Unlocking the potential of cryo-electron tomography by simplification of the sample preparation workflow

ended

"The interest for cryo electron microscopy (cryo-EM) has risen tremendously since the Nobel Prize in Chemistry 2017 was given for Cryo-EM. The next step in Cryo EM, Cryo Electron Tomography (cryo-ET), makes it possible to resolve tertiary and quaternary protein structure interactions in relevant biological samples such as cells and bacteria. However, in the current cryo-ET workflow the sample preparation is the bottleneck. Today, sample preparation is a manual process of 4-8 hours, involves 22 steps and is performed by a PhD level operator. Even so, >80% of the samples end up unusable, due to the extreme complexity of making samples. Sample preparation is therefore also incredibly costly, as imaging time on expensive Cryo-TEMs is wasted on trying to image unusable samples. In order to make cryo-ET fulfil its potential, the sample preparation has to become fast, cheap and reliable. DELMIC has completely reimagined the cryo-ET workflow, with the ultimate vision of completely automating sample preparation. Central to this workflow is the cryo-SECOM, which integrates a correlated cryo light microscope with a FIB/SEM system. Additionally, a unified carrier simplifies the placing and carrying samples around and the sample handling and loading/unloading procedures are automatized. We will tie all workstations together, basically creating a ‘cryo-ET sample prep robot’. This fully integrated workflow approach reduces the switching between many workstations, gives higher yield, and offers unprecedented precision in targeting the area of interest. By simplifying the workflow and reducing the preparation time, the Cryo-SECOM Workflow will allow researchers to innovate faster, decreasing the sample preparation time by 87% and improving the yield by 8-fold. The cost per sample will be greatly reduced by 90%. The Cryo-SECOM Workflow will be key in unlocking the full potential cryo-ET, opening new horizons in structural biology research. "" "