Deconstructing 3D growth rates from transmission microscopy images of facetted crystals as captured in situ within supersaturated aqueous solutions

J Appl Crystallogr. 2024 Sep 25;57(Pt 5):1557-1565. doi: 10.1107/S1600576724008173. eCollection 2024 Oct 1.

Abstract

Here, a morphologically based approach is used for the in situ characterization of 3D growth rates of facetted crystals from the solution phase. Crystal images of single crystals of the β-form of l-glutamic acid are captured in situ during their growth at a relative supersaturation of 1.05 using transmission optical microscopy. The crystal growth rates estimated for both the {101} capping and {021} prismatic faces through image processing are consistent with those determined using reflection light mode [Jiang, Ma, Hazlehurst, Ilett, Jackson, Hogg & Roberts (2024 ▸). Cryst. Growth Des. 24, 3277-3288]. The growth rate in the {010} face is, for the first time, estimated from the shadow widths of the {021} prismatic faces and found to be typically about half that of the {021} prismatic faces. Analysis of the 3D shape during growth reveals that the initial needle-like crystal morphology develops during the growth process to become more tabular, associated with the Zingg factor evolving from 2.9 to 1.7 (>1). The change in relative solution supersaturation during the growth process is estimated from calculations of the crystal volume, offering an alternative approach to determine this dynamically from visual observations.

Keywords: 3D crystal growth evolution; crystal morphological images; facet-based crystal-growth-rate measurements; in situ characterization; l-glutamic acid; polyhedral image analysis; supersaturation; transmission microscopy.

Grants and funding

The authors are grateful for the financial support of EPSRC UK through the Shape4PPD project (EP/W003678/1) in collaboration with AstraZeneca, Cambridge Crystallographic Data Centre, Infineum, Keyence, Pfizer, Roche, Syngenta, Imperial College, the University of Hertfordshire and the University of Strathclyde. One of the authors (CJ) thanks EPSRC UK for the Doctoral Training Partnership award (EP/W524372/1), which is co-sponsored by Syngenta in collaboration with Neil George, Jennifer Webb and Raphael Stone. Thanks are also due to the EPSRC Centre for Doctoral Training in Complex Particulate Products and Processes (EP/L015285/1) who support CJ as an aligned student. Finally, we would like to recognize the funding support in digital design workflow modelling of crystallization processes from the UK’s Advanced Manufacturing Supply Chain Initiative through the ‘Advanced Digital Design of Pharmaceutical Therapeutics’ (ADDoPT) project (grant No. 14060) in collaboration with AstraZeneca, Bristol–Myers Squibb, Britest, Cambridge Crystallographic Data Centre, GlaxoSmithKline, Perceptive Engineering, Pfizer, Process Systems Enterprise, Science and Technology Facilities Council’s Hartree Centre, and the Universities of Cambridge and Strathclyde.