Computational Refractive Index Light-sheet Microscopy (CORILIM)

计算折射率光片显微镜 (CORILIM)

• 批准号: MR/Y003977/1
• 负责人: Tom Vettenburg
• 金额: $ 75.8万
• 依托单位: University of Dundee
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FY003977%2F1
• 关键词: Computational; Refractive; Index; Light; sheet; Computational; Refractive; Index; Light; sheet

Developing future therapies, the first of EPSRC's Healthcare Technologies Grand Challenges, is essential to keep the National Health Service sustainable. Currently, an estimated 70% of the UK's healthcare expenditure goes towards the management of chronic diseases. Regenerative medicine is expected to significantly reduce costs as it can turn chronic, degenerative, diseases into curable conditions. Realising this potential requires the right tools to study the biological development process as it progresses from the single cell to the complex structure of entire organs.The invention of the optical microscope, and in particular the phase contrast microscope, made it possible to highlight the fine features of living cells with unprecedented clarity. However, cells isolated on a microscope slide often do not behave as tissue in its natural, three-dimensional, environment. The recent development of the planar illumination light-sheet microscope enabled the visualisation of the intact, fluorescently-labelled, organisms during development. While light-sheet microscopy is highly successful for transparent zebrafish or chemically cleared tissue, many tissues are too opaque to be studied beyond the first layer of cells. A prime example is the chick embryo in its early stages of development. The complex collective behaviour of the cells in the initial layer can be studied in exquisite detail, yet as soon as the primitive streak forms, to grow the embryo in the third dimension, we lack the tools to keep track of the cell migration and differentiation. The images are too blurred.Correlative refractive index light-sheet microscopy aims to make the invisible visible. It is based on the realization that the turbidity of biological samples is due to the same refractive index variations that yield structural information in phase-contrast microscopy. The distribution of optical properties within the specimen not only contains valuable structural information for the biologist, it also enables the adaptive wavefront correction needed for high resolution fluorescence imaging. By developing a hybrid instrument that maps the optical property distribution in parallel with the fluorescence image, this proposal will enable high-resolution deep-tissue imaging in turbid biological specimen. A direct view into the inner workings of the biological development process is essential to develop effective regenerative-medicine therapies.

EPSRC的医疗保健技术的第一个挑战发展未来的疗法对于保持国家卫生服务局的可持续性至关重要。目前，估计英国医疗保健支出的70％用于管理慢性病。预计再生医学将显着降低成本，因为它可能会使慢性，退化性疾病变成可治愈的疾病。意识到这一潜力需要正确的工具来研究生物发育过程，因为它从单个细胞发展到整个器官的复杂结构，光学显微镜的发明，尤其是相比显微镜，使其可以突出具有前所未有的清晰度的活细胞的良好特征。然而，在显微镜载玻片上分离的细胞通常在天然，三维环境中表现为组织。平面照明显微镜的最新发展使得在发育过程中可以看到完整，荧光标记的生物。虽然光显微镜对于透明的斑马鱼或化学清除的组织非常成功，但许多组织过于不透明，无法在第一层的细胞之外进行研究。一个典型的例子是雏鸡的发育早期阶段。可以用精美的细节研究单元中细胞的复杂集体行为，但是，一旦形成原始条纹，就可以在第三维中生长胚胎，我们缺乏跟踪细胞迁移和分化的工具。这些图像太模糊了。相反的折射率灯页显微镜旨在使无形可见。它基于这样的意识到，生物样品的浊度是由于相同的折射率变化引起的，在相互对比显微镜下产生结构信息。样品中光学特性的分布不仅包含生物学家的有价值的结构信息，还可以实现高分辨率荧光成像所需的自适应波前校正。通过开发与荧光图像并行映射光特性分布的混合仪器，该提案将在浑浊的生物样品中实现高分辨率的深入组织成像。对生物发展过程的内部运作的直接观点对于开发有效的再生中医学疗法至关重要。