(13g) Assessing the Reliability of Crystal Size Distribution Measurements Obtained by in Situ Video Microscopy and Image Analysis

Advanced control of crystal shape, size distribution, and polymorphic form (internal lattice structure) in suspension crystallization processes has been hindered by the limitations of available on-line sensors. High-speed, in situ video microscopy is a promising technology for measuring these critical solid-phase properties. However, automatically extracting the desired measurements from in situ images in a robust and efficient manner remains challenging. Furthermore, the reliability of these measurements depends on various factors, including the PSD, the particle shape, the solids concentration, the camera focal depth, the field of view, and the hydrodynamics of the imaged volume. Hence, assessing the reliability of measurements obtained using in situ video microscopy is difficult. We have developed a novel image analysis algorithm that automatically extracts particle size information from in situ images of needle-like crystals[1]. Using images acquired during a pharmaceutical crystallization experiment, we have shown that the algorithm's PSD measurements are consistent with measurements obtained through manual, human analysis of the images. Further, we have characterized the reliability of the algorithm's PSD measurement using artificially-generated images. The characterization is given in terms of a single variable that lumps various process and imaging conditions. We have also characterized the reliability of the measurement in terms of the measured image complexity. Finally, we have demonstrated the effectiveness of two elegant but not widely-known methods for correcting the size-dependent sampling bias caused by the finite size of the imaging frame.

[1]Paul A. Larsen, James B. Rawlings, and Nicola J. Ferrier. An algorithm for analyzing noisy, in situ images of high-aspect-ratio crystals to monitor particle size distribution. Accepted for publication in Chemical Engineering Science , March 2006.