Rapid, Point-of-Care scFv-SERS Assay for Femtogram Level Detection of SARS-CoV-2

Delphine Antoine, Moein Mohammadi, Madison Vitt, Julia Marie Dickie, Sharmin Sultana Jyoti, Maura A. Tilbury, Patrick A. Johnson, Karen E. Wawrousek, J. Gerard Wall

Research output: Contribution to a Journal (Peer & Non Peer)Articlepeer-review

52 Citations (Scopus)

Abstract

Rapid, sensitive, on-site identification of SARS-CoV-2 infections is an important tool in the control and management of COVID-19. We have developed a surface-enhanced Raman scattering (SERS) immunoassay for highly sensitive detection of SARS-CoV-2. Single-chain Fv (scFv) recombinant antibody fragments that bind the SARS-CoV-2 spike protein were isolated by biopanning a human scFv library. ScFvs were conjugated to magnetic nanoparticles and SERS nanotags, followed by immunocomplex formation and detection of the SARS-CoV-2 spike protein with a limit of detection of 257 fg/mL in 30 min in viral transport medium. The assay also detected B.1.1.7 ("alpha"), B.1.351 ("beta"), and B.1.617.2 ("delta") spike proteins, while no cross-reactivity was observed with the common human coronavirus HKU1 spike protein. Inactivated whole SARS-CoV-2 virus was detected at 4.1 × 104genomes/mL, which was 10-100-fold lower than virus loads typical of infectious individuals. The assay exhibited higher sensitivity for SARS-CoV-2 than commercial lateral flow assays, was compatible with viral transport media and saliva, enabled rapid pivoting to detect new virus variants, and facilitated highly sensitive, point-of-care diagnosis of COVID-19 in clinical and public health settings.

Original languageEnglish
Pages (from-to)866-873
Number of pages8
JournalACS Sensors
Volume7
Issue number3
DOIs
Publication statusPublished - 25 Mar 2022

Keywords

  • COVID-19
  • diagnostic
  • point-of-care
  • Raman spectroscopy
  • SARS-CoV-2
  • scFv antibody fragment
  • SERS

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