Automated digital high-precision, high-throughput tissue microarray (TMA) system

这里申请的大型装置是由各种部件组成的系统，包括用于数字化组织切片准备的载玻片扫描仪，用于夹紧60个供体石蜡组织块和12个受体石蜡切片的组织微阵列(TMA)打孔机，以及相关的计算机软件和硬件。该系统将被集成到一个新的“高级组织成像和数字病理学”核心设施中，该核心设施将在图宾根大学医院的病理研究所建立，在那里它将作为一个中心组件使用。该系统中的载玻片扫描仪将需要对石蜡块的新鲜切割的苏木素和曙红(H&E)染色的组织切片进行数字化。然后在TMA穿孔机中拍摄每个供体组织块的高分辨率石蜡块切面照片，自动数字对准数字化的H&E染色切片。然后在计算机上对要整合到TMA中的准确组织区域进行高精度注释。TMA冲床的钻芯尺寸从0.6 mm到2.0 mm不等。传统的手工制作TMA，就像病理研究所目前使用2006年购买的设备所做的那样，以这种精度是不可想象的，并且没有必要的生产能力来服务于众多项目。此外，自动打孔机允许同时生产多达12份TMA复制品(12个接收器块)，用于准备多种着色剂，例如，用于合作运输。高精度的TMA对于先进的组织成像(高度复合显微镜)是必要的，以表征生物标记物以及分析肿瘤微环境中的细胞相互作用。目前，高度多元化的显微镜不允许高通量，使得许多组织放在载玻片上进行实验和进一步分析。TMA穿孔机还有一个聚合酶链式反应模块，可以将样品输出到样品瓶中提取DNA/RNA。大量的研究目前正在计划中，将使用所需的仪器进行，包括皮肤T细胞淋巴瘤、胃食管腺癌、腹膜间皮瘤、结直肠癌、恶性黑色素瘤、胶质母细胞瘤等的研究。此外，建议的设备将用于目前正在应用的合作研究中心1623“免疫持久性”的中心项目、Tübingen大学医院的生物库服务项目和临床研究/分子肿瘤委员会。

The large-scale device applied for here is a system consisting of various components, including a slide scanner for digitizing histological section preparations, a tissue microarray (TMA) punching machine for clamping 60 donor paraffin tissue blocks and 12 recipient paraffin blocks, as well as the associated computer software and hardware. This system is to be integrated into a new "Advanced Tissue Imaging & Digital Pathology" Core Facility to be established at the Institute of Pathology at the University Hospital of Tübingen, where it will be used as a central component. The slide scanner in this system will be required to digitize freshly cut hematoxylin and eosin (H&E)-stained tissue sections of the paraffin blocks. A high-resolution photograph of the cut surface of the paraffin block is then taken of each donor tissue block in the TMA puncher, which is automatically digitally aligned to the digitized, H&E-stained section. High-precision annotations are then made on the computer of the exact tissue regions to be integrated into the TMA. The TMA punching machine has different drill core sizes between 0.6 and 2.0 mm. Conventional, manual creation of TMAs, as is currently done at the Institute of Pathology with the device acquired in 2006, is unthinkable with this precision and does not have the necessary throughput to serve numerous projects. In addition, the automatic punching machine allows up to 12 duplicates of the TMA to be produced simultaneously (12 receiver blocks) for the preparation of numerous stains and, for example, for shipping in collaborations. The high-precision TMAs are necessary for advanced tissue imaging (highly multiplexed microscopy) to characterize biomarkers as well as to analyze cellular interactions in the tumor microenvironment. Currently, highly multiplexed microscopy does not allow for high throughput, making many tissues on a slide central to performing experiments and further analysis. The TMA puncher also has a PCR module that allows output of cores into sample vials for DNA/RNA extraction.Numerous studies are currently being planned and will be processed using the requested instrument, including studies on cutaneous T-cell lymphoma, gastroesophageal adenocarcinoma, peritoneal mesothelioma, colorectal carcinoma, malignant melanoma, glioblastoma, etc. In addition, the proposed device will be used in a central project of the Collaborative Research Center 1623 "ImmunoPersist" currently in application, in biobank service projects of the University Hospital Tübingen and for clinical studies / molecular tumor board.