Automated Multiscale Super-resolution Confocal Microscope

摘要 拉霍亚免疫研究所(LJI)是美国首屈一指的免疫学研究机构，其 20名首席调查人员得到了NIH约3900万美元的赠款和合同的支持。在LJI，我们研究 免疫细胞在美国和世界各地主要疾病中的行为，包括1型病毒生物学 糖尿病、动脉粥样硬化、癌症和炎症。我们几乎所有的科学家都使用成像技术来可视化细胞 与发表在《自然》、《科学》和其他著名期刊上的研究结果的相互作用、信号传递和作用。 然而，随着我们研究目标的发展，以及在本申请中列出的研究项目中取得进一步进展， 我们需要一个可靠的、多功能的、具有多尺度成像能力的超分辨率共聚焦显微镜。这个 LJI显微镜和组织学核心设施是一个动态的、科学驱动的、多用户的资源，具有 巨大的增长潜力。LJI显微镜核心设备中的仪器包括老化的蔡司 LSM 780，被NIH资助的许多项目使用，目的从研究基质蛋白 SARS-CoV-2中的组装，动脉粥样硬化中的新细胞类型，导致1型糖尿病的分子途径， 还有其他许多人。该系统的使用寿命即将结束，需要更换一台显微镜。 在这里，我们寻求支持购买一台自动化的、最先进的、超分辨率显微镜 允许对老鼠和人类组织进行多尺度、高通量的研究。动态生物学 由于创新的软件、高灵敏度的探测器和无与伦比的 获取速度。在比较了所有大公司的市场工具后，很明显， 配备AiryScan 2系统的蔡司LSM 980最适合LJI调查人员和合作者的需求， 如果得到资助，它无疑将对美国国立卫生研究院支持的科学进步产生重大影响。

ABSTRACT The La Jolla Institute for Immunology (LJI) is a premier immunology research institute in the US whose 20 principal investigators are supported by ~$39 million in NIH grants and contracts. At LJI, we study the behavior of immune cells in diseases prominent in the US and around the world, including viral biology, type 1 diabetes, atherosclerosis, cancer, and inflammation. Nearly all of our scientists use imaging to visualize cellular interactions, signaling, and function with results published in Nature, Science, and other prominent journals. However, as our research aims evolve, and to progress further in the research projects listed in this application, we need a reliable and versatile super-resolution confocal microscope with multiscale imaging capability. The LJI Microscopy and Histology Core Facility is a dynamic, scientifically driven, multi-user resource with a remarkable potential for growth. The instrumentation in the LJI Microscopy Core Facility includes an aging Zeiss LSM 780 that is used by many NIH funded projects, with aims ranging from the investigation of matrix protein assembly in SARS-CoV-2, novel cell types in atherosclerosis, molecular pathways leading to Type 1 diabetes, and many others. This system is nearing the end of its useful lifetime and a replacement microscope is needed. Here, we seek support for purchasing an automated, state-of-the-art, super-resolution microscope that allows for multiscale, high-throughput investigation of mouse and human tissues. Dynamic biological processes can be probed thanks to innovative software, highly sensitive detectors, and unparalleled acquisition speed. After comparing instruments on the market from all major companies, it is clear that the Zeiss LSM 980 with Airyscan 2 system is the best suited for the needs of LJI investigators and collaborators, and if funded, it will undoubtedly have a significant impact on NIH-supported scientific progress.