Optical photothermal IR (O-PTIR) microscopy for chemical imaging of living cells at sub-micron resolution

Optical photothermal IR (OPTIR) microscopy for chemical imaging of living cells at
sub-micron resolution
Project Summary/Abstract
Photothermal Spectroscopy Corp (PSC) and Prof. Ji-Xin Cheng of Boston University in collaboration with Prof. Rohith Reddy
(University of Houston) propose to develop, validate, and commercialize a novel technical called Optical Photothermal
Infrared (OPTIR) spectroscopy. This optical microscope-based instrument that will provide microscopic chemical analysis
and chemical imaging for the life sciences with sub-micron spatial resolution. The new OPTIR technique is based on
infrared (IR) spectroscopy, one on the most commonly used analytical techniques for chemical analysis. IR spectroscopy
has already been applied to diverse research problems in the biomedical sciences, but it has not been widely applied for
live cell research because of two key limitations. First, fundamental limits on spatial resolution (~3 – 30 µm) have
prevented broad application of IR microscopy to single-cell and sub-cellular investigations. Second, strong IR absorption
by water has dramatically hindered application of IR spectroscopy to live cells and other hydrated samples. Leveraging
successful Phase I research, this proposal aims to overcome the key barriers of conventional IR spectroscopy, while also
providing ~10X better spatial resolution.
This project will involve two major thrusts: (1) the development of a commercial OPTIR microscope that is designed
specifically for the life sciences research community; (2) demonstration and validation of the OPTIR technology on specific
problems in cancer research. Commercial instrument development will be performed at PSC facilities in Santa Barbara CA
in collaboration with the group of Prof. Ji-Xin Cheng at Boston University. The cancer related research will be performed
at both Boston University and the University of Houston. Instrument development activities will include the development
of a fully engineering OTPIR prototype for the life sciences community, focus on improvements in spatial resolution,
measurement speed, ease of use, and compatibility with measurements of live cells and other hydrated samples in
physiological environments. Cancer related research will focus on using the OPTIR technique to measure and map key
spectroscopic markers that are indicators of cancerous cells and cancer aggressiveness. Further studies will investigate
correlations between IR spectroscopic markers and tumor fighting efficacy.
The project team is uniquely qualified to perform this work. PI Prof. Cheng is an award-winning research pioneer in
development and application of novel spectroscopic and imaging techniques for the life sciences while the technical and
commercial team at PSC has decades of successful experience developing and commercializing high resolution imaging
and analytical instrumentation. Project collaborator Prof. Reddy is an award winning researcher with extensive expertise
in the application of infrared spectroscopy to issues in cancer research. Successful completion of this project will lead to
a next-generation single-cell analysis tool that will profoundly impact cellular and sub-cellular biology by providing
functional information about changes in cellular state, including membrane order, protein folding, and DNA damage.
These changes can be measured in live cells and over time to provide new insights into processes in health and disease.Optical photothermal IR (OPTIR) microscopy for chemical imaging of living cells at
sub-micron resolution
Project narrative
This STTR project will develop a new optical microscope-based platform that performs label-free chemical analysis with
sub-cellular spatial resolution using a novel form of high resolution infrared spectroscopy. This instrument will enable
chemical analysis on life sciences samples including tissue and live cells with sub-micron spatial resolution via optical
photothermal infrared (OPTIR) spectroscopy. This next-generation single-cell analysis tool and its ability to measure and
map cancer related biomolecules on a sub-cellular level will profoundly impact cancer research, impacting fundamental
understandings of cancer progression and treatment.