ComplexEye - a 96/384-well plate array microscope for simultaneous time-lapse video microscopy, enabling high-throughput single-cell analyses of rapidly migrating cells

• Applicants: Jianxu Chen, Ph.D.; Professor Dr. Anton Grabmaier; Professor Dr. Matthias Gunzer
• Subject Area: Biomedical Systems Technology ; Immunology ; Methods in Artificial Intelligence and Machine Learning
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 554888774

The aim of this proposal is to build ComplexEye, a highly ambitious and innovative new microscope. It forms the basis for a disruptive technology that unleashes the power of high-throughput (HT) cell-migration and -movement analysis as a novel approach for drug screening and early diagnosis of escalating immune responses. Rapid migration of cells, especially immune cells like neutrophils is central for the development and homeostasis of the body, but also mediates life-threatening diseases like sepsis and cancer. The fundamentals of cell migration are among the best-studied principles in biomedicine. Nevertheless, immune cell motility is not used as a metric for diagnostics or as a target for novel drugs (migration modifiers) due to the lack of instruments for HT tracking of fast migrating cells to routinely measure motility in a clinical setting or identify migration modifiers. Following the arthropod eye paradigm, we will realize a highly parallelized microscope. Thin lenses based on a proprietary design that fit under single wells of 96-well plates are combined with individual illumination and image detection to form stand-alone video microscopes. An array of 96 microscopes simultaneously records 96 or 384 movies of migrating cells per high-density plate. With real-time tracking of single cell movements and shapes by embedded artificial intelligence during movie recording ComplexEye will provide migration data more than 100x faster than any current technology, making immune cell migration amenable for HT analysis for the first time. This will allow to (A) screen compound libraries for substances that can modulate neutrophil migration to tumors or sites of sterile inflammation, (B) screen compounds for potential toxicity to moving cells (visual toxicity) and (C) measure spontaneous or stimulated migration of neutrophils from the blood of patients at risk of sepsis. Detecting migration-based early warning signs for a developing health crisis will provide clinicians precious time for intervention and ultimately save patients’ lives. Analyzing other migrating immune cells in the future will provide the "migrome" as disruptive new screening parameter and emerge as a paradigm-shift for disease monitoring and drug development. In this proposal, both, the complete 96-lens microscope and the software for "on the fly tracking" in real time will be developed and its performance tested in real-world examples from a laboratory of basic and applied biomedical research. Also, the principal requirements for the incorporation of fluorescence excitation and detection in the narrow physical constraints of ComplexEye will be worked out. Together this requires the knowledge of all three scientific teams. The result will be a fully working model of ComplexEye to which we will provide community-access in two technical workshops.

• DFG Programme: New Instrumentation for Research
• Participating Institution: Leibniz-Institut für Analytische Wissenschaften -ISAS- e.V.; Abteilung Biospektroskopie