A magnetic modulation biosensing-based molecular assay for rapid and highly sensitive clinical diagnosis of COVID-19

The COVID-19 pandemic demands fast, sensitive, and specific diagnostic tools for virus surveillance and containment. Current methods for diagnosing the COVID-19 are based on direct detection of either viral antigens or viral ribonucleic acids (RNA) in swab samples. Antigen-targeting tests are simple, have fast turnaround times, and allow rapid testing. Unfortunately, compared with viral RNA-targeting tests, their sensitivity is low, especially during the initial stages of the disease, which limits their adoption and implementation. Direct detection of SARS-CoV-2 RNA using reversetranscription quantitative polymerase chain reaction (RT-qPCR) is sensitive and specific, making it a golden standard in SARS-CoV-2 detection. However, it had not seen a significant update since its introduction three decades ago. It has a long turnaround time, requires a high number of amplification cycles, and a complicated and expensive detection system for real-time monitoring of the signal. While insignificant for research applications, these limitations present severe problems for mass testing required to contain the disease. Here, we introduce a diagnostic platform for rapid and highly sensitive clinical diagnosis of COVID-19. Based on the biochemical principles of the RT-PCR, it utilizes the endpoint detection by the magnetic modulation biosensing (MMB) system, allowing the detection of as little as two copies of SARS-CoV-2 in ∼30 minutes. Testing 309 RNA samples from verified SARS-CoV-2 carriers and healthy subjects resulted in 97.8% sensitivity, 100% specificity, and 0% crossreactivity. This level of performance is on par with the gold standard (RT-qPCR) but requires 1/3 of the time. The platform can be easily adapted to detect almost any other pathogen of choice.