Monday, 24 April 2006 - 8:00 AM
12a

Crystal Size and Shape Monitoring Using High-Speed, in-Situ Video Imaging and Model-Based Recognition

Paul A. Larsen1, Nicola J. Ferrier2, and James B. Rawlings1. (1) Department of Chemical and Biological Engineering, University of Wisconsin-Madison, 1415 Engineering Drive, Madison, WI 53706, (2) Department of Mechanical Engineering, University of Wisconsin-Madison, 1415 Engineering Drive, Madison, WI 53706

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 information from in-situ images in a robust and efficient manner remains challenging, especially for highly non-spherical shapes. Needle-like crystals are particularly challenging, typically exhibiting a high degree of overlap. We have developed a novel image analysis algorithm that automatically extracts particle size information for needle-like crystals in in-situ images.1 We have validated its performance experimentally by comparing its results with the results obtained by manually sizing crystals imaged over the duration of a pharmaceutical crystallization experiment. The algorithm's results agree well with the results obtained by manual sizing, and the speed with which it analyzes the images appears suitable for real-time PSD monitoring and control. We have also developed a method for identifying crystals of arbitrary shape provided that the shape can be represented by a parameterized three-dimensional model. We have demonstrated the method's ability to extract particle size and shape information using noisy, in-situ images of a pharmaceutical system in which the different polymorphic forms exhibit different crystal shapes. 1 P.A. Larsen, J.B. Rawlings, and N.J. Ferrier, "An algorithm for analyzing noisy, in situ images of high-aspect-ratio crystals to monitor particle size distribution", submitted to Chemical Engineering Science.

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