Date of Award

5-2018

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

Committee Chair

Garth J. Simpson

Committee Member 1

Chengde Mao

Committee Member 2

Adam Wasserman

Committee Member 3

Chittaranjan Das

Abstract

The work in this dissertation is focused on extending the information content for second harmonic generation (SHG) and two-photon excited fluorescence (TPEF) imaging. Despite the simplicity and symmetry selectivity of nonlinear optical processes, limited information on chemical composition can be recovered solely based on intensity measurements. To further explore the potential for second order nonlinear optical (NLO) measurements, additional dimensions were added to the NLO imaging platforms. By combining NLO microscopy with powder X-ray diffraction, a novel approach was established for accessing percent crystallinity in amorphous solid dispersions (ASDs) with a limit of detection in the ppm range. ASDs are preferable alternative for crystalline forms when formulating poorly soluble active pharmaceutical ingredients (APIs). However, the high detection limit for current available methods limited the study of long term stability for ASDs at early stage. Besides adding additional modalities to NLO microscopy, polarization dependent SHG provides rich information on local structures for collagen fibers in tissues. However, significant loss in polarization purities occurs when light penetrate through the tissue. A new theoretical framework was introduced to extract information with partially or fully depolarized light. In addition, a video-rate hyperspectral TPEF imaging system was demonstrated with over 2,200 fluorescence channels throughput spatial-spectral multiplexing.

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