Breakthrough sub-cellular 3D chemical composition research platform for live cells, based on the new invention of nanoscale - confocal photothermal IR micro-spectroscopy (n-CPIR) - Abstract
This proposal will lead to a Breakthrough sub-cellular 3D chemical composition research platform for live
cells, based on the new invention of sub-micron confocal photothermal IR micro-spectroscopy (CPIR).
Label-free sub-micron chemical imaging and spectroscopy has long been sought for visualization of
biomolecules and materials in complex living systems. Many diseases first manifest themselves at the
cellular, or subcellular level. IR micro-spectroscopy is a powerful technique but its use in life sciences in
general and cellular analysis in particular has been limited due to the following 2 key limitations:
a) Spatial resolution limited by diffraction to ~ 10 µm.
b) Inability for in-vivo imaging due to strong IR absorption by water.
This proposal eliminates both of the above limitations and is based on a recently published patent-
pending breakthroughby the PI, Prof. Ji-Xin Cheng of Boston University and is licensed exclusively by
Anasys Instruments for commercialization. Prof. Cheng is one of the world's leading vibrational
spectroscopy researchers and is the co-inventor of the CARS (Coherent Anti-Stokes Raman Scattering)
microscope, which is a major innovation in the field of Raman Spectroscopy. Anasys pioneered the field
of AFM (Atomic force microscope) based photothermal nanoscale IR Spectroscopy where an AFM
probe detects the photothermal signal induced by IR absorption.
The goal of this proposal is to create a high speed confocal optical microscopy platform capable of 300
nm IR Spectroscopy in fluid. This platform can be used in sub-cellular chemical composition research of
live cells which has many applications in the life sciences.
The proposed CPIR platform is highly innovative because it would enable real-time imaging of lipid
metabolites in single live tumor cells based on fingerprint IR bands. Compared to the widely studied
genetic aspect of cancer and the well-known Warburg effect, appreciation of the role of lipids in cancer
development is still emerging. Aberrant expressions of lipogenic genes have been found in brain,
mammary, prostate and many other cancer. Even with these discoveries, lipid metabolism has not been
used as a prognostic factor for cancer aggressiveness due to lack of differential detection and
quantitation technology. Our proposal aims to fill this gap by quantifying the amount and composition of
lipid droplets, an important aspect of lipogenesis in tumor cells. Though we focus on lipid metabolites
here, our spectroscopic imaging platform is generally applicable to monitor the intracellular dynamics of
other metabolites, anti-cancer drugs, and nutrition molecules such as fatty acids and amino acids, thus
having a far-reaching impact on cancer research.
