SBIR-STTR Award

This Small Business Innovation Research (SBIR) Phase I project aims to develop a laser source for label-free microscopy technique, in particular coherent Raman scattering (CRS) microscopy. In contrast to other techniques, CRS requires excitation with two synchronized laser pulse trains (picosecond pulse duration) with a difference frequency that can be tuned to the precision of a typical line width of Raman spectra (<1nm). The key innovation of the proposal is the realization that the difference frequency of the two major gain media used in the telecommunication industry, Erbium (Er) and Ytterbium (Yb), corresponds to the high-wavenumber region of Raman spectra, where most CRS imaging is performed. Based on recent advances in robust all-fiber design, the application proposes to develop a novel dual-color Er-Yb-laser-system based on optical synchronization of two picosecond power amplifiers using super-continuum generation. While this could provide an elegant, economical laser source for CRS, the physics associated with the required high peak powers in fibers is challenging. The broader impact/commercial potential of this project is in the area of biological and material science research, and ultimately medical diagnostics. CRS allows microscopic imaging with chemical contrast based on intrinsic spectroscopic properties of the sample. It circumvents the issues associated with fluorescent labeling or dye staining, which can be especially problematic for imaging of molecules that are smaller than typical labels or for use in vivo in patients. Wide ranging applications include studying lipid metabolism, trans-dermal drug delivery, biomass conversion to biofuel, and tumor margin delineation during cancer surgery has been demonstrated. While laser systems have come a long way and different approaches exist at various degrees of commercialization, they are expensive (~$300,000), require experienced optics personnel for operation, and are not robust. This greatly limits the access to this exciting new technology and prevents use in medical diagnostics. The light-source proposed in this SBIR application aims to overcome these limitations, as it is based on a all-fiber design from robust and low-cost telecommunication components

This Small Business Innovation Research (SBIR) Phase II project aims to develop a novel research microscope based on coherent Raman scattering (CRS). In contrast to other techniques, CRS is a label-free method that requires excitation with two synchronized laser pulse trains (ultra-short pulse duration) with precisely tunable wavelengths (<1nm). The key innovation of the Phase I proposal was the realization that the difference frequency of the two major gain media used in the telecommunication industry, Erbium and Ytterbium, corresponds to the wavelength range where most CRS imaging is performed. This provided a path to an economical laser source for CRS based on a robust all-fiber implementation of low-cost telecom components. Following successful proof-of-concept in Phase I, the Phase II proposal aims to complete the development of the laser system and integrate it into an easy-to-use and environmentally stable solution for CRS microscopy.

The broader impact/commercial potential of this project is in the area of biological and material science research, and ultimately medical diagnostics. CRS allows microscopic imaging with chemical contrast based on intrinsic spectroscopic properties of the sample. It circumvents the issues associated with fluorescent labeling or dye staining, which can be especially problematic for imaging molecules that are smaller than typical labels or for use in vivo in patients. Wide ranging applications including studying lipid metabolism, trans-dermal drug delivery, biomass conversion to biofuel, and tumor margin delineation during cancer surgery, have been demonstrated. Current laser systems for CRS are expensive, require experienced personnel for operation, and are not robust. This greatly limits access to this exciting new technology and prevents use in medical diagnostics. The proposed integrated CRS microscopy solution aims to overcome these limitations