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    NanoMEGAS SPRL

    Brussels-based instrumentation hardware and software manufacturer NanoMEGAS (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 nano-crystalline and amorphous materials. NM also provides scientific consulting for pharmaceutical companies wishing to apply nano-crystalline and amorphous pharmaceutical characterization.

    Activities/Products

    NanoMEGAS is the originator of several patented technologies for phase /orientation mapping, strain mapping and 3D shape characterization of nanoparticles (in liquids).

    Its main technology platforms include:

    • DigiSTAR: a novel digital precession unit that can be adapted to most commercial TEM (100-400 kV) units, adding 3D Electron Diffraction tomography to solve nanocrystalline structures that are difficult to determine using conventional X-Ray diffraction techniques
    • ASTAR: ASTAR with Precession Electron Diffraction (PED) can turn any TEM into a very powerful analytical tool enabling orientation–phase imaging, producing precise phase and orientation maps down to 1 nm resolution for FEG TEM
    • TOPSPIN: Topspin provides a digital STEM, Beam Precession and Analytical Experiment Framework including a suite of beam precession-enabled advanced analytical 4D STEM experiments. The TOPSPIN platform allows automated strain mapping by comparing PED diffraction patterns from unstrained and strained areas in the same crystalline materials

    Pharmaceutical Applications

    Electron Crystallography is considered as the method of choice for structure determination of nanocrystalline compounds (crystals as small as 20 nm to several microns). Such nano-crystallites reveal typically “X‐Ray amorphous” powder diffraction patterns for sizes down to 10nm where is very difficult to identify and characterize their structures using X-Ray diffraction techniques.

    Used in combination or separately, NanoMEGAS technologies support a range of advanced electron crystallography analytical applications for pharmaceutical companies and life sciences organizations that include:

    • Crystal structure determination of an Active Pharmaceutical Ingredient (API) and its polymorph in TEM using 3D electron diffraction (ED) or MicroED techniques
    • TEM study for traces (< 0.01%) and early crystallization detection in Amorphous Solid Dispersion (ASD)
    • Sample composition and phase separation study in ASD (TEM-EDS & EELS)
    • Liquid Cell Transmission Electron Microscopy (LC-TEM) for in situ (dynamic studies) analysis and study of material in native liquid environments
    • Particle size distribution analysis using LC-TEM and Cryo-TEM
    • 3D shape characterization (3D Image Tomography reconstruction and facet determination) of pharmaceutical nanoparticles in dry and in liquid medium
    • ASD stability prediction using Quantum molecular dynamics (QMD) for polymorphic phase and impurity analysis using phase and orientation mapping

    3D electron diffraction is a particularly potent tool for analyzing crystal structures of active pharmaceutical ingredients (APIs) and investigating the polymorphism that is key to the pharmaceutical industry where the physical properties of materials depend on their precise crystal structures.

    Trace analysis with TEM Virtual Bright and Dark Field imaging and electron diffraction is a technique that enables detection of very small traces of crystalline material. This technique allows trace crystals at sizes as small as 10nm to be observed even where very low quantities (< 0.01%) are present.  Structure characterization (like phase confirmation) of such small crystals can be done using 3D Electron Diffraction or MicroED on individual crystallites.

    Company History and Structure

    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 in the 1950s in the USSR and USA, and also by later developments in the 1990s in the USA, and on precession electron diffraction at Bristol, UK, the NanoMEGAS team was first to develop and market its “spinning star” universal precession device for TEM in 2004.

    Since then, NanoMEGAS has grown to the point where it now has more than 200 precession diffraction related instruments and has contributed more than 1000 scientific publications related to its instrumentation and solutions (see Resources).

    In the USA, the company has received the Microscopy Today 2011 Innovation Award for the development of its ASTAR phase mapping system and the 2014 Innovation Award for development of the Topspin strain mapping system for nm scale strain characterization in materials.

    NanoMEGAS has its headquarters in Brussels, Belgium, where its research facilities include a fully equipped TEM microscope. The company has scientific collaboration agreements with several academic and research institutions worldwide, including CNRS/INP Grenoble in France, University of Mainz in Germany, University of Barcelona in Spain, and IIT Pisa in Italy. It is also an active partner of the Electron Crystallography Commission of International Union of Crystallography (IUCr).

    The company has participated in several EU funded projects, including MUMMERING, NanED, EUROSTARS and the Enabling Science and Technology through European Electron Microscopy (ESTEEM2 and ESTEEM3) programs.

    The company’s founders are Dr. Stavros Nicolopoulos (CEO) and Daniel Bultreys, with leadership also provided by other research scientists including Dr. Partha Pratim Das, Dr. Alejandro Gómez Pérez, Dr. Thanos Galanis, and Evangelos Grivas.

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