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光源，特别是相干拉曼散射(CRS)显微镜。与其他技术不同，CRS需要用两个同步的激光脉冲串(皮秒脉冲持续时间)激发，其不同的频率可以调到典型的拉曼光谱线宽(1 Nm)的精度。该方案的关键创新在于认识到，电信行业中使用的两种主要增益介质--Erb(Er)和Yb(Yb)的差频对应于拉曼光谱的高波数区域，大多数CRS成像都是在该区域进行的。基于稳健性全光纤设计的最新进展，该申请提出了一种新型的双色Er-Yb激光系统，该系统基于两个皮秒功率放大器的光学同步，使用超连续谱产生。虽然这可以为CRS提供一种优雅、经济的激光光源，但与光纤中所需的高峰值功率相关的物理问题是具有挑战性的。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，最终是医疗诊断领域。CRS允许根据样品的固有光谱特性进行具有化学对比度的显微成像。它避开了与荧光标记或染料染色相关的问题，后者对于成像比典型标记更小的分子或用于患者体内可能特别有问题。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，以及癌症手术期间肿瘤边缘的描绘已被证明。虽然激光系统已经走过了很长的路，不同的方法存在于不同程度的商业化，但它们昂贵(约300,000美元)，需要经验丰富的光学人员来操作，而且不结实。这极大地限制了这一令人兴奋的新技术的使用，并阻止了在医疗诊断中的使用。此SBIR应用中提出的光源旨在克服这些限制，因为它基于坚固耐用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.