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基于折射物镜。 这些透镜的性能接近理论极限，然而，它们的使用仅限于 可见光到近红外光谱范围。即使在这个范围内，它们的性能也只有 保证在一个相对狭窄的范围内，宽带使用总是受到影响的彩色 失常。另一个问题是群延迟色散，这些透镜引入到短 光脉冲，这降低了非线性光学（NLO）信号生成的效率。 显微镜总之，这些缺点严重损害了成像性能。 几种NLO成像模式，如三光子激发荧光和三次谐波 一代另外，折射物镜根本不能用于NLO技术， 结合中红外（MIR）范围内的激发光，例如光热成像， 和频产生，基于MIR分子对比度的有前途的技术。唯一的 可行的替代方案是全反射的施瓦兹希尔德-卡塞格伦（SC）物镜，它本质上是 但是遭受非理想点扩散函数和中心遮蔽， 吞吐量由于这些局限性，SC透镜尚未在生物医学中广泛使用。 成像应用。这种性能的缺乏也是令人兴奋的新技术进步的原因。 基于MIR的NLO成像技术已经被扼杀：根本没有高性能 高数值聚焦选项可用于支持这些新兴的成像技术。 在这个项目中，我们开发了一种新型的高数值孔径透镜，克服了所有 SC聚焦透镜的限制。利用基于非线性的折射和反射元件， 同心布局，这种新的反射折射设计的特点是从紫外线传输到 中红外线，具有广阔的视野和扩展的工作距离， 群延迟分散，并通过消除中心显著提高吞吐量 所有的黑暗在一起。这种透镜不仅推进了现有的NLO模式， 宽带辐射，而且还使光热成像和SFG等新技术成为可能 显微镜迄今为止遭受低性能聚焦光学器件。最终这 成像工具将使研究人员能够进行单细胞和组织研究的各种交叉， 切割生物医学应用，而不管所使用的照明源。