Dataset Information

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.

SUBMITTER: Taylor IM

PROVIDER: S-EPMC5512874 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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

Taylor I Mitch IM Du Zhanhong Z Bigelow Emma T ET Eles James R JR Horner Anthony R AR Catt Kasey A KA Weber Stephen G SG Jamieson Brian G BG Cui X Tracy XT

Journal of materials chemistry. B 20170306 13

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 <i>in vivo</i> ...[more]

PMID: 28729901

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Project description:Soft and conductive nanomaterials like carbon nanotubes, graphene, and nanowire scaffolds have expanded the family of ultraflexible microelectrodes that can bend and flex with the natural movement of the brain, reduce the inflammatory response, and improve the stability of long-term neural recordings. However, current methods to implant these highly flexible electrodes rely on temporary stiffening agents that temporarily increase the electrode size and stiffness thus aggravating neural damage during implantation, which can lead to cell loss and glial activation that persists even after the stiffening agents are removed or dissolve. A method to deliver thin, ultraflexible electrodes deep into neural tissue without increasing the stiffness or size of the electrodes will enable minimally invasive electrical recordings from within the brain. Here we show that specially designed microfluidic devices can apply a tension force to ultraflexible electrodes that prevents buckling without increasing the thickness or stiffness of the electrode during implantation. Additionally, these "fluidic microdrives" allow us to precisely actuate the electrode position with micron-scale accuracy. To demonstrate the efficacy of our fluidic microdrives, we used them to actuate highly flexible carbon nanotube fiber (CNTf) microelectrodes for electrophysiology. We used this approach in three proof-of-concept experiments. First, we recorded compound action potentials in a soft model organism, the small cnidarian Hydra. Second, we targeted electrodes precisely to the thalamic reticular nucleus in brain slices and recorded spontaneous and optogenetically evoked extracellular action potentials. Finally, we inserted electrodes more than 4 mm deep into the brain of rats and detected spontaneous individual unit activity in both cortical and subcortical regions. Compared to syringe injection, fluidic microdrives do not penetrate the brain and prevent changes in intracranial pressure by diverting fluid away from the implantation site during insertion and actuation. Overall, the fluidic microdrive technology provides a robust new method to implant and actuate ultraflexible neural electrodes.

Project description:The number of people aged 12 years and older using illicit drugs reached 59.3 million in 2020, among which 5.2 million are cocaine users based on the national data. In order to fully understand cocaine addiction and develop effective therapies, a tool is needed to reliably measure real-time cocaine concentration and neural activity in different regions of the brain with high spatial and temporal resolution. Integrated biochemical sensing devices based upon flexible microelectrode arrays (MEA) have emerged as a powerful tool for such purposes; however, MEAs suffer from undesired biofouling and inflammatory reactions, while those with immobilized biologic sensing elements experience additional failures due to biomolecule degradation. Aptasensors are powerful tools for building highly selective sensors for analytes that have been difficult to detect. In this work, DNA aptamer-based electrochemical cocaine sensors were integrated on flexible MEAs and protected with an antifouling zwitterionic poly (sulfobetaine methacrylate) (PSB) coating, in order to prevent sensors from biofouling and degradation by the host tissue. In vitro experiments showed that without the PSB coating, both adsorption of plasma protein albumin and exposure to DNase-1 enzyme have detrimental effects on sensor performance, decreasing signal amplitude and the sensitivity of the sensors. Albumin adsorption caused a 44.4% sensitivity loss, and DNase-1 exposure for 24 hr resulted in a 57.2% sensitivity reduction. The PSB coating successfully protected sensors from albumin fouling and DNase-1 enzyme digestion. In vivo tests showed that the PSB coated MEA aptasensors can detect repeated cocaine infusions in the brain for 3 hrs after implantation without sensitivity degradation. Additionally, the same MEAs can record electrophysiological signals at different tissue depths simultaneously. This novel flexible MEA with integrated cocaine sensors can serve as a valuable tool for understanding the mechanisms of cocaine addiction, while the PSB coating technology can be generalized to improve all implantable devices suffering from biofouling and inflammatory host responses.

Project description:OBJECTIVE:Needle EMG remains the standard clinical test for neuromuscular disease (NMD) assessment, but it only characterizes myofiber membrane depolarization. On the other hand, electrical impedance provides non-electrically active structural and compositional data of tissues. Here, we designed a prototype of needle electrode integrating electrical impedance and EMG measurement capabilities, the so-called I-EMG needle electrode. APPROACH:We use finite element method models to study the impedance recording characteristics of I-EMG needle electrodes. The simulated electrical and mechanical design specifications are then manufactured to create a prototype of an I-EMG needle electrode. We pilot these new needle electrodes by conducting in vivo impedance measurements with muscle at rest on healthy wild-type (wt, n = 5) and muscular dystrophy (mdx, n = 5) mice. Comparisons between wt and mdx mice are performed using Mann-Whitney test, two-tailed, p < 0.05. The electrical characterization of the EMG electrode in the developed I-EMG needles was performed in vitro on saline solution and through EMG detection in wt animal at rest and during voluntary contractions. RESULTS:Muscle impedance demonstrate good repeatability (p < 0.05 and p < 0.005 for resistance and reactance at 50 kHz, respectively) and agreement between different I-EMG needles. Impedance data allows us to discriminate between mdx and wt muscle (p < 0.05 and p < 0.005 for resistance and reactance at 10 kHz, respectively). EMG broadband noise power and peak amplitude using the I-EMG needle were similar to that of a commercial monopolar EMG needle. EMG recordings using the I-EMG needle measured electrical activity similar to a standard monopolar needle with muscle at rest and during voluntary contraction. SIGNIFICANCE:Needle I-EMG technology may offer the opportunity to enhance the diagnostic capability and quantification of NMD beyond that possible with either impedance or EMG techniques separately. Ultimately, needle I-EMG could serve as a new bedside tool to assess NMD without increasing the complexity or duration of the EMG test.

Dataset Information

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

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

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