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

了解细胞的生物学，它们的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UCL这样的研究密集型机构来说，要保持生物医学科学的竞争力，必须采用变革性成像技术，当它们的力量得到认可时，该技术是负担得起的，很好地理解并确立为变革性生物科学工作的可行性。进一步了解健康和疾病需要深入了解细胞，其成分及其在生命早期阶段的发展。如何在高空间和光谱分辨率下对完整的、大规模的、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。UCL作为生物科学/生物医学发现的关键贡献者的国际声誉部分是成功的，因为它一直致力于成为新的变革性技术的早期采用者。一个新的和强大的途径实现这一目标是直接成像（不使用报告探针分子）的化学和生物化学性质的细胞和组织随着时间的推移。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高速捕获图像的设备来完成，以便可以发现和研究迄今为止未知的过程。拉曼成像技术特别适用于研究胚胎发生、组织分化、健康和疾病期间表型变化及其生化功能表现期间生物分子的关键分布和性质。CIP-DB将为生命和生物医学科学的前沿研究提供新的支持。拉曼显微镜是一种独特的系统，能够逐像素获取组织或细胞样本化学成分的高度详细的定性和定量信息。根据该数据，可以构建显示化学物质分布的图像，非常像多维虚拟染色，但不引入探针、染料、抗体或遗传编码的标记。这些图像提供了丰富的生物化学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正交，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。此外，共焦和近红外照明将允许样品的深度探测和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。这将允许分析未处理的组织样本以及厚度在实验期间通过生长、膨胀或其他变化而变化的样本。因此，该提案的主要共同申请人是：伦敦大学学院的研究小组和附近研究机构的同事，他们的重点是分子细胞和发育生物学和生物化学方面，试图阐明基本过程和关键事件。健康和疾病中生物体发展的基础因素。此外，显微镜将可用于大量不同的研究项目，解决基础生物科学中许多悬而未决的问题。所要求的资金将使我们能够获得领先的拉曼显微镜之一，这将大大提高我们的研究能力，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.