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.
