A tight squeeze: geometric effects on the performance of three-electrode electrochemical-aptamer based sensors in constrained, in vivo placements

A tight squeeze: geometric effects on the performance of three-electrode electrochemical-aptamer based sensors in constrained, in vivo placements
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DOI:
10.1039/d2an02096c
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发表时间:
2023-03-01
期刊:
影响因子:
4.2
通讯作者:
Plaxco, Kevin W.
Plaxco, Kevin W.
中科院分区:
化学2区
文献类型:
--
作者:
Leung, Kaylyn K.;Gerson, Julian;Plaxco, Kevin W.

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电化学,基于适配体(EAB)的传感器是第一种分子监测技术,它是(1)基于受体结合而不是目标的反应性,使其相当普遍,和(2)能够支持高频率,实时测量在活体原位。迄今为止,EAB衍生的体内测量主要是使用三个电极(工作,参考,计数器)捆绑在一起的导管插入到大鼠颈静脉。通过探索这种架构,我们发现这些电极在导管内腔内部或外部的放置会显著影响传感器性能。具体而言,我们发现将对电极保留在导管内会增加其与工作电极之间的电阻,从而增加电容背景。相比之下,将对电极延伸到导管的管腔外减少了这种效应,显著增强了静脉内分子测量的信噪比。进一步探索对电极的几何形状,我们发现它们不需要大于工作电极。将这些观察结果放在一起,我们开发了一种新的静脉内EAB架构,该架构在保持足够短以安全地放置在大鼠颈静脉中的同时实现了改进的性能。这些发现,虽然在这里探索与EAB传感器可能被证明是重要的许多电化学生物传感器的设计。
Electrochemical, aptamer-based (EAB) sensors are the first molecular monitoring technology that is (1) based on receptor binding and not the reactivity of the target, rendering it fairly general, and (2) able to support high-frequency, real-time measurements in situ in the living body. To date, EAB-derived in vivo measurements have largely been performed using three electrodes (working, reference, counter) bundled together within a catheter for insertion into the rat jugular. Exploring this architecture, here we show that the placement of these electrodes inside or outside of the lumen of the catheter significantly impacts sensor performance. Specifically, we find that retaining the counter electrode within the catheter increases the resistance between it and the working electrode, increasing the capacitive background. In contrast, extending the counter electrode outside the lumen of the catheter reduces this effect, significantly enhancing the signal-to-noise of intravenous molecular measurements. Exploring counter electrode geometries further, we find that they need not be larger than the working electrode. Putting these observations together, we have developed a new intravenous EAB architecture that achieves improved performance while remaining short enough to safely emplace in the rat jugular. These findings, though explored here with EAB sensors may prove important for the design of many electrochemical biosensors.