Super-resolution structured illumination microscope

描述（由申请人提供）：本提案旨在获得一种新型商用Zeiss ELYRA S.1超分辨率结构照明显微镜（SR-SIM），该显微镜具有独特的多通道超分辨率能力，可供一组细胞生物学家研究细胞分裂、迁移、极性和细胞器动力学及遗传等过程的分子结构。光学显微镜用于研究细胞结构和功能的主要限制之一是无法分辨低于光学系统衍射极限的结构。ELYRA S.1 SR-SIM使用结构化照明生成的图像在横向（X，Y）和轴向（Z）方向上均超过正常分辨率屏障两倍。ELYRA S.1 SR-SIM提供了其他市售SR-SIM中没有的罕见组合：上级性能（用户友好的三通道高分辨率3D SIM成像，以及快速的活细胞SIM成像）和低成本。所要求的仪器的主要用户都是经验丰富的细胞生物学家，他们在过去的工作中广泛使用了光显微镜方法。该小组试图使用ELYRA S.1 SR-SIM扩展其NIH资助的研究，以获得有关细胞骨架与膜相互作用，细胞器基因组结构和定位，动粒动力学和核膜结构等过程的更高分辨率信息。该小组成员之间已经存在协作互动，预计这将有助于采用将增强超分辨率显微镜实用性的程序和技术。该仪器将作为哥伦比亚大学已建立并得到良好支持的成像中心的一部分进行管理，这将有助于将该仪器广泛暴露于其他用户。用ELYRA S.1 SR-SIM获得的更高分辨率的信息应该扩展我们对现有光学显微镜分辨率以下发生的基本细胞过程的知识。这些信息将有助于确定开发治疗方法的新途径，用于治疗癌症、炎症和心脏病等疾病，这些疾病部分是由于细胞结构的适当组织缺陷造成的。

DESCRIPTION (provided by applicant): This proposal is to obtain a new commercial Zeiss ELYRA S.1 Super-Resolution Structured Illumination Microscope (SR-SIM) that has unique multi-channel super- resolution capabilities for a group of cell biologists studying the molecular architecture of processes including cell division, migration, polarity and organelle dynamics and inheritance. One of the major limitations of light microscopy for the study of cell structure and function has been the inability to resolve structures below the diffraction limit imposed on optica systems. The ELYRA S.1 SR-SIM uses structured illumination to generate images that exceed the normal resolution barrier by two-fold in both lateral (X, Y) and axial (Z) directions. The ELYRA S.1 SR-SIM provides a rare combination that is not found in other commercially available SR-SIMs: superior performance (user- friendly high-resolution 3D SIM imaging in three channels, and rapid live-cell SIM imaging) and low cost. The major users of the requested instrument are all experienced cell biologists who have made extensive use of light microscopic approaches in their past work. This group seeks to use the ELYRA S.1 SR-SIM to extend their NIH-funded studies to obtain higher-resolution information on processes such as the interaction of cytoskeleton with membranes, organelle genome structure and localization, kinetochore dynamics, and nuclear envelope structure. Collaborative interactions already exist within members of this group and this is expected to facilitate adoption of procedures and techniques that will enhance the utility of the super-resolution microscope. The instrument will be administered as part of an established and well-supported imaging center at Columbia University, which will facilitate broad exposure of the instrument to additional users. The higher-resolution information obtained with the ELYRA S.1 SR- SIM should extend our knowledge of fundamental cellular processes occurring below the resolution of our existing light microscopes. This information will be helpful in identifying new avenues for the development of therapeutic approaches for the treatment of diseases such as cancer, inflammation and heart disease that result in part from deficits in the proper organization of cellular architecture.