Accessible, high-performance cryo-EM at 200 kV

The Thermo Scientific Glacios 3 Cryo-TEM is an advanced platform for 200 kV cryo-EM imaging, expanding the capabilities and performance of the established Glacios platform. This latest system brings optical innovations to improve productivity and usability.

 

The Glacios 3 Cryo-TEM is equipped with the Thermo Scientific READY System, a built-in series of components that dramatically reduce infrastructure demands and facilitate installation. This integrated protection system would have eliminated the need for facility renovations at 80–95% of sites previously surveyed by Thermo Fisher Scientific for electron microscopy installations over the last decade.

 

With its new, compact footprint and integrated READY System, the Glacios 3 Cryo-TEM simplifies installation and infrastructure needs, enabling more organizations to bring cryo-EM in-house, integrating it earlier in the discovery and development pipelines.


Easier installation with the READY System brings cryo-EM to more lab spaces

Acoustic & temperature

A patent-pending enclosure includes five layers of insulation that significantly reduce sound-related interference and temperature variations. The instrument now allows for shifts of up to 2°C peak to peak in 24 hours, which can be maintained by standard HVAC systems.

Electromagnetic interference

Optional, built-in electromagnetic interference (EMI) sensors, along with an active suppression system directly within the instrument frame, mitigate EMI.

Vibration

Active vibration blocks can be optionally integrated into the system base to guard against both routine and unexpected disturbances, such as new construction.

Compact design with a shorter height

All Glacios 3 Cryo-TEM configurations fit in rooms with minimum dimensions of 4.2 x 3.8 x 2.7 m (WxLxH), a 22% reduction in size compared to previous Glacios systems. This provides compatibility with standard United States ceiling heights.

Lower cost, faster cryo-TEM installations

The Glacios 3 Cryo-TEM reduces the need for potential renovations by combining a smaller footprint with the READY System for integrated protection. With fewer upgrades required at most sites, installations are lower cost, and timelines could potentially be lowered from a year or more to only a few months.


Frequently asked questions about the Thermo Scientific Glacios 3 Cryo-TEM

  • What is the Glacios 3 Cryo-TEM, and what applications does it support?
    The Thermo Scientific Glacios 3 Cryo-TEM is a high-performance 200 kV transmission electron microscope designed for advanced cryo-electron microscopy workflows in structural biology and drug discovery. It supports multiple high-resolution cryo-EM techniques, including single particle analysis, cryo-ET, and microED. 

  • How does the Glacios 3 Cryo-TEM deliver high-resolution 200 kV cryo-EM performance?
    The Glacios 3 Cryo-TEM integrates advanced electron optics, detectors, and software to support high-resolution imaging at 200 kV. Key technologies and capabilities that enable this performance include: 
    • A low energy spread cold field emission gun (E-CFEG)
    • The Thermo Scientific Falcon 4i Detector
    • A Thermo Scientific Selectris/Selectris X Energy Filter
    • The READY System for environmental protection
    • AFIS/FFI for high productivity data collection

These advancements enable researchers to perform high-resolution structural determination with high throughput and reliability. 

  • How does the Glacios 3 Cryo-TEM support drug discovery and structure-based drug design? 
    Cryo-EM has become an essential tool in drug discovery, as it enables the visualization of protein-ligand interactions, conformational changes, and dynamic binding pockets. The Glacios 3 Cryo-TEM supports applications such as antibody candidate selection, structure-based vaccine and CAR-T design, gene-editing enzyme discovery and optimization, as well as comprehensive particle characterization of viral and lipidic delivery vehicles. The Glacios 3 Cryo-TEM helps accelerate structural biology insights that inform biological research and therapeutic development by combining high-resolution imaging with improved throughput and usability at 200 kV. 

  • Why is the Glacios 3 Cryo-TEM easier to install than previous Glacios instruments? 
    The Glacios 3 Cryo-TEM has a compact footprint and the new Thermo Scientific READY System, which features built-in mitigation of environmental disturbances such as acoustic noise, temperature variations, EMI, and vibration. This supports the installation of the Glacios 3 Cryo-TEM in laboratory environments that previously would have required room renovations. All system configurations fit in rooms with minimum dimensions of 4.2 x 3.8 x 2.7 m (W x L x H), which is compatible with standard US ceiling heights.  

  • What is aberration-free image shift and how does it increase cryo-EM throughput? 
    Aberration-free image shift (AFIS) accelerates cryo-EM data collection by moving the electron beam instead of the sample stage when shifting between foil holes. AFIS is further enhanced in the Glacios 3 Cryo-TEM with increased targeting accuracy greater than 100 nm within a 12 µm radius, as well as faster imaging across the grid. These improvements increase throughput and reduce the number of images required per sample, contributing to faster time to results. 

  • How does fringe-free imaging improve data yield in cryo-EM? 
    Fringe-free imaging is an optical mode that reduces beam-induced damage around the impact area on the sample. By increasing data yield per sample, FFI reduces the total amount of data collection required for high-resolution protein reconstructions. This also lowers long-term data storage demands and improves experimental efficiency. 

  • What are the benefits of E-CFEG for cryo-EM? 
    The low-energy-spread cold field emission gun (E-CFEG) of the Glacios 3 Cryo-TEM consists of a stable electron beam with high brightness, coherence, image contrast and resolution, along with low energy spread. This makes it easier to visualize small or low-contrast biological structures. The E-CFEG also has a longer source lifetime, reducing service costs and minimizing system downtime. 

  • How does AI-powered software improve cryo-EM productivity with the Glacios 3 Cryo-TEM? 
    The Glacios 3 Cryo-TEM integrates AI-powered Thermo Scientific software to automate and optimize cryo-EM workflows. These software solutions support both single particle analysis (with Smart EPU Software) and cryo-electron tomography (with the CryoTomo Software Suite), helping streamline grid screening, data acquisition, and analysis. These software tools reduce microscope idle time, accelerate session setup, and shorten overall time to structural insights. 

  • How does the Glacios 3 Cryo-TEM support cryogenic sample transfer and cryo-ET workflows? 
    The system integrates into connected cryo-EM workflows through a Vacuum Capsule (which is compatible with Autoloader-equipped Thermo Scientific cryo-TEM systems and keeps the specimen in an enclosed reservoir) and compatibility with Thermo Scientific TomoGrid Sample Carriers (which maintain correct sample orientation of cryo-FIB-prepared lamellae). This workflow integration improves sample integrity, alignment precision, and overall experimental success. 

High accuracy and improved throughput with aberration-free image shift

AFIS (aberration-free image shift) is a standard optical mode in Thermo Scientific cryo-TEMs that speeds up data collection without sacrificing image quality. Traditionally, the sample stage moves to align each foil hole with the electron beam, which slows down imaging, as the stage requires up to 30 seconds to relax after each movement. With AFIS, the beam is instead moved between foil holes while automatically correcting for astigmatism and coma. 

 

Further improved with the Glacios 3 Cryo-TEM, AFIS now provides enhanced targeting accuracy, ultimately accelerating data acquisition with higher-quality imaging across the grid. The result is faster imaging with greater accuracy and less data required per experiment for high-resolution reconstruction, thereby reducing data storage demands.

Automated beam-centering improves on-target fringe-free imaging

Fresnel fringes create artifacts during cryo-EM imaging; fringe-free imaging (FFI) is an optical mode that minimizes these artifacts while allowing for a narrow electron beam to be used. This means more particles can be acquired per grid for higher throughput with single particle analysis. In cryo-ET, this allows more regions per lamella to be captured for better cellular coverage. 

 

New to the Glacios 3 Cryo-TEM, an automated beam-centering routine for FFI helps ensure that the beam remains precisely aligned at the center of the field of view. This supports long-term, on-target data acquisition, increasing the amount of usable information captured in every image. As a result, fewer total images are needed to achieve high-resolution reconstructions, reducing overall data collection requirements per experiment, and consequently lowering long-term storage demands.


Easier cryo-TEM set-up with new optical model

During cryo-TEM experimental set-up, configuration of illumination parameters requires in-depth knowledge of electron optics. The 2-condenser lens system of a cryo-TEM makes the parallel beam illumination have discrete beam diameters and steps in the flux, which increase non-linearly (exponentially). Even for expert users, multiple tries are often needed to optimize the system configuration, and the ideal flux is difficult to achieve. 

 

A new optical model in the Glacios 3 Cryo-TEM takes the guesswork out of cryo-EM experimental set-up. In a single click, it calculates all the lens current required along the optical path and sets the electron beam in parallel with the desired flux. As a result, set-up is now faster and easier, particularly for less experienced users. This also shortens the learning curve for new users.


Glacios Cryo-TEM webinar

High-resolution insights at 200 kV: A twist to bacterial gyrase inhibition

Professor Jesko Köhnke presents how he used the Glacios Cryo-TEM to investigate cystobactamids, antibacterial compounds that inhibit DNA gyrase and topoisomerase IV. Cryo-EM analysis revealed a new structural mode of target engagement, providing a framework to guide further antibiotic optimization.

For Research Use Only. Not for use in diagnostic procedures.