ReScan, a Multiplex Diagnostic Pipeline, Pans Human Sera for SARS-CoV-2 Antigens

Cell Rep Med. 2020 Oct 20;1(7):100123. doi: 10.1016/j.xcrm.2020.100123. Epub 2020 Sep 24.


Comprehensive understanding of the serological response to SARS-CoV-2 infection is important for both pathophysiologic insight and diagnostic development. Here, we generate a pan-human coronavirus programmable phage display assay to perform proteome-wide profiling of coronavirus antigens enriched by 98 COVID-19 patient sera. Next, we use ReScan, a method to efficiently sequester phage expressing the most immunogenic peptides and print them onto paper-based microarrays using acoustic liquid handling, which isolates and identifies nine candidate antigens, eight of which are derived from the two proteins used for SARS-CoV-2 serologic assays: spike and nucleocapsid proteins. After deployment in a high-throughput assay amenable to clinical lab settings, these antigens show improved specificity over a whole protein panel. This proof-of-concept study demonstrates that ReScan will have broad applicability for other emerging infectious diseases or autoimmune diseases that lack a valid biomarker, enabling a seamless pipeline from antigen discovery to diagnostic using one recombinant protein source.

Keywords: COVID-19; SARS-CoV-2; assay development; diagnostics; phage display; serology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Viral / blood
  • Antigens, Viral / immunology*
  • COVID-19 / blood
  • COVID-19 / diagnosis*
  • COVID-19 Serological Testing / methods*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Peptide Library
  • Protein Array Analysis
  • Proteome / immunology
  • Reproducibility of Results
  • SARS-CoV-2 / immunology
  • SARS-CoV-2 / isolation & purification*
  • Sensitivity and Specificity
  • Viral Proteins / immunology


  • Antibodies, Viral
  • Antigens, Viral
  • Peptide Library
  • Proteome
  • Viral Proteins