A Chemical Imaging Platform for Discovery Biosciences (CIP-DB).

了解细胞的生物学、其组成分子以及聚集成组织时的行为和特征一直是生命科学和医学的关键目标。显微镜的进步正在深刻地改变细胞、亚细胞结构、分子和组织的研究方式。对于像伦敦大学学院这样的研究密集型机构，要想在生物医学科学领域保持具有竞争力的领先地位，至关重要的是采用变革性成像技术，前提是这些技术的威力得到认识，该技术负担得起，得到很好的理解，并被确定为可行的变革性生物科学工作。要加深我们对健康和疾病的了解，需要对细胞、其成分及其从生命早期阶段的发育有深入的了解。如何以高空间和光谱分辨率对完整、大规模、活的或保存的死后细胞、组织和生物体进行成像仍然是一个关键挑战。伦敦大学学院作为生物科学/生物医学发现的关键贡献者，其国际声誉之所以成功，部分原因是它始终致力于成为新的、变革性技术的早期采用者。实现这一目标的一个新的有效途径是直接成像(不使用报告探针分子)随着时间的推移细胞和组织的化学和生化特性。这必须使用能够以足够精细的空间细节和非常高的化学分辨率以高速图像捕获的设备来完成，以便能够发现和研究迄今未知的过程。拉曼成像技术特别适合于研究生物分子在胚胎发生、组织分化、健康和疾病期间的表型变化以及它们的生化功能表现中的关键分布和性质。CIP-DB将为生命和生物医学科学的尖端研究提供新的支持。拉曼显微镜是一种独特的系统，能够逐个像素地获取关于组织或细胞样本的化学成分的高度详细、定性和定量的信息。根据这些数据，可以构建出类似于多维虚拟染色的显示化学物种分布的图像，但不需要引入探针、染料、抗体或遗传编码标记。这些图像提供了丰富的生化和分子生物学信息及其空间分布。生物样品的这种表征基本上与通过其他光学显微镜技术收集的样品是正交的，例如在现代细胞生物科学中几乎普遍和专门使用的荧光成像技术。此外，共焦和近红外照明将允许对样品进行深度探测和3D化学图像重建。轮廓跟踪技术将允许将该技术应用于非平坦、粗糙或复杂的表面。这将允许分析未经处理的组织样本，以及随着实验过程中生长、肿胀或其他变化而厚度发生变化的样本。因此，这项建议的主要共同申请者是伦敦大学学院的研究小组和附近研究机构的同事，他们专注于分子细胞、发育生物学和生物化学方面的研究，试图阐明在健康和疾病中支撑生物发育的基本过程和关键事件/因素。此外，显微镜将可用于解决基础生物科学中许多悬而未决的问题的大量不同研究项目。申请的资金将使我们能够获得一台领先的拉曼显微镜，这将显著增强我们的研究能力，并导致新的科学发现。

Understanding the biology of cells, their component molecules and behaviors and characteristics when aggregated into tissues has always been a key goal in life science and medicine. Advances in microscopy are profoundly changing the way cells, sub-cellular structures, molecules and tissues can be studied. For a research intensive institution, such as UCL, to remain a competitive leader in biomedical sciences, it is essential to adopt transformative imaging technologies when their power is recognized, the technology is affordable, well understood and established as viable for transformative bioscience work. Furthering our understanding of health and diseases requires a deep knowledge of the cell, its constituents and their development from very early stages of life. How to image intact, large-scale, live or preserved postmortem cells, tissues and organisms at high spatial and spectroscopic resolution with and sensitivity remains a key challenge.UCL's international reputation as a key contributor in bioscience/biomedical discoveries has, in part, been successful because of it's sustained commitment to be an early adopter of new, transformative technologies. One new and powerful pathway toward this goal is to image directly (without the use of reporter probe molecules) the chemical and biochemical properties of cells and tissues over time. This must be done with equipment that is capable of capturing at high speed images with sufficient fine spatial detail and at very high chemical resolution so that hitherto, unknown processes can be discovered and studied. Raman imaging technology is particularly suited to the study of key distibutions and properties of biomolecules during embryogenesis, tissue differentiation, changes in phenotype during health and disease and performance of their biochemical function. CIP-DB will add a new dimension of support to cutting edge research in life and biomedical sciences. The Raman microscope is a unique system that enables acquisition of highly detailed, qualitative and quantitative information on the chemical composition of a tissue or cellular sample pixel-by-pixel. From this data images displaying the distribution of chemical species much like a multi-idimensional virtual staining, but without the introduction of probes, dyes, antibodies or genetically encoded markers, can be constructed. These images provide rich biochemical and molecular biological information and their spatial distribution. This characterization of biological samples is essentially orthogonal to that collected through other light microscopic techniques like the fluorescence imaging used almost universally and exclusively in modern cellular biosciences. Furthermore confocality and near infrared illumination will allow deep probing of samples and 3D chemical image reconstruction. Contour tracking technology will allow application of the technique to non-flat, rough or complex surfaces. This will allow unprocessed tissue samples to be analysed as well as samples where the thickness is changing over the duration of the experiment through growth, swelling or other changes.The main co-applicants on this proposal are, therefore, research groups at UCL and colleagues in nearby research institutes whose focus is on aspects of molecular cell and developmental biology and biochemistry trying to elucidate the fundamental processes and key events/factors that underlie organismal development in both health and disease. In addition, the microscope will be accessible to a large number of diverse research projects addressing many outstanding questions in fundamental biosciences. The requested funds will enable us to obtain a one of the leading Raman microscope that will significantly enhance our research capabilities and lead to new scientific discoveries.