申请人在光学成像领域中发表学术论文96篇（重要作者67篇）总计被引用超过6000次。获得专利授权28个。近年来申请人所带领的研究团队在多光子深层组织快速成像技术领域始终保持世界最高水平。申请人开创了同步时空聚焦双光子显微技术（Simultaneous Spatial and Temporal Focusing two-photon fluorescence microscopy， SSTF-TPM，）。该技术提供了一种全新的高速、具有光学切片功能的宽场成像手段,为深层组织的荧光和二次谐波成像提供了新思路。国内合作者陈良怡教授（基金委优秀青年基金获得者）长期以来利用先进光学成像技术研究糖尿病相关的激素分泌过程，目前希望在活体的斑马鱼和小鼠上能够实时观察到胰岛内alpha和beta细胞的分泌过程，并将它应用在糖尿病的动物模型的发病机制研究中。该申请如能获批，将为双方的合作提供一个重要的契机。

Chris Xu is Professor of Applied and Engineering Physics at Cornell University. His current research areas are fiber optics and biomedical imaging, with major thrusts in multiphoton microscopy, multiphoton endoscopy, and ultrafast and nonlinear fiber optics. Prior to Cornell, he was a member of technical staff in Advanced Photonic Research at Bell Laboratories from 1999 to 2002. He joined Bell Laboratories as a postdoctoral member in Biological Computation Research in 1997. His main research focus at Bell Labs was on fiber optics and optical communications. He received his Ph.D. from Applied Physics, Cornell University, working on multiphoton microscopy. He earned his B.S. in physics from Fudan University. Dr. Xu has chaired or served on numerous conference organization committees and NSF/NIH review panels. He currently serves as Associate Editor for Biomedical Optics Express, and is on the editorial board of several journals. He has published 100 journal articles and has 6000 total citations (ISI Web of Science). He has written 8 book chapters and 7 invited reviews, and has 28 patents granted or pending. He has won the NSF CAREER award, Bell Labs team research award, and the Tau Beta Pi and two other teaching awards from Cornell Engineering College. He is a fellow of the Optical Society of America. He has developed Simultaneous Spatial and Temporal Focusing two-photon fluorescence microscopy(SSTF-TPM)，which enable fast two-photon excitation of large field of view and recording of rapid dynamics. The miniaturization of this technique will help fluorescence imaging and Second Harmonic Generation (SHG) imaging within deep-tissue in live animals. .Professor Liangyi Chen received his bachelor degrees in biomedical engineering from Xian Jiaotong University in 1995, and earned his Ph.D. degree in biomedical engineering in 2001 from the Huazhong University of Science and technology. From 2001-2004, he worked as a postdoc researcher in University of Washington. Using electrophysiology and calcium imaging techniques, he studied calcium regulation mechanism and exocytosis in primary pancreatic beta cells. From 2004-2010, he worked as associate professor in Institute of Biophysics, Chinese Academy of Sciences, using the state-of-the-art imaging techniques to study insulin secretion mehcanism. In July 2010, he became a professor in Institute of Molecular Medicine in Peking University. His current research focus on imaging whole islet mass and function in situ and in vivo, trying to directly visualize autocrine/paracrine regulations of insulin and glucagon secretion in normal islets and islets from diabetic animal. This is a new frontier that potentially leads to unprecedented understanding of disease progression in vivo. If this application gets approved, it shall provide a platform that incubates novel ideas and stimulate novel findings..

我们自主设计并组装、测试了目前分辨率最高的微型化双光子显微镜(FIRM-TPM)。头戴式微型化双光子显微镜重量仅有2.15克，耦合自主研发的920nm光纤激光器。FIRM-TPM能够以高时空分辨率 (横向为0.654μm，轴向为3.305μm，256×256像素为40Hz) 进行生物学成像，与最好的商业台式双光子显微镜相当。其微机电系统扫描器还能够实现随机存取能力和高达10,000 Hz的自由扫描。应用我们自主研发的高速高分辨率微型化双光子显微镜，我们第一次在自由运动小鼠上看到了单个神经突触上的局部钙信号。因此，我们的新一代微型显微镜为神经科学家在清醒动物的突触水平的大脑成像提供了新的选择。另外，为了探寻促进β细胞功能成熟的因子，我们利用自主研发的双光子三轴扫描光片显微镜，在单细胞水平在体实时观测斑马鱼胰岛β细胞功能。我们的研究揭示了胚胎期胰岛微循环系统的建立精确调控了逐渐升高的葡萄糖进入胰岛外围和内部的β细胞内，而合适的葡萄糖浓度通过激活calcineurin/NFAT信号通路导致胰岛β细胞的功能成熟。在缺乏微循环系统的条件下，体外培养小鼠新生胰岛β细胞无法实现胰岛外围和内部的β细胞受到相同最适浓度的葡萄糖的刺激而获得最大程度的成熟。而有趣的是，这个缺陷可以通过在培养基中加入calcineurin的激活剂而得到纠正。我们的发现将为体外诱导人胚胎干细胞分化为功能完全成熟的β细胞提供一个新的策略。