A Simplistic Label-Free Electrochemical Immunosensing Approach for Rapid and Sensitive Detection of Anti-SARS-COV-2 Nucleocapsid Antibodies

Rapid and precise detection of SARS-CoV-2 antibodies is paramount for effective outbreak monitoring and vaccine efficacy assessment. While existing approaches for antibody detection often rely on complex electrochemical immunosensing with nanomaterial functionalization targeting S-protein antibodies, their limitations in sensitivity and complexity have hindered widespread application. Here, we present a simplistic immunosensing platform designed for the rapid, and precise detection of SARS-CoV-2 specific IgG and Nucleocapsid antibodies. Notably, this study marks only the second exploration of SARS-CoV-2 N-protein antibody detection. The platform utilizes traditional self-assembled monolayers to establish selective bio-affinity between SARS-CoV-2 specific Nucleocapsid antibodies and a gold electrode functionalized with the N-protein antigen. Interestingly, despite the absence of nanomaterial functionalization, the developed platform achieves sensitivity comparable to existing sensors across a wide detection range (0.025 to 1 ng/mL) with an impressive limit of detection (0.019 ng/mL). The simplicity of the approach, relying solely on immunocomplex reactions, underscores that effective binding efficiency may be achieved in the absence of complex functionalization and determines its affordability, specificity, and high sensitivity. By eliminating the need for additional functionalization steps, the platform offers a streamlined solution for SARS-CoV-2 antibody detection and demonstrates the possibility of N-protein antibody detection as a promising avenue for widespread application in SARS-CoV-2 outbreak monitoring and vaccine efficacy assessment particularly in underdeveloped regions. Efficient monitoring and assessing the efficacy of vaccines against SARS-CoV-2 hinges on swiftly detecting its antibodies. Current methods, often intricate and reliant on nanomaterials, struggle with sensitivity and complexity, limiting their broad use. The immunosensing platform utilized in this work is tailored for quick and precise identification of SARS-CoV-2-specific IgG and Nucleocapsid antibodies. Noteworthy, this platform marks only the second attempt at detecting N-protein antibodies. Unlike its counterparts, it employs traditional self-assembled monolayers to foster a selective bond between SARS-CoV-2-specific Nucleocapsid antibodies and a gold electrode coated with the N-protein antigen. Remarkably, despite eschewing nanomaterials, it matches existing sensors ' sensitivity over a broad detection range (0.025 to 1 ng/mL) with an outstanding limit of detection (0.019 ng/mL). The method's simplicity, reliant solely on immunocomplex reactions, underscores the possibility of achieving effective binding without complex functionalization, rendering it affordable, specific, and highly sensitive. By streamlining the process and eliminating additional steps, this platform presents a practical solution for SARS-CoV-2 antibody detection. Its success in N-protein antibody detection suggests promise for widespread application, especially in resource-limited settings, for outbreak surveillance and vaccine efficacy evaluation. image