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J Mater Chem B. 2017 Apr 7;5(13):2445-2458. doi: 10.1039/C7TB00095B. Epub 2017 Mar 6.

Aptamer-functionalized neural recording electrodes for the direct measurement of cocaine in vivo.

Author information

1
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261, USA.
2
Shenzhen Key Lab of Neuropsychiatric Modulation and Collaborative Innovation Center for Brain Science, CAS Center for Excellence in Brain Science, Shenzhen Institute of Advanced Technologies, Chinese Academy of Sciences, Shenzhen, 518055, China.
3
Diagnostic Biochips, Glen Burnie, MD 21061, USA.
4
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA.

Abstract

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.

KEYWORDS:

aptamer; cocaine; in vivo; neural recording probe; sensor; square wave voltammetry

Conflict of interest statement

I.M. Taylor, Z. Du, J.R. Eles, A.R. Horner, K.A. Catt, S.G. Weber and X.T. Cui have no conflicts of interest. During this study, E.T. Bigelow was the VP of research and development and B.G. Jamieson is the CTO at Diagnostic Biochips. Diagnostic Biochips has a potential to commercialize the technology.

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