Method for micromachining a biological sample for creating a lamella for analysis in a cryo-charged particle microscope

A method for micromachining a biological sample for creating a lamella for analysis in a Cryo-Charged Particle Microscope (Cryo-CPM), the method comprising:

• providing a biological sample on a sample carrier;
• locating a sample area on the sample carrier, said sample area surrounding a region of interest having biological material from which a lamella can be created;
• micromachining at least part of the sample carrier so as to remove material in a part of the sample area adjacent to the region of interest, in order to increase a visual contrast between the biological material in the region of interest and a portion of the sample area surrounding the biological material;
• identifying, by a processing unit using the increased visual contrast between the biological material in the region of interest and its surroundings, a location within the biological material in the region of interest from which a lamella can be created;
• and
• micromachining the sample to produce said lamella from the identified location within the biological material.