MedTech Initiative 2020

Precision Drives for Electron Microscopy
Precision Drives for Positioning and Moving of Specimen in TEM, Scanning TEM, Cryo-TEM, SEM
and for the Vitrification of Samples for Cryo-TEM Onto Metal Grids

Physik Instrumente (PI) GmbH & Co. KG, Auf der Roemerstrasse 1, 76228 Karlsruhe, Germany
Phone +49 721 4846-0, Fax +49 721 4846-1019, Email info@pi.ws, www.pi.ws

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Precision Drives for Electron Microscopy

Electron Microscopy
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 Prizein 2017, the samples have to be precisely nanopositioned
with precision in an XYZ coordinate and then tilted around
one axes to produce a certain number of transmission images
for image reconstruction. Especially in the Cryo-TEM, whichuses very thin, vitrified slices of samples of typically 50nm
thickness, the contrast is low. Therefore, typically thousandsof images from several tilt angles are needed forreconstruction.
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 thenanometer and sub-nanometer 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.
Besides sample holder for the sample movements sometimes
also slit assays have to be actuated by a precision motiondrive.
To achieve highest dynamics, smallest outer dimensions of
the microscope and highest convenience for the user, thesedrives 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 non-magnetic materials and for Cryo-TEM
additionally the working temperature of liquid ethane (-160°C) or even liquid nitrogen (-196° C).
A topical example application case for Cryo-TEM is the fightagainst COVID-19. Here Cryo-TEM had already played and iscontinuously playing a crucial role in identifying the protein
surface structure of the SARS-CoV-2 virus. Like othercoronaviruses, SARS-CoV-2 particles are spherical and haveproteins called spikes protruding from their surface. Thesespikes latch onto human cells, then undergo a structuralchange that allows the viral membrane to fuse with the cellmembrane. The viral genes can then enter the host cell to becopied, producing more viruses. After the genome sequenceof SARS-CoV2 by scientists in China in January 2020 acollaborative team including scientists from Dr. Jason
McLellan’s lab at the University of Texas at Austin and theNIAID Vaccine Research Center (VRC) isolated a piece ofthe genome predicted to encode for its spike protein basedon sequences of related coronaviruses. The team then used
cultured cells to produce large quantities of the protein foranalysis.

Scientific Publication by: NIAID Vaccine Research Center, 2020
The researchers used Cryo-TEM to take detailed pictures ofthe structure of the spike protein. This involves vitrifying,means freezing virus particles and then taking tens ofthousands of TEM images at different tilt angles. Theseimages are then combined to yield a detailed 3D view of thevirus. The researchers found that the SARS-CoV-2 spike was
10 to 20 times more likely to bind on human cells than thespike from the SARS virus from 2002. This may enable SARSCoV-2 to spread more easily from person to person than theearlier virus.

Scientific Publication by: UT Austin, McLellan Lab, 2020

Precision Drives for Electron Microscopy

Motion Solutions from PI
Typically the drive requirements for 3, 4, 5 or 6 - dimensionsof freedom are solved by stacked drives. But also a fullyparallel kinematic drive in form of a miniature hexapod isavailable. Some examples for potentially suitable drives,
below. Cryo-versions only on specific request:
P-752 High-Precision Nano-positioning Stage
Piezo-flexure stage, capacitive sensors, repeatability:±1nm, travel range to 35 μm, UHV compatible, nonmagneticSolutions 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 atabout minus 160°C by two ethane jets, which are offset toeach other by 180 degrees.

Voice Coil Direct Drives

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, UHVcompatible, non-magnetic

Piezo Actuators for Vibration Damping

Sensitive instrumentation such as electron microscopes
requires precise vibration isolation to exclude disturbing
influences from the environment, so a proper
performance is ensured. For this task, active vibration
cancellation stages can be designed by the use of PICA
Stack Actuators or PICMA® Piezo Linear Actuators. Due tothe piezoelectric effect, these elements work both as
sensors and actuators compensating ambient vibrations.
The actuators exhibit high forces, short reaction times
and superior durability, which makes them suitable forthe use in complex systems made for performance overlong periods of time.

P-911 UHV-Compatible Miniature Piezo Hexapod
NEXLINE® piezo stepping, position resolution down to0.1 μm in the linear axes, UHV-compatible to 10–9 hPa,
Non-magnetic
PICA Piezoelectric Stack Actuators

PICMA® Stack Multilayer Piezo Actuators

Further recommended drives see PI brochure BRO037E.

Precision Drives for Electron Microscopy