Flourescence-detected photothermal spectromicroscopy: Integration of interferometric spectroscopic methods

Although infrared spectroscopy provides extensive chemical information, its spatial resolution is constrained by the diffraction limit of infrared light, rendering it inadequate for quantifying and characterizing sub-micron systems of interest. Introduced in 2021, fluorescence-detected photothermal infrared spectroscopy (F-PTIR) addresses this limitation through the detection of modulation of a fluorescent probe during on-and-off periods of an infrared source to report on infrared absorption. Quantum cascade laser (QCL) sources, owing to their pulsed nature, are readily adaptable to photothermal methods; however, these sources currently face limitations in both acquisition speed and spectral range. The findings presented herein detail the integration and associated challenges of two distinct interferometric-based infrared sources into photothermal measurements to address these challenges individually: QCL-based dual-comb F-PTIR and synchrotron-based F-PTIR. While dual-comb mid-infrared spectroscopy enables faster acquisition using an accessible QCL-based interferometer, synchrotron-F-PTIR overcomes the limit on spectral range at the Advanced Light Source at Lawrence Berkeley National Lab. Furthermore, a computational approach, multi-agent consensus equilibrium, is introduced to overcome aid in potential limitations of either approach.