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

这个小企业创新研究（SBIR）第二阶段项目旨在开发一种基于相干拉曼散射（CRS）的新型研究显微镜。与其他技术相比，CRS是一种无需标记的方法，需要用两个具有精确可调波长（1 nm）的同步激光脉冲串（超短脉冲持续时间）激发。第一阶段提案的关键创新是实现了电信行业中使用的两种主要增益介质铒和镱的差频对应于执行大多数CRS成像的波长范围。这为CRS提供了一条经济的激光源之路，其基础是低成本电信组件的稳健的全光纤实现。在第一阶段成功的概念验证之后，第二阶段的提案旨在完成激光系统的开发，并将其集成到一个易于使用和环境稳定的CRS显微镜解决方案中。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，这对于比典型标记更小的成像分子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，透皮给药，生物质转化为生物燃料，肿瘤手术中的肿瘤边缘划定，已被证明。当前用于CRS的激光系统是昂贵的，需要有经验的人员进行操作，并且不坚固。这极大地限制了对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。所提出的集成CRS显微镜解决方案旨在克服这些限制。

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.