Nonlinear Microscopy for Materials Analysis and Clinical Pathology

Abstract

From understanding biological systems to characterizing materials, microscopy has facilitated the analysis of micro and nanoscale systems across scientific disciplines. The optical transparency of different biological features allows pathologists to relate what they see on a microscope slide to fundamental mechanisms of disease. The same notions of micro-nano sized features and optical transparency make microscopy an extremely effective technique for analyzing material properties. Nonlinear microscopy (two-photon absorption fluorescence) was used to image surgical specimens in a clinical pathology practice. The optical system design of the instrument is explained, and its performance in terms of diagnostic accuracy (sensitivity/specificity) and speed is presented. Exploratory, qualitative studies of imaging histopathologies beyond breast and prostate tissue are also provided. Towards the development of high efficiency frequency converters for visible-near infrared light, periodic poling of thin film lithium niobate (TFLN) was conducted. State-of-the-art poling for quasi phase matching was achieved via an iterative process. Devices were poled in a custom-built high voltage probing setup and imaged with a second harmonic generation (SHG) microscope to provide feedback on the poling parameters. A select number of samples were also imaged with piezo force microscopy. The effect of poling parameters on grating quality is analyzed, and the effect of the SHG microscope system design on image quality is quantified. Finally, a successful demonstration of SHG in a TFLN device is shown.