The coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread into a global pandemic. Early and accurate diagnosis and quarantine remain the most effective mitigation strategy. Although
reverse transcriptase polymerase chain reaction (RT-qPCR) is the gold standard for
COVID-19 diagnosis, recent studies suggest that
nucleic acids were undetectable in a significant number of cases with clinical features of
COVID-19. Serologic assays that detect human
antibodies to SARS-CoV-2 serve as a complementary method to diagnose these cases, as well as to identify asymptomatic cases and qualified convalescent serum donors. However, commercially available
enzyme-linked
immunosorbent assays (ELISA) are laborious and non-quantitative, while point-of-care assays suffer from low detection accuracy. To provide a serologic assay with high performance and portability for potential point-of-care applications, we developed
DNA-assisted nanopore sensing for quantification of SARS-CoV-2 related
antibodies in human serum. Different
DNA structures were used as detection reporters for multiplex quantification of
immunoglobulin M (
IgM) and
immunoglobulin G (
IgG)
antibodies against the
nucleocapsid protein of SARS-CoV-2 in serum specimens from patients with conformed or suspected
infection. Comparing to a clinically used point-of-care assay and an ELISA assay, our technology can reliably quantify SARS-CoV-2
antibodies with higher accuracy, large dynamic range, and potential for assay automation.