A platform for retaining native morphology at sub-second time scales in cryogenic transmission electron microscopy.

The advantage of cryogenic transmission electron microscopy for morphological analysis of complex fluids is the ability to capture native specimen morphology in solution. This is often limited by available sample preparation devices and procedures, which expose the sample to high shear rates leading to non-native artifacts, are unable to capture evolving samples at a time resolution shorter than a few seconds, and often non-specifically adsorb sample species from suspension resulting in a non-native sample concentration on the grid. In this paper we report the development of a new sample preparation device based on capillary action that overcomes all of these limitations. The use of a removal capillary placed parallel to the grid results in reduced shear and lower absorption of particulate material from the sample. A deposition capillary placed perpendicular to the grid allows for precise and sub-second resolution for time resolved studies. We demonstrate each of the features of this platform using model samples, and where appropriate, compare our results to those prepared using current vitrification platforms. Our results confirm that this new sample vitrification device opens up previously unattainable regimes for sample preparation and imaging and is a powerful new tool for cryogenic transmission electron microscopy.