SBIR Phase I: Dual-Wavelength Picosecond Fiber Laser Source for Label-Free Microscopy

这个小型企业创新研究（SBIR）第一阶段项目旨在开发一种用于无标记显微镜技术的激光源，特别是相干拉曼散射（CRS）显微镜。与其他技术相比，CRS需要用两个同步的激光脉冲序列（皮秒脉冲持续时间）激发，其具有可以被调谐到拉曼光谱的典型线宽（1 nm）的精度的差频。该提案的关键创新在于实现了电信行业中使用的两种主要增益介质铒（Er）和镱（Yb）的差频对应于拉曼光谱的高波数区域，在该区域执行大多数CRS成像。基于鲁棒全光纤设计的最新进展，该申请提出开发一种基于使用超连续谱产生的两个皮秒功率放大器的光学同步的新型双色Er-Yb激光器系统。虽然这可以为CRS提供优雅、经济的激光源，但是与光纤中所需的高峰功率相关联的物理学是具有挑战性的。该项目更广泛的影响/商业潜力是在生物和材料科学研究领域，最终是医学诊断领域。CRS允许基于样品的固有光谱特性的具有化学对比度的显微成像。它避免了与荧光标记或染料染色相关的问题，这对于比典型标记小的分子的成像或用于患者体内尤其有问题。广泛的应用包括研究脂质代谢，经皮给药，生物质转化为生物燃料，以及癌症手术期间的肿瘤边缘勾画。虽然激光系统已经取得了长足的进步，并且在不同程度的商业化上存在不同的方法，但它们价格昂贵（~ 300，000美元），需要经验丰富的光学人员进行操作，而且不耐用。这极大地限制了这项令人兴奋的新技术的使用，并阻止了其在医疗诊断中的应用。该SBIR应用中提出的光源旨在克服这些限制，因为它基于坚固且低成本的电信组件的全光纤设计。

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.