Liquid Phase Experiments: Describing Experiments in Liquids and the Special Requirements and Considerations for Such Experiments

Abstract

Electron microscopy of specimens in liquid is possible using several different approaches. A cooled sample can be studied in a modified vacuum chamber containing a wet environment comprising vapor and liquid, whereby a thin liquid layer is maintained over the specimen via environmental scanning electron microscopy (ESEM). The sample can also be hermetically sealed from the vacuum by enclosure in a liquid chamber containing at least one thin and electron transparent window. Liquid specimen holders for transmission electron microscopy (TEM) and scanning TEM (STEM) or scanning electron microscopy (SEM) are now commercially available. A variant of this concept is the closure of the vacuum chamber by a window, whereby the electron beam penetrating through a thin window irradiates a sample in liquid outside the vacuum chamber. This chapter provides an overview of the most popular experimental approaches, including correlative light- and electron microscopy. Examples from our research demonstrate how three of these approaches were applied to the study of epidermal growth factor receptor (EGFR) dimerization in the plasma membranes of intact cells, the native structure of yeast, gold nanoparticle uptake, and the formation of gold dendrites.