NanoMEGAS participates in study to determine structure of organic pharmaceuticals using Timepix direct electron detection camera

Brussels, Belgium: – NanoMEGAS SPRL, the world-leading instrumentation hardware and software specialist and innovator in advanced electron diffraction technologies in Transmission Electron Microscopy (TEM) has participated in a ground-breaking study exploring use of direct electron detection camera for structure determination of nanocrystals of organic pharmaceutical compounds.

The study ‘Ab initio structure determination of nanocrystals of organic pharmaceutical compounds by electron diffraction at room temperature using a Timepix quantum area direct electron detector’ is published by the journal Acta Crystallographica Section A Foundations and Advances (2015).

The work highlights a method for structure determination of beam-sensitive nanocrystals that does  not require electron diffraction tomography data collection at liquid-nitrogen temperature, thereby avoiding collateral beam damage to the material being studied.

High dynamic range and S/N ratio

The study shows that the advanced Timepix detector, which combines high dynamic range with a very high signal-to-noise (S/N) ratio and single-electron sensitivity, enables high quality electron diffraction data towards ab initio phasing of beam-sensitive organic compounds.

The team used continuous rotation method with the Timepix to collect low-dose electron diffraction data from two small-molecule compounds, carbamazepine and nicotinic acid, at room temperature (RT). They ascertained that the data were of sufficient quality for structure solution using direct methods using software developed for X-ray and electron crystallography.

The team found that the Electron diffraction data recorded with the new Timepix ASI detector in continuous rotation mode were of sufficiently high quality to solve both organic crystal structures with direct methods.

Future applications

The researchers say the techniques and methods shown in the study should pave the way to solving compounds with a larger unit cell at non-cryo conditions (RT), with possibility of solving the structures of even more beam-sensitive compounds like pharmaceuticals containing solvents.

“Based on the experience from this project, we are improving the instrumental design of both detector and diffraction instrument. We are also currently investigating how to produce better quality data. This will include processing programs dedicated to electron diffraction data and programs that take the effects of dynamic scattering into account,” the study concludes.

The project was supported by NanoMEGAS, among others, with additional funding from the European Union Seventh Framework Programme under grant agreement 312483 – ESTEEM2 (Integrated Infrastructure Initiative-I3).

About NanoMEGAS

Brussels-based instrumentation hardware and software manufacturer NanoMEGAS SPRL (NM) is a specialist and innovator in advanced electron diffraction technologies in Transmission Electron Microscopy (TEM), with exciting applications for the pharmaceutical industry.

NanoMEGAS produces and distributes hardware and software solutions for TEM applications that can be used for academic and industrial characterization of nanocrystalline and amorphous nanomaterials for pharmaceuticals and for polymorphic analysis. NM also provides scientific consulting for pharmaceutical companies wishing to characterize  nano-crystalline and amorphous pharmaceuticals.

NanoMEGAS was founded in 2004 by a team of scientists and experts in the field of electron crystallography and catalysis. Inspired by pioneering work carried out on electron crystallography using  precession electron diffraction at Bristol, UK at 1996 the NanoMEGAS team was first to develop and market its “spinning star” universal precession device for TEM in 2004. Today, there are more than 220 installations worldwide and more than 800 scientific publications related with NanoMEGAS applications & instrumentation in various fields , including pharmaceuticals.

Learn more at https://nanomegas.com

Resources

Click on Ab initio structure determination of nanocrystals of organic pharmaceutical compounds by electron diffraction at room temperature using a Timepix quantum area direct electron detector to read full study.