At the intersection of X-ray diffraction and nonlinear optics

Justin A Newman, Purdue University


The high brilliance of synchrotron facilities have led synchrotron X-ray diffraction to become an indispensable tool for crystallographers to determine both high resolution structures of proteins, as well as, to detect trace crystallinity of active pharmaceutical ingredients (APIs) within amorphous mixtures. However, as demand increases for time on synchrotron beamlines around the world, so to has arisen a need for high throughput, crystal specific methods for finding and locating the crystals within the synchrotron beam for structural analysis. Nonlinear optical (NLO) methods, such as second harmonic generation (SHG) and two-photon ultraviolet fluorescence (TPE-UVF) have emerged as rapid and reliable methods for finding protein crystals and APIs. Recently a multimodal NLO microscope was designed and installed at a synchrotron facility and is capable of detecting protein crystals and locating them in the center of the synchrotron beam for further structural analysis. This microscope was also used to monitor the damaging effects of synchrotron beam on the sample by SHG imaging. The limit of detection for powder X-ray diffraction (PXRD) of trace API crystallites within an amorphous powder was extended into the ppm range using the integrated NLO microscope for SHG guided PXRD.




Simpson, Purdue University.

Subject Area

Analytical chemistry

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