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Main Authors: Clark, Vincent, Yuan, Yuchan, Guzman, Frederick, Demek, Erin, Lukeman, Philip S., Powell-Gray, Bethany, Arroyo-Currás, Netzahualcóyotl
Format: Preprint
Published: 2024
Subjects:
Online Access:https://arxiv.org/abs/2406.17208
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author Clark, Vincent
Yuan, Yuchan
Guzman, Frederick
Demek, Erin
Lukeman, Philip S.
Powell-Gray, Bethany
Arroyo-Currás, Netzahualcóyotl
author_facet Clark, Vincent
Yuan, Yuchan
Guzman, Frederick
Demek, Erin
Lukeman, Philip S.
Powell-Gray, Bethany
Arroyo-Currás, Netzahualcóyotl
contents Nucleic acid-based electrochemical sensors (NBEs) have emerged as a promising approach to continuous molecular monitoring in vivo. NBEs consist of electrically conducting gold surfaces coated with self-assembled monolayers of a mixture of electrode-passivating alkylthiols and functional alkylthiol-modified oligos. These oligos also display binding sites for the target analyte and redox reporters able to transfer electrons to the underlying gold electrode. Although sufficiently robust for continuous, multi-hour sensing of small molecules and proteins in biological fluids both in vitro and in vivo, NBEs decay over periods longer than 12 hours of continuous operation in these fluids. To address this issue, here we report a biofluid mimetic that can be leveraged to specifically study competitive displacement of oligonucleotides from NBEs, a critical sensor degradation pathway. Using this mimetic, we demonstrate three strategies that drastically mitigate competitive displacement and improve sensor stability in vitro. A combination of these strategies also improves sensor stability in vivo, demonstrated here via sensors emplaced in the brain cortex of live rats.
format Preprint
id arxiv_https___arxiv_org_abs_2406_17208
institution arXiv
publishDate 2024
record_format arxiv
spellingShingle Extending the Operational Lifetime of Nucleic Acid-Based Electrochemical Sensors via Protection Against Competitive Displacement of Oligonucleotides
Clark, Vincent
Yuan, Yuchan
Guzman, Frederick
Demek, Erin
Lukeman, Philip S.
Powell-Gray, Bethany
Arroyo-Currás, Netzahualcóyotl
Biological Physics
Nucleic acid-based electrochemical sensors (NBEs) have emerged as a promising approach to continuous molecular monitoring in vivo. NBEs consist of electrically conducting gold surfaces coated with self-assembled monolayers of a mixture of electrode-passivating alkylthiols and functional alkylthiol-modified oligos. These oligos also display binding sites for the target analyte and redox reporters able to transfer electrons to the underlying gold electrode. Although sufficiently robust for continuous, multi-hour sensing of small molecules and proteins in biological fluids both in vitro and in vivo, NBEs decay over periods longer than 12 hours of continuous operation in these fluids. To address this issue, here we report a biofluid mimetic that can be leveraged to specifically study competitive displacement of oligonucleotides from NBEs, a critical sensor degradation pathway. Using this mimetic, we demonstrate three strategies that drastically mitigate competitive displacement and improve sensor stability in vitro. A combination of these strategies also improves sensor stability in vivo, demonstrated here via sensors emplaced in the brain cortex of live rats.
title Extending the Operational Lifetime of Nucleic Acid-Based Electrochemical Sensors via Protection Against Competitive Displacement of Oligonucleotides
topic Biological Physics
url https://arxiv.org/abs/2406.17208