Multiphoton spectroscopic fiber probe with remote axial scanning

描述(申请人提供)：该研究计划的目标是开发一种灵活、紧凑和无源的光纤探头，能够轴向扫描组织层以进行癌症检测和诊断，然后展示所建议的来源在体内生物医学光谱和内窥镜检查中的价值。提出的光纤探头的创新基于最近在多光子成像中演示的空间和时间同时聚焦(SSTF)的新概念，其中，除了传统的空间聚焦之外，通过对超短脉冲进行时间聚焦来实现额外的轴向限制程度。结果表明，通过调整光纤探头近端输入脉冲的光谱相位，我们可以在远端的SSTF装置中远程扫描焦平面。因此，可以实现无源、超致密光纤探头，其在数百微米的扫描深度上提供多光子激发的荧光和/或谐波产生的高分辨率z截面。利用SSTF的最新理论和实验发展，并充分利用用于脉冲传输和信号采集的大模面积光纤的最新进展，拟议的研究计划旨在创造一种实用而坚固的光纤探头，专门用于癌症检测和诊断。这项研究计划涉及PI和Co-PI之间的密切合作(Zipfel博士)。研究小组的综合专业知识包括开展拟议研究所需的所有科学和技术。如果成功完成这项拟议的计划，将导致一种用于癌症早期检测和诊断的新型光纤探测器。通过柔性光纤探头的多光子激发的优势，结合远程轴向扫描能力，允许深度分辨信号激发和检测，并可显著改善非侵入性早期癌症检测的诊断特征。此外，所提出的用于多光子内窥镜光谱学的光纤探针在临床环境中具有很高的实用性，提供了快速商业化的可能性，并立即产生了现实世界的影响。

DESCRIPTION (provided by applicant): The goal of this research program is to develop a flexible, compact, and passive fiber optic probe that is capable of axially scanning the tissue layers for cancer detection and diagnostic, and then demonstrate the value of the proposed sources for in vivo biomedical spectroscopy and endoscopy. The innovation of the proposed fiber optic probe is based on the new concept of simultaneous spatial and temporal focusing (SSTF) that was recently demonstrated in multiphoton imaging, where, in addition to conventional spatial focusing, an extra degree of axial confinement is achieved by temporally focusing an ultrashort pulse. We show that by adjusting the spectral phase of the input pulse at the proximal end of the fiber probe, we can scan the focal plane in an SSTF setup at the distal end remotely. Thus, a passive, ultracompact fiber probe can be achieved that provides high resolution z-sectioning of multiphoton excited fluorescence and/or harmonic generation over a scan depth of hundreds of microns. Leveraging the latest theoretical and experimental development of SSTF, and taking full advantage of the recent advancement of large mode area fiber for pulse delivery and signal collection, the proposed research program aims to create a practical and robust fiber optic probe that is tailored specifically for cancer detection and diagnostics. This research program involves close collaboration between the PI and Co-PI (Dr. Zipfel). The combined expertise of the research team includes all of the science and technologies required for conducting the proposed research. The proposed program, if successfully completed, leads to a novel fiber optic probe for early cancer detection and diagnosis. The advantage of multiphoton excitation through the flexible fiber probe, combined with the remote axial scanning capability, allows depth resolved signal excitation and detection, and can provide significantly improved diagnostic signature for non- invasive early cancer detection. Furthermore, the proposed fiber probe for multiphoton endoscopic spectroscopy is highly practical in a clinical environment, providing the possibility of rapid commercialization and having an immediate real-world impact.