Fiber Laser Excitation CARS Microscopy with Auto-Synchronized Chirped Femtosecond

描述(申请人提供)：该项目的目标是建立一个新的，坚固，紧凑的光源，相干反斯托克斯拉曼光谱(CARS)显微镜基于光纤激光器。CARS是一种潜在的强大的显微镜技术，因为细胞成分(如脂质、蛋白质或DNA)的分子身份可以在不需要荧光标记的情况下进行成像。由于对脉冲强度的非线性依赖，光学分割是CARS过程的固有特性。此外，近红外波长可用于增加组织渗透率。因此，CARS显微镜有可能成为一种重要的生物医学和临床工具。然而，所需的激光光源通常体积庞大、价格昂贵且难以操作，因此到目前为止，CARS显微镜的应用有限。我们建议开发一种基于光纤激光器的技术：光纤激光激励CARS(FLEX-CARS)，它使用单个光纤激光器作为泵浦和斯托克斯脉冲的源。将使用非线性光纤(光子晶体光纤)来移位斯托克斯脉冲的波长。因此，泵浦、探测和斯托克斯在时间上自动同步。我们将开发基于1030 nm光纤激光器的FLEX-CARS。利用泵浦脉冲和斯托克斯脉冲的全脉冲功率，采用一种新颖的脉冲“啁啾”方法，可以显著提高FLEX-CARS的频率分辨率。斯托克斯光束的波长可以在微秒的时间尺度上快速调谐或切换，从而允许新的方法来探测多个振动频率。通过实施偏振和延时方法来选择振动共振信号，通过抑制非共振背景分量将提高信号质量。该系统独特的快速波长切换能力也使得调频(FM)车变得简单，这有助于进一步抑制非共振背景。Flex-CARS将首先应用于标准样本，然后应用于脑组织，以展示该方法作为CARS微球的强大系统的潜力。

DESCRIPTION (provided by applicant): The goal of this project is to build a new, robust, and compact source for Coherent anti-Stokes Raman Spectroscopy (CARS) microscopy based on fiber lasers. CARS is a potentially powerful technique for microscopy because the molecular identity of cellular components (e.g. lipids, proteins, or DNA) can be imaged without the need for fluorescence labeling. Optical sectioning is intrinsic to the CARS process because of the nonlinear dependence on pulse intensity. In addition, near-infrared wavelengths can be used for increased tissue penetration. Therefore, CARS microscopy has the potential to be an important biomedical and clinical tool. However, the laser sources required are typically bulkly, expensive and hard to handle, and as a result CARS microscopy has so far found limited application. We propose to develop a technique based on fiber lasers: Fiber Laser EXcitation CARS ("FLEX- CARS"), which uses a single fiber laser as the source of pump and "Stokes" pulses. A nonlinear optical fiber (photonic crystal fiber) will be used to shift the wavelength of the Stokes pulses. As a result, pump, probe, and Stokes are automatically synchronized in time. We will develop FLEX- CARS based on a fiber laser at 1030 nm. The frequency resolution of FLEX-CARS will be significantly improved by a novel pulse "chirping" method that utilizes the full pulse power of pump and Stokes pulses. The wavelength of the Stokes beam can be tuned or switched rapidly on the microsecond time scale, allowing new methods to probe multiple vibrational frequencies. Signal quality will be enhanced by rejection of nonresonant background components through the implementation of polarization and time-delay methods to select the vibrationally resonant signal. The unique capability for fast wavelength switching in the proposed system also makes frequency modulated (FM) CARS straightforward, which helps further rejection of non-resonant background. FLEX-CARS will be applied first to standard samples and then to brain tissue to demonstrate the potential of the method as a robust system for CARS microsocpy.