Nicolas A. Alba

Carbon nanotube nanoreservior for controlled release of anti-inflammatory dexamethasone

On demand release of anti-inflammatory drug or neurotropic factors have great promise for maintaining a stable chronic neural interface. Here we report the development of an electrically controlled drug release system based on conducting polymer and carbon nanotubes. Drug delivery research using carbon nanotubes (CNTs) has taken advantage of the ability of CNTs to load large amounts of drug molecules on their outer surface. However, the utility of the inner cavity of CNTs, which can increase the drug loading capacity, has not yet been explored. In this paper, the use of multi-wall CNTs as nanoreserviors for drug loading and controlled release is demonstrated. The CNTs are pretreated with acid sonication to open their ends and make their outer and inner surfaces more hydrophilic. When dispersed and sonicated in a solution containing the anti-inflammatory drug dexamethasone, experiments show that the pretreated CNTs are filled with the drug solution. To prevent the unwanted release of the drug, the open ends of the drug-filled CNTs are then sealed with polypyrrole (PPy) films formed through electropolymerization. The prepared electrode coating significantly reduced the electrode impedance, which is desired for neural recording and stimulation. More importantly, the coating can effectively store drug molecules and release the bioactive drug in a controlled manner using electrical stimulation. The dexamethasone released from the PPy/CNT film was able to reduce lipopolysaccharide induced microglia activation to the same degree as the added dexamethasone.

Novel Hydrogel-Based Preparation-Free EEG Electrode

The largest obstacles to signal transduction for electroencephalography (EEG) recording are the hair and the epidermal stratum corneum of the skin. In typical clinical situations, hair is parted or removed, and the stratum corneum is either abraded or punctured using invasive penetration devices. These steps increase preparation time, discomfort, and the risk of infection. Cross-linked sodium polyacrylate gel swelled with electrolyte was explored as a possible skin contact element for a prototype preparation-free EEG electrode. As a superabsorbent hydrogel, polyacrylate can swell with electrolyte solution to a degree far beyond typical contemporary electrode materials, delivering a strong hydrating effect to the skin surface. This hydrating power allows the material to increase the effective skin contact surface area through wetting, and noninvasively decrease or bypass the highly resistive barrier of the stratum corneum, allowing for reduced impedance and improved electrode performance. For the purposes of the tests performed in this study, the polyacrylate was prepared both as a solid elastic gel and as a flowable paste designed to penetrate dense scalp hair. The gel can hold 99.2% DI water or 91% electrolyte solution, and the water content remains high after 29 h of air exposure. The electrical impedance of the gel electrode on unprepared human forearm is significantly lower than a number of commercial ECG and EEG electrodes. This low impedance was maintained for at least 8 h (the longest time period measured). When a paste form of the electrode was applied directly onto scalp hair, the impedance was found to be lower than that measured with commercially available EEG paste applied in the same manner. Time-frequency transformation analysis of frontal lobe EEG recordings indicated comparable frequency response between the polyacrylate-based electrode on unprepared skin and the commercial EEG electrode on abraded skin. Evoked potential recordings demonstrated signal-to-noise ratios of the experimental and commercial electrodes to be effectively equivalent. These results suggest that the polyacrylate-based electrode offers a powerful option for EEG recording without scalp preparation.

Structural modifications in chronic microwire electrodes for cortical neuroprosthetics: a case study

Long-term viability of chronic invasive neural probes is a necessary condition for extracting robust control signals directly from neural tissue. Although immune/tissue response is a leading factor in the degradation of single neuron recording, we investigate a second component of signal degradation connected to the structural changes associated with microwire electrodes chronically exposed to extracellular environments in vivo. Scanning electron microscopy is used to assess the surface modifications to the electrodes after an implantation duration of four weeks in rats. The electrode developed a smooth fracture surface, a reduction of the metal diameter, and pitting in the insulation of the electrode structure. Over the duration of implantation, recording properties of the electrode were marked by a reduction in the peak-to-peak amplitude in neuronal firing.

In Vivo Electrochemical Analysis of a PEDOT/MWCNT Neural Electrode Coating

Neural electrodes hold tremendous potential for improving understanding of brain function and restoring lost neurological functions. Multi-walled carbon nanotube (MWCNT) and dexamethasone (Dex)-doped poly(3,4-ethylenedioxythiophene) (PEDOT) coatings have shown promise to improve chronic neural electrode performance. Here, we employ electrochemical techniques to characterize the coating in vivo. Coated and uncoated electrode arrays were implanted into rat visual cortex and subjected to daily cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) for 11 days. Coated electrodes experienced a significant decrease in 1 kHz impedance within the first two days of implantation followed by an increase between days 4 and 7. Equivalent circuit analysis showed that the impedance increase is the result of surface capacitance reduction, likely due to protein and cellular processes encapsulating the porous coating. Coating’s charge storage capacity remained consistently higher than uncoated electrodes, demonstrating its in vivo electrochemical stability. To decouple the PEDOT/MWCNT material property changes from the tissue response, in vitro characterization was conducted by soaking the coated electrodes in PBS for 11 days. Some coated electrodes exhibited steady impedance while others exhibiting large increases associated with large decreases in charge storage capacity suggesting delamination in PBS. This was not observed in vivo, as scanning electron microscopy of explants verified the integrity of the coating with no sign of delamination or cracking. Despite the impedance increase, coated electrodes successfully recorded neural activity throughout the implantation period.

Design and Fabrication of a Flexible Substrate Microelectrode Array for Brain Machine Interfaces

We report a neural microelectrode array design that leverages the recording properties of conventional microwire electrode arrays with the additional features of precise control of the electrode geometries. Using microfabrication techniques, a neural probe array is fabricated that possesses a flexible polyimide-based cable. The performance of the design was tested with electrochemical impedance spectroscopy and in vivo studies. The gold-plated electrode site has an impedance value of 0.9 MOmega at 1 kHz. Acute neural recording provided high neuronal yields, peak-to-peak amplitudes (as high as 100muV), and signal-to-noise ratios (27dB)

Nanostructured Coatings for Improved Charge Delivery to Neurons

This chapter explores the variability and limitations of traditional stimulation electrodes by first appreciating how electrical potential differences lead to efficacious activation of nearby neurons and examining the basic electrochemical mechanisms of charge transfer at an electrode/electrolyte interface. It then covers the advantages and current challenges of emerging micro-/nanostructured electrode materials for next-generation neural stimulation microelectrodes.

Conducting Polymer-based Aptamer Biosensor for in situ Monitoring of Cytokine

Neural prostheses often suffer from undesired chronic inflammatory tissue response. Therefore; a sensitive and real-time biosensor for inflammatory cytokine detection would provide invaluable information toward solving this problem. Such a biosensor based on an aptamer probe doped in polypyrrole and subsequent electrochemical impedance spectroscopy (EIS) has been developed. PDGF, an important inflammatory cytokine, has been successfully measured in both offline EIS characterization and real-time impedance monitoring. For in situ detection of PDGF, the best sensitivity of 10 ng/ml has been achieved.