DDW App Note: The ZE5 Cell Analyzer in the fight against COVID-19

This paid-for app note by Bio-Rad appeared in DDW Volume 22, Issue 1 – Winter 2020/21.

As COVID-19 has taken the world by storm, much has been learnt about the various aspects of viral infections ranging from immune surveillance to the therapeutic development of vaccines. One of the technologies that has played a large part in our understanding of this infection is flow cytometry. This technique allows single cell solutions to be analysed for specific properties, as they pass through a laser. It is these properties that have been instrumental in furthering our knowledge in fields ranging from drug libraries and antibody screening to epitope mapping.

At the beginning of the pandemic, it was clear that an understanding of antibody cross-reactivity between seasonal human coronaviruses and SARS-CoV-2 would prove beneficial. Labs started developing robust serological testing for immune surveillance, with healthcare workers in mind. When The Francis Crick Institute in London established a robust serology pipeline to facilitate screening of serum antibodies reactive to SARS-CoV-2 antigens, the main considerations were high-speed, high-throughput, and automation-capable instrumentation.

Andy Riddell, the Science and Technology Platform Lead at The Francis Crick Institute, commented: “We wanted to have a plate loader so that we could scan through many samples quickly. We came across the ZE5 Cell Analyzer platform from Bio-Rad, a system that comes with its own sample loader to allow for the quick scanning of numerous samples.”

Not only does the ZE5 Cell Analyzer have an integrated sample loader, but also up to five lasers with 30 detectors, which allows for the unattended acquisition of an entire plate of 384 samples in less than 60 minutes. The team at the Francis Crick Institute developed clinical-grade processes within the flow cytometry facility, which enabled them to look at specific COVID-19 antibodies. Their published works demonstrate they are looking at disease progression through longitudinal epidemiological studies. (Ng KW et al. (2020). Preexisting and de novo humoral immunity to SARS-CoV-2 in humans. Science. Nov 6; eabe1107. Russell E et al. (2020). Adapting to the coronavirus pandemic: building and incorporating a diagnostic pipeline in a shared resource laboratory. Cytometry A. Oct 29.)

“The ZE5 Cell Analyzer is reliable, simple, and worked for us every single time. This is essential as consistency and reproducibility are key,’’ explained Riddell. “Bio-Rad has designed the ZE5 Cell Analyzer to promote simplicity, with the QC management system and calibration already built into the platform.”

The integrated sample loader on the ZE5 Cell Analyzer supports multiple formats, enabling flexibility in panel design, automating probe washes, providing on-board temperature control, and consistently producing reliable results. While the Francis Crick Institute used the ZE5 Cell Analyzer to facilitate the identification of conserved epitopes targeted by SARS-CoV-2 neutralising antibodies, scientists at Humabs Biomed SA in Switzerland took that one step further. They found and characterised potent SARS-CoV-2 neutralizing antibodies isolated from a 2003 SARS survivor, and mapped neutralizing and immunodominant sites on the spike receptor-binding domain. Complementary work run on the ZE5 Cell Analyzer was also done by scientists at La Jolla Institute, San Diego, CA for Immunology, where prevalent T cell
cross-reactivity in unexposed individuals was observed.

The ZE5 Cell Analyzer helped characterise cell-mediated immune responses providing critical insights into COVID-19 pathogenesis and immune correlates of protection and disease progression, which pave the way for the development of effective diagnostics and therapeutics.

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