Zeiss Lightsheet 7

项目摘要 凯斯西储大学医学院的光学显微镜成像核心(SOM-LMIC) 申请资助一台蔡司LightSheet 7显微镜，这将为我们的活跃分子带来巨大的好处 研究社区。目前，克利夫兰地区还没有商用光片显微镜(LSM) 可供其研究人员使用。考虑到LSM的激动人心和越来越多的使用，这尤其令人惊讶。 获得这一成像系统将使我们能够继续为我们不断扩展的 用户群。蔡司灯片7提供了我们当前的仪器无法提供的几个优势， 允许我们目前的用户提出新的问题，并吸引我们目前无法支持的新项目。 首先，该系统使人们能够在相当大的视野内获得细胞分辨率。我们的许多用户都有 努力评估分子变化在更大区域(例如，整个大脑区域， 整个胚胎心脏、前列腺活检等)。其次，蔡司LightSheet 7的购买量要高得多 比标准的共聚焦显微镜要快得多。因为与逐点比较，整个工作表是收集的 对于共焦，采集率要高得多。这将使我们的所有用户受益，因为他们可以 节省时间，逼真地为研究拍摄更大的样本，或为实时成像提供更高的时间分辨率。 第三，我们的几个用户存在光漂白或光毒性问题(例如，实时成像应用)。 蔡司灯片7只照亮正在成像的组织，这大大降低了所需的光强度 与共聚焦显微镜相比，光漂白/光毒性。蔡司灯片7将确保 许多NIH资助的项目在CWRU和附近的机构继续取得成功。对于这项提议，我们有 确定了10个主要用户和4个次要用户。这一成像系统将让我们的用户为多样化的 多个领域，包括发育生物学(Atit，Beeller，Jenkins，Ward)，3D组织病理学(Gupta， Madabhushi)、病毒学(Levine)、耳鼻喉科(McDermott)、亚细胞动力学(Mears、Kisley)、心脏病学 (罗林斯)、神经学(特萨尔、派珀)和微流体的临床应用(Gurkan)。我们预计这将是 工具将促进我们用户组内的协作，其他用户将从该资源中受益 尤其是在他们意识到它的潜力之后。在没有蔡司灯片7的情况下，许多描述的项目 在这项提议中将是不可能的。作为凯斯西部储备大学的11个机构核心设施之一， 我们在行政和基础设施方面进行了大量投资，以支持我们的日常运营。至 支持这一工具的长期运行，该大学已同意进一步捐赠近13万欧元。 所需的蔡司说明书7对我们不断发展的研究、临床和翻译需求至关重要 计划，并将在未来扩大可行项目的范围。

Project Summary The School of Medicine’s Light Microscopy Imaging Core (SOM-LMIC) at Case Western Reserve University requests funding for a Zeiss Lightsheet 7 microscope, which would have an enormous benefit to our active research community. Currently, the Cleveland area does not have a commercial light-sheet microscope (LSM) available to its researchers. This is particularly surprising considering the excitement and increased use of LSM. Obtaining this imaging system would allow us to continue to provide state-of-the-art imaging to our expanding user base. The Zeiss Lightsheet 7 provides several advantages that our current instrumentation cannot provide, allowing our current users to ask new questions as well as attracting new projects we currently cannot support. First, the system enables one to acquire cellular resolution over sizeable fields of view. Many of our users have struggled to assess the spatial extent of molecular changes over larger regions (e.g., entire brain region, throughout embryonic heart, prostate biopsy, etc.). Second, the Zeiss Lightsheet 7 has much higher acquisition rates than standard confocal microscopy. Because an entire sheet is collected in comparison to point by point for confocal, the acquisition rates are much higher. This will benefit all of our users by enabling them to either save time, realistically image larger samples for a study, or provide higher temporal resolution for live imaging. Third, several of our users have problems with photobleaching or phototoxicity (e.g., live imaging applications). The Zeiss Lightsheet 7 only illuminates tissue that is being imaged which greatly reduces the required light levels and photobleaching/phototoxicity compared to confocal microscopy. The Zeiss Lightsheet 7 will ensure the continued success of many NIH-funded programs at CWRU and nearby institutions. For this proposal, we have identified 10 major and 4 minor users. This imaging system will allow our users to make contributions to a diverse number of fields including developmental biology (Atit, Bearer, Jenkins, Ward), 3D histopathology (Gupta, Madabhushi), virology (Levine), otolaryngology (McDermott), subcellular dynamics (Mears, Kisley), cardiology (Rollins), neurology (Tesar, Pieper), and clinical applications of microfluidics (Gurkan). We anticipate that this instrument will foster collaborations within our user groups and that other users will benefit from this resource especially after they become aware of its potential. Without the Zeiss Lightsheet 7 many of the projects described in this proposal will not be possible. As one of Case Western Reserve University’s 11 Institutional Core Facilities, significant investment into administration and infrastructure has been made to support our daily operations. To support the long-term operation of this instrument, the University has agreed to further contribute nearly 130k. The requested Zeiss Lightsheet 7 is essential to the needs of our evolving research, clinical and translational programs and will expand the range of viable projects in the future.