Simpson, Garth J. - Purdue University - Department of Chemistry

个人简介

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

研究领域

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.

近期论文

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Scott, J. Toth; Paul D. Schmitt; Greg R. Snyder; Niraj S. Trasi; Shane Z. Sullivan; Irene A. George; Lynne S. Taylor; Garth J. Simpson. Ab Initio Prediction of the Diversity of Second Harmonic Generation from Pharmaceutically Relevant Materials. Crystal Growth & Design, 2015, 15(2), 581-586. Dettmar, C. M.; Newman, J. A.; Toth, S. J.; Becker, M.; Fischetti, R. F.; Simpson, G. J. Imaging local electric fields produced upon synchrotron X-ray exposure. Proceedings of the National Academy of Sciences of the United States of America, 2015, in press. Ryan Muir; Nicholas Pogranichney; John Muir; Shane Sullivan; Kevin Battaile; Anne Mulichak; Scott Toth; Lisa Keefe; Garth Simpson. Linear Fitting of Multi-Threshold Counting Data with a Pixel-Array Detector for Spectral X-Ray Imaging. Journal of Synchrotron Radiation, 2014, 21(5), 1180-1187. Shane Z. Sullivan; Ryan D. Muir; Justin A. Newman; Mark S. Carlsen; Suhas Sreehari; Chris Doerge; Nathan J. Begue; R. Michael Everly; Charles A. Bouman; Garth J. Simpson. High Frame-Rate Multichannel Beam-Scanning Microscopy Based on Lissajous Trajectories. Optics Express, 2014, 22(20), 24224-24234. Sullivan, Shane; Schmitt, Paul; Muir, Ryan; DeWalt, Emma; Simpson, Garth. Digital Deconvolution Filter Derived from Linear Discriminant Analysis and Application for Multi-Photon Fluorescence Microscopy. Anal. Chem., 2014, 86(7), 3508-3516. Emma L. DeWalt; Shane Z. Sullivan; Paul D. Schmitt; Ryan M. Muir; Garth J. Simpson. Polarization-Modulated Second Harmonic Generation Ellip-sometric Microscopy at Video Rate. Anal. Chem., 2014, 86(16), 8448-8456. Ryan Muir; Shane Sullivan; Rob Oglesbee; Garth Simpson. Synchronous Digitization for High Dynamic Range Lock-in Amplification in Beam-Scanning Microscopy. Rev. Sci. Instrum., 2014, 85, 033703. Chowdhury, A. U.; Dettmar, C. M.; Sullivan, S. Z.; Zhang, S.; Jacobs, K. T.; Kissick, D. J.; Wanapun, D.; Maltais, T.; Simpson, G. J., Kinetic trapping of metastable amino acid polymorphs. Journal of the American Chemical Society, 2014, 136(6), 2404-2412. Gregory R. Snyder; Azhad U. Chowhury; Garth J. Simpson, Exciton Coupling Model for the Emergence of Second Harmonic Generation from Assemblies of Centrosymmetric Molecules. J. Phys. Chem. A, 2014, 118(24), 4301-4308. Madden, J. T.; Toth, S. J.; Dettmar, C. M.; Newman, J. A.; Oglesbee, R. A.; Hedderich, H. G.; Everly, R. M.; Becker, M., Ronau, J. A.; Buchanan, S. K.; Cherezov, V.; Morrow, M. E.; Xu, S.; Ferguson, D.; Makarov, O.; Das, C.; Fischetti, R. F.; Simpson, G. J. Integrated nonlinear optical imaging microscope for on-axis crystal detection and centering at a synchrotron beamline. Journal of Synchrotron Radiation, 2013, 30, 531-540. Closser, R. G.; Gualtieri, E. J.; Newman, J. A.; Simpson, G. J. Characterization of salt interferences in second-harmonic generation detection of protein crystals. Journal of Applied Crystallography, 2013, 46, 1903-1906. DeWalt, Emma L.; Begue, Victoria J.; Ronau, Judith A.; Sullivan, Shane Z.; Das, Chittaranjan; Simpson, Garth J., Polarization-resolved second-harmonic generation microscopy as a method to visualize protein-crystal domains. Acta Crystallographica, Section D: Biological Crystallography, 2013, D69(1), 74-81. Pavone, F. S. & Campagnola, P. J. Second Harmonic Generation Imaging. Vol. 3 (Taylor & Francis, 2013). Hu, C. R.; Simpson, G. J. et al. Stimulated Raman scattering imaging by continuous-wave laser excitation. Opt. Lett., 2013, 38, 1479-1481. Hsu, H. Y.; Toth, S.; Simpson, G. J.; Taylor, L. S.; Harris, M. T., Drop printing of pharmaceuticals: effect of molecular weight on the crystallization and dissolution of PEG coated-NAP/PEG solid dispersions. J. Pharm. Sci. (Submitted August 2013). Madden, J. T.; Simpson, G. J. et al., Development of a High-Throughput Laser-Induced Acoustic Desorption Probe and Raster Sampling For Laser-Induced Acoustic Desorption/Atmospheric Pressure Chemical Ionization. Anal. Chem., 2013, 85 (12), 5720-5726. Ghorab, M. K.; Toth, S. J.; Simpson, G. J. et al. Water–solid interactions in amorphous maltodextrin-crystalline sucrose binary mixtures. Pharm. Dev. Technol., 2013, 0(0), 1-10. Madden, J. T.; Toth, S. J.; Dettmar, C. M.; Newman, J. A.; Simpson G. J. et al. Integrated nonlinear optical imaging microscope for on-axis crystal detection and centering at a synchrotron beamline. J. Synchrotron Radiat., 2013, 20, 531-540. Hsu, H. Y.; Toth, S.; Simpson, G. J.; Taylor, L. S.; Harris, M. T., Effect of substrates on naproxen-polyvinylpyrrolidone solid dispersions formed via the drop printing technique. J. Pharm. Sci., 2013, 102(2), 638-48. DeWalt, E. L.; Begue, V. J.; Ronau, J. A.; Sullivan, S. Z.; Das, C.; Simpson, G. J., Polarization-resolved second-harmonic generation microscopy as a method to visualize protein-crystal domains. Acta. Crystallogr. D Biol. Crystallogr. 2013, 69(1), 74-81.