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Cryo-electron microscopy

Accelerate hit-to-lead with cryo-EM

To accelerate your hit-to-lead campaign, we utilise cryo-electron microscopy (cryo-EM) to provide you with 3D structures of your challenging drug targets in complex with your compounds of interest. Our specialised protein science labs produce high-quality fresh protein samples, suitable for direct use in in-house grid preparation for cryo-EM. With regular access to high-end cryo-EM microscopes and over 16 years of cumulative industry experience, our team uses our cryo-EM platform to help ensure you receive detailed structural insights to drive your drug discovery efforts forward. Partner with us to leverage our expertise and state-of-the-art technology for your most demanding projects. 

Scientist pipetts sample on cryo-EM grid 

Tailored Cryo-EM projects for industry 

We offer a range of cryo-EM solutions tailored to fit your needs, including:

  • Stand-alone electron microscopy (EM) packages, such as negative-staining EM, to confirm sample quality
  • Adaptation of literature-described cryo-EM structure-determination methods to deliver target–ligand complex structures
  • Complete gene-to-high-resolution-structure determination for new targets.

If your target is potentially suited for both X-ray and cryo-EM methods, we offer parallel feasibility studies to evaluate both, allowing for an experimentally driven decision on the optimal structure-determination strategy. Our EM projects are modular and milestone-based—after each phase, we discuss the results and conclusions with you and offer expert recommendations on how to proceed. 

 

Enabling the highest protein quality for your challenging cryo-EM target 

Cryo-EM provides access to high-resolution 3D structures for challenging targets not typically accessible to classical X-ray crystallography. Our large-pharma-experienced protein science group supports your EM projects through: 

  • Expertise in producing all typical cryo-EM target classes, including membrane proteins such as GPCRs and ion channels, protein–protein and protein–nucleic acid complexes and antibody–antigen complexes 
  • Delivery of fresh protein directly from the final purification step for immediate in-house EM grid production, helping ensure the highest sample quality and avoiding detrimental longer incubation times and repeated freezing/thawing cycles, thanks to our teams being located under the same roof 
  • Confirmation of ligand binding to the target – since the presence of a ligand can often only be confirmed at the later stages of data processing, we offer early biophysical verification of ligand binding to the cryo-EM protein construct under conditions similar to the cryo-EM condition. 
 

Fast EM optimisation cycles for efficient EM projects 

Iterative cycles of protein optimisation and grid screening are typically required to deliver high-resolution EM structures. Our EM platform provides access to fast cycle times, including: 

  • Initial negative-staining EM quality checks, which are quick and require minimal sample, allowing for early optimisation of sample quality 
  • Cryo-EM grid screening, which optimises cryo-EM grid freezing conditions to obtain an ideally suited grid for data collection 
  • Regular access to both negative-staining and cryo-EM screening microscopes, enabling us to provide quick feedback to our protein science team and grid production for optimising the sample and cryo-EM grid freezing conditions. 

 

Flowchart illustrating our EM services

 
 

Delivering high-resolution cryo-EM structures for your projects 

Once the optimal cryo-EM freezing condition is identified, we collect high-resolution cryo-EM data at external high-end cryo-EM microscopes (e.g., Titan Krios G4 with Falcon 4 detector and energy filter). Data processing is conducted in-house on our new, ultra-fast cryo-EM GPU data processing server, equipped with state-of-the-art software such as cryoSPARC, RELION 5, TOPAZ and cisTEM. Our EM scientists then validate and interpret the structure, providing you with all the necessary information and guidance to best support your hit-to-lead campaign. 

Related topics & resources

Discussing new lead optimization strategies identified from a new target-compound structure.

X-ray crystallography

Nuvisan´s X-ray crystallography solutions offer detailed insights into molecular structures, aiding in drug design and development.

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Scientists in the lab carry out protein analysis experiment

Protein sciences

Our protein sciences team specialises in producing high-quality proteins essential for your research and development needs.

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Placing samples into the instrument for SPR analysis

Biophysical solutions

Our biophysical methods help validate interactions and optimise drug candidates.

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