Unlocking Scientific Discoveries at a Core Imaging Facility: Gaining Perspective from the Champalimaud Foundation in Lisbon

Since August 2017, Dr. Davide Accardi has been leading the Advanced BioImaging and BioOptics Experimental Platform (ABBE Platform) at the Champalimaud Foundation (CF) in Lisbon, Portugal.

Almost seven years ago, Prof. Rui Costa (now director of Columbia's Zuckerman Institute) tasked him with building a world-class imaging facility. With complete trust and freedom, he built the facility to meet the standards of a top neuroscience and cancer research institute.

In any scientific facility, the instruments that form the core backbone play a critical role in the success of diverse research endeavors. When selecting an instrument like the LSM 980 confocal microscope, essential attributes such as flexibility, reliability, and ease of use are paramount. The specifications and features required must not only meet current scientific demands but also anticipate future needs.

The LSM 980 confocal microscope is heavily utilized, with core systems booked for approximately 4,000 hours a year, translating to an average of 10 to 12 hours of usage daily.

The dynamics of usage vary significantly among research groups, depending on their specific project phases – whether they are in hypothesis formulation, data collection, analysis, writing, submission, or revision. This leads to periods of tightly compressed experimental activity, where the microscopes are required to operate 24/7, followed by more relaxed phases.

With more than 30 research groups at the institute, the imaging demand is highly diversified. As such, the facility experiences heavy usage not only from groups conducting long experiments but also from those performing numerous short observations.

To ensure that researchers and students use the LSM 980 effectively and efficiently, Accardi and team cover essential hardware handling in their trainings, including:

• Turn on/off procedures
• Lens inspection and cleaning
• Stage insert exchange
• CO₂ and temperature control module placement and activation

On the software side, they begin by guiding researchers through the AI Sample Finder, a significant improvement that provides an overview of the specimen, acting as a map of coordinates to navigate relevant parts of the sample with multiple objective lenses without needing to switch back and forth between eyepieces and scanning mode.

The automatic channel setup (or Smart Setup) further enhances user experience, making it easier to understand and quick to set up. The animated triangle indicating resolution, speed, and sensitivity serves as an effective tool for explaining the trade-offs involved in different acquisition modalities when using the Airyscan detector or Multiplex mode.

While acknowledging the value of these automated tools, we prefer a hands-on approach with users. We explain the system’s light path—from light sources to detectors—and optimize it according to each user's scientific needs. Researchers learn how to calculate resolution and apply the Nyquist-Shannon sampling principle, enabling them to critically determine acquisition parameters based on the observed structures.

For users requiring higher resolution, fast acquisition modes, or increased detection sensitivity, training includes the use and alignment of the Airyscan detector and Multiplex mode. The LSM 980 has greatly facilitated the Airyscan detector alignment process, allowing automatic alignment across all the tracks needed for the experiment.

The reliability of the LSM 980 is crucial for our researchers, who engage in both descriptive and quantitative microscopy. Reproducibility in signal detection, structure imaging, and measurements is key.

To ensure the LSM 980 produces consistent and accurate results, we conduct weekly quality check that include laser and lamp power measurements, lens inspections, and system alignment. More thorough assessments are performed quarterly, covering scanner calibration, AI Sample Finder calibration, and sharpness and scan field tests. "Additionally, maintaining premium service contracts with ZEISS guarantees preventive maintenance and rapid responses, which are crucial for minimizing system downtime", Accardi says.

One of the most significant challenges in maintaining microscope reliability and robustness while ensuring efficient facility operations is balancing time and personnel. Achieving an optimal user-to-specialist ratio – approximately 50:1, as outlined in "Advanced light microscopy core facilities: Balancing service, science and career"; Ferrando-May et al. (2016) – is essential for upholding high standards. This balance, alongside systematic scheduling of checks, helps us maintain both efficiency and system reliability.