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

Project description

Cryo-electron tomography gets a boost from automated sample preparation

Super-resolution microscopy techniques have revolutionised fields ranging from materials science to medicine. Cryo-electron microscopy (cryo-EM) has been a game-changer for high-resolution imaging of biological tissues and molecules. Biological molecules are sensitive to destruction and contamination when their aqueous environments are disrupted. Cryo-EM maintains the advantages of transmission electron microscopy and extends utility by using cryogenically cooled samples embedded in an environment of vitreous water. Cryo-electron tomography (cryo-ET) makes the best even better with computer-aided alignment of 2D images to yield a 3D reconstruction of the sample. However, sample preparation time and complexity result in a high proportion of failures. Cryo-SECOM Workflow is developing a completely automated sample preparation platform to ensure biomedical researchers realise the amazing promise of cryo-ET.

Objective

"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.
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SME-2 - SME instrument phase 2

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Call for proposal

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(opens in new window) H2020-EIC-SMEInst-2018-2020

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Coordinator

DELMIC BV
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 143 750,00
Address
KANAALWEG 4
2628EB DELFT
Netherlands

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SME

The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed.

Yes
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 3 062 500,00
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