Innovative Techniques for Precise Site-Specific Sample Preparation and In situ Structural Study of Cells

<正>Nanomachines and ultrastructures inside cells are the basic units involved in life activities. They perform specific physiological functions through close cooperation with each other. Seeing is believing. Studying the in situ assembly and function of these complicated and precise nanostructures has been a hot topic in life science. Cryo-electron tomography(cryo-ET) is currently the main technique for in situ structural analysis. However, due to the limitation of electron beam penetration, cell and tissue samples should be milled to lamella of ～200 nanometers using focused ion beams(FIB) for imaging. However, the random milling technique brings great challenges to the study of specific targets with relatively low abundance in cells. The prepared cryo-lamella sample often fails to retain the target of interest.