Generating Multiscale Gold Nanostructures on Glass without Sidewall Deposits Using Minimal Dry Etching Steps.

The advent of recent technologies in the nanoscience arena requires new and improved methods for the fabrication of multiscale features ( e.g., from micro- to nanometer scales). Specifically, biological applications generally demand the use of transparent substrates to allow for the optical monitoring of processes of interest in cells and other biological materials. Whereas wet etching methods commonly fail to produce essential nanometer scale features, plasma-based dry etching can produce features down to tens of nanometers. However, dry etching methods routinely require extreme conditions and extra steps to obtain features without residual materials such as sidewall deposits (veils). This work presents the development of a gold etching process with gases that are commonly used to etch glass. Our method can etch gold films using reactive ion etching (RIE) at room temperature and mild pressure in a trifluoromethane (CHF3)/oxygen (O2) environment, producing features down to 50 nm. Aspect ratios of 2 are obtainable in one single step and without sidewall veils by controlling the oxygen present during the RIE process. This method generates surfaces completely flat and ready for the deposition of other materials. The gold features that were produced by this method exhibited high conductivity when carbon nanotubes were deposited on top of patterned features (gold nanoelectrodes), hence demonstrating an electrically functional gold after the dry etching process. The production of gold nanofeatures on glass substrates would serve as biocompatible, highly conductive, and chemically stable materials in biological/biomedical applications.

Access resistance of stimulation electrodes as a function of electrode proximity to the retina.

OBJECTIVE: Epiretinal prostheses seek to effectively stimulate the retina by positioning electrode arrays close to its surface so current pulses generate narrow retinal electric fields. Our objective was to evaluate the use of the electrical impedance of insulated platinum electrodes as a measure of the proximity of insulated platinum electrodes to the inner surface of the retina. APPROACH: We examined the impedance of platinum disk electrodes, 0.25 mm in diameter, insulated with two widths (0.8 and 1.6 mm outer diameter) of transparent fluoropolymer in a rabbit retinal eyecup preparation. Optical coherence tomography measured the electrode's proximity to the retinal surface which was correlated with changes in the voltage waveform at the electrode. Electrode impedance changes during retinal deformation were also studied. MAIN RESULTS: When the 1.6 mm diameter insulated electrodes advanced towards the retinal surface from 1000 µm, their voltage step at current pulse onset increased, reflecting an access resistance increase of 3880 ± 630 Ω, with the 50% midpoint averaging 30 µm, while thin 0.8 mm insulated electrode advancement showed an access resistance increase 50% midpoint averaging 16 µm. Using impedance spectroscopy, electrode-retina proximity differences were seen in the 1.6 mm insulated electrode impedance modulus between 1 and 100 kHz and the waveform phase angle at 0.3-10 kHz, while thin 0.8 mm insulated electrode advancement produced smaller impedance modulus changes with retinal proximity between 3 and 100 kHz. These impedance changes with retinal proximity may reflect different sized zones of eye wall being coupled in series with the insulated platinum electrode. SIGNIFICANCE: The proximity of stimulus electrodes to neural tissue in fluid-filled spaces can be estimated from access resistance changes in the stimulus pulse waveform. Because many prosthetic devices allow back telemetry communication of the stimulus electrode waveform, it is possible these series resistance increases observed with retinal proximity could be used as a metric of stimulus electrode placement.

Lifetime assessment of atomic-layer-deposited Al2O3-Parylene C bilayer coating for neural interfaces using accelerated age testing and electrochemical characterization.

The lifetime and stability of insulation are critical features for the reliable operation of an implantable neural interface device. A critical factor for an implanted insulation's performance is its barrier properties that limit access of biological fluids to the underlying device or metal electrode. Parylene C is a material that has been used in FDA-approved implantable devices. Considered a biocompatible polymer with barrier properties, it has been used as a substrate, insulation or an encapsulation for neural implant technology. Recently, it has been suggested that a bilayer coating of Parylene C on top of atomic-layer-deposited Al2O3 would provide enhanced barrier properties. Here we report a comprehensive study to examine the mean time to failure of Parylene C and Al2O3-Parylene C coated devices using accelerated lifetime testing. Samples were tested at 60°C for up to 3 months while performing electrochemical measurements to characterize the integrity of the insulation. The mean time to failure for Al2O3-Parylene C was 4.6 times longer than Parylene C coated samples. In addition, based on modeling of the data using electrical circuit equivalents, we show here that there are two main modes of failure. Our results suggest that failure of the insulating layer is due to pore formation or blistering as well as thinning of the coating over time. The enhanced barrier properties of the bilayer Al2O3-Parylene C over Parylene C makes it a promising candidate as an encapsulating neural interface.

Dynamic steering of in vitro cortical neurons using field stimulation.

Neurological disorders are often characterized by abnormal neuronal activity. In the case of epilepsy, this can manifest itself in the form of uncontrolled synchronous activity often in the form of bursting. Pattern steering is the ability to apply stimulation to a network that effectively changes its dynamical firing pattern. In an epileptic network, the stimulation would be used to move the seizing network from its abnormal state to a normal state. This idea is explored here in cultured networks of cortical neurons plated on microelectrode arrays. Stimulation was applied to the bath resulting in an electric field generated throughout the network. This field was verified as sub-threshold in strength using a finite element model simulation. Stimulated networks showed a significant suppression in the number of bursts and increase in the interburst interval as compared to control networks. This observed burst suppression suggests that the sub-threshold stimulating field moved networks from a state of high frequency bursting to a state of low frequency bursting.

In vivo electrochemical characterization and inflammatory response of multiwalled carbon nanotube-based electrodes in rat hippocampus.

Stimulating neural electrodes are required to deliver charge to an environment that presents itself as hostile. The electrodes need to maintain their electrical characteristics (charge and impedance) in vivo for a proper functioning of neural prostheses. Here we design implantable multi-walled carbon nanotubes coating for stainless steel substrate electrodes, targeted at wide frequency stimulation of deep brain structures. In well-controlled, low-frequency stimulation acute experiments, we show that multi-walled carbon nanotube electrodes maintain their charge storage capacity (CSC) and impedance in vivo. The difference in average CSCs (n = 4) between the in vivo (1.111 mC cm(-2)) and in vitro (1.008 mC cm(-2)) model was statistically insignificant (p > 0.05 or P-value = 0.715, two tailed). We also report on the transcription levels of the pro-inflammatory cytokine IL-1beta and TLR2 receptor as an immediate response to low-frequency stimulation using RT-PCR. We show here that the IL-1beta is part of the inflammatory response to low-frequency stimulation, but TLR2 is not significantly increased in stimulated tissue when compared to controls. The early stages of neuroinflammation due to mechanical and electrical trauma induced by implants can be better understood by detection of pro-inflammatory molecules rather than by histological studies. Tracking of such quantitative response profits from better analysis methods over several temporal and spatial scales. Our results concerning the evaluation of such inflammatory molecules revealed that transcripts for the cytokine IL-1beta are upregulated in response to low-frequency stimulation, whereas no modulation was observed for TLR2. This result indicates that the early response of the brain to mechanical trauma and low-frequency stimulation activates the IL-1beta signaling cascade but not that of TLR2.

Charge storage: stability measures in implantable electrodes.

Here we report on long-term (300 to 600 hours) stability measures for implantable stimulating electrodes. We have considered several measures of stability as they refer to reliability of charge carrying capacity in implantable electrodes. We have designed and manufactured coatings for large area (1 to 2mm(2)) stainless steel substrates. Materials tested were electrodeposited iridium oxide films, multi-walled carbon nanotube mesh, and PEDOT:PSS. Traditional characterization techniques such as cyclic voltammetry and electrochemical impedance spectroscopy cover a small fraction of the characterization framework needed for ensuring the safety and performance of electrodes designed for long-term implants. The stability measures suggested here rely on continuous low frequency cycling and evaluation of cathodic charge storage capacity during cycling. We experimentally show, in this paper, that the stability may be measured and is relevant for long-term applications of such coatings.