Aptamer-functionalized neural recording electrodes for the direct measurement of cocaine in vivo.
Aptamer-functionalized neural recording electrodes for the direct measurement of cocaine in vivo.
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DOI：
10.1039/c7tb00095b
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发表时间：
2017-04-07
期刊：
影响因子：
--
通讯作者：
Cui XT
中科院分区：
文献类型：
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作者：
Taylor IM;Du Z;Bigelow ET;Eles JR;Horner AR;Catt KA;Weber SG;Jamieson BG;Cui XT
可卡因是一种高度成瘾的精神兴奋剂，通过竞争性抑制多巴胺转运蛋白发挥作用。为了充分了解可卡因滥用和成瘾的区域特异性神经病理学，开发能够直接测量在整个暴露的药代动力学时间过程中不同脑区域局部的实时可卡因瞬态事件的可卡因传感技术是明确必要的。我们已经开发了一种基于电化学适体的体内可卡因传感器上的硅基神经记录探针平台，能够直接测量可卡因从离散的大脑位置，使用方波伏安法（SWV）。传感器对可卡因的灵敏度遵循修改的指数朗缪尔模型关系，并且在< 2秒内发生完全的适体-靶标结合，并且在< 4秒内解除结合。由此产生的时间分辨率是传统微透析采样方法的75倍。当植入大鼠背侧纹状体时，可卡因传感器表现出稳定的SWV信号漂移（使用对数指数方程建模），并且能够测量对重复局部可卡因输注以及全身IV可卡因注射的实时体内响应。体内传感器能够在接近3小时的时间段内获得可再现的测量，之后信号幅度可能由于组织包囊而显著降低。最后，适体功能化的神经记录探针成功地检测脑中的自发和诱发的神经活动。这种双重功能使可卡因传感器成为一种强大的工具，能够以高的空间和时间分辨率监测生化和电生理信号。
Cocaine is a highly addictive psychostimulant that acts through competitive inhibition of the dopamine transporter. In order to fully understand the region specific neuropathology of cocaine abuse and addiction, it is unequivocally necessary to develop cocaine sensing technology capable of directly measuring real-time cocaine transient events local to different brain regions throughout the pharmacokinetic time course of exposure. We have developed an electrochemical aptamer-based in vivo cocaine sensor on a silicon based neural recording probe platform capable of directly measuring cocaine from discrete brain locations using square wave voltammetry (SWV). The sensitivity of the sensor for cocaine follows a modified exponential Langmuir model relationship and complete aptamer-target binding occurs in < 2 sec and unbinding in < 4 sec. The resulting temporal resolution is a 75X increase from traditional microdialysis sampling methods. When implanted in the rat dorsal striatum, the cocaine sensor exhibits stable SWV signal drift (modeled using a logarithmic exponential equation) and is capable of measuring real-time in vivo response to repeated local cocaine infusion as well as systemic IV cocaine injection. The in vivo sensor is capable of obtaining reproducible measurements over a period approaching 3 hours, after which signal amplitude significantly decreases likely due to tissue encapsulation. Finally, aptamer functionalized neural recording probes successfully detect spontaneous and evoked neural activity in the brain. This dual functionality makes the cocaine sensor a powerful tool capable of monitoring both biochemical and electrophysiological signals with high spatial and temporal resolution.