Ultrasensitive Crystal Probe

A novel laser-based method can detect nucleation and onset of crystallization of chiral compounds up to 100 million times more sensitively than conventional detection methods, according to researchers at Purdue University who developed the technique (Anal. Chem., DOI: 10.1021/ac100564f). The procedure provides an exceptionally sensitive way to probe nucleation and growth kinetics at the earliest stages of crystal formation. In addition, the technique may be useful for studying pharmaceutical agents, which often need to be inhibited from crystallizing to avoid reducing their bioavailability (C&EN, May 31, page 13). Purdue’s Duangporn Wanapun, Garth J. Simpson, Lynne S. Taylor, and coworkers melted samples of griseofulvin and chlorpropamide (antifungal and diabetes drugs, respectively) and then cooled the melts while probing them for crystal formation with their newly developed nonlinear optical imaging method. The method’s detection limit, roughly 1 part in 10 billion by volume, enabled the group to observe crystals with dimensions as small as 150 nm, they report. That limit is lower by a factor of 10⁸ compared with common spectroscopy and diffraction methods and represents a five-order-of-magnitude improvement relative to optical microscopy.