Development of a fiber-based, holographic coherent anti-Stokes Raman scattering microscope for label-free imaging

开发基于光纤的全息相干反斯托克斯拉曼散射显微镜，用于无标记成像

• 批准号: 8834488
• 负责人: Perry Edwards
• 金额: $ 35万
• 依托单位: ATOPTIX, LLC
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-01-15 至 2016-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8834488
• 关键词: Advanced Development; Area; Biological; Biological Process; Caliber; Cells; Chemicals; Collaborations; Color; Complex; Coupled; Detection; Development; Fiber; Frequencies; Goals; Holography; Image; Imaging Device; Label; Lasers; Lead; Measurement; Microscope; Microscopy; Monitor; Nature; Noise; Output; Performance; Phase; Physiologic pulse; Process; Pump; Research Personnel; Resolution; Sampling; Scanning; Seeds; Signal Transduction; Small Business Innovation Research Grant; Source; Spectrum Analysis; Speed; System; Techniques; Three-Dimensional Image; Three-Dimensional Imaging; Time; Tissues; Universities; Width; Work; base; cost; design; digital; imaging modality; imaging system; improved; innovation; instrument; meetings; non-invasive imaging; programs; prototype; public health relevance

DESCRIPTION (provided by applicant): Coherent Raman microscopy has emerged as an important label-free imaging modality, which can enable long duration non-invasive imaging of cells and tissues. However, current coherent Raman systems require scanning to obtain three-dimensional images, hindering studies of rapid dynamic biological processes. Additionally, coherent Raman imaging systems usually rely on complex and expensive laser sources, which limit their accessibility. In this Phase I SBIR study, Atoptix, LLC. proposes to develop a fiber-based holographic coherent anti-Stokes Raman scattering (CARS) microscope to overcome these limitations of scanning and system complexity. The key innovation, CARS holography, merges the unique capabilities of CARS spectroscopy and holographic imaging by recording of a digital CARS hologram which captures both the amplitude and the phase of an anti-Stokes image signal. CARS holography can thus perform label-free, 3D imaging without scanning, and have an improved sensitivity over conventional CARS due to its homodyne detection nature. Furthermore, the proposed system will use a robust, turn-key fiber laser based excitation system which overcomes the complexities and high costs associated with existing coherent Raman systems. To perform this work, Atoptix will collaborate with Penn State University researchers who are the inventors of CARS holography. Specific Aim 1 is to develop a synchronized two-color ultrafast fiber laser system that will provide the CARS pump/probe and Stokes excitation sources. Specific Aim 2 is to develop the prototype holographic CARS microscope. The system will be characterized and optimized to assess performance and capability for Phase II development of an advanced prototype system.

描述（由申请人提供）：相干拉曼显微术已经成为一种重要的无标记成像模式，其可以实现细胞和组织的长时间非侵入性成像。然而，目前的相干拉曼系统需要扫描以获得三维图像，这阻碍了快速动态生物过程的研究。此外，相干拉曼成像系统通常依赖于复杂且昂贵的激光源，这限制了它们的可访问性。在这项I期SBIR研究中，Atoptix，LLC.提出开发基于光纤的全息相干反斯托克斯拉曼散射（汽车）显微镜，以克服扫描和系统复杂性的这些限制。关键的创新，汽车全息，合并汽车光谱和全息成像的独特功能，通过记录数字汽车全息图，捕获反斯托克斯图像信号的振幅和相位。因此，汽车全息术可以在没有扫描的情况下进行无标记的3D成像，并且由于其零差检测性质，其灵敏度优于传统的汽车。此外，所提出的系统将使用鲁棒的、基于交钥匙光纤激光器的激发系统，其克服了与现有相干拉曼系统相关联的复杂性和高成本。为了完成这项工作，Atoptix将与宾夕法尼亚州立大学的研究人员合作，他们是汽车全息术的发明者。具体目标一是研制一套同步双色超快光纤激光器系统，提供汽车泵浦/探测和斯托克斯激发光源。具体目标二是研制全息汽车显微镜样机。将对该系统进行表征和优化，以评估先进原型系统第二阶段开发的性能和能力。