Disease detection by ultrasensitive quantification of microdosed synthetic urinary biomarkers

J Am Chem Soc. 2014 Oct 1;136(39):13709-14. doi: 10.1021/ja505676h. Epub 2014 Sep 23.


The delivery of exogenous agents can enable noninvasive disease monitoring, but existing low-dose approaches require complex infrastructure. In this paper, we describe a microdose-scale injectable formulation of nanoparticles that interrogate the activity of thrombin, a key regulator of clotting, and produce urinary reporters of disease state. We establish a customized single molecule detection assay that enables urinary discrimination of thromboembolic disease in mice using doses of the nanoparticulate diagnostic agents that fall under regulatory guidelines for "microdosing."

Publication types

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

MeSH terms

  • Animals
  • Biomarkers / urine
  • Dose-Response Relationship, Drug
  • Female
  • Mice
  • Nanoparticles* / administration & dosage
  • Nanoparticles* / chemistry
  • Thrombin* / administration & dosage
  • Thrombin* / chemistry
  • Venous Thromboembolism / diagnosis*


  • Biomarkers
  • Thrombin