Video Rate Photothermal Infrared Spectroscopy (VR-PTIR)

Project Summary Abstract This Phase II project aims to develop and commercialize Video Rater Photothermal Infrared (VR-PTIR) imaging and spectroscopy. The proposed VR-PTIR will provide 10-30X better spatial resolution than conventional IR spectroscopy and will operate up to 1000X faster than previous photothermal infrared microscope systems. Infrared (IR) spectroscopy can provide rich analysis of molecular bonds and has been used in life sciences research to study tissue classification, drug/tissue interaction, neurodegenerative diseases, cancer, and other areas. Conventional IR spectroscopy, however, has a fundamental spatial resolution limit (i.e., roughly how small an object it can analyze) of around 10 micrometers, similar to the size of an average biological cell. Thus, conventional IR spectroscopy has been extremely limited for many biomedical applications where the structures of interest are smaller than a cell. Optical photothermal infrared (O-PTIR) is a rapidly emerging field that uses a tightly focused visible probe beam to detect infrared absorption in samples with <500 nm spatial resolution, far below the conventional optical diffraction limit for mid-infrared wavelengths. Current commercial O-PTIR instruments, however, have relatively slow measurement speeds requiring up to several minutes for a single image, and 10+ hours for a hyperspectral measurement at high spatial and spectral resolution. This project aims to develop and commercialize a breakthrough spectroscopic instrument that will enable super-resolution photothermal infrared spectroscopy at video rates enabling label-free chemical imaging of cells and tissue and high- resolution hyperspectral analysis in minutes. This project will leverage two recent breakthroughs from project partner Prof. Ji-Xin Cheng’s group at Boston University, specifically the development of synchronized laser scanning and single pulse photothermal demodulation. Preliminary research has already demonstrated following key advances: (1) imaging of live cells at up to 10 frames per second including tracking of lipid dynamics in cells; (2) compositional/structural analysis of tissue relevant to neurodegenerative disease, (3) hyperspectral arrays in minutes; (4) metabolic imaging with IR tags; (5) complementary confocal laser fluorescence. This project is well aligned with NIH goals as it incorporates several key thrusts of the National Institute of Biomedical Imaging and Bioengineering, including optical imaging and spectroscopy, IR imaging, confocal microscopy, and multimodal imaging. VR-PTIR is anticipated to enable breakthroughs in two main application areas: (1) high throughput spectral analysis; and (2) cellular dynamic analysis. Completion of this project will lead to the commercialization of a new multimodal microscope that will offer profound benefits for biomedical research including cancer, neurodegenerative diseases, metabolic studies, and many other areas.