Dr. Garth Simpson

New and remarkable interactions between light and matter arise in sufficiently intense optical fields, including the generation of new frequencies of light and the simultaneous absorption of multiple photons. At the core, our research group is devoted to the theoretical development and experimental application of new instrumental methods taking advantage of unique nonlinear optical interactions. Recent interests include detection and analysis of crystals formed from chiral molecules, building on a long-standing interest in understanding the role of chirality and polarization-dependent effects in nonlinear optics.

Sensitive and selective detection of protein crystals
Second harmonic generation microscopy is being explored for sensitive detection and characterization or protein crystals. High-resolution structures of proteins reveal insights into function and enable rational drug design. Crystal formation is a critical step in protein structure determination by X-ray or electron diffraction (see figure). The range of possible crystallization conditions to be explored is vast, while both time and protein are precious. Efforts are underway to dramatically reduce both the time and protein burden required for identification of conditions resulting in well-formed crystals amenable to diffraction analysis.

These efforts take advantage of the unique symmetry properties of second harmonic generation (SHG) to enable early detection of protein microcrystals. Coherent SHG disappears completely in isotropic media, but is allowed by symmetry in ALL single-component crystals generated from chiral molecules, including crystals of proteins. As such, SHG microscopy provides exceptional selectivity for protein crystal formation. The Simpson group is working with numerous academic and commercial collaborators to further improve instrumentation for crystal detection and to apply the emerging methods to address key bottlenecks in protein crystal structure determination.

Crystallization of Active Pharmaceutical Ingredients.
We are exploring applications of SHG microscopy for early detection of crystal formation to aid in optimizing pharmaceutical formulations. The shelf-life and bioavailability of a drug can be greatly impacted by the nature of the formulation. Often, formulations designed to prevent crystallization can improve bioavailability by speeding dissolution. In such cases, shelf-life can be substantially reduced by nucleogenesis. Preliminary experiments suggest detection limits of 1 part in 300 billion by volume for crystal formation, corresponding to a percent crystallinity of ~3?10-8. By comparison, the most common comparable analysis methods typically generate detection limits of a few % crystallinity.

Nonlinear optical Stokes ellipsometry
The Simpson research group has long standing fundamental and practical interests in the polarization-dependence of nonlinear optical interactions. Recently, we have demonstrated an approach for high-sensitivity polarization analysis in second harmonic generation measurements and incorporated this method into a nonlinear optical microscope for thin film and materials characterization. This method is particularly well-suited for microparticle and surface characterization.

Education

• B.S., Western Washington University, 1995
• Ph.D., University of Colorado, Boulder, 2000
• Postdoctoral Fellow, Stanford University, Life Sciences Research Foundation, 2001

Awards

• College of Science Research Award, 2014
• College of Science Interdisciplinary Award, 2010
• Faculty Scholar, 2010
• ACS Division of Analytical Chemistry Arthur F. Findeis Award for Achievements by a Young Analytical Scientist, 2007
• Research Fellow, 2005
• Beckman Young Investigator Award, 2004
• Cottrell Scholar, 2004
• Eli Lilly Analyitical Chemistry Young Faculty Award, 2003
• ACS Victor K. LaMer Award, 2001
• Camille and Henry Dreyfus New Faculty Award, 2001
• Research Corporation Research Innovation Award, 2001

Publications

List of publications