Magnetic nanoparticles as transducers for quick and direct virus detection in clinical samples

Innovative strategies for the rapid diagnosis of viral infections at primary medical facilities have gained significant relevance in recent years. In clinical settings, RT-PCR is the gold standard for virus detection due to its high accuracy and sensitivity. However, the unprecedented demand for PCR consumables during the COVID-19 pandemic led to global supply chain constraints, impacting not only healthcare systems but also academic or industrial sectors. In this study, we present a one-step, PCR-free methodology based on conjugated magnetic nanoparticles for rapid and direct detection of the SARS-CoV-2 virus in clinical samples as a case study. For this purpose, we employed commercial magnetite nanocrystals conjugated with antibodies against the S1 glycoprotein on the corona spikes, enabling the recognition of the virus. The proposed method requires minimal processing, taking advantage of dynamic magnetization changes following biomolecular recognition. Within 40 minutes, our in vitro diagnostic methodology can detect the presence of virions in minimally processed, COVID-19 positive clinical samples. The dynamic magnetization signal of the conjugated magnetic nanoparticles varies in the absence and presence of the virus. These magnetic signal changes consequently evidence the direct detection of the virus in patient samples. Our findings reveal that higher/lower viral loads exhibited more/less pronounced magnetization changes. The one-step methodology was validated by checking specificity and sensitivity in distinct control clinical samples (negative for SARS-CoV-2 and positive/negative for other respiratory viruses). Our evidence highlights the robustness and potential of magnetic nanoparticles acting as transducers for in vitro diagnostic applications in minimally processed clinical samples. Notably, this magnetic nanoparticle-based strategy is extremely versatile for detecting other viral species by simply modifying the targeting antibody.