High-Content-Screening Microscope System (renewal)

• Subject Area: Basic Research in Biology and Medicine
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 578925932

Here we apply for upgrading an existing high-content screening microscope with water im-mersion objective lenses, additional LEDs and an additional low-magnifying objective lens. By that, we aim to extend the overall operating time by improving the resolution to the level of modern confocal microscopes. Consequently, the device will be used for new projects with high resolution and automation requirements. The extension of the LEDs will enable new as-says to be carried out on the microscope, which increases and extends its use. The high-content screening microscope was acquired in 2018 to enable higher sample throughput and elaborated image analysis in the scope of fluorescence microscopy. Since then, the device has been used for various studies and is well established at our site. There is demand from several research groups to upgrade the device with water immersion objectives and additional LEDs to improve the optical resolution in XYZ and expand the range of applica-tions in terms of dye combinations. In the current device setup, the system offers three air objectives and four LEDs. Due to the lack of water immersion, we have so far been severely limited as soon as three-dimensional structures are to be imaged, such as organoids or plants. Additionally, the detection of small structures such as mitochondria or cytoskeletal filaments in living cells requires better resolu-tion in order to perform robust quantifications. By installing water objectives, it would be fur-thermore possible to capture weak fluorophores that currently cannot be detected with the device, as the NA of the existing air objectives is significantly lower. In order to increase the degree of automation, when imaging large samples, e.g., plant roots or organoids, a low mag-nification objective will be helpful to enable automated fast scanning of the entire sample. High-resolution detailed images could then be taken with the water objectives in the automatically detected areas. The higher degree of automation shortens the running times of experiments and thus makes the device available to more users. In addition, although the existing LEDs are suitable for common fluorophores, they are particu-larly limiting in terms of compatibility with some important fluorescence proteins (e.g., mCeru-lean, CFP, mVenus, YFP, iRFP) and multiplex assays such as cell painting.

• DFG Programme: Major Research Instrumentation
• Major Instrumentation: Automatisiertes High-Content-Screening Mikroskop System (Erneuerung)
• Instrumentation Group: 5042 Mikroskope für Hochdurchsatz und Screening
• Applicant Institution: Heinrich-Heine-Universität Düsseldorf
• Leader: Professorin Dr. Stefanie Weidtkamp-Peters