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

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.

开发未来疗法是 EPSRC 医疗技术重大挑战的第一个，对于保持国家卫生服务的可持续发展至关重要。目前，估计英国 70% 的医疗保健支出用于慢性病的管理。再生医学有望显着降低成本，因为它可以将慢性退行性疾病转变为可治愈的疾病。实现这一潜力需要正确的工具来研究生物发育过程，因为它从单细胞发展到整个器官的复杂结构。光学显微镜，特别是相差显微镜的发明，使得以前所未有的清晰度突出活细胞的精细特征成为可能。然而，在显微镜载玻片上分离的细胞通常不像其自然的三维环境中的组织那样表现。最近开发的平面照明光片显微镜使得能够在发育过程中观察完整的、荧光标记的生物体。虽然光片显微镜对于透明斑马鱼或化学清除的组织非常成功，但许多组织太不透明，无法研究第一层细胞之外的情况。一个典型的例子是处于发育早期阶段的鸡胚。可以对初始层细胞复杂的集体行为进行详细研究，但是一旦原始条纹形成，为了在三维中生长胚胎，我们缺乏跟踪细胞迁移和分化的工具。图像太模糊。相关折射率光片显微镜的目的是让不可见的东西变得可见。它基于这样的认识：生物样品的浊度是由于在相差显微镜中产生结构信息的相同折射率变化造成的。样本内光学特性的分布不仅包含对生物学家有价值的结构信息，还能够实现高分辨率荧光成像所需的自适应波前校正。通过开发一种与荧光图像并行映射光学特性分布的混合仪器，该提案将能够实现混浊生物样本的高分辨率深层组织成像。直接了解生物发育过程的内部运作对于开发有效的再生医学疗法至关重要。