our instruments’ tailor-made user interface makes operation an intuitive process, especially when combined with our easy-to-use app. This Scientific Workflows app guides you through the cryo-EM single-particle analysis workflow and offers advanced calculations like recommended data acquisition magnification and estimated acquisition time. It also contains step-by-step guides tailored to a given set of system configurations and sample/grid characteristics. If more assistance is required, applications experts are available for on-site support and training, ensuring you are ready to perform your research with a high level of confidence in your results.

Download the free app:

Cryo-EM access as a service

Visualizing your structure provides unprecedent competitive advantage in your structure-based drug design projects. We believe that access to our technology should be accessible for every scientist, which is why we offer a range of cryo-EM services for any size of company.

Learn more

 

Style Sheet for Komodo Tabs
Style Sheet to change H2 style to p with em-h2-header class
Style Sheet to change H3 to p with em-h3-header class
Style Sheet to change Applications H3 to p with em-h3-header class

Media Gallery

Ask the Experts | April 1, 2021

Integrating cryo-EM into your existing drug development process

Ask the Experts session on integrating cryo-EM into your existing drug development process. Get answers to common questions like how and when to integrate, find out which samples are suitable for cryo-EM and when to choose that technology over traditional methods like crystallography and nuclear magnetic resonance, and learn more about your options for outsourcing cryo-EM. This session includes a short presentation from NanoImaging Services followed by our Q&A.


Cryo-EM in Drug Discovery | March 11, 2021

Cryo-EM in Drug Discovery - Accelerating Drug Design for Intractable Targets

Thought-provoking presentations by four keynote speakers. Dr. Corey Strickland, Merck, presents From Concept to Reality: Cryo-EM as an Integral Part of Drug Discovery and Development. Dr. Lionel Rougé, Genentech, shares his insights on Structural Characterization of Different TRPA1 Inhibitors. Dr. Kenneth Borelli. Schrödinge, speaks about Improving Protein-Ligand Modeling into Cryo-EM Data and the use of those Models in Drug Discovery Efforts. And Prof. Patrick Sexton, Monash University, explains the Use of Cryo-EM for GPCR Drug Discovery and Development.

Cryo-EM in Drug Discovery - Panel Discussion

Dr. Jeffrey Lengyel, Thermo Fisher Scientific, Dr. Benjamin Apker, Mitegen, Dr. Corey Strickland, Merck, and Dr. Denis Zeyer, Novalix, will elaborate their opinion on how cryo-EM technology accelerates drug design of intractable targets.

Ask the Experts | December 9, 2020

Enhanced automation for high throughput cryo-EM screening and data collection for drug design

Ask the Experts webinar highlighting recent advances in cryo-EM automation for increased productivity to provide structural insights for your drug discovery pipeline. Andreas Schenk, Novartis, and Ben Apker, MiTeGen, discuss how the state-of-the-art cryo-EM workflow automations compares to X-ray crystallography in terms throughput and resolution.

Cryo-EM in Drug Discovery Virtual Event | September 29, 2020

Latest scientific developments in cryo-electron microscopy and electron diffraction

Two keynote lectures from leaders in the field of cryo-EM and electron diffraction will present latest results and how these techniques enable them to push the boundaries of their pipeline and research projects.

Cryo-EM solution optimized for drug discovery

Learn more on our recently launched iSPA Workflow solution, specifically designed to accelerate the structure-based drug discovery process.

Round table discussion

Experts in the field will elaborate about their experiences with getting cryo-EM technology in-house and offer practical consideration for how to setup a successfully running cryo-EM workflow.

Ask the Experts | April 1, 2021

Integrating cryo-EM into your existing drug development process

Ask the Experts session on integrating cryo-EM into your existing drug development process. Get answers to common questions like how and when to integrate, find out which samples are suitable for cryo-EM and when to choose that technology over traditional methods like crystallography and nuclear magnetic resonance, and learn more about your options for outsourcing cryo-EM. This session includes a short presentation from NanoImaging Services followed by our Q&A.


Cryo-EM in Drug Discovery | March 11, 2021

Cryo-EM in Drug Discovery - Accelerating Drug Design for Intractable Targets

Thought-provoking presentations by four keynote speakers. Dr. Corey Strickland, Merck, presents From Concept to Reality: Cryo-EM as an Integral Part of Drug Discovery and Development. Dr. Lionel Rougé, Genentech, shares his insights on Structural Characterization of Different TRPA1 Inhibitors. Dr. Kenneth Borelli. Schrödinge, speaks about Improving Protein-Ligand Modeling into Cryo-EM Data and the use of those Models in Drug Discovery Efforts. And Prof. Patrick Sexton, Monash University, explains the Use of Cryo-EM for GPCR Drug Discovery and Development.

Cryo-EM in Drug Discovery - Panel Discussion

Dr. Jeffrey Lengyel, Thermo Fisher Scientific, Dr. Benjamin Apker, Mitegen, Dr. Corey Strickland, Merck, and Dr. Denis Zeyer, Novalix, will elaborate their opinion on how cryo-EM technology accelerates drug design of intractable targets.

Ask the Experts | December 9, 2020

Enhanced automation for high throughput cryo-EM screening and data collection for drug design

Ask the Experts webinar highlighting recent advances in cryo-EM automation for increased productivity to provide structural insights for your drug discovery pipeline. Andreas Schenk, Novartis, and Ben Apker, MiTeGen, discuss how the state-of-the-art cryo-EM workflow automations compares to X-ray crystallography in terms throughput and resolution.

Cryo-EM in Drug Discovery Virtual Event | September 29, 2020

Latest scientific developments in cryo-electron microscopy and electron diffraction

Two keynote lectures from leaders in the field of cryo-EM and electron diffraction will present latest results and how these techniques enable them to push the boundaries of their pipeline and research projects.

Cryo-EM solution optimized for drug discovery

Learn more on our recently launched iSPA Workflow solution, specifically designed to accelerate the structure-based drug discovery process.

Round table discussion

Experts in the field will elaborate about their experiences with getting cryo-EM technology in-house and offer practical consideration for how to setup a successfully running cryo-EM workflow.

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 ›


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.

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 ›

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.

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 ›

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

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

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

EM Services for Pharma

  • Maximize output with system uptime and throughput commitments
  • Drive improvement with enhanced visibility to system data
  • Comprehensive maintenance and applications support

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

Style Sheet for Support and Service footer
Style Sheet for Fonts
Style Sheet for Cards