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。 事实上，所有用于生物成像的光学显微镜都基于折射物镜。 这些镜头的性能接近理论极限，但是它们的用途仅限于 可见光到近红外光谱范围。即使在这个范围内，它们的性能也只是 保证在相对较窄的范围内，并且宽带使用总是受到色差的影响 像差。另一个问题是这些镜头在短距离内引入的群延迟色散 光脉冲，这降低了非线性光（NLO）信号生成的效率 显微镜。总而言之，这些缺点严重损害了成像性能 几种非线性光学成像模式，例如三光子激发荧光和三次谐波 一代。此外，折射物镜根本不能用于 NLO 技术，因为 结合中红外（MIR）范围内的激发光，例如光热成像和 和频生成，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史瓦西卡塞格林 (SC) 目标，其本质上是 消色差，但受到非理想点扩散函数和限制的中心遮光的影响 吞吐量。由于这些限制，SC 镜片尚未在生物领域得到广泛应用。 成像应用。这种性能的缺乏也是令人兴奋的新产品取得进展的原因 基于 MIR 的 NLO 成像技术已受到抑制：根本没有高性能 高数值聚焦选项可支持这些新兴成像技术。 在这个项目中，我们开发了一种新型高数值孔径镜头，克服了所有问题 SC 聚焦镜头的局限性。利用基于非反射元件的折射和反射元件 同心布局，这种新的折反射设计具有从紫外线到可见光的传输特性 中红外，具有宽视野和延长工作距离，大大减少 群延迟分散，并通过消除中心显着提高吞吐量 一切都蒙蔽在一起。该镜头不仅改进了现有的 NLO 模式，这些模式依赖于 宽带辐射，还支持光热成像和 SFG 等新技术 迄今为止，显微镜一直受到聚焦光学性能低下的困扰。最终，这 成像工具将使研究人员能够针对各种交叉研究进行单细胞和组织研究 无论使用何种照明源，都可以切割生物医学应用。