Ultra-broadband multimodal microscopy with a catadioptric lens

带有折反射透镜的超宽带多模态显微镜

• 批准号: 10600776
• 负责人: Adam M Hanninen
• 金额: $ 29.05万
• 依托单位: TRESTLE OPTICS LLC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-03 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10600776
• 关键词: Address; Adipose tissue; Affect; Astronomy; Biological; Biopsy; Cells; Chemicals; Collagen Type I; Collection; Color; Computer software; County; Dermis; Deterioration; Development; Diamond; Electromagnetics; Elements; Engineering; Exhibits; Fluorescence; Frequencies; Generations; Geometry; Housing; Image; Imaging Device; Imaging Techniques; Imaging technology; Light; Lighting; Lipids; Measurement; Methods; Microscope; Microscopy; Modality; Molecular; Multimodal Imaging; Mus; Optics; Oranges; Outcome; Performance; Phase; Photons; Physiologic pulse; Property; Radiation; Research Personnel; Resolution; Signal Transduction; Source; Specific qualifier value; Specimen; Sum; Surface; System; Techniques; Technology; Testing; Tissue imaging; Tissues; biomedical imaging; contrast imaging; design; fabrication; flexibility; high resolution imaging; imaging modality; imaging properties; improved; innovation; instrument; lens; multimodality; multiphoton microscopy; new technology; novel; operation; optical imaging; prevent; prototype; supply chain; tool; transmission process; two-photon; ultraviolet; usability; virtual

Abstract. Virtually all optical microscopes for biological imaging are based on refractive objective lenses. The performance of these lenses approaches the theoretical limit, however, their use is limited to the visible to near-infrared spectral range. Even within this range, their performance is only guaranteed over a relatively narrow range, and broadband use is invariably affected by chromatic aberrations. Another problem is the group delay dispersion that these lenses introduce to short optical pulses, which reduces the efficiency of nonlinear optical (NLO) signal generation in the microscope. Taken together, these shortcomings seriously compromise the imaging properties of several NLO imaging modalities such as three-photon excited fluorescence and third-harmonic generation. In addition, refractive objectives simply cannot be used for NLO techniques that incorporate excitation light in the mid-infrared (MIR) range, such as photothermal imaging and sum-frequency generation, promising technologies based on MIR molecular contrast. The only viable alternative is the all-reflective Schwarzschild-Cassegrain (SC) objective, which is inherently achromatic but suffers from a non-ideal point spread function and a center obscuration that limits throughput. Because of these limitations, SC lenses have not found widespread use in biological imaging applications. This lack of performance is also the reason why advances in exciting new MIR-based NLO imaging technologies have been stifled: there simply are no high-performance high numerical focusing options available to support these emerging imaging technologies. In this project, we develop a novel high numerical aperture lens that overcomes all limitations of the SC focusing lens. Leveraging refractive and reflective elements based on a non- concentric layout, this new catadioptric design features transmission from the ultra-violet to the mid-infrared, exhibits a wide field of view and extended working distance, dramatically reduces group delay dispersion and significantly improves throughput by eliminating the center obscuration all together. This lens not only advances existing NLO modalities that rely on broadband radiation, but also enables new technologies such as photothermal imaging and SFG microscopy that have thus far suffered from low performance focusing optics. Ultimately, this imaging tool will enable researchers to perform single-cell and tissue studies for a variety of cross- cutting biomedical applications regardless of the illumination source used.

抽象的。 几乎所有用于生物成像的光学显微镜都是基于折射率镜片的。 这些镜头的性能接近理论限制，但是，它们的使用仅限于 可见到近红外光谱范围。即使在这个范围内，他们的表现也只是 保证在相对狭窄的范围内，并且宽带的使用总是受到色彩的影响 畸变。另一个问题是这些镜片引入简短的群体延迟分散体 光脉冲降低了非线性光学（NLO）信号产生的效率 显微镜。综上所述，这些缺点严重损害了成像特性 几种NLO成像模态，例如三光激发荧光和第三次谐波 一代。此外，屈光目标根本不能用于NLO技术 将激发光纳入中红外（miR）范围，例如光热成像和 总和产生，基于miR分子对比的有前途的技术。唯一的 可行的替代方案是全反射的Schwarzschild-cassegrain（SC）目标，这是天生的 可观的，但遭受非理想点的扩散功能和中心的掩饰限制 吞吐量。由于这些局限性，SC镜头尚未发现在生物学中广泛使用 成像应用。缺乏性能也是令人兴奋的新事物的原因 基于miR的NLO成像技术已经被扼杀：根本没有高性能 可用于支持这些新兴成像技术的高数值聚焦选项。 在这个项目中，我们开发了一种新颖的高数值光圈镜头，它克服了所有 SC聚焦镜头的局限性。基于非 - 同心布局，这种新的catadioptric Design具有从紫外线到 中红外，展示了广阔的视野和延长的工作距离，大大减少了 小组延迟分散并通过消除中心大大改善吞吐量 默默无闻。该镜头不仅可以推动依赖的现有NLO模式 宽带辐射，但还可以实现新技术，例如光热成像和SFG 到目前为止，显微镜遭受了低性能聚焦光学元件的困扰。最终，这个 成像工具将使研究人员能够进行单细胞和组织研究，以进行多种交叉 切割生物医学应用，无论使用的照明源如何。