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

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, pat...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 114; no. 4; pp. 645 - 650
Main Authors Arroyo-Currás, Netzahualcóyotl, Somerson, Jacob, Vieira, Philip A., Ploense, Kyle L., Kippin, Tod E., Plaxco, Kevin W.
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 24.01.2017
Subjects
Animals
Aptamers, Nucleotide - metabolism
Biological Sciences
Biomarkers
Biosensing Techniques - methods
Cattle
Detection limits
Electrochemistry
Humans
Limit of Detection
Male
Medical treatment
Metabolites
Pharmaceutical Preparations - blood
Pharmaceutical Preparations - metabolism
Pharmacokinetics
Physical Sciences
Rats
Rats, Sprague-Dawley
Sensors
Small Molecule Libraries - metabolism
precision medicine
in vivo
square-wave voltammetry
aptamer
E-DNA
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Summary: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.
Bibliography:SourceType-Scholarly Journals-1
ObjectType-Feature-1
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Edited by Jack W. Szostak, Massachusetts General Hospital, Boston, MA, and approved December 5, 2016 (received for review August 12, 2016)
Author contributions: N.A.-C., P.A.V., T.E.K., and K.W.P. designed research; N.A.-C., J.S., P.A.V., and K.L.P. performed research; N.A.-C., P.A.V., and T.E.K. contributed new reagents/analytic tools; N.A.-C. and J.S. analyzed data; and N.A.-C., J.S., P.A.V., K.L.P., T.E.K., and K.W.P. wrote the paper.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1613458114