A compact electron microscope uses a removable sample holder having walls that form a part of the vacuum region in which the sample resides. By using the removable sample holder to contain the vacuum, the volume of air requiring evacuation before imaging is greatly reduced and the microscope can be evacuated rapidly. In a preferred embodiment, a sliding vacuum seal allows the sample holder to be positioned under the electron column, and the sample holder is first passed under a vacuum buffer to remove air in the sample holder.