A Journey to the Nanocosmos

Applications for electron microscopy cover a broad spectrum from semiconductor inspection through materials research to molecular biology research. In conventional TEM as well as in the newer Cryo-TEM, which was awarded the Nobel Prize in 2017, the samples have to be nanopositioned with high precision in an XYZ coordinate and then tilted around one axis to produce a certain number of transmission images for image reconstruction. Especially in Cryo-TEM, which uses very thin, vitrified slices of samples of typically 50 nm thickness, the contrast is low. Therefore, typically thousands of images from several tilt angles are needed for reconstruction.

However, when scanning samples with TEM or SEM (Scanning Electron Microscopy) not only is the precise initial positioning of the specimen a main aspect of the method but also a very precise scanning of the specimen in the nanometer and subnanometer range.

This means, all electron microscopy methods need precision drives for several dimensions of freedom, typically between three and six dimensions, including XYZ, rotations, and tilt movements depending on the specific hardware setup.

To achieve the highest dynamics, smallest outer dimensions of the microscope, and highest convenience for the user, these drives have to be placed preferably inside the vacuum chamber with pressure requirements typically between 10^-4 mbar to 10-6 mbar. Further requirements for the drives are the use of nonmagnetic materials and for Cryo-TEM the working temperature of liquid ethane (-160° C) or even liquid nitrogen (-196° C).

A current example application case for Cryo-TEM is in the fight against COVID-19. This technology playes a crucial role in identifying the protein surface structure of the SARS-CoV-2 virus. The knowledge gained about the outer shell of the virus offers important clues on mechanisms and possibilities of fighting it. The spherical coronavirus, typically has so called spikes protruding from its surface. These spikes not only gave it its name, corona = crown, but are possibly responsible for the high infectiousness of the virus. These spikes easily latch onto human cells and can stay there long enough to fuse the virus' DNA with that of the human cells. Since viruses can quickly change their structure, i.e. they mutate constantly, their appearance is an indicator for mutations.