Multispectral High-Throughput Slide Scanner

• Subject Area: Medicine
• Term: Funded in 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 550234049

The requested large-scale equipment is a system for spatially resolved detection of proteins ("Spatial Proteomics"), which has the capacity for single-cell and subcellular resolution and a very high throughput. This system is to be integrated into the "Advanced Tissue Imaging & Digital Pathology" Core Facility to be established at the Institute of Pathology and the M3 Research Center of the University Hospital Tübingen, where it will be used as a central component. In recent years, spatially resolved proteomics and transcriptomics technologies have developed enormously. While some systems for spatial proteomics based on imaging mass spectrometry can display up to 40 proteins at the same time, the new optical methods, which are based on repetitive staining/bleaching or DNA-labeled antibodies, have capacities for 100+ proteins. High-multiplex microscopy has fundamentally changed our understanding of the tumor microenvironment and how immune cells communicate within it, providing numerous new insights. However, the aforementioned technologies have the disadvantage that imaging takes a very long time (about 3-4 days for a region of approximately 1 cm2 at 40-plex and 200x magnification), and that the reagents (antibodies, lanthanide metals, oligonucleotides, etc.) are relatively expensive. Thus, these high-multiplex technologies are only suitable for smaller "discovery" patient cohorts or tissue microarrays, in which numerous tissue cores from different paraffin blocks are combined in one paraffin block. However, this method does not optimally represent tumor heterogeneity. For the validation of data generated through high-multiplex microscopy, for extension to larger patient cohorts, for a better representation of tumor heterogeneity, for the further development of identified (spatial) biomarkers into an examination method applicable in routine pathology, and for a proof-of-concept towards a possible future use for patients, e.g., within the framework of molecular tumor boards, a different type of device is necessary: the multispectral high-throughput slide scanner. With this device (at "low-plex", up to 9 simultaneous biomarkers), up to 80 full sections (3 cm2) can be scanned per 1.5 days at 400x magnification. This opens up the possibility of examining large, multicentric clinical cohorts whose tissues are stored in the paraffin archives of pathology institutes. Numerous studies are currently in planning and are intended to be processed with the requested device, including on cutaneous T-cell lymphoma, gastroesophageal adenocarcinoma, colorectal carcinoma, diffuse large B-cell lymphoma, glioblastoma, urothelial carcinoma, malignant melanoma, etc. (see section 3.1.3 and further projects of the individuals involved in the application).

• DFG Programme: Major Research Instrumentation
• Major Instrumentation: Multispektraler Hochdurchsatz-Slidescanner
• Instrumentation Group: 5042 Mikroskope für Hochdurchsatz und Screening
• Applicant Institution: Eberhard Karls Universität Tübingen
• Leader: Professor Christian Schürch, Ph.D.