Low dose scanning transmission electron microscopy of organic crystals by scanning moiré fringes. (May 2019)

• Record Type: Journal Article
• Authors: S'ari, Mark; Cattle, James; Hondow, Nicole; Brydson, Rik; Brown, Andy
• Is Part Of: Micron. Volume 120(2019)
• Page Start: 1
• Page End: 9
• Publication Date: 2019-05
• Subjects: Low dose -- Bright field STEM -- Organic crystals -- Scanning moiré fringes -- Dose-limited resolution; Microscopy -- Periodicals; Electron Probe Microanalysis -- Periodicals; Microscopy -- Periodicals; Microscopie -- Périodiques; Microscopy; Periodicals; 502.82
• DOI: 10.1016/j.micron.2019.01.014
• Languages: English
• ISSNs: 0968-4328

Abstract

Highlights: Scanning moiré fringes were used to image crystal lattices of organic compounds. All organic compounds analysed were highly electron beam sensitive materials. Increase in phase contrast provided improvements to the dose-limited resolution. Disruption to the scanning moiré fringe pattern can identify lattice defects. May be useful tool to analyse crystalline defects in drug formulations. Abstract: In the pharmaceutical industry, it is important to determine the effects of crystallisation and processes, such as milling, on the generation of crystalline defects in formulated products. Conventional transmission electron microscopy and scanning transmission electron microscopy (STEM) can be used to obtain information on length scales unobtainable by other techniques, however, organic crystals are extremely susceptible to electron beam damage. This work demonstrates a bright field (BF) STEM method that can increase the information content per unit specimen damage by the use of scanning moiré fringes (SMFs). SMF imaging essentially provides a magnification of the crystal lattice through the interference between closely aligned lattice fringes and a scanning lattice of similar spacing. The generation of SMFs is shown for three different organic crystals with varying electron beam sensitivity, theophylline, furosemide and felodipine. The electron fluence used to acquire the BF-STEM for the most sensitive material, felodipine was approximately 3.5 e − /Å 2 . After one additional scan of felodipine (total fluence of approximately 7.0 e − /Å 2 ), the SMFs were no longer visible due to extensive damage caused to the crystal. Irregularity in the SMFs suggested the presence of defects in all the organic crystals. Further effort is required to improve the data analysis and interpretation of the resulting SMF images, allowing more information regarding the crystal structure and defects to be extracted.