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Scientific Background The LACDR, Leiden University Cell Observatory Facility seeks to acquire its second fully automated high-content imaging platform integrating a high-speed confocal microscope with robotic capabilities and multiple well plate storage in a fully controlled environment. Our research primarily utilizes human induced pluripotent stem (iPS) cell models for drug and basic research. These models require live-cell imaging in a highly controlled incubator due to their sensitivity to environmental changes and human handling. Additionally, our imaging demands continue to grow, driven by an increasing number of Master’s students and high-throughput screening research projects (including RISKHUNT3R, PARC, EFSA and ScreeninC). Thus, automation is urgently needed to boost throughput and maximize the use of our imaging instruments. The LIPSI system will meet these needs, offering a hotel with a capacity of 20 plates and maintaining a stable, controlled environment that minimizes handling stress on sensitive cell lines. The platform will support both educational and research activities for principal investigators at the Cell Systems and Drug Safety (CDS) division, including Profs. Bob van de Water, Erik Danen, Micha Drukker, Joost Beltman, and the head of the HCS facility, Dr. Sylvia Le Dévédec. It will also be accessible to other LACDR PIs and Master's students for advanced imaging projects, with dedicated professional supervision from our microscopist technician. To fulfil these needs, the high-content imaging platform with integrated automation must meet the following criteria: • Automatically image multiple plate types in a stable environment. • Accommodate independent experiments from multiple users simultaneously. • Support multiple optical configurations for different users. • Provide high X, Y, Z reloading precision. • Offer fast, high-resolution imaging across various plate formats. • Be sensitive to low fluorescent signals and minimize phototoxicity. • Generate data in a format compatible with Omero and adhere to FAIR data principles. • Offer smart microscopy with real-time image analysis and acquisition adjustments. Vendor exclusivity Hardware NIKON is the exclusive supplier of the required high-content imaging platform, integrating a confocal microscope with robotics and plate storage in a fully incubated system. The LIPSI system allows 96-well plate imaging in under a minute while maintaining sensitive cells in a temperature-controlled, stress-free environment. It demonstrated the highest X, Y, Z accuracy across numerous imaging cycles, essential for single-cell tracking analysis. LIPSI leverages the full capabilities of the Eclipse Ti2 inverted microscope, including its 25mm field of view and high-speed imaging, with modularity for future upgrades with additional confocal modalities and accessories. Software The NIS image acquisition software includes a user-friendly scheduler supporting multi-user functionality, with imaging frequency as fast as 10 minutes or less. It also integrates smart microscopy features through Jobs and General Analysis 3 software, enhancing imaging speed and data quality. Support NIKON will provide comprehensive support for all components of the platform and has agreed to deliver personalized training for our microscopist technician. His experience with the LIPSI A1R and the dedicated training will ensure rapid and efficient integration of the LIPSI AXR system.