Linear and nonlinear photothermal spectroscopy and hyperspectral imaging with a fiber laser probe
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Recent years have seen a push to provide a fast, sensitive, and quantitative diagnostic tool for biomedical applications. A search for new methods that can perform label-free and bond-specific determination of tissue and disease types with high spatial resolution is much desired. To address these needs, we have developed a mid-infrared photothermal system for sensitive and non-destructive characterization of samples. Our system utilizes a mid-infrared pump with a near-infrared probe for label-free spectroscopy and high spatial resolution imaging. In particular, this research focuses on optimization of the photothermal system, exploration of novel nonlinear photothermal phenomena, and development of a sub-diffraction limited mid-infrared imaging system. Photothermal spectroscopy is a pump-probe technique that utilizes a thermal lens effect in the sample for contrast. With the use of a high brightness mid-infrared pump laser, we extend photothermal spectroscopy into the mid-infrared regime for sensitive detection with high signal contrast. Targeting vibrational modes intrinsic to the sample allows for label-free characterization. Use of a fiber laser probe provides improved spatial resolution and takes advantage of the well-developed detector technology at near-infrared wavelengths. The research presented will be divided into three parts: optimization of the photothermal system, investigation of novel nonlinear photothermal phenomena, and photothermal spectroscopy and imaging for biomedical applications. Optimization of fiber laser design and experimental setup results in >100x increase in signal strength and over an order of magnitude improvement in signal contrast. With an optimized system, linear and nonlinear mid-infrared photothermal spectroscopy of a liquid crystal sample is demonstrated. For the first time, multiple bifurcations are reported in the nonlinear regime, shedding insight on the photothermal laser-matter interaction across phase transitions of a liquid crystal sample. Using a raster-scanning approach, sub-diffraction limited mid-infrared imaging is demonstrated. With this technique, various tissue types within the brain can be distinguished from one another, including differentiation between healthy and tumor tissue. Hyperspectral imaging of biological tissues demonstrates the potential of this technique to combine both spectral and spatial information for sample characterization. We present a photothermal system with the potential to meet the demands in drug and food safety, environmental monitoring, biomedicine, and security.