多光子成像是皮肤科学研究，例如皮肤病诊断、药品渗透性测试等应用的重要研究手段。目前，临床商用多光子成像系统的标称深度仅为200µm，采用800nm波段飞秒脉冲激发。突破这一深度瓶颈、实现更深层成像对皮肤科学研究意义重大。我们最近研究表明：1700nm波段具有更深层成像能力，对脑组织的无损成像深度是800nm波段的两倍。在此基础上，本项目拟开展1700nm波段深层皮肤多光子成像技术研究。实验上：1）建造该波段高能量、MHz重复频率飞秒脉冲光源；2）建造1700nm波段优化设计的激光扫描显微镜；3）利用整套系统开展皮肤样品的深层、多模态多光子成像研究并与800nm波段对比。本项目旨在构建超过现有商用水平成像深度的深层皮肤多光子成像系统，演示其在生物样品中的成像，与现有技术进行对比以体现其成像深度优势，以期为（深层）皮肤科学研究提供新的技术解决方案，并为其在临床应用于人体提供最初的实验依据。

Multiphoton microscopy (MPM) is a key technology to visualize structures and dynamics for dermatology research. So far, commercial MPM systems for clinical use with 800-nm femtosecond excitation are limited to an imaging depth of 200 µm. Further boosting imaging depth to enable visualization of deeper structures is of vital importance to dermatology research. Our recent research shows that excitation at the 1700-nm window enables twice larger imaging depth into the brain compared with that at the 800-nm window. Based on these results, here we propose to perform research on multiphoton microscopy of deep skin tissue at the 1700-nm window. Experimentally, we will 1) build a high-energy femtosecond laser source at the 1700-nm window with MHz repetition rate, 2) build a laser scanning microscope optimized for 1700-nm MPM, and 3) utilizing the laser and microscope system, perform deep-tissue multimodal MPM of skin tissue and compare it with MPM excited at the 800-nm window. Our main goal in this proposal is to establish a MPM system suitable for dermatology research, with imaging depth transcending that can be achieved by the current commercially available technologies. We will demonstrate its application to biological samples. By doing this, we will establish the technological advantages of our 1700-nm deep skin MPM and provide new solution to (deep) skin research, and pave the way for its final application to clinical use on human subjects.