Balu Mihaela, Liu Gangjun, Chen Zhongping, Tromberg Bruce J, Potma Eric O
Laser Microbeam and Medical Program (LAMMP), Beckman Institute and Medical Clinic, 1002 Health Sciences Road East, University of California, Irvine, 92612, USA.
Opt Express. 2010 Feb 1;18(3):2380-8. doi: 10.1364/OE.18.002380.
We demonstrate a fiber-based probe for maximum collection of the coherent anti-Stokes Raman scattering (CARS) signal in biological tissues. We discuss the design challenges including capturing the backscattered forward generated CARS signal in the sample and the effects of fiber nonlinearities on the propagating pulses. Three different single mode fibers (fused silica fiber, photonic crystal fiber and double-clad photonic crystal fiber) were tested for the probe design. We investigated self-phase modulation, stimulated Raman scattering (SRS) and four-wave-mixing (FWM) generation in the fiber: nonlinear processes expected to occur in a two-beam excitation based probe. While SPM and SRS induced spectral broadening was negligible, a strong non phase-matched FWM contribution was found to be present in all the tested fibers for excitation conditions relevant to CARS microscopy of tissues. To spectrally suppress this strong contribution, the pro design incorporates separate fibers for excitation light delivery and for signal detection, in combination with dichroic optics. CARS images of the samples were recorded by collecting the back-scattered forward generated CARS signal in the sample through a multi-mode fiber. Different biological tissues were imaged ex vivo in order to assess the performance of our fiber-delivered probe for CARS imaging, a tool which we consider an important advance towards label-free, in vivo probing of superficial tissues.
我们展示了一种基于光纤的探头，用于在生物组织中最大程度地收集相干反斯托克斯拉曼散射（CARS）信号。我们讨论了设计挑战，包括捕获样品中背向散射的前向产生的CARS信号以及光纤非线性对传播脉冲的影响。为了进行探头设计，测试了三种不同的单模光纤（熔石英光纤、光子晶体光纤和双包层光子晶体光纤）。我们研究了光纤中的自相位调制、受激拉曼散射（SRS）和四波混频（FWM）产生：这些是非线性过程，预计会在基于双光束激发的探头中发生。虽然自相位调制和受激拉曼散射引起的光谱展宽可以忽略不计，但在与组织的CARS显微镜相关的激发条件下，发现所有测试光纤中都存在强烈的非相位匹配四波混频贡献。为了在光谱上抑制这种强烈贡献，探头设计结合了用于激发光传输和信号检测的单独光纤，并与二向色光学器件相结合。通过多模光纤收集样品中背向散射的前向产生的CARS信号，记录样品的CARS图像。对不同的生物组织进行离体成像，以评估我们的光纤传输探头用于CARS成像的性能，我们认为这一工具是朝着无标记的浅表组织体内探测迈出的重要一步。
