SARS-CoV-2 detection using a nanobody-functionalized voltammetric device

Plain language summaryOur ability to control SARS-CoV-2, the virus that causes COVID-19, relies on access to rapid and sensitive technologies that can detect the virus, and differentiate SARS-CoV-2 infections from infections with other viruses. One potential approach to detect SARS-CoV-2 is to use sensors comprising specific surfaces and chemicals that can detect changes in the properties of samples containing the virus. Here, we develop one of these sensors and test it in samples from people with COVID-19 or other viral infections, or people without. We show that our portable device can quickly and accurately detect SARS-CoV-2 and can also detect different variants. We also show that signals from our device are specific for SARS-CoV-2. Our device may provide another tool for COVID-19 diagnosis, with benefits being portability and speed compared with current gold-standard approaches. BackgroundAn ongoing need during the COVID-19 pandemic has been the requirement for accurate and efficient point-of-care testing platforms to distinguish infected from non-infected people, and to differentiate SARS-CoV-2 infections from other viruses. Electrochemical platforms can detect the virus via its envelope spike protein by recording changes in voltammetric signals between samples. However, this remains challenging due to the limited sensitivity of these sensing platforms.MethodsHere, we report on a nanobody-functionalized electrochemical platform for the rapid detection of whole SARS-CoV-2 viral particles in complex media such as saliva and nasopharyngeal swab samples. The sensor relies on the functionalization of gold electrode surface with highly-oriented Llama nanobodies specific to the spike protein receptor binding domain (RBD). The device provides results in 10 min of exposure to 200 & mu;L of unprocessed samples with high specificity to SARS-CoV-2 viral particles in human saliva and nasopharyngeal swab samples.ResultsThe developed sensor could discriminate between different human coronavirus strains and other respiratory viruses, with 90% positive and 90% negative percentage agreement on 80 clinical samples, as compared to RT-qPCR.ConclusionsWe believe this diagnostic concept, also validated for RBD mutants and successfully tested on Delta variant samples, to be a powerful tool to detect patients' infection status, easily extendable to other viruses and capable of overcoming sensing-related mutation effects. Pagneux et al. developed a nanobody-functionalized electrochemical platform with smartphone readout to detect SARS-CoV-2 in clinical samples. They demonstrated that their device can rapidly and accurately detect SARS-CoV-2 in saliva and nasopharyngeal swab samples and discriminate between this virus and other respiratory viruses.