Cryo Sample Transfer Solution of Correlated Light and Electron Microscopy

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Abstract

The Nobel Prize in Chemistry in 2017 went to the development of cryo-electron microscopy, which contributed to the discovery of new cells and viruses, the diagnosis of unknown diseases, the mapping of human genomes and the manufacturing of semiconductors. Cryo Correlative light and electron microscopy (Cryo-CLEM), is the combination of using fluorescence microscopy and cryo-electron microscopy to image cryo-immobilized bio-samples. These samples (at a temperature lower than −165ᵒC), require critical conditions in preparation and preservation to prevent contamination and heating which have a negative influence on the imaging results. In the current sample transfer workflow, almost 90% of the samples transferred end up being wasted due to the unideal protection and transfer gap. Therefore, an integrated high-vacuum sample transfer system which fits the interfaces of CLEM devices and actively protects the samples from heating and contamination in transfer has been designed to conquer the problems, ensure better imaging results, and increase the process yield. COMSOL simulations on its thermal and mechanical behaviors have been carried out to theoretically verify and iterate the design. The new transfer system provides a cheaper, faster, easier, more contamination-free, more temperature-stable, more user-friendly workflow that can increase the yield of sample transfer from 10% to 90%.