Fiber Laser Excitation CARS Microscopy with Auto-Synchronized Chirped Femtosecond

描述（由申请人提供）：该项目的目标是基于光纤激光器，为相干反斯托克斯拉曼光谱（CARS）显微镜建立一个新的，强大的，紧凑的光源。CARS是一种潜在的强大显微镜技术，因为细胞成分（如脂质、蛋白质或DNA）的分子特性可以成像，而无需荧光标记。由于脉冲强度的非线性依赖，光学切片是CARS过程的固有特性。此外，近红外波长可用于增加组织穿透。因此，CARS显微镜有潜力成为重要的生物医学和临床工具。然而，所需的激光源通常体积庞大，价格昂贵且难以处理，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：光纤激光激发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。非线性光纤（光子晶体光纤）将被用来移动斯托克斯脉冲的波长。因此，泵、探头和Stokes会自动及时同步。我们将开发基于1030nm光纤激光器的FLEX- CARS。采用一种新颖的脉冲“啁啾”方法，利用泵浦脉冲和斯托克斯脉冲的全脉冲功率，将显著提高FLEX-CARS的频率分辨率。斯托克斯光束的波长可以在微秒时间尺度上快速调谐或切换，从而允许使用新方法探测多个振动频率。通过极化和延时方法选择振动共振信号，抑制非谐振背景分量，提高信号质量。该系统中快速波长切换的独特能力也使调频（FM） CARS变得简单，这有助于进一步抑制非谐振背景。FLEX-CARS将首先应用于标准样本，然后应用于脑组织，以证明该方法作为CARS显微系统的强大潜力。

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.