Time-gated confocal Raman microscope

时间选通共焦拉曼显微镜

• 批准号: 7587294
• 负责人: Vladislav V. Yakovlev
• 金额: $ 7.14万
• 依托单位: UNIVERSITY OF WISCONSIN MILWAUKEE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2010-10-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7587294
• 关键词: Biological; Biological Models; Biological Sciences; Blindness; Cells; Chemicals; Collagen; Collagen Type I; Collection; Complex; Confocal Microscopy; Dental; Dental caries; Detection; Development; Diagnostic; Discrimination; Evaluation; Fluorescence; Goals; Image; Imaging Techniques; Lateral; Life; Masks; Measures; Medical; Medical Research; Microscope; Microscopic; Microscopy; Modality; Molecular; Molecular Structure; Noise; Optics; Organism; Performance; Raman Spectrum Analysis; Research; Research Proposals; Resolution; Signal Transduction; Solutions; Structure; Structure of retinal pigment epithelium; System; Techniques; Testing; Time; Tissues; bone; clinical application; design; fundamental research; imaging modality; improved; in vivo; innovation; instrument; molecular imaging; novel; optical imaging; prevent; prototype; self organization; tool; transmission process

DESCRIPTION (provided by applicant): Progress in the Life Sciences depends upon the development of new tools and instruments. Our ability to understand the function of living systems on a cellular and molecular level is greatly enhanced by imaging techniques capable of providing structural and chemical information in vivo. Raman spectroscopy is truly non-invasive, and it could provide significant information on the chemical composition and physical structure of biological tissues. This small-scale (R03) research proposal aims to develop an innovative approach for non-invasive microspectroscopy in order to unambiguously explore changes in chemical composition in cells and tissues. To achieve this goal, the PI will utilize the concept of time-gated Raman imaging, applied for the first time to microscopy to achieve confocal imaging with superior discrimination against the fluorescence background. It is expected that it will provide at least an order of magnitude improvement in the signal-to-noise ratio, which transforms into at least 100 times faster acquisition rates, while improving spatial resolution and eradicating possible ambiguities in resolving complex Raman bands. The first specific aim is building the prototype of a novel instrument and characterizing its performance. The second specific aim is pilot testing of a new instrument for molecular, cellular and tissue imaging for several model systems: 1) collagen self-organization and structural transformation, which leads to bone structure development, 2) photodegradation of retinal pigment epithelium cells, which is considered to be the major cause of blindness, and 3) early caries detection in dental tissues. Many medical research and diagnostic applications require microscopic molecular imaging with minimum invasiveness. Raman microspectroscopy, being a non-invasive, chemically specific technique for molecular imaging, suffers a dramatic drawback due to a strong fluorescent background, which significantly reduces the signal-to-noise ratio and makes it difficult to reveal the fine structure of vibrational bands. The proposed research provides a solution to this problem for microscopic imaging by time-gating the useful signal in a specially designed optical arrangement.

描述（由申请人提供）：生命科学的进展取决于新工具和工具的开发。通过能够提供体内结构和化学信息的成像技术，大大增强了我们在细胞和分子水平上理解生命系统功能的能力。拉曼光谱确实是无创的，它可以提供有关生物组织的化学组成和物理结构的重要信息。这项小规模（R03）的研究建议旨在开发一种非侵入性微光谱镜检查的创新方法，以明确探索细胞和组织中化学成分的变化。为了实现这一目标，PI将使用时间门控拉曼成像的概念，该概念首次适用于显微镜，以实现对荧光背景的优越歧视的共聚焦成像。预计它将至少提供信噪比的数量级提高，从而将其转变为至少100倍的采集率，同时改善空间分辨率并消除解决复杂的拉曼频段中可能的歧义。第一个具体目的是构建新型仪器的原型并表征其性能。第二个具体目的是对几种模型系统的分子，细胞和组织成像的新仪器进行试验测试：1）胶原蛋白自组织和结构转化，这导致骨结构的发展，2）视网膜色素上皮细胞的光降解被认为是失明的主要原因，3）牙科组织中的早期龋齿检测。许多医学研究和诊断应用都需要微观成像，并具有最小的侵入性。拉曼显微光谱是一种非侵入性、化学特异性的分子成像技术，由于强烈的荧光背景而存在显着的缺点，这会显着降低信噪比，并使其难以揭示振动带的精细结构。拟议的研究通过在特殊设计的光学布置中对有用的信号进行时间门控为微观成像提供了解决方案。

项目成果

Stimulated Raman scattering: old physics, new applications.

受激拉曼散射：旧物理学，新应用。

• 发表时间: 2009-10-01
• 影响因子: 1.3
• 作者: Yakovlev, Vladislav V;Petrov, Georgi I;Zhang, Hao F;Noojin, Gary D;Denton, Michael L;Thomas, Robert J;Scully, Marlan O
• 通讯作者: Scully, Marlan O

Structural changes of human serum albumin in response to a low concentration of heavy ions.

人血清白蛋白响应低浓度重离子的结构变化。

• 发表时间: 2010-10
• 作者: Saha, Anushree;Yakovlev, Vladislav V
• 通讯作者: Yakovlev, Vladislav V

Detection of picomolar concentrations of lead in water using albumin-based fluorescence sensor.

使用基于白蛋白的荧光传感器检测水中铅的皮摩尔浓度。

• 发表时间: 2009-10-05
• 影响因子: 4
• 作者: Saha, Anushree;Yakovlev, Vladislav V
• 通讯作者: Yakovlev, Vladislav V

Ex-CARS: exotic configuration for coherent anti-Stokes Raman scattering microspectroscopy utilizing two laser sources.

Ex-CARS：利用两个激光源进行相干反斯托克斯拉曼散射显微光谱的奇异配置。

• 发表时间: 2010-10
• 作者: Yakovlev, Vladislav V;Petrov, Georgi I;Noojin, Gary D;Harbert, Corey;Denton, Michael;Thomas, Robert
• 通讯作者: Thomas, Robert

Stimulated Raman photoacoustic imaging.

受激拉曼光声成像。

• 发表时间: 2010-11-23
• 影响因子: 11.1
• 作者: Yakovlev, Vladislav V;Zhang, Hao F;Noojin, Gary D;Denton, Michael L;Thomas, Robert J;Scully, Marlan O
• 通讯作者: Scully, Marlan O