CoVSense: Ultrasensitive Nucleocapsid Antigen Immunosensor for Rapid Clinical Detection of Wildtype and Variant SARS‐CoV‐2

Abstract

Abstract The widespread accessibility of commercial/clinically‐viable electrochemical diagnostic systems for rapid quantification of viral proteins demands translational/preclinical investigations. Here, Covid‐Sense (CoVSense) antigen testing platform; an all‐in‐one electrochemical nano‐immunosensor for sample‐to‐result, self‐validated, and accurate quantification of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) nucleocapsid (N)‐proteins in clinical examinations is developed. The platform's sensing strips benefit from a highly‐sensitive, nanostructured surface, created through the incorporation of carboxyl‐functionalized graphene nanosheets, and poly(3,4‐ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) conductive polymers, enhancing the overall conductivity of the system. The nanoengineered surface chemistry allows for compatible direct assembly of bioreceptor molecules. CoVSense offers an inexpensive (<$2 kit) and fast/digital response (<10 min), measured using a customized hand‐held reader (<$25), enabling data‐driven outbreak management. The sensor shows 95% clinical sensitivity and 100% specificity (Ct<25), and overall sensitivity of 91% for combined symptomatic/asymptomatic cohort with wildtype SARS‐CoV‐2 or B.1.1.7 variant (N = 105, nasal/throat samples). The sensor correlates the N‐protein levels to viral load, detecting high Ct values of ≈35, with no sample preparation steps, while outperforming the commercial rapid antigen tests. The current translational technology fills the gap in the workflow of rapid, point‐of‐care, and accurate diagnosis of COVID‐19.

Keywords

• clinical investigation
• electrochemical nanobiosensors
• graphene nanosheets
• point‐of‐care diagnostics