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

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.

Enhancing surface immobilization of bioactive moleculesviaa silica nanoparticle based coating

“…1 Incorporation of biological molecules such as the brain-derived neurotropic factor (BDNF) 2 increases tissue regeneration when applied to regenerative scaffolds for tissue engineering. Biosensors incorporate bio-recognition molecules such as aptamers, 3 enzymes, 4,5 and antibodies 6 onto their surface. Immobilized enzymes may aid in CO 2 removal for artificial lungs.…”

Facile Synthesis of a 3,4-Ethylene-Dioxythiophene (EDOT) Derivative for Ease of Bio-Functionalization of the Conducting Polymer PEDOT

“…For biosensors and bioelectrode applications, surface modifications with functional biological molecules that can recognize specific analytes are highly desirable. Pt-Ir microwires were coated with a thin layer of PEDOT-EM and post-functionalized with a DNA aptamer previously used for cocaine sensing (Baker et al, 2006; Taylor et al, 2017a). The aptamer contains a thiol group on 5′ that can be used as anchoring site and a methylene-blue group on 3′ that serves as electrochemical reporters.…”

Using Aptamers as a Novel Method for Determining GnRH/LH Pulsatility

“…Recently described aptamer-based devices include a lateral flow strip for the detection of hepatitis C core antigen in serum (with a colour-change produced by a positive result visible to the naked eye within 10 min) [ 58 ], a microfluidic paper device for detection of aflatoxin B1 in milk [ 59 ] and standard blood glucose meters have been adapted for quantification of interferon-γ [ 60 ] and cocaine in human serum [ 61 ] using aptamers. Additionally, aptamer-based devices have also been used for in vivo measurement of cocaine in different regions of rat brains using modified electrodes [ 62 ] and for in vivo measurement of antibiotics in ambulatory rats using implanted sensors [ 63 ].…”

“…As aptamers have been used in conjunction with modified implantable electrodes (i.e., gold-coated electrodes functionalized with cocaine-specific aptamers) to measure cocaine in vivo in rat brains [ 62 ]; a similar approach could be used to measure GnRH in the hypothalamus in animals. This would provide invaluable information such as changes in GnRH pulsatility during different stages of reproductive maturity and senescence, and in rodent models of human reproductive orders such as PCOS (the most common reproductive disorder affecting pre-menopausal women [ 14 ]).…”