3D electron diffraction of small molecules on the MerlinEM detector.

Session

Poster Session Three

Authors

Dr Pedro Nunes (1), Dr. Matus Krajnak (2), Dr. Adriana L. Klyszejko (2), Dr. Alistair C. Siebert (1)

Affiliations

1. Diamond Light Source, Harwell Science and Innovation Campus, OX11 0DE
2. Quantum Detectors Ltd, R103 Rutherford Appleton Laboratory, Harwell Science and Innovation Campus, OX11 0QX

Keywords

3D electron diffraction; 3DED; microED; electron diffraction tomography; small molecules; drug discovery; chemical compounds; R&D

Abstract text

The MerlinEM/Medipix3 is a versatile detector widely used for scanned electron diffraction, precession, dynamic transmission electron microscopy (TEM) and scanning transmission electron microscopy (4D STEM). It can be used to image direct probes (up to 300kV) while still retaining the ability to count single electrons for the weaker diffraction spots (1). It contains two 12-bit counters, enabling zero dead time acquisitions and noiseless readout. This makes MerlinEM an attractive solution for low-dose techniques in many areas of electron microscopy.

We are particularly interested in the application of micro electron diffraction (3DED, microED) techniques for structure determination of small molecules of biological and pharmaceutical importance (2). 3DED has been growing in popularity in recent years thanks to the development of more sensitive detectors and stable automated diffraction setups. Electron diffraction has the essential advantage over X-ray crystallography when crystal size is concerned. It produced multiple medium to high resolution structures from nano crystals and from artificially thinned (by focused ion beam milling) crystals (3 and 4). Furthermore, electrons have an advantage over X-rays as they interact orders of magnitude more strongly with samples. This allows hydrogen atoms to be located within the structure to gain insights into the chemical properties of small compounds. This is essential in chemical research, pharmaceutical drug discovery and other industries (5). Furthermore, performing electron diffraction tomography on multiple crystals in an automated manner enables efficient collection of large datasets. For this reason, we worked closely with the team at Quantum Detectors. A recently available plugin for MerlinEM to the academic SerialEM software environment (6) has enabled low-dose 3DED data collections on the MerlinEM Quad 4S installed on the FEI Tecnai F30 cryo electron microscope at the Rosalind Franklin institute. We present data obtained on small compounds of pharmaceutical interest by HeXI at Diamond Light Source using 3DED with MerlinEM.

References

References:

1. Medipix3 has been commercialised as a MerlinEM detector by a collaboration between the University of Glasgow and Quantum Detectors Ltd.

2. Shi et al., 2013

3. Duyvesteyn et al., 2018

4. Beale et al., 2020

5. Palatinus et al., 2015

6. Mastronarde, 2005