Abstract: The disclosure relates to a method for micromachining a biological sample for creating a lamella for analysis in a Cryo-Charged Particle Microscope (Cryo-CPM). The method comprising the steps of providing a biological sample on a sample carrier; Locating a sample area on the sample carrier, said sample area comprising a region of interest having biological material from which a lamella can be created; and Micromachining at least part of the biological sample so as to remove material in a part of the sample area surrounding the region of interest, in order to increase a visual contrast between the biological material in the region of interest and its surroundings. With the increased visual contrast a location for a potential lamella can be identified.

Abstract: Disclosed herein are scientific instrument support systems, as well as related methods, computing devices, and computer-readable media. For example, in some embodiments, a support apparatus is provided for a charged particle microscope. The support apparatus is configured to apply automated image processing to an image representing a lamella sample to segment the image into a plurality of segmented classes. The support apparatus is also configured to identify, based on the plurality of segmented classes, a subset of candidate structures-of-interest in the lamella sample and to select, from the subset of candidate structures-of-interest in the lamella sample, a selected structure-of-interest for milling. The support apparatus is also configured to set, based on the selected structure-of-interest for milling, at least one milling parameter for the scientific instrument. An automated method performed via a computing device for providing such scientific instrument support is also provided.

Abstract: Methods and apparatus apply focus stacking to sample preparation, improving accuracy of analytic tasks, facilitating automation, and improving throughput. Focus stacking is applied to a set of sample images having different focus depths, to produce a composite image in which features at different depths are in focus and, optionally, a depth map. A sample location is selected from the composite image and a localized material removal, measurement, or imaging operation is performed based on the sample location. A depth value from the depth map is used to set a working depth of a tool for performing the localized operation. Applications include lamella preparation for cryogenic TEM analysis of biological samples. Other applications, techniques, and variations are disclosed.