On-Chip Expansion Microscopy

片上膨胀显微镜

• 批准号: 9896270
• 负责人: Yu Shrike Zhang
• 金额: $ 8.95万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-01 至 2021-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9896270
• 关键词: 3-Dimensional; Architecture; Biocompatible Materials; Biological; Biology; Biomimetics; Bioreactors; Cell physiology; Cells; Chemicals; Chemistry; Communities; Complex; Custom; Development; Diffusion; Drug Formulations; Drug Screening; Engineering; Excision; Fluorescence Microscopy; Generations; Goals; Human; Human body; Image; Imaging Techniques; Imaging technology; In Situ; In Vitro; Intercellular Fluid; Label; Light; Location; Methodology; Microfluidic Microchips; Microfluidics; Microscopic; Microscopy; Molecular; Molecular Profiling; Morphology; Nature; Optics; Organoids; Penetration; Pharmaceutical Preparations; Pharmacologic Substance; Physiology; Play; Process; Property; Reaction; Research; Resolution; Role; Scheme; Site; Specimen; Structure; System; Technology; Thick; Three-Dimensional Imaging; Time; Tissue Model; Tissue Preservation; Tissues; behavioral response; biofabrication; bioprinting; body system; chemical synthesis; design; fluorescence imaging; imaging modality; improved; in vivo; innovation; millimeter; miniaturize; multi-photon; nanomedicine; nanoscale; novel therapeutics; organ on a chip; personalized therapeutic; polymerization; pressure; screening

Abstract By generating three-dimensional (3D) microtissues or organoids that accurately mimic the in vivo cellular functions, the organ-on-a-chip technologies have been playing an increasingly important role in exploiting biology and screening pharmaceutical compounds. Their successful utility is accompanied by the high demand for on- site imaging of the microtissues’ morphology, function, and molecular signatures that allow us to understand their behaviors and responses. Clearly, to image the 3D microtissues, the imaging technique should ideally provide volumetric information, together with microscopic resolutions for cellular or even subcellular analyses. On-chip imaging of intact 3D microtissues within microfluidic devices is however, fundamentally hindered by intratissue optical scattering. The overall goal of this proposal thus seeks to innovate a methodology, where a meticulously designed microfluidic bioreactor platform will be developed to enable simultaneous expansion and clearing of intact microtissues directly on-chip for in situ, super-resolution, and volumetric characterizations, breaking limits in both imaging depth and optical diffraction with conventional fluorescence microscopy.

抽象的 通过生成准确模仿体内细胞的三维 (3D) 微组织或类器官 功能，器官芯片技术在生物学开发中发挥着越来越重要的作用 和筛选药物化合物的成功应用伴随着对on-的高需求。 对微组织的形态、功能和分子特征进行现场成像，使我们能够了解 显然，为了对 3D 微组织进行成像，理想的成像技术应该是 提供体积信息以及用于细胞甚至亚细胞分析的微观分辨率。 然而，微流体装置内完整 3D 微组织的片上成像从根本上受到阻碍 因此，该提案的总体目标是寻求创新一种方法，其中 将开发精心设计的微流控生物反应器平台，以实现同时扩展和 直接在芯片上清除完整的微组织，以进行原位、超分辨率和体积表征， 突破了传统荧光显微镜成像深度和光学衍射的限制。