Soft X-ray tomography and cryogenic light microscopy: the cool combination in cellular imaging

Soft X-ray tomography (SXT) is ideally suited to imaging sub-cellular architecture and organization, particularly in eukaryotic cells. SXT is similar in concept to the well-established medical diagnostic technique computed axial tomography (CAT), except SXT is capable of imaging with a spatial resolution of 50 nm, or better. In SXT, cells are imaged using photons from a region of the spectrum known as the 'water window'. This results in quantitative, high-contrast images of intact, fully hydrated cells without the need to use contrast-enhancing agents. The cells that are visualized are in close-to-native, fully functional state. The utility of SXT has recently been enhanced by the development of high numerical aperture cryogenic light microscopy for correlated imaging. This multi-modal approach allows labelled molecules to be localized in the context of a high-resolution 3-D tomographic reconstruction of the cell.