High-resolution spectroscopic imaging with infrared nonlinear optical (IR-NLO) microscopy

使用红外非线性光学 (IR-NLO) 显微镜进行高分辨率光谱成像

• 批准号: 9903403
• 负责人: Eric Olaf Potma
• 金额: $ 13.51万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9903403
• 关键词: Adopted; Biological; Biology; Cells; Cellular Structures; Chemicals; Clinical; Cultured Cells; Data; Development; Diagnostic; Disease; Exhibits; Fingerprint; Fourier Transform; Frequencies; Generations; Goals; Image; Imaging Device; Imaging Techniques; Imaging technology; Label; Laboratories; Lasers; Lateral; Light; Maps; Measurable; Methods; Microscope; Microscopy; Modality; Molecular; Molecular Profiling; Optics; Pathology; Performance; Property; Raman Spectrum Analysis; Research; Resolution; Sampling; Scanning; Scheme; Science; Signal Transduction; Source; Specimen; Spectrum Analysis; Speed; Structure; Sum; System; Techniques; Technology; Testing; Time; Tissue imaging; Tissues; absorption; base; bioimaging; chemical bond; chemical group; high resolution imaging; image reconstruction; imaging approach; imaging modality; imaging platform; imaging properties; imaging study; improved; infrared microscopy; innovation; microscopic imaging; novel; optical imaging; programs; spectroscopic imaging; technology validation; tool; vibration

Project Summary A genuine label-free imaging technology, vibrational microscopy provides maps of cells and tissues with exceptionally high chemical contrast as it directly probes the fundamental vibrational modes of samples. Vibrational imaging approaches include IR-absorption micro-spectroscopy and confocal Raman microscopy, methods that have been successfully commercialized (a growing 500 million dollar market) and are now common tools of inquiry found in analytical and biological laboratories. Over the past four decades, these techniques have had a measurable impact in the fields of biology and biomedicine, offering a spatially resolved assessment of healthy and diseased tissues from a molecular perspective. This proposal aims to significantly improve the capabilities of vibrational microscopy. We propose a new imaging approach that merges the desirable properties of IR absorption microscopy with some of the unique properties of coherent, nonlinear optical (NLO) excitation of molecules. This novel IR-NLO technique improves the spatial resolution of IR absorption microscopy by tenfold, while offering higher sensitivity to fingerprint molecular vibrations relative to Raman-based microscopy methods. Our team is comprised of experts in coherent Raman scattering microscopy and IR microspectroscopic imaging. Our innovation makes it possible to rapidly acquire IR absorption images of fingerprint vibrational modes with a resolution of 0.5 micrometer or better. The preliminary data shows that the IR-NLO approach can be successfully adopted in a rapid laser-scanning microscope, allowing convenient vibrational imaging of tissue specimens. In our proposal we develop, test, and improve the new IR-NLO technology. The validation of the technology is achieved through extensive biomedical imaging studies and comparison with the state of the art IR microscopy available today. The proposed program tackles a major challenge in IR spectroscopic microscopy, namely the improvement of imaging resolution. This new capability is significant, as the higher resolution enables the identification of sub-micrometer intra- and extra-cellular structures in the tissue, which hitherto have remained invisible in IR-imaging. The high-resolution imaging property thus dramatically improves the diagnostic capabilities of the technique. By setting a new resolution standard for fingerprint vibrational imaging, the IR-NLO technology is likely to have a significant impact in tissue imaging and can enable its use in both research and clinical domains for pathology.

项目摘要 振动显微镜提供了真正的无标签成像技术，可提供细胞和组织的地图 具有异常高的化学对比度，因为它直接探测了基本振动模式 样品。振动成像方法包括IR吸收微光谱和共聚焦 拉曼显微镜，成功商业化的方法（一种增长了5亿 美元市场）现在是分析和生物实验室中发现的常见探究工具。 在过去的四十年中，这些技术对生物学领域产生了可衡量的影响 和生物医学，从A 分子观点。该建议旨在显着提高振动的能力 显微镜。我们提出了一种合并IR的理想特性的新成像方法 吸收显微镜具有连贯的非线性光学（NLO）的某些独特特性 分子的激发。这种新型的IR-NLO技术改善了IR吸收的空间分辨率 显微镜通过十倍，同时对指纹分子振动具有更高的敏感性 基于拉曼的显微镜方法。 我们的团队由连贯的拉曼散射显微镜和IR的专家组成 微光谱成像。我们的创新使快速获取IR吸收图像成为可能 指纹振动模式的分辨率为0.5微米或更高。初步数据 表明可以在快速激光扫描显微镜中成功采用IR-NLO方法， 允许组织样品的方便振动成像。在我们的建议中，我们开发，测试和 改善新的IR-NLO技术。该技术的验证是通过广泛的 生物医学成像研究和与当今可用的最新IR显微镜的比较。 拟议的程序应对红外光谱显微镜的重大挑战，即 改进成像分辨率。这种新功能很重要，因为较高的分辨率可以实现 在组织中的亚微米计内和细胞外结构的鉴定，迄今为止 在IR成像中仍然是看不见的。高分辨率成像属性因此很大 提高该技术的诊断能力。通过为新的分辨率标准设定 指纹振动成像，IR-NLO技术可能对组织产生重大影响 成像，并可以在研究和临床领域中用于病理学。