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ECL-based Infectious Pathogen (bio)SEnsor

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Portable pathogen detector offers rapid response to disease

The threat of pandemics highlights an urgent need for low-cost detection tools. The EU-funded ECLIPSE project developed a nanobiotechnological platform offering rapid, simple and reliable tests for a range of pathogens.

Many lower-income countries lack the necessary infrastructure to cope with outbreaks of infectious diseases: trained staff to collect samples, logistical networks to transport these to laboratories, and equipment that can identify the pathogen. The ECLIPSE(opens in new window) project, supported by the European Innovation Council(opens in new window), was set up to meet this challenge by developing a prototype for a reliable and cheap portable pathogen detector. “ECLIPSE started at the onset of the SARS-CoV-2 pandemic, which highlighted the urgent need for next-generation multi-pathogen detection tools around the world,” says Luca Prodi, project coordinator. “We aim to produce a gold standard pathogen identification kit well-suited to mass screening, to help stop future epidemics becoming the next pandemic.”

Shining a light on outbreaks

The ECLIPSE team’s key innovation lay in overcoming two challenges. The first was to target a pathogen, or its nucleic acid, with high precision. The project created a probe using a ‘phage-sandwich assay’, which makes use of molecular machinery from viruses that binds to the surface of a pathogen of interest. To increase accuracy, this type of probe uses two different molecules that bind to two different spots on the microbe, forming a ‘sandwich’ around the target. The second challenge was generating a sufficiently strong signal even when there is little pathogen present in a sample. To address this, the team used electrochemiluminescence (ECL), a sensitive detection technique based on light emission, complemented by biotechnological strategies that greatly amplify the signal. When a sample of blood, saliva or urine is introduced into the ECLIPSE platform, magnetic microbeads fitted with viral probes attach to the pathogen of interest. Light-emitting reporter molecules then bind to that target. A magnet pulls the microbead tags onto an electrode, where an electrical pulse triggers the reporters to light up, with the intensity proportional to the amount of pathogen present in the sample. “Conventional ECL assays typically rely on antibodies carrying only a few luminescent tags, whereas our nanoparticle- and phage-based systems carry thousands of luminescent units per sample, resulting in a much stronger detectable signal. Compared to more typical antibody assay techniques, it’s like switching from a lamp to a chandelier,” explains Prodi, a professor of Chemistry at the University of Bologna(opens in new window) in Italy. To demonstrate the platform’s versatility, it was used to identify three pathogens: the SARS-CoV-2 virus, the Pseudomonas bacterium and the Leishmania protozoan parasite. “With both the SARS-CoV-2 virus and the Pseudomonas bacterium, the platform performed at a high rate of sensitivity and specificity. But many variables, such as fluctuating suppliers’ sample quality, compromised reproducibility,” notes Prodi. “Detecting parasites was challenging, as they must be found within host cells, requiring a more tailored future approach, such as targeting infected white blood cells.”

Pandemic preparedness

With many experts warning that it is a question of when, not if, the next pandemic arrives, ECLIPSE’s proof of concept could offer a game changer for rapid and reliable infection testing and tracking. “The platform is designed to be adaptable to other diseases, including cancer,” adds Prodi. “It can also be used routinely for fast diagnoses, by general practitioners for example, informing therapeutic decisions, such as whether to prescribe antibiotics or not.” With patents and a spin-off company(opens in new window) already established, market options are being explored. These are expected to initially introduce the platform to the veterinary market, before developing human applications.

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