Photonics-based Fluorescence Imaging for Research, Diagnostics, and Pathology

用于研究、诊断和病理学的基于光子学的荧光成像

• 批准号: 10329143
• 负责人: Joseph R. LAKOWICZ
• 金额: $ 38.63万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10329143
• 关键词: 2019-nCoV; Area; Binding; Biological Assay; Biological Sciences; Cell membrane; Cells; Cellular Phone; Centenarian; Collaborations; Complex; Coupled; Detection; Devices; Diagnostic; Dimensions; Electronics; Fiber Optics; Flow Cytometry; Fluorescence; Fluorescence Microscopy; Generations; Goals; HIV; Image; Imaging Device; Immunoassay; Light; Measurement; Medicine; Microscope; Optics; Pathology; Pharmaceutical Preparations; Photons; Positioning Attribute; Property; Research; Slide; Specimen; Structure; Technology; Transistors; Virion; Virus; base; brain tissue; cellular imaging; clinical application; consumer product; detector; drug discovery; fluorescence imaging; fluorescence microscope; fluorophore; genetic testing; high throughput screening; imaging detector; in vivo; instrument; lens; medical schools; multi-photon; pathology imaging; photonics; plasmonics; point-of-care diagnostics; senior faculty; whole slide imaging

Abstract - Photonics-based Fluorescence Imaging for Research, Diagnostics and Pathology During the past several decades fluorescence detection has become a central technology throughout the biosciences. The basic applications include studies of biomolecule function, properties of cell membranes and localization of target molecules in cells. The more clinical applications include immunoassays, flow cytometry, point-of-care diagnostics, genetic testing, and cell imaging by fluorescence microscopy. Fluorescence is expanding to include in-vivo measurements on brain tissues using multi-photon excitation. While fluorescence technology has advanced, it has not kept pace with the advances in electronics and array detectors (cameras). The sizes of optical components such as lenses and filters are much larger than electronic components as can be seen from a cell phone with millions of transistors, but only one or two lenses in a cell phone. This mismatch in size cannot be circumvented by making smaller lenses, filters or fiber optics. These optical components require dimensions of many wavelengths to manipulate freely propagating light. We propose to overcome this limitation by using fluorophores positioned within sub-wavelength near-field distances from the plasmonic, photonic or plasmonic multi-layer structures (MLS). We are NOT proposing to use the fluorophores as electronic components, but rather to directly couple their emission into CMOS imaging detectors with MLSs without free-space propagation of light. The MLS controls the propagation of optical energy, can separate wavelengths and can direct the energy (coupled photons) towards nearby detectors. This concept will provide the basis for new devices for research and medicine. To demonstrate the usefulness of these devices we have established collaborations with senior faculty in the School of Medicine. These collaborations include detection of weak binding in drug discovery or high throughput screening (HTS) because much of the HTS is used with drug fragments which bind weakly to target molicules. Most of the MLS retain spatial information in the x-y plane which allows either ensemble or virus particle counting assays for HIV and the Covid-19 virus SARS-CoV-2. The wide field of view will allow whole slide imaging of pathology specimens. Our goal is to develop this new area of near-field effects in fluorescence, with easy to fabricate strruvtures, to enable a new generation of instruments and devices for fluorescence detection in research, sensing and imaging.

基于光子学的荧光成像在研究、诊断和病理学中的应用 在过去的几十年里，荧光检测已经成为整个人类社会的核心技术 生物科学。其基本应用包括生物分子功能的研究、细胞膜的性质研究和 靶分子在细胞中的定位。更多的临床应用包括免疫分析，流式细胞术， 医疗点诊断、基因测试和荧光显微镜细胞成像。荧光是 扩展到包括使用多光子激发对脑组织进行活体测量。 虽然荧光技术有所进步，但它没有跟上电子和电子技术的进步 阵列探测器(摄像机)。透镜和滤光片等光学部件的尺寸远远大于 从一部手机上可以看到的电子元件，有数百万个晶体管，但只有一两个透镜 在手机里。这种尺寸上的不匹配不能通过制造更小的透镜、滤光片或光纤来避免。 这些光学元件需要许多波长的尺寸才能操纵自由传播的光。 我们建议通过使用位于亚波长近场的荧光团来克服这一限制。 离等离子体、光子或等离子体多层结构(MLS)的距离。我们并不打算使用 将荧光团作为电子元件，而不是将其发射直接耦合到cmos成像中。 带有MLSS的探测器，没有光的自由空间传播。MLS控制光能的传播， 可以分离波长，并可以将能量(耦合光子)引导到附近的探测器。这一概念 将为研究和医学的新设备提供基础。 为了证明这些设备的实用性，我们与资深教职员工在 医学院。这些协作包括检测药物发现中的弱结合或高结合 吞吐量筛选(HTS)，因为许多HTS与与靶结合较弱的药物片段一起使用 小分子。大多数最大似然法保留了x-y平面上的空间信息，这允许集合或病毒粒子 对艾滋病毒和新冠肺炎病毒SARS-CoV-2进行计数分析。宽广的视场将允许整个幻灯片成像 病理标本。 我们的目标是开发这一新的近场荧光效应领域，具有易于制造的结构， 使新一代荧光检测仪器和设备能够在研究、传感和 成像。