Automated, live-infection imaging in a CL3 lab with Hermes microscope
The Hermes high content imaging system is now starting operation, for the first time, in the demanding, strict CL3 environment (Containment Level 3 in the UK, similar to BSL3 in the USA), the safety level required for working with infectious human pathogens.
Research in the Noursadeghi lab at the University College London (UCL) department of infection and immunity focuses on host-pathogen interactions to increase our understanding of the innate immune responses to infectious diseases. Their work aims to inform the development of novel diagnostics and therapeutic approaches. Of particular interest, projects in the lab study the mechanisms by which important human pathogens, such as HIV-1 and Mycobacterium Tuberculosis, can either evade host defense mechanisms in macrophages or stimulate harmful immune responses. The work of Noursadeghi group at UCL extends from in vitro laboratory models to challenging clinical experiments in humans, including sampling of tissues at the site of disease in order to understand host-pathogen interactions in vivo.
Microscopy is a key tool for studying the infection process across many projects in the lab. For imaging, the Noursadeghi lab relies on the WiScan® Hermes high content screening platform from IDEA Bio-Medical. They achieve rapid, robust screens of biological samples to produce high quality images and insightful data. With this approach, they and their collaborators have revealed unexpected adaptations in the SARS-CoV-2 and HIV viruses to manipulate the innate immune system to evade detection and facilitate infection [1-3].
“In recent years, we have come to rely on the Hermes system’s versatility, speed and ease of use when performing our infection-immunity studies. Galvanized by the COVID-19 pandemic, our need to perform live-cell imaging studies of highly infectious pathogens grew, and we needed a solution for running automated, rapid live-cell imaging under the proper biosafety requirements in our CL3 facility. Together with IDEA Bio-Medical, we made this possible, placing one of our Hermes imaging systems in our CL3 facility at the department of infection and immunity at UCL, London”, says Dr. Matthew V. X. Whelan, Postdoctoral Research Fellow in HCS Microscopy and Image Analysis at the University College London.
A Containment Level 3 (CL3) laboratory typically conducts research into or work on microbes that are either indigenous or exotic and can cause serious or potentially lethal human disease, often through inhalation.
Because of the potentially life-threatening illness the microbes found within CL setting can cause, research work is strictly controlled and registered through the government agencies. Laboratory personnel are also under regular medical surveillance and may require immunizations for the microbes they work with, if available. Access to a CL-3 laboratory is restricted and controlled at all times.
Work at CL3 requires enhanced facility design, operational controls and special practices, which places special requirements for equipment permitted inside such lab. For instance, any equipment placed in CL3 must be able to operate under negative air pressure. Instrument robustness is critical since servicing of equipment in CL3 facilities is challenging. On-site repair or inspection requires technicians to be supervised at all times and they must wear all protective wear while they work (usually a gown, 2 pairs of gloves, and mask). Often, the space available inside the CL3 facility is in short supply and hence the equipment must have a small footprint. Additionally, it is not trivial to move equipment in and out of a CL3 facility since the lab may need to be temporarily shut down, which is unfavorable as research must also stop. Hence suitable equipment must be robust and reliable on the long term without on-site servicing.
The Noursadeghi group currently has two Hermes microscopes and decided to place one into their CL3 facility in their department to enable automated, live-cell microscopy. The Hermes microscope is a benchtop high content screening system with minimal footprint. Hence, it only required a bit of a standard lab bench to accommodate the system, which can be appreciated in the photo of a CL3 user obtaining images. To support the Noursadeghi group in their live-infection experiments on the Hermes, IDEA Bio-Medical upgraded their system on-site to include temperature control for long duration time-lapse experiments. The system was re-installed in the CL3 facility at UCL during the summer of 2022 and has been working since then around the clock with fixed samples, supporting UCL’s infection-community researchers while risk assessment for live-cell work is finalized.
Dr. Whelan: “We look forward to doing all sorts of experiments with the Hermes at the CL3 facility, mainly with HIV-1, Mycobacterium tuberculosis and even the notorious SARS-CoV-2 virus interacting with live cells. We have exciting times ahead!”
About Hermes high content screening system
Hermes system was cited in over 140 scientific papers in peer-reviewed life science magazines. The Hermes microscope maximizes flexibility by offering compatibility with optional environmental chambers for live-cell or hypoxic conditions, and by supporting Z-stack image acquisition, up to 7 fluorescence channels and magnifications in the range of 2x to 60x with high NA (air, water and oil objectives supported).
Athena software, Hermes system’s accompanying proprietary image analysis software, is suitable for a broad range of biological applications based on the company’s unique library of algorithms, which are continuously improved and upgraded. Athena software’s design is intuitive and designed for users having any level of microscopy expertise.
 Thorne, L.G., Reuschl, A.K., Zuliani-Alvarez, L., et al. SARS-CoV-2 sensing by RIG-I and MDA5 links epithelial infection to macrophage inflammation. EMBO Journal. 2021; 40: e107826, doi.org/10.15252/embj.2021107826
 Thorne, L.G., Bouhaddou, M., Reuschl, A.K., et al. Evolution of enhanced innate immune evasion by SARS-CoV-2. Nature. 2022; 602: 487-495, doi.org/10.1038/s41586-021-04352-y
 Reuschl, A.K., Mesner, D., Shivkumar, M., et al. HIV-1 Vpr drives a tissue residency-like phenotype during selective infection of resting memory T cells. Cell Reports. 2022; 39 (2): 110650, doi.org/10.1016/j.celrep.2022.110650