Fiber-Delivered Programmable Supercontinuum Laser Adaptive to EvolvingNeurophotonic Research

总结 神经光子学，包括光遗传学的突出例子，一直是大脑研究的驱动力 也是2013年成立的NIH BRAIN计划的一个重点领域。与遗传和生物光子 改变这一领域的进步，这些进步背后的激光源技术的进步， 技术进步滞后，导致三个技术障碍限制了下一个科学水平 脑和行为科学的成就：（1）神经科学家和生物光子科学家已经有限 由于现成的商业激光器可能不是其预期应用的最佳解决方案， 很大程度上是由于在诸如波长、功率和时间分布的参数中缺乏完全可调谐性;（2）用户- 可调谐客户或商业激光器的不友好操作阻碍了激光源的扩展 技术超越了非激光专家和专门的光学实验室，以及（3）缺乏适应安装 具有自由空间光束传输的激光器经常使它们过时，当新的神经科学需要和 应用程序出现。一种光纤可传输的可编程超连续谱激光器， 在学术实验室工作，有可能同时克服这三个技术障碍。 这种激光器的原型已经显示出适用于一般神经科学的希望，包括各种 种属（小动物、啮齿动物和人类）、状态（体外/离体、头部固定和自由行为）、设置 （光学实验室、动物设施、病理学部门和手术室），操作者（激光专家， 影像神经科学家、兽医、病理学家和神经外科医生）和目标（基础研究、治疗学 开发、药物发现、精确病理学、术中评估和激光辅助手术）。 因此，在小企业环境中寻求进一步的研发机会是可取的， 没有接受过激光源工程方面的广泛培训的神经科学界可以使用这种激光器。在这 项目，研发工作将首先致力于克服阻碍无缝连接的剩余技术障碍。 相干光纤超连续谱产生和可编程脉冲整形集成，双光子 技术本身是激光源工程的必需品，但对于激光源工程来说是不可缺少的 针对神经科学随后，该激光器将在两个原型系统中进行广泛的测试 具有和不具有神经干预的神经光子应用的代表。构建更加 该激光器的可靠原型及其在两个原型神经光子中的可行性的证明 系统将使这一研发工作（SBIR第一阶段）顺利过渡到第二阶段。整个项目 最终可能会促进广泛的神经科学广泛使用尖端的超快激光技术， 社区，与NIH BRAIN计划的一个目标一致，将创新技术转化为 从学术界到市场的大脑或行为研究。

SUMMARY Neurophotonics, including the prominent example of optogenetics, has been the driving force for brain research and one focal area of the NIH BRAIN Initiative established in 2013. In contrast to the genetic and biophotonic advancements that have transformed this field, the progress in laser source technology underlying these advancements has lagged behind, resulting in three technical barriers that limit the next level of scientific achievement in brain and behavioral sciences: (1) neuroscientists and biophotonic scientists have been limited by readily available commercial lasers that may not be the best solutions for their intended applications, due largely to the lack of full tunability in parameters such as wavelength, power, and temporal profile; (2) the user- unfriendly operation of tunable customer or commercial lasers has hindered the extension of laser source technology beyond non-laser experts and dedicated optical laboratories, and (3) the lack of adaption of installed lasers with free-space beam delivery often render them obsolete when new neuroscience needs and applications emerge. A fiber-deliverable programmable supercontinuum laser, based on systematic preliminary work in an academic laboratory, has potential to simultaneously overcome the three technical barriers. The prototype of this laser has shown promise to be applicable to general neuroscience, including diverse species (small animals, rodents, and humans), states (in vitro/ex vivo, head-fixed, and freely behaving), settings (optical laboratory, animal facility, pathology department, and operating room), operators (laser experts, imaging neuroscientists, veterinarians, pathologists, and neurosurgeons), and goals (basic study, therapeutics development, drug discovery, precision pathology, intraoperative assessment, and laser-assisted surgeries). It is thus desirable to seek further R&D opportunity in a small business environment, in order to allow wide access to this laser by the neuroscience community not trained extensively in laser source engineering. In this project, the R&D effort will first aim to overcome the remaining technical obstacles that hinder the seamless integration of coherent fiber supercontinuum generation and programmable pulse shaping, two photonic technologies dispensable for laser source engineering per se but indispensable for the laser source engineering that targets neuroscience. Subsequently, this laser will be tested in two prototypical systems broadly representative of neurophotonic applications with and without neural intervention. The construction of a more reliable prototype of this laser and the demonstration of its feasibility in the two prototypical neurophotonic systems will enable smooth transition of this R&D effort (SBIR Phase I) to Phase II stage. The whole project may ultimately facilitate wide access to cutting-edge ultrafast laser technology by the broad neuroscience community, in consistency with one goal of the NIH BRAIN Initiative to translate innovative technologies for brain or behavioral research from academia to the marketplace.