Label-free detection of single protein using a nanoplasmonic-photonic hybrid microcavity

Venkata R. Dantham, Stephen Holler, Curtis Barbre, David Keng, Vasily Kolchenko, Stephen Arnold

Research output: Contribution to journalArticlepeer-review


Recently we reported the detection and sizing of the smallest RNA virus MS2 with a mass of 6 ag from the resonance frequency shift of a whispering gallery mode-nanoshell hybrid resonator (WGM-h) upon adsorption on the nanoshell and anticipated that single protein above 0.4 ag should be detectable but with considerably smaller signals. Here, we report the detection of single thyroid cancer marker (Thyroglobulin, Tg) and bovine serum albumin (BSA) proteins with masses of only 1 ag and 0.11 ag (66 kDa), respectively. However, the wavelength shifts are enhanced beyond those anticipated in our earlier work by 240% for Tg and 1500% for BSA. This surprising sensitivity is traced to a short-range reactive field near the surface of our Au nanoshell receptor due to intrinsic random bumps of protein size, leading to an unanticipated increase in sensitivity to single protein, which grows larger as the protein diminishes in size. As a consequence of the largest signal-to-noise ratio in our BSA experiments (S/N ≈ 13), we conservatively estimated a new protein limit of detection for our WGM-h of 5 kDa.

Original languageEnglish (US)
Pages (from-to)3347-3351
Number of pages5
JournalNano Letters
Issue number7
StatePublished - Jul 10 2013


  • BSA protein
  • Whispering gallery mode
  • hybrid microcavity
  • label-free detection
  • nanoshell
  • single protein detection
  • surface plasmons
  • thyroid cancer marker

ASJC Scopus subject areas

  • Bioengineering
  • General Chemistry
  • General Materials Science
  • Condensed Matter Physics
  • Mechanical Engineering


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