Rapid and ultrasensitive electromechanical detection of ions, biomolecules and SARS-CoV-2 RNA in unamplified samples

The detection of samples at ultralow concentrations (one to ten copies in 100 μl) in biofluids is hampered by the orders-of-magnitude higher amounts of ‘background’ biomolecules. Here we report a molecular system, immobilized on a liquid-gated graphene field-effect transistor and consisting of an aptamer probe bound to a flexible single-stranded DNA cantilever linked to a self-assembled stiff tetrahedral double-stranded DNA structure, for the rapid and ultrasensitive electromechanical detection (down to one to two copies in 100 μl) of unamplified nucleic acids in biofluids, and also of ions, small molecules and proteins, as we show for Hg2+, adenosine 5′-triphosphate and thrombin. We implemented an electromechanical biosensor for the detection of SARS-CoV-2 into an integrated and portable prototype device, and show that it detected SARS-CoV-2 RNA in less than four minutes in all nasopharyngeal samples from 33 patients with COVID-19 (with cycle threshold values of 24.9–41.3) and in none of the 54 COVID-19-negative controls, without the need for RNA extraction or nucleic acid amplification. A self-assembled DNA-based system immobilized on a liquid-gated graphene field-effect transistor can electromechanically detect ultralow levels of unamplified ions, nucleic acids, small molecules and proteins in biofluids.