Cryo EM Applications | Glacios Cryo TEM | Thermo Fisher Scientific

Cryo-EM that fast-tracks discovery

The Thermo Scientific Glacios 3 Cryo-TEM provides access to a range of high-performance cryo-EM techniques, including single particle analysis, cryo-electron tomography (cryo-ET), and microcrystal electron diffraction (microED).

AI-powered software facilitates cryo-electron microscopy workflows with real-time feedback that guides decisions, screens samples, and automates complex tasks, significantly increasing throughput and data quality while reducing the dedicated staff needed for daily operation.

Leveraging the innovative technology within the 200 kV Glacios 3 Cryo-TEM, these techniques and workflows are helping to fast-track structure-based drug design and groundbreaking research.

Cryo-EM techniques enabled by the Glacios 3 Cryo-TEM

Cryo-electron tomography

Cryo-ET reveals the 3D structures of macromolecules and biological components in their cellular context.

Image: 3D visualization of a Golgi apparatus in the green alga C. reinhardti, obtained with the the Glacios Cryo-TEM.

Single particle analysis

With single particle analysis, 3D structures of purified proteins and macromolecules can be obtained from a suspension of vitreous ice.

Image: 3G08 Fab-HIV envelope trimer. Reconstructed from EMDB-48286. (Original study by Caniels et al.)

Microcrystal electron diffraction

MicroED enables the fast, high-resolution structural determination of small molecules and proteins.

Image: The structure of the wildtype 20-34 amyloid-β fragment. Recreated from EMD-20082. (Original study by Warmack et al.)

Fast-tracking therapeutic discovery with structure-based drug design

Cryo-EM has become an essential tool in rational drug design, enabling researchers to directly observe protein-ligand interactions, conformational changes, and dynamic binding pockets at atomic or near-atomic scale. Cryo-EM can help reduce late-stage trial failures by determining high-resolution drug-target structures and by defining the mechanism of action at early discovery stages. From target selection to IND, structure-based drugs have been found to have 2x the rate of clinical success at 50% of preclinical time and cost.

More organizations are adopting 200 kV cryo-EM, with its balance of performance and accessibility, to fast-track the development of biotherapeutic drugs across a range of modalities, including:

Antibody candidate selection with fast, accurate epitope information
Structure-based design of vaccines and CAR-T candidates 
Discovery, engineering, and optimization of novel gene-editing enzymes 
Comprehensive particle characterization of viral and lipidic delivery vehicles

Examples of 200 kV cryo-EM in therapeutic discovery and design

Therapeutic potential of SLC transporters

Single particle analysis of the VMAT1 dimer complex, both unbound and bound to reserpine, solved with 200 kV cryo-TEM. Recreated from EMDB-41238. (Original study by Ye et al.)

Progress towards an HIV vaccine

Single particle analysis of 3G08 Fab in complex with the HIV envelope trimer, solved with 200 kV cryo-TEM. Recreated from EMDB-48286. (Original study by Caniels et al.)

Characterizing liposome-encapsulated drug delivery vectors 

Liposome encapsulation involves the enclosing of a drug inside a liposome made of one or more lipid bilayers, mimicking biological membranes. This is a well-established and increasingly common method of drug packaging, especially for certain drug classes that benefit from controlled delivery or reduced toxicity.

Cryo-ET is used to directly visualize nanoscale drug delivery systems in their native, hydrated state to validate formulations, detect early problems, help ensure quality and stability, and optimize therapeutic performance. 

Liposome-encapsulated doxorubicin, a chemotherapy drug formulation, imaged with 200 kV cryo-ET. Purple shows liposomes correctly packaged for drug delivery while yellow indicates improperly packaged liposome.

200 kV cryo-EM in biological discovery

Advancements in 200 kV cryo-TEMs have significantly narrowed their performance gap with 300 kV systems, offering resolutions that can readily support high-impact structural biology.

Modern 200 kV instruments are powerful tools for single particle analysis, resolving complex biomolecular structures with high accuracy and throughput. Additionally, 200 kV systems now offer sufficient contrast and resolution for cryo-ET, generating detailed subcellular and macromolecular imaging. 200 kV microscopes strike a practical balance between performance, affordability, and operational simplicity, democratizing structural biology while meeting the rigorous standards expected of top-tier publications. 

The example here shows how a team at the Southern University of Science and Technology, China, uses cryo-ET to visualize mitochondria as they work to understand the mechanistic foundation of disease. Their work, published in Wang et al., reveals high-resolution structural details that could inform the diagnosis and treatment of mitochondria-related illnesses.

Further examples showcasing the performance and versatility of modern 200 kV cryo-TEMs for structural biology are shown below.

Energy production inside mitochondria

In-situ structure of complex I (part of the mammalian respiratory supercomplex) acquired with single particle analysis on a 200 kV cryo-TEM. Recreated from EMD-42166. (Original study by Zheng et al.)

Components of the type III CRISPR-Cas system

Single particle analysis of a protease filament associated with certain type-III CRISPR systems, solved with 200 kV cryo-TEM. Recreated from EMD-41358. (Original study by Steens et al.)

Virus assembly and budding

Chikungunya virus assembly and budding, visualized in situ using sub-tomogram averaging with 200 kV cryo-TEM. Recreated from EMD-26448. (Original study by Chmielewski et al.)

Neurological proteins and complexes

Helical reconstruction of mouse alpha-synuclein fibrils. Data acquired with 200 kV cryo-TEM. Recreated from EMD-50023. (Original study by Sokratian et al.)