The Papp Team at EMBL Grenoble has developed two prototypes, EasyGrid and EasyGrid Control, to automate sample preparation and quality control for cryo-electron microscopy (cryo-EM).
A breakthrough in automating cryo-EM sample preparation and quality control has been published in Nature Methods, promising to dramatically improve reproducibility and data quality.
Key Innovations
The new systems address the long-standing bottleneck of manual sample preparation. Here are the core features:
- EasyGrid: A fully automated and modular platform designed for high-throughput sample vitrification.
- EasyGrid Control: An instrument that automatically screens samples—whether prepared with EasyGrid or traditional methods—to check their quality before advanced microscopy.
- Advanced Technology: The platforms use pressure waves to spread samples across grids, paired with an ethane jet-based vitrification system that uses bare grids. This improves cooling rates, enabling deeper vitrification within cells.
- Broad Application: The platforms are suitable for cryo-EM, cryo-electron tomography, and X-ray nano-imaging.
A sevenfold improvement in vitrification quality was demonstrated in large human cell nuclei compared to traditional methods.
Background
Cryo-EM is a pivotal method for determining the three-dimensional structure of proteins. However, manual sample preparation limits reproducibility and quality, often leading to costly and time-consuming experimental failures. The new automated systems aim to eliminate this variability.
Development and Validation
The development was a collaborative effort involving researchers from EMBL sites and partner institutes in France (Inserm, Institut Pasteur, Sorbonne Université, Institute of Advanced Biosciences). The team successfully obtained high-resolution maps of several macromolecular complexes, validating the system's performance.
Technology Transfer and Commercialization
The prototypes have already been transferred to the EMBL Imaging Centre in Heidelberg. Looking ahead, the team is merging the two technologies into a third version that combines both sample preparation and quality control in a single instrument.
- As an interim step, the current systems will be available as a service through Instruct-ERIC.
- A spin-off company, led by Vic Armijo, will commercialize the prototypes. The initial product will be EasyGrid Control, which will feature improved resolution and an optional fluorescence microscopy module.
Funding
This project was supported by a robust portfolio of European funding, including the EU projects Fragment-Screen and IMAGINE, the ARISE programme, iNEXT-Discovery, and Marie Skłodowska-Curie Actions, among other sources.