Quantitative high-throughput spinning-disk confocal microscope

• Subject Area: Biological Chemistry and Food Chemistry
• Term: Funded in 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 512574446

For further equipment of the infrastructure center Frankfurt Center for Innovation & Technologies (FCiT, currently being established) a confocal spinning-disk microscope for high-throughput analyses is requested. Within the FCiT, several life science and biomedical oriented devices in different categories are brought together and operated jointly. In particular, the instruments serve the interface between basic and preclinical research and provide the technological basis for various joint research consortia. These include the Structural Genomics Consortium (EUbOPEN, since 2017), the Innovative Medicine Initiative EUbOPEN (since 2020), the Cluster Initiative ENABLE (since 2021) and the Cluster for Future PROXIDRUGS (since 2021). In contrast to classical cell biology projects, in which individual cellular structures are analyzed by high-resolution confocal microscopy (required technologies provided by the Frankfurt Institute for Advanced Light Microscopy (FCAM)), the above-mentioned collaborative projects require much higher throughput (hardware) and correspondingly optimized and automated analysis capabilities (software). Especially the automated microscopic analysis of cells in microtiter plate formats are crucial here. In the Cellular & Phenotypical Screening Platform (Head: Dr. Alexandra Stolz), chemical libraries are examined microscopically in cell-based, medium- to high-throughput analyses. Analyses start with the examination of single chemical substances in different concentrations and extend to screens of relatively large chemical libraries (e.g. FDA approved drug library of ~3,000 cpds). Advanced, more detailed microscopic analyses is performed subsequently in collaboration with the FCAM. The automated confocal high-content screening microscope with specific software applied for, can scan fixed cells/tissues as well as live cultures in a wide variety of plate formats in quantitative long-term microscopy in a semi-automated manner and process the acquired data by means of intelligent, user-specific logarithms and analysis protocols. Equipment for the screening microscope includes multiple laser and filter combinations, objectives, a high-performance camera, temperature and gas regulation of the incubation chamber, and various software packages for automated image analysis. The scope of the instrument includes various microscopy-based techniques for the analysis of 2D and 3D cultured cells as well as tissues, including those necessary for localization studies, morphology studies, screens for identification, characterization and validation of chemical compounds (drug discovery; PROTACs; small molecules), studies for identification of altered cellular signaling pathways, protein-protein interactions, degradation studies of cellular proteins and cell characterization (cellomics).

• DFG Programme: Major Research Instrumentation
• Major Instrumentation: Quantitatives konfokales Hoch-Durchsatz Spinning-Disk Mikroskop
• Instrumentation Group: 5090 Spezialmikroskope
• Applicant Institution: Goethe-Universität Frankfurt am Main
• Leader: Dr. Alexandra Stolz