Rapid Discrimination of Polymorphic Crystal Forms by Nonlinear Optical Stokes Ellipsometric Microscopy

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• 作者：Paul D. Schmitt ; Emma L. DeWalt ; Ximeng Y. Dow ; Garth J. Simpson
• 刊名：Analytical Chemistry
• 出版年：2016
• 出版时间：June 7, 2016
• 年：2016
• 卷：88
• 期：11
• 页码：5760-5768
• 全文大小：447K
• 年卷期：0
• ISSN：1520-6882

文摘

The use of nonlinear optical Stokes ellipsometric (NOSE) microscopy for rapid discrimination of two polymorphic forms of the small molecule d-mannitol is presented. Fast (8 MHz) polarization modulated beam-scanning microscopy and a recently developed iterative, nonlinear least-squares fitting algorithm were combined to allow discrimination of orthorhombic and monoclinic crystal structures of d-mannitol with data acquisition times of <7 s per field of view with a signal-to-noise ratio (SNR) of ∼300. Discrimination between polymorphic forms within the 99.99% confidence interval was achieved by standard statistical tests of the recovered probability density functions for the measured observables following two class linear discriminant analysis. These measurements target bottlenecks in small-volume, high-throughput solid form screening experiments for polymorph discovery in the development of emerging active pharmaceutical ingredients.