Antibody-Free Rapid Detection of SARS-CoV‑2 Proteins Using Corona Phase Molecular Recognition to Accelerate Development Time

To develop better analytical approaches for future global pandemics, it is widely recognized that sensing materials are necessary that enable molecular recognition and sensor assay development on a much faster scale than currently possible. Previously developed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) point-of-care devices are based on the specific molecular recognition using subunit protein antibodies and protein receptors that selectively capture the viral proteins. However, these necessarily involve complex and lengthy development and processing times and are notoriously prone to a loss of biological activity upon sensor immobilization and device interfacing, potentially limiting their use in applications at scale. Here, we report a synthetic strategy for nanoparticle corona interfaces that enables the molecular recognition of SARS-CoV-2 proteins without any antibody and receptor design. Our nanosensor constructs consist of poly­(ethylene glycol) (PEG)phospholipid heteropolymers adsorbed onto near-infrared (nIR) fluorescent single-walled carbon nanotubes (SWCNTs) that recognize the nucleocapsid (N) and spike (S) protein of SARS-CoV-2 using unique three-dimensional (3D) nanosensor interfaces. This results in rapid and label-free nIR fluorescence detection. This antibody-free nanosensor shows up to 50% sensor responses within 5 min of viral protein injections with limit of detection (LOD) values of 48 fM and 350 pM for N and S proteins, respectively. Finally, we demonstrate instrumentation based on a fiber-optic platform that interfaces the advantages of antibody-free molecular recognition and biofluid compatibility in human saliva conditions.