Cryo-Electron Microscopy Sample Preparation
SUMMARY: Cryo Electron Microscopy (Cryo-EM) sample preparation is a challenging process because it requires complicated sample preparation
Automated micro dispensing at low temperature is potentially a very promising process
A very good example of this has been shown by the group of Gergely Papp using the EasyGrid platform
Background
Cryo-EM is a remarkable technology that was honored with a Nobel Prize in 2017, awarded to Jacques Dubochet, Joachim Frank, and Richard Henderson.
This technology is especially significant because, coupled with the revolution in imagine sensor electronics, it has greatly improved the study of cellular and molecular structures, which would have been impossible using traditional methods like X-ray diffraction.[1]
Challenges in Cryo-EM Sample Preparation impair scaling up
Imaging biological macromolecules in their native state with single-particle cryo-electron microscopy (cryo-EM) or in situ cryo-electron tomography (cryo-ET) requires optimized approaches for the preparation and vitrification of biological samples. This is by no means straightforward, as it requires:
- Handling tiny volumes on delicate grid structures, such as the removal of water.
- Handling at very cold temperatures without interruptions to ensure vitrification, which is needed to form amorphous ice crystals.
- Preparing several samples at once can be quite tricky and time-consuming
Automated sample preparation with microdispensing can help parallelize this process for higher-throughput
Recently the group of Gergely Papp at EMBL Grenoble (https://www.embl.org/groups/papp/ ) has been working on an automated platform that addresses these challenges. The platform is called EasyGrid [2] . It is a versatile system that can be tailored for advanced sample preparation for cellular and structural biology. This automated platform combines in-line plasma treatment, microfluidic dispensing, blot-less sample spreading, jet-based vitrification, and on-the-fly grid quality control using light interferometry to streamline cryo-EM sample preparation and optimization.
As part of this process, a microdrop dispenser head was used to dispense the tiny amounts of liquid protein solution onto the grid. This platform also allows better vitrification of large, mammalian cells compared to standard plunge-freezing methods. Therefore, the automated sample preparation with EasyGrid establishes an advanced, high-throughput platform for both single-particle cryo-EM and cellular cryo-ET sample preparation. This will likely play a key role in guiding the preparation of samples, ensuring greater reproducibility and improved data quality.
References
Acknowledgement
A special thank you goes to Gergely Papp and his team for further information, collaboration and contributions to this story. You can find more info on EMBL and EMBL Grenoble
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