Ultra-high-multiplex tissue scanner

超高复合组织扫描仪

• 批准号: 534266004
• 金额: --
• 依托单位: Eberhard Karls Universität Tübingen
• 依托单位国家: 德国
• 项目类别: Major Research Instrumentation
• 财政年份: 2023
• 资助国家: 德国
• 起止时间: 2022-12-31 至 无数据
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/534266004?language=en
• 关键词: Ultra; multiplex; tissue; scanner

The large-scale device applied for here is a system for the spatially resolved detection of proteins and RNA transcripts ("Spatial Proteomics & Transcriptomics"), which has the capacity for single cell and subcellular resolution. This system is to be integrated into the "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. In recent years, there has been a tremendous surge in the development of spatially resolved proteomics and transcriptomics. While some systems for spatial proteomics based on imaging mass spectrometry can only image approx. 40 proteins can be visualized at a time, the new optical methods based on repetitive staining/bleaching or DNA-labeled antibodies have capacities of 100+ proteins. Whereas until recently spatial transcriptomics could only display dots of approximately 50-100 micrometers in diameter, new instruments that came to the market in 2022 enable resolution in the 100-200 nanometer range, i.e., at the single cell level and even subcellular. Only this single-cell resolution allows the assignment of proteins and RNA transcripts to certain cell types in the tissue, which is essential for understanding the interactions between different cell types by means of messengers such as cytokines and chemokines, which often cannot be visualized by means of pure proteomics. In addition, until recently, only fresh-frozen tissue samples could be analyzed; however, the technologies have now been extended to paraffin-embedded tissues. This opens up the possibility of studying large clinical cohorts whose tissues are stored in the paraffin archives of pathology institutes. Most importantly, the new technologies will allow a combination of spatial proteomics and transcriptomics, which will once again fundamentally change our understanding of the tumor microenvironment, and how immune cells within it communicate with each other. These technologies will reveal new ways to improve the prediction of response to (immuno)therapies and play a crucial role in the discovery of new therapeutic targets. Numerous studies are currently being planned and will be addressed with the requested device, including cutaneous T-cell lymphoma, gastroesophageal adenocarcinoma, colorectal carcinoma, chronic myeloid leukemia, malignant melanoma, etc.

这里应用的大规模设备是用于蛋白质和RNA转录物的空间分辨检测的系统（“空间蛋白质组学和转录组学”），其具有单细胞和亚细胞分辨率的能力。该系统将被纳入将在蒂宾根大学医院病理学研究所建立的“高级组织成像和数字病理学”核心设施，并将作为核心组成部分使用。近年来，空间分辨蛋白质组学和转录组学的发展突飞猛进。而一些基于成像质谱的空间蛋白质组学系统只能成像约100 μ m。一次可以观察40种蛋白质，基于重复染色/漂白或DNA标记抗体的新光学方法具有100+蛋白质的能力。直到最近，空间转录组学只能显示直径约50-100微米的点，而2022年上市的新仪器能够实现100-200纳米范围的分辨率，即，在单细胞水平甚至亚细胞水平。只有这种单细胞分辨率才能将蛋白质和RNA转录物分配给组织中的某些细胞类型，这对于理解不同细胞类型之间通过信使（如细胞因子和趋化因子）的相互作用至关重要，这通常无法通过纯蛋白质组学可视化。此外，直到最近，只能分析新鲜冷冻的组织样本;然而，该技术现在已扩展到石蜡包埋的组织。这开辟了研究大型临床队列的可能性，这些队列的组织存储在病理学研究所的石蜡档案中。最重要的是，新技术将允许空间蛋白质组学和转录组学的结合，这将再次从根本上改变我们对肿瘤微环境的理解，以及其中的免疫细胞如何相互交流。这些技术将揭示改善对（免疫）治疗反应预测的新方法，并在发现新的治疗靶点方面发挥关键作用。目前正在计划进行大量研究，并将使用申请的器械进行研究，包括皮肤T细胞淋巴瘤、胃食管腺癌、结直肠癌、慢性髓性白血病、恶性黑色素瘤等。