Abstract: Methods and systems for performing sample lift-out and protective cap placement for highly reactive materials within charged particle microscopy systems are disclosed herein. Methods include preparing a nesting void in a support structure, translating at least a portion of a sample into the nesting void, and milling material from a region of the support structure that defines the nesting void. The material from the region of the support structure is milled such that at least some of the removed material redeposits to form an attachment bond between the sample and a remaining portion of the support structure. In various embodiments, the sample can then be investigated using one or more of serial sectioning tomography on the sample, enhanced insertable backscatter detector (CBS) analysis on the sample, and electron backscatter diffraction (EBSD) analysis on the sample.