13TSB_TIBio: Enabling Technologies for Advanced Multiphoton Microscopy

基础生物学研究和生物技术发展的一个主要挑战是在活细胞和组织中测量细胞和亚细胞尺度上的化学成分的异质性。获得在这种规模上可视化化合物分布的能力将是一个重大进步。目前生物成像的标准是荧光显微镜，它通过分子靶标探针提供化学上特定的图像对比。然而，这些探针太大了，不能标记小分子，如脂类、碳水化合物、代谢物和许多在活细胞和组织的功能中发挥重要作用的药物。相干拉曼散射(CRS)显微镜已经成为从振动光谱中产生信号的强大工具，从而提供实时的生物分子无标记映射。然而，由于对激光的专门要求，这项技术目前仅限于少数几个拥有操作这种激光系统的资源和专业知识的专门实验室。该项目旨在开发一种简单、紧凑的模块，该模块将升级目前用于生物显微镜的脉冲激光，以提供更广泛的CRS成像途径。

A major challenge in fundamental biological research and the development of biotechnology is to measure heterogeneity in chemical composition at the cellular and subcellular scale in living cells and tissues. Gaining the ability to visualise the distribution of compounds at this scale would represent a major advancement. The current standard in biological imaging, fluorescence microscopy, provides chemically specific image contrast by molecularly targeted probes. However, these probes are too bulky for labelling small molecules such as lipids, carbohydrates, metabolites and many drugs that play essential roles in the function of living cells and tissues. Coherent Raman scattering (CRS) microscopy has emerged as powerful tool to generate signals from vibrational spectroscopy to provide label-free mapping of biomolecules in real-time. However, due to the specialised laser requirements, this technique is currently confined to a handful of specialised laboratories with the resources and expertise to operate such laser systems. This project aims to develop a simple, compact module that will upgrade pulsed lasers currently used in biological microscopes to provide wider access to CRS imaging.