Ultra-broadband multimodal microscopy with a catadioptric lens

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物镜的。 这些镜片的性能接近理论极限，然而，它们的使用仅限于 从可见光到近红外的光谱范围。即使在这个范围内，他们的表现也只是 保证在相对较窄的范围内使用，并且宽带使用总是受到色度的影响 像差。另一个问题是这些透镜给Short带来的群延迟色散 光脉冲，这降低了非线性光(NLO)信号在 显微镜。综上所述，这些缺陷严重损害了 三光子激发荧光和三次谐波等几种非线性光学成像方式 一代。此外，屈光镜根本不能用于以下的NLO技术 在中红外(MIR)范围内加入激发光，如光热成像和 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施瓦茨柴尔德-卡塞格伦(SC)目标，这是内在的 消色差，但存在非理想点扩散函数和中心遮挡 吞吐量。由于这些局限性，SC镜片还没有在生物学上得到广泛的应用 成像应用程序。这种性能的缺乏也是为什么在令人兴奋的新技术方面取得进展的原因 基于MIR的NLO成像技术被扼杀：根本没有高性能 支持这些新兴成像技术的高数值调焦选项。 在这个项目中，我们开发了一种新型的大数值孔径透镜，它克服了 SC调焦透镜的局限性。利用基于非 同心设计，这种新的折反射设计具有从紫外线到 中红外，表现出宽广的视场和延长的工作距离，大大减少了 群延迟色散，并通过消除中心显著提高吞吐量 所有的遮挡都在一起。这种透镜不仅改进了现有的NLO模式，而且依赖于 宽带辐射，但也使光热成像和SFG等新技术成为可能 到目前为止一直受到低性能聚焦光学系统影响的显微镜。归根结底，这 成像工具将使研究人员能够对各种交叉细胞进行单细胞和组织研究 切割生物医学应用，而不考虑所使用的光源。

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.