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 precisely nanopositioned in an XYZ position 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.

Motion and Positioning Solutions from PI

Typically, the drive requirements for 3, 4, 5, or 6 degrees of freedom are solved by stacked drives. A fully parallel-kinematic drive in form of a miniature hexapod is also available. Below, are some examples of potentially suitable drives.

P-752 High-Precision Nanopositioning Stage

Travel range to 35 μm
Capacitive sensors
Piezo-flexure stage
Repeatability ±1 nm

N-310 Nexact Miniature Linear Motor

Travel range 10 to 125 mm
Feed force to 10 N / holding force to 12 N
Resolution 0.03 nm (open loop) and 5 nm (closed loop)
Velocity to 10 mm/s

P-911 UHV-Compatible Miniature Piezo Hexapod

  • NEXLINE® piezo walking drive
  • Position resolution down to 0.1 μm in the linear axes
  • UHV-compatible to 10–9 hPa
  • Nonmagnetic

Solutions for Cryo-TEM Sample Vitrification

With the Cryo-TEM sample vitrification, first a nanoliter droplet of the liquid specimen is placed onto a hydrophilic metal grid. For this purpose, a small applicator with a sharp tip is positioned at high velocities and with nanometer precision by XYZ drives. Afterwards, the grid with the droplet is placed into a vitrification chamber where it is vitrified at about minus 160 °C by two ethane jets, which are offset to each other by 180 degrees.

You can find an overview of suitable piezo-based drives in our "Electron and Ion Microscopy" brochure.



Electron- and Ion Microscopy

Nonmagnetic and vacuum-compatible actuators positioning systems
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