Label-Free Digital Detection of Intact Virions by Enhanced Scattering Microscopy

Nantao Li, Xiaojing Wang, Joseph Tibbs, Congnyu Che, Ana Sol Peinetti, Bin Zhao, Leyang Liu, Priyash Barya, Laura Cooper, Lijun Rong, Xing Wang, Yi Lu, Brian T Cunningham

Research output: Contribution to journalArticlepeer-review


Several applications in health diagnostics, food, safety, and environmental monitoring require rapid, simple, selective, and quantitatively accurate viral load monitoring. Here, we introduce the first label-free biosensing method that rapidly detects and quantifies intact virus in human saliva with single-virion resolution. Using pseudotype SARS-CoV-2 as a representative target, we immobilize aptamers with the ability to differentiate active from inactive virions on a photonic crystal, where the virions are captured through affinity with the spike protein displayed on the outer surface. Once captured, the intrinsic scattering of the virions is amplified and detected through interferometric imaging. Our approach analyzes the motion trajectory of each captured virion, enabling highly selective recognition against nontarget virions, while providing a limit of detection of 1 × 103 copies/mL at room temperature. The approach offers an alternative to enzymatic amplification assays for point-of-collection diagnostics.

Original languageEnglish (US)
Pages (from-to)1498-1502
Number of pages5
JournalJournal of the American Chemical Society
Issue number4
Early online dateDec 20 2021
StatePublished - Feb 2 2022


  • SARS-CoV-2

ASJC Scopus subject areas

  • General Chemistry
  • Biochemistry
  • Catalysis
  • Colloid and Surface Chemistry


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