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Fast cryo-EM sample preparation: Recent developments and applications

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Since the ‘resolution revolution’, the field of cryo-electron microscopy (cryo-EM) has continued its rapid development with new and improved hardware and processing algorithms. Sample preparation for cryo-EM is increasingly becoming a bottleneck, and alternatives to the traditional blotting method are needed. We have been developing methods for fast droplet-based sample preparation, which allow grid preparation on the timescale of ~10 ms. This has been instrumental to better understand the interactions between particles and the air-water interface and has allowed time-resolved structural studies. As an example, we have solved the first structure of an actomyosin complex in the pre-power stroke state by time-resolved cryo-EM. Our current work focuses on reducing the timescale of grid preparation to less than 1 ms, and on characterising the interactions between proteins and the air-water interface in more detail

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