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

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Cryo-electron tomography (cryo-ET) is a powerful technique that can faithfully image the native cellular environment at nanometer resolution and enables the acquisition of 3D images of large and pleomorphic objects, such as cells and organelles, with unprecedented resolution. The main problem in the current cryo tomography workflow is the multiple critical steps needed to make the sample suitable for analysis. Current labs use a workflow that involves at least 22 steps, limiting the throughput to the creation of only one sample a day, and with a low yield of the analysis due to contamination of the sample during the transfer steps. 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, cryo-SECOM 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%. Cryo-SECOM will be key in unlocking the full potential cryo-ET, opening new horizons in structural biology research that will have broad application to address fundamental questions in microbiology.