Time-resolved single-step protease activity quantification using nanoplasmonic resonator sensors

Cheng Sun*, Kai Hung Su, Jason Valentine, Yazmin T. Rosa-Bauza, Jonathan A. Ellman, Omeed Elboudwarej, Bipasha Mukherjee, Charles S. Craik, Marc A. Shuman, Fanqing Frank Chen, Xiang Zhang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


Protease activity measurement has broad application in drug screening, diagnosis and disease staging, and molecular profiling. However, conventional immunopeptidemetric assays (IMPA) exhibit low fluorescence signal-to-noise ratios, preventing reliable measurements at lower concentrations in the clinically important picomolar to nanomolar range. Here, we demonstrated a highly sensitive measurement of protease activity using a nanoplasmonic resonator (NPR). NPRs enhance Raman signals by 6.1 × 1010 times in a highly reproducible manner, enabling fast detection of proteolytically active prostate-specific antigen (paPSA) activities in real-time, at a sensitivity level of 6 pM (0.2 ng/mL) with a dynamic range of 3 orders of magnitude. Experiments on extracellular fluid (ECF) from the paPSA-positive cells demonstrate specific detection in a complex biofluid background. This method offers a fast, sensitive, accurate, and one-step approach to detect the proteases' activities in very small sample volumes.

Original languageEnglish (US)
Pages (from-to)978-984
Number of pages7
JournalACS nano
Issue number2
StatePublished - Feb 23 2010


  • Plasmonic resonator
  • Prostate cancer
  • Protease
  • Sensing
  • Surface-enhanced raman scattering

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)


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