With 3D Electron Diffraction Tomography
For industrial applications, it is of great interest to understand and determine the crystal structure, identify / characterise several possible polymorphs and to detect / quantify the crystallinity / amorphous phase of final products, since many important chemical and physical properties depend on the crystal structure properties.
Carbamazepine (CBZ), is a drug used primarily in the treatment of epilepsy and neuropathic pain. It may be used in schizophrenia along with other medications and as a second line agent in bipolar disorder. CBZ exists in several polymorphic forms.
Electron Diffraction Tomography analysis with TEM using ultrasensitive Timepix detector with no cooling holder allowed to collect diffraction tomography data from individual nanocrystals (size about 200 nm) and reconstruct the reciprocal space.
Unit cell determination and structure solution from the measured intensity helped to identify same crystal structure as reported by X-ray diffraction.
Electron Diffraction Tomography analysis with TEM using ultrasensitive Timepix detector with no cooling holder allowed to collect diffraction tomography data from individual nanocrystals (size about 200 nm) and reconstruct the reciprocal space.
Unit cell determination and structure solution from the measured intensity helped to identify same crystal structure as reported by X-ray diffraction.
Electron Diffraction Tomography technique by TEM microscope is particularly useful in case of polyphasic systems (several polymorphs), nm size crystals, and poorly crystalised samples
Trace analysis with TEM high resolution imaging and electron diffraction
High Resolution Virtual Dark Field (VDF) in TEM is a technique that enables detection of very small trace of crystalline material; in the example shown above, trace crystals of very small sizes (eg 10nm) can be observed at very low quantity (< 0.01%).
Structure characterisation (like phase confirmation) of such small crystals can be done using Electron Diffraction on individual crystallites.
Drug polymorph structure analysis with TEM 3D electron diffraction tomography
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 < 10nm) where is very difficult to identify and characterise their structures using X-Ray diffraction techniques.
Use of precession 3D electron diffraction (PED) with TEM makes possible unit cell and structure determination on individual nanocrystals. Using 3D diffraction tomography, a 3D reconstruction of the reciprocal space can be performed by tilting the sample and recording ED patterns (Fig. 1) (typically ±45° every 1°).
Collected electron diffraction (ED) patterns can be processed to precisely determine the unit cell and reveal the space group symmetry of the API crystal. Full atomic crystal structure can also be performed after collection and precise measurement of ED intensities.
Contact our Technical Director, Dr. Shayz Ikram, to discuss Electron Precession Diffraction and YOUR application. Email Shayz below or call (01372) 378822.
