Spinning Disk Confocal Microscope

• Subject Area: Statistical Physics, Nonlinear Dynamics, Complex Systems, Soft and Fluid Matter, Biological Physics ; Basic Research in Biology and Medicine
• Term: Funded in 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 569462014

Complex reciprocal interactions between cells and their three-dimensional (3D) tissue microenvironment are fundamental for the development and function of multicellular organisms, as well as disease progression. These interactions are regulated by biochemical and mechanical cues that are presented to resident cells by a surrounding 3D extracellular matrix (ECM). To gain a holistic understanding of how structure and function on the level of cells, tissues, organs and whole organisms arise from these interactions, experimental investigations have to be performed in this natural 3D context. The interactions between cells and their environment occur on several length and time scales, ranging from micrometers to millimeters and from seconds to days. Spinning disk confocal microscopy (SDCM) is a well-established technology that is optimally suited to investigate processes at these length and time scales in living specimens. Furthermore, recent software developments bring such dynamic, multi-scale studies to another level by enabling adaptive feedback microscopy, in which newly acquired images are analyzed in real-time and used to adapt temporal or spatial resolution to capture sparse and rare events. The primary participating research group has extensive experience in investigating how biochemical and mechanical cues from the ECM influence cell and tissue function. By using custom-designed 3D model tissues that recapitulate key structural and signaling properties of native tissue microenvironments, we have already gained critical insights into various fundamental cellular processes. The requested SDCM will be absolutely essential to continue this line of research. Specifically, the system has to enable deep imaging of a well-established biomimetic model of angiogenesis, which encompasses a 3D hydrogel inside a microfluidic device. To follow the rapid dynamics of cell-ECM and cell-cell interactions in the large 3D volume of these hydrogels, fast acquisition speeds combined with minimal light exposure to reduce phototoxicity are needed, for which an SDCM is optimally suited. Finally, adaptive feedback microscopy is critical to capture rare events at high temporal resolution, for example to study the initial interactions of cancer cells with the vascular system. The requested SDCM will also be incorporated into an imaging core facility that will be established at the Department of Chemistry and Chemical Biology of TU Dortmund University. Thereby, the microscope will be available for a broad group of additional users that can capitalize on the benefits of SDCM, such as imaging of rapid processes that occur within individual cells and image-based screens to develop small molecule inhibitors of cancer-related targets. Taken together, the unique features of a SDCM with a simple and flexible implementation of feedback microscopy will enable smart automation of imaging tasks, and will thereby facilitate detailed analysis of complex processes in cells.

• DFG Programme: Major Research Instrumentation
• Major Instrumentation: Spinning Disk Konfokalmikroskop
• Instrumentation Group: 5090 Spezialmikroskope
• Applicant Institution: Technische Universität Dortmund
• Leader: Professorin Dr. Britta Trappmann