Optical Interference for the Guidance of Cryogenic Focused Ion Beam Milling Beyond the Axial Diffraction Limit

作者：Anthony V. Sica, Magda Zaoralová, Cali Antolini, Daan B Boltje, Judit J. Pénzes, Lilyana M. Malmqvist, Grant J. Jensen, Jason T. Kaelber, Peter D. Dahlberg · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2024 · DOI：10.1101/2024.11.01.621231 · 被引用次数：3 · 研究领域：Ion-surface interactions and analysis、Integrated Circuits and Semiconductor Failure Analysis、Electron and X-Ray Spectroscopy Techniques

Abstract Using a tri-coincident cryogenic FIB-SEM-LM system, we identify an interferometric optical response that can be used for targeting lamella production to fluorescently labelled structures with accuracy beyond the diffraction limit. We demonstrate the approach using synthetic samples of fluorescent beads embedded in micron-scale droplets of water. We then apply the approach to capture virions inside host cells. Successful targeting is confirmed by cryogenic electron tomography revealing clusters of virions in intracellular vesicles.