TY - JOUR
T1 - Subsecond-Resolved Molecular Measurements in the Living Body Using Chronoamperometrically Interrogated Aptamer-Based Sensors
AU - Arroyo-Currás, Netzahualcóyotl
AU - Dauphin-Ducharme, Philippe
AU - Ortega, Gabriel
AU - Ploense, Kyle L.
AU - Kippin, Tod E.
AU - Plaxco, Kevin W.
N1 - Funding Information:
This work was sponsored in part by the Institute for Collaborative Biotechnologies through grant W911NF-09-0001 from the U.S. Army Research Office and, in part, by the Defense Advanced Research Projects Agency (DARPA) Biological Technologies Office (BTO) Electrical Prescriptions (ElectRx) program under the auspices of Dr. Eric Van Gieson through the DARPA Contracts Management Office Contract No. HR001117C0122. N.A.C. was supported by the Otis Williams Postdoctoral Fellowship of the Santa Barbara Foundation. P.D.-D. was supported by the Natural Sciences and Engineering Research Council of Canada with postdoctoral fellowship. G.O. is supported by the Postdoctoral Program of the Basque Government.
Publisher Copyright:
© 2017 American Chemical Society.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2018/2/23
Y1 - 2018/2/23
N2 - Electrochemical, aptamer-based (E-AB) sensors support the continuous, real-time measurement of specific small molecules directly in situ in the living body over the course of many hours. They achieve this by employing binding-induced conformational changes to alter electron transfer from a redox-reporter-modified, electrode-attached aptamer. Previously we have used voltammetry (cyclic, alternating current, and square wave) to monitor this binding-induced change in transfer kinetics indirectly. Here, however, we demonstrate the potential advantages of employing chronoamperometry to measure the change in kinetics directly. In this approach target concentration is reported via changes in the lifetime of the exponential current decay seen when the sensor is subjected to a potential step. Because the lifetime of this decay is independent of its amplitude (e.g., insensitive to variations in the number of aptamer probes on the electrode), chronoamperometrically interrogated E-AB sensors are calibration-free and resistant to drift. Chronoamperometric measurements can also be performed in a few hundred milliseconds, improving the previous few-second time resolution of E-AB sensing by an order of magnitude. To illustrate the potential value of the approach we demonstrate here the calibration-free measurement of the drug tobramycin in situ in the living body with 300 ms time resolution and unprecedented, few-percent precision in the determination of its pharmacokinetic phases.
AB - Electrochemical, aptamer-based (E-AB) sensors support the continuous, real-time measurement of specific small molecules directly in situ in the living body over the course of many hours. They achieve this by employing binding-induced conformational changes to alter electron transfer from a redox-reporter-modified, electrode-attached aptamer. Previously we have used voltammetry (cyclic, alternating current, and square wave) to monitor this binding-induced change in transfer kinetics indirectly. Here, however, we demonstrate the potential advantages of employing chronoamperometry to measure the change in kinetics directly. In this approach target concentration is reported via changes in the lifetime of the exponential current decay seen when the sensor is subjected to a potential step. Because the lifetime of this decay is independent of its amplitude (e.g., insensitive to variations in the number of aptamer probes on the electrode), chronoamperometrically interrogated E-AB sensors are calibration-free and resistant to drift. Chronoamperometric measurements can also be performed in a few hundred milliseconds, improving the previous few-second time resolution of E-AB sensing by an order of magnitude. To illustrate the potential value of the approach we demonstrate here the calibration-free measurement of the drug tobramycin in situ in the living body with 300 ms time resolution and unprecedented, few-percent precision in the determination of its pharmacokinetic phases.
KW - E-AB
KW - aptamer
KW - chronoamperometry
KW - electrochemical sensors
KW - in vivo
KW - precision medicine
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U2 - 10.1021/acssensors.7b00787
DO - 10.1021/acssensors.7b00787
M3 - Article
C2 - 29124939
AN - SCOPUS:85042555417
SN - 2379-3694
VL - 3
SP - 360
EP - 366
JO - ACS sensors
JF - ACS sensors
IS - 2
ER -