Abstract
In the past decade, many developments have advanced the cryo-EM field in imaging technologies and processing methodologies. Still, there are many challenging samples that cannot be structurally characterized with conventional cryo-EM preparation procedures because they cannot be preserved natively in vitreous ice with traditional plunge freezing or, in some cases, even microfluidic assisted spray-plunge freezing. These recalcitrant specimens can touch the air-water interface, aggregate, or bind to the support film rather than remain suspended in the film's holes.
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