Idoia Mikelez Alonso , Javier Sánchez-Martínez , Carlos M. Boubeta , Emilio J Artés-Ibáñez , Georkgi K Tsirov , Ivan Sanz-Muñoz , Aitziber L. Cortajarena and Francisco José J Teran
First published on 13th October 2025
Innovative strategies for rapid viral infection diagnosis at primary medical assistance 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 COVID-19 pandemic led to global supply chain constraints, impacting not only healthcare systems but also academia or industry sectors. In this study, we present a one-step PCR-free methodology based on conjugated magnetic nanoparticles for rapid and direct detection of SARS-CoV-2 virus in clinical samples, as a study case. For this purpose, we have employed commercial magnetite nanocrystal conjugated with antibodies against the S1 glycoprotein on the corona spikes, enabling the recognition of the virus. The proposed method requires minimal processing, taking the advantage of dynamical magnetization changes following the biomolecular recognition. In 40 minutes, our in vitro diagnostic methodology can detect virions presence in minimally processed positive COVID-19 clinical samples. The dynamical magnetization signal of conjugated magnetic nanoparticles varies in absence and in presence of virus. This magnetic signal changes consequently evidence the direct virus detection 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 evidences highlight the robustness and potential of the magnetic nanoparticles acting as transducers for in vitro diagnosis 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.