Electron microscopy

Electron image of pharmaceutical nano-crystal. Electron image of pharmaceutical nano-crystal.
Our highly sensitive detectors can be retrofitted to existing Transmission Electron Microscopes (TEMs) and obtain high-resolution 3D diffraction data from nano-sized 3D crystals of beam sensitive material. These crystals are too small to be studied using high intensity X-rays at synchrotrons. Our detector system demonstrates how disruptive high sensitivity can be for applications where ultra-low intensity is imperative.
Refined atomic structure using ShellX (Pictures and data by courtesy of Max Clabbers, Eric van Genderen and Jan Pieter Abrahams, Leiden University)Refined atomic structure using ShellX.
Pictures and data are courtesy of van Genderen et al. Acta A (2016).

Electron 3D nano-crystallography with a Cheetah detector

Rotation diffraction set of the same crystal (0.8 Å).
In the case of electron diffraction, recent results in collaboration with the Jan Pieter Abrahams’ Lab at Leiden university show that complete sampling of Bragg spacings can be achieved with ASI’s Cheetah 120 or ASI’s first electron camera detector in combination with continuous crystal rotation. This detector holds a 512×512 pixels Timepix chip (pixel size 55 μm) and is of unprecedented sensitivity with a high dynamic range (13.5 bit) and very high signal-to-noise ratio. Rotational electron diffraction data at room temperature of pharmaceutical compounds and protein nano-crystals was collected at 200 keV (λ=0.025 Å) with a frame rate of 9.1 fps at extreme low dose conditions (±0.01 e-.Å-2.s-1). Furthermore, it was demonstrated that in the case of pharmaceuticals, 50° of continuous rotation data could be collected at room temperature from 200 nm thin compound nano-crystals showing high resolution Bragg spots up to 0.8 Å. The atomic structure could be solved using direct methods.

Pictures and data are courtesy of van Genderen et al. Acta A (2016).

Protein Crystallography

The biggest bottleneck in protein crystallography is that many proteins do not form crystals large enough for 3D structure determination by X‐ray crystallography. For sub-micron sized 3D protein crystals there are several alternatives: intense XFEL sources, electron diffraction and electron imaging. Recently, known crystal structures of 3D sub-micron protein crystals could be refined using XFEL and electron diffraction data. ASI’s detector has been used to collect rotation electron diffraction of 100 nm protein crystals with better than 2 Ångstrom resolution. This will pave the way for Electron Crystallography as a new tool to determine the structures of proteins that do not grow X-ray diffraction grade crystals.
Single frame of a 20 degree data set of a +/- 100 nm thick protein crystal. The diffraction exceeds the ring which represents 2 Ångstrom.
Pictures and data are courtesy of Clabbers et al. Acta D (2017) .