Structure determination with ED: summary of a compelling argument

As part of a series of five sessions on electron diffraction, our first webinar with Tim Grüne sparked interesting discussions. We were more than happy to host it and we are committed to foster growth for our scientific community. The next session will be on December 9 and our invited speaker, Mauro Gemmi from the Italian Institute of Technology Pisa, will tackle the revolutionary aspect of ED for nano-crystallography.

Please register for the webinar here.  

For those who want to know what is in store, we are summarizing some interesting angles that were discussed during our first online meeting and, given that we had a Q&A session, will be sharing a couple of insightful questions and their answers.

Electron diffraction is a fresh and disruptive topic for crystallographers. The heightened attention for this technique sparked from two independent scientific publications in 2018: two teams across different continents – one led by by Dr. Tim Grüne from the Paul Scherrer Institute Switzerland, another one from UCLA USA came to similar results using the same research starting point: electron diffraction. Naturally, this parallel publication triggered a great deal of attention in the field.

As for the name – up to now, many diverse terms have been used to designate the same technique. This is precisely why the paper by Mauro Gemmi (IIT Pisa) et al. proposed unifying all the similar terms under the umbrella of 3D Electron Diffraction, which – simply put – describes structure determination of crystalline materials with electron diffraction. More about this paper, its implications and its scientific background will be divulged in our next webinar with the author, on December 9.

In brief, what is the main advantage of electron diffraction for scientists? Being able to solve structures from a single nano-crystal. Moreover, the difference between electron diffraction and X-ray diffraction is not that great: both use the same principles – determining the position and intensity for each diffraction spot – being the two main elements that define the crystal structure. Other important benefit is the strong interaction of the electrons with light atoms like hydrogen or lithium for example, and therefore a more accurate position determination. Furthermore, different polymorphic forms in a single batch can be easily identified.

Electron diffraction can change crystallographic research state from now on, because the ability to obtain seamless access to very small crystalline compounds will lead to various applications, pinpointing the start for improvement at the atomic level for drug uptake and catalyst efficiency – among others.

Why an electron diffractometer? Q&A session

The questions the registrants asked during the session with Tim Grüne and the answers they received were too interesting for us not to re-iterate them here. We welcome you to send any question you might have about our product or electron diffraction to the email address of our CSO – santiso@eldico.ch. Or, if you wish to register for our upcoming webinar, please do so here.

I’m wondering how 3D-ED would handle concomitant polymorphs. That is, if you have a powder that contains two polymorphs of the same molecule. I’m certain you could have a program/protocol that can separate the two-unit cells over many, many crystals.

Tim Grüne: There is a way to separate polymorphs of the same molecule – data collection and processing can be automated by clustering the crystal in units. This way we can solve the structure of individual crystals  since we can find out the structures of individual polymorphs. This is the advantage ED has over X-rays: you have the the best of both worlds by combining diffraction and single crystal capabilities in the same instrument.

Gustavo Santiso-Q.: ED is indeed a game-changer. Powders can be studied in much more detail and as often possible with XRPD methods. Not only can you obtain a unit cell for easy phase-ID, but a complete single-crystal structure can be done in a very short time – very valuable for patent and IP issues! This is easy to repeat within minutes for as many crystallites on the grid as you needs. With some automation, up to thousands of crystallites can be analysed, overnight, for example, to obtain a quantitative analysis of the nano-powders.

Will the rotation of the beam be fixed with the Eldico device?

Gustavo Santiso-Q.: Eldico is building a dedicated electron diffractometer. This means we are optimizing the goniometer, rotation, the electron lenses so we get the most out of it. We are actively working towards solving most of the issues already identified in research. Moreover, we are also working on the dynamic scattering – given that we are using X-ray software; however, in time, and with ED-dedicated software, the process will become as precise as X-ray diffraction.

Will the new Eldico ED-system use TEM grids and will it have a cryo-stage?

Gustavo Santiso-Q.: We are using the same grids –the grid will be transferred to an extremely accurate goniometer with a vertical rotation axis to guarantee  the sample remains in the e-beam throughout the entire measurement process. Our goniometer is prepared for the cryo-stage and we have the plans for a cryo attachment in place. Realisation will start in May, so we estimate it will be ready in Q4 of 2021.