Noah Goshi

Highly Stable Glassy Carbon Interfaces for Long-Term Neural Stimulation and Low-Noise Recording of Brain Activity

We report on the superior electrochemical properties, in-vivo performance and long term stability under electrical stimulation of a new electrode material fabricated from lithographically patterned glassy carbon. For a direct comparison with conventional metal electrodes, similar ultra-flexible, micro-electrocorticography (μ-ECoG) arrays with platinum (Pt) or glassy carbon (GC) electrodes were manufactured. The GC microelectrodes have more than 70% wider electrochemical window and 70% higher CTC (charge transfer capacity) than Pt microelectrodes of similar geometry. Moreover, we demonstrate that the GC microelectrodes can withstand at least 5 million pulses at 0.45 mC/cm2 charge density with less than 7.5% impedance change, while the Pt microelectrodes delaminated after 1 million pulses. Additionally, poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT-PSS) was selectively electrodeposited on both sets of devices to specifically reduce their impedances for smaller diameters (<60 μm). We observed that PEDOT-PSS adhered significantly better to GC than Pt, and allowed drastic reduction of electrode size while maintaining same amount of delivered current. The electrode arrays biocompatibility was demonstrated through in-vitro cell viability experiments, while acute in vivo characterization was performed in rats and showed that GC microelectrode arrays recorded somatosensory evoked potentials (SEP) with an almost twice SNR (signal-to-noise ratio) when compared to the Pt ones.

Multilayer poly(3,4-ethylenedioxythiophene)-dexamethasone and poly(3,4-ethylenedioxythiophene)-polystyrene sulfonate-carbon nanotubes coatings on glassy carbon microelectrode arrays for controlled drug release

The authors present an electrochemically controlled, drug releasing neural interface composed of a glassy carbon (GC) microelectrode array combined with a multilayer poly(3,4-ethylenedioxythiophene) (PEDOT) coating. The system integrates the high stability of the GC electrode substrate, ideal for electrical stimulation and electrochemical detection of neurotransmitters, with the on-demand drug-releasing capabilities of PEDOT-dexamethasone compound, through a mechanically stable interlayer of PEDOT-polystyrene sulfonate (PSS)-carbon nanotubes (CNT). The authors demonstrate that such interlayer improves both the mechanical and electrochemical properties of the neural interface, when compared with a single PEDOT-dexamethasone coating. Moreover, the multilayer coating is able to withstand 10 × 106 biphasic pulses and delamination test with negligible change to the impedance spectra. Cross-section scanning electron microscopy images support that the PEDOT-PSS-CNT interlayer significantly improves the adhesion between the GC substrate and PEDOT-dexamethasone coating, showing no discontinuities between the three well-interconnected layers. Furthermore, the multilayer coating has superior electrochemical properties, in terms of impedance and charge transfer capabilities as compared to a single layer of either PEDOT coating or the GC substrate alone. The authors verified the drug releasing capabilities of the PEDOT-dexamethasone layer when integrated into the multilayer interface through repeated stimulation protocols in vitro, and found a pharmacologically relevant release of dexamethasone.

Incorporation of Silicon Carbide and Diamond-Like Carbon as Adhesion Promoters Improves In Vitro and In Vivo Stability of Thin-Film Glassy Carbon Electrocorticography Arrays

Thin‐film neural devices are an appealing alternative to traditional implants, although their chronic stability remains matter of investigation. In this study, a chronically stable class of thin‐film devices for electrocorticography is manufactured incorporating silicon carbide and diamond‐like carbon as adhesion promoters between glassy carbon (GC) electrodes and polyimide and between GC and platinum traces. The devices are aged in three solutions—phosphate‐buffered saline (PBS), 30 × 10−3 and 150 × 10−3m H2O2/PBS—and stressed using cyclic voltammetry (2500 cycles) and 20 million biphasic pulses. Electrochemical impedance spectroscopy (EIS) and image analysis are performed to detect eventual changes of the electrodes morphology. Results demonstrate that the devices are able to undergo chemically induced oxidative stress and electrical stimulation without failing but actually improving their electrical performance until a steady state is reached. Additionally, cell viability tests are carried out to verify the noncytotoxicity of the materials, before chronically implanting them into rat models. The behavior of the GC electrodes in vivo is monitored through EIS and sensorimotor evoked potential recordings which confirm that, with GC being activated, impedance lowers and quality of recorded signal improves. Histological analysis of the brain tissue is performed and shows no sign of severe immune reaction to the implant.

A Direct Comparison of Glassy Carbon and PEDOT-PSS Electrodes for High Charge Injection and Low Impedance Neural Interfaces

For neural applications, materials able to interface with the brain without harming it while recording high-fidelity signals over long-term implants are still sought after. Glassy Carbon (GC) and Poly (3,4-ethylenedioxythiophene)-poly (styrenesulfonate) (PEDOT-PSS) have proved to be promising materials for neural interfaces as they show – compared to conventional metal electrodes - higher conductivity, better electrochemical stability, very good mechanical properties and therefore seem to be very promising for in vivo applications. We present here, for the first time, a direct comparison between GC and PEDOT-PSS microelectrodes in terms of biocompatibility, electrical and electrochemical properties as well as in vivo recording capabilities, using electrocorticography microelectrode arrays located on flexible polyimide substrate. The GC microelectrodes were fabricated using a traditional negative lithography processes followed by pyrolysis. PEDOT-PSS was selectively electrodeposited on the desired electrodes. Electrochemical performance of the two materials was evaluated through electrochemical impedance spectroscopy and cyclic voltammetry. Biocompatibility was assessed through in-vitro studies evaluating cultured cells viability. The in vivo performance of the GC and PEDOT-PSS electrodes was directly compared by simultaneously recording neuronal activity during somatosensory stimulation in Long-Evans rats. We found that both GC and PEDOT-PSS electrodes outperform metals in terms of electrochemical performance and allow to obtain excellent recordings of somatosensory evoked potentials from the rat brain surface. Furthermore, we found that both GC and PEDOT-PSS substrates are highly biocompatible, confirming that they are safe for neural interface applications.

Improved long-term stability of thin-film glassy carbon electrodes through the use of silicon carbide and amorphous carbon

Long-term stability of neural interfaces is a challenge that has still to be overcome. In this study, we manufactured a highly stable multi-layer thin-film class of carbon-based devices for electrocorticography (ECoG) incorporating silicon carbide (SiC) and amorphous carbon (DLC) as adhesion promoters between glassy carbon (GC) electrodes and polyimide (PI) substrate and between PI and platinum (Pt) traces. We aged the thin-film electrodes in 30 mM H2O2 at 39 °C for one week - to mimic the effects of post-surgery inflammatory reaction - and subsequently stressed them with 2500 CV cycles. We additionally performed stability tests stimulating the electrodes with 15 million biphasic pulses. Finally, we implanted the electrodes for 6 weeks into rat models and optically characterized the explanted devices. Results show that the fabricated ECoG devices were able to withstand the in vitro and in vivo tests without significant change in impedance and morphology.

Investigation Into the Effects of Nucleotide Content on the Electrical Characteristics of DNA Plasmid Molecular Wires

In this study, we investigate the effect of nucleotide content on the conductivity of plasmid length DNA molecular wires covalently bound to high aspect-ratio gold electrodes. The DNA wires were all between 2.20-2.35μ in length (>6000bp), and contained either 39%, 53%, or 64% GC base-pairs. We compared the current-voltage (I-V) and frequency-impedance characteristics of the DNA wires with varying GC content, and observed statistically significantly higher conductivity in DNA wires containing higher GC content in both AC and DC measurement methods. Additionally, we noted that the conductivity decreased as a function of time for all DNA wires, with the impedance at 100 Hz nearly doubling over a period of seven days. All readings were taken in humidity and temperature controlled environments on DNA wires suspended above an insulative substrate, thus minimizing the effect of experimental and environmental factors as well as potential for nonlinear alternate DNA confirmations. While other groups have studied the effect of GC content on the conductivity of nanoscale DNA molecules (<;50bp), we were able to demonstrate that nucleotide content can affect the conductivity of micrometer length DNA wires at scales that may be required during the fabrication of DNA-based electronics. Furthermore, our results provide further evidence that many of the charge transfer theories developed from experiments using nanoscale DNA molecules may still be applicable for DNA wires at the micro scale.

Effect of temperature and UV illumination on charge transport mechanisms in DNA

Research into the use of DNA molecules as building blocks for nanoelectronics as well as nanosystems continues. Recently, our group has reported significant electrical conductivity in λ-DNA through direct and in-direct measurements involving high-aspect ratio electrodes that eliminate the effect of the substrate. Our results demonstrate that, at moderate to high frequencies, λ-DNA molecular wires show low impedance. In addition, to prove that the conductivity is indeed from DNA bridge, we studied the effect of temperature and UV irradiation on DNA molecular wires. The temperature results indicate that λ-DNA molecular wires have differing impedance responses at two temperature regimes: impedance increases between 4°C - 40°C, then decreases from 40°C to the melting point (~110°C) at which λ-DNA denatures resulting in a complete loss of current transduction. This hysteric and bi-model behavior makes DNA a candidate for nanoelectronics components such as thermal transistors and switches. The data from UV exposure experiments indicates decreased conductivity of λ-DNA molecular wires after UV exposure, due to damage to GC base pairs and phosphate groups reducing the path available for both charge hopping and short-range electron tunneling mechanisms. The lessons learned from these conductivity experiments along with our knowledge of different charge transport mechanisms within DNA can be applied to the design of synthetic molecular wires for the construction of nanoelectronic devices.