High-Throughput High-Resolution Cell Imaging System

这项应用的目的是建立基于活细胞和体外产生的三维细胞组织的定量三维长期显微镜的药理学高通量分析。因此，需要一种能够以全自动方式分析基于微滴定板的复杂样本集的显微系统。例如，在天然产物数据库的筛选中，数据集的复杂性需要一种量身定制且同时灵活适用的软件解决方案，该解决方案一方面将图像与所有必要的元信息一起组织和存储，另一方面使得能够以自动化的方式进行诸如分割、协同定位或强度分析之类的复杂分析，因为由于数据的大小而不能处理手动分析。由于主要研究的是人类“工程生物材料”，如肿瘤球体/器官体和体外产生的表皮或(与疾病相关的)全层皮肤模型，因此需要一种广域共聚焦系统，以实现高时间分辨率的3D显微镜。增加的共焦定量图像细胞仪应该提供最佳和独特的组合，易于使用/分析和最新类型的强大的高速共焦显微镜在一个盒子里，这样它基本上可以在任何非黑暗的实验室空间工作。理想情况下，它将是一个台式共聚焦成像和分析系统，带有集成的气候室和孵化控制。所要求的共聚焦成像系统的中心要求是它是否适用于三维仿生(共培养)模型，这些模型是微型化的(96或384微滴定板格式)，被表征并用于测试小分子候选药物。我们的目标是获得一种坚固耐用的仪器，允许共焦分辨率、相对较高的吞吐量以及无故障的常规操作。

The aim of this application is to establish pharmacological high-throughput analyses based on quantitative three-dimensional long-term microscopy of living cells and in vitro generated three-dimensional cell tissues. Therefore, a microscopy system is needed that can analyze complex sample sets based on microtiter plates in a fully automated manner. The complexity of the data sets in e.g. screenings of natural product databases requires a tailor-made and at the same time flexibly applicable software solution, which on the one hand organizes and stores images together with all necessary meta-information, and on the other hand enables complex analyses such as segmentations, co-localizations or intensity analyses in an automated way, because manual analyses cannot be handled due to the size of the data. Since primarily human "engineered living materials" such as tumor spheroids/organoids and in vitro generated epidermis or (disease-relevant) full-thickness skin models will be investigated, a wide-field confocal system will be required that allows 3D microscopy with high temporal resolution. The addition of a Confocal Quantitative Image Cytometer should provide an optimal and unique combination of ease of use/analysis and powerful, high-speed confocal microscope of the latest type in a box, so that it could basically work in any non-darkened laboratory space. Ideally, it would be a benchtop confocal imaging and analysis system with an integrated climate chamber and incubation control. The central requirement for the requested confocal imaging system is its suitability for three-dimensional biomimetic (co-culture) models that are miniaturized (in 96- or 384-microtiter plate format), characterized and used for testing small molecule drug candidates. The goal is to procure a robust instrument that allows confocal resolution, comparatively high throughput in combination with trouble-free routine operation.