Real-time measurement of small molecules directly in awake, ambulatory animals

Proc Natl Acad Sci U S A. 2017 Jan 24;114(4):645-650. doi: 10.1073/pnas.1613458114. Epub 2017 Jan 9.

Abstract

The development of a technology capable of tracking the levels of drugs, metabolites, and biomarkers in the body continuously and in real time would advance our understanding of health and our ability to detect and treat disease. It would, for example, enable therapies guided by high-resolution, patient-specific pharmacokinetics (including feedback-controlled drug delivery), opening new dimensions in personalized medicine. In response, we demonstrate here the ability of electrochemical aptamer-based (E-AB) sensors to support continuous, real-time, multihour measurements when emplaced directly in the circulatory systems of living animals. Specifically, we have used E-AB sensors to perform the multihour, real-time measurement of four drugs in the bloodstream of even awake, ambulatory rats, achieving precise molecular measurements at clinically relevant detection limits and high (3 s) temporal resolution, attributes suggesting that the approach could provide an important window into the study of physiology and pharmacokinetics.

Keywords: E-DNA; aptamer; in vivo; precision medicine; square-wave voltammetry.

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
  • Aptamers, Nucleotide / metabolism
  • Biosensing Techniques / methods
  • Cattle
  • Humans
  • Limit of Detection
  • Male
  • Pharmaceutical Preparations / blood*
  • Pharmaceutical Preparations / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Small Molecule Libraries / metabolism*

Substances

  • Aptamers, Nucleotide
  • Pharmaceutical Preparations
  • Small Molecule Libraries