Nathalia Peixoto

Gas sensitive porous silicon devices: responses to organic vapors

Geometrically scaled PS-based structures were fabricated in order to develop gas sensing devices by exploring porous silicon (PS) electrical characteristics. The electrical behavior of PS devices respond to polar organic vapors (as acetone and ethanol) reversibly in a reproducible way. Devices were fabricated with three different perimeters, maintaining a constant area (5.76 mm 2 ) and constant PS porosity (60%) throughout samples, in order to evaluate their electrical impedance depending on the area/perimeter ratio. Electrical impedance was measured from 10 kHz to 10 MHz in acetone, ethanol and vacuum (as reference) environments. The results obtained show the general aspect for impedance variation as expected for disordered materials such as amorphous semiconductors or polymers. Measured impedance is fitted proportionally to (2pf) s , where f is the excitation frequency. The exponential factor ‘‘s’’ was found to be around � 0.55 for ethanol and � 0.45 for acetone, whereas in vacuum s equals � 0.97, thus providing a method for identifying polar molecules. The parameter ‘‘s’’ for the tested environments is independent of device geometry. # 2003 Elsevier Science B.V. All rights reserved.

Improving the performance of poly(3,4-ethylenedioxythiophene) for brain–machine interface applications

Conducting polymers, especially poly(3,4-ethylenedioxythiophene) (PEDOT) based materials, are important for developing highly sensitive and microscale neural probes. In the present work, we show that the conductivity and stability of PEDOT can be significantly increased by switching the widely used counter anion poly(styrenesulfonate) (PSS) to the smaller tetrafluoroborate (TFB) anion during the electrodeposition of the polymer. Time-dependent impedance measurements of polymer modified implantable microwires were conducted in physiological buffer solutions under accelerated aging conditions and the relative stability of PEDOT:PSS and PEDOT:TFB modified microwires was compared over time. This study was also extended to carbon nanotube (CNT) incorporated PEDOT:PSS which, according to some reports, is claimed to enhance the stability and electrical performance of the polymer. However, no noticeable difference was observed between PEDOT:PSS and CNT:PEDOT:PSS in our measurements. At the biologically relevant frequency of 1kHz, PEDOT:TFB modified microwires exhibit approximately one order of magnitude higher conductivity and demonstrate enhanced stability over both PEDOT:PSS and CNT:PEDOT:PSS modified microwires. In addition, PEDOT:TFB is not neurotoxic and we show the proof-of-concept for both in vitro and in vivo neuronal recordings using PEDOT:TFB modified microelectrode arrays and chronic electrodes, respectively. Our findings suggest that PEDOT:TFB is a promising conductive polymer coating for the recording of neural activities.

Improved sleep-wake and behavior discrimination using MEMS accelerometers.

State of vigilance is determined by behavioral observations and electrophysiological activity. Here, we improve automatic state of vigilance discrimination by combining head acceleration with EEG measures. We incorporated biaxial dc-sensitive microelectromechanical system (MEMS) accelerometers into head-mounted preamplifiers in rodents. Epochs (15s) of behavioral video and EEG data formed training sets for the following states: Slow Wave Sleep, Rapid Eye Movement Sleep, Quiet Wakefulness, Feeding or Grooming, and Exploration. Multivariate linear discriminant analysis of EEG features with and without accelerometer features was used to classify behavioral state. A broad selection of EEG feature sets based on recent literature on state discrimination in rodents was tested. In all cases, inclusion of head acceleration significantly improved the discriminative capability. Our approach offers a novel methodology for determining the behavioral context of EEG in real time, and has potential application in automatic sleep-wake staging and in neural prosthetic applications for movement disorders and epileptic seizures.

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 insulations 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.

Seizure entrainment with polarizing low-frequency electric fields in a chronic animal epilepsy model

Neural activity can be modulated by applying a polarizing low-frequency (<<100 Hz) electric field (PLEF). Unlike conventional pulsed stimulation, PLEF stimulation has a graded, modulatory effect on neuronal excitability, and permits the simultaneous recording of neuronal activity during stimulation suitable for continuous feedback control. We tested a prototype system that allows for simultaneous PLEF stimulation with minimal recording artifact in a chronic tetanus toxin animal model (rat) of hippocampal epilepsy with spontaneous seizures. Depth electrode local field potentials recorded during seizures revealed a characteristic pattern of field postsynaptic potentials (fPSPs). Sinusoidal voltage-controlled PLEF stimulation (0.5-25 Hz) was applied in open-loop cycles radially across the CA3 of ventral hippocampus. For stimulated seizures, fPSPs were transiently entrained with the PLEF waveform. Statistical significance of entrainment was assessed with Thomsons harmonic F-test, with 45/132 stimulated seizures in four animals individually demonstrating significant entrainment (p < 0.04). Significant entrainment for multiple presentations at the same frequency (p < 0.01) was observed in three of four animals in 42/64 stimulated seizures. This is the first demonstration in chronically implanted freely behaving animals of PLEF modulation of neural activity with simultaneous recording.

Use of cortical neuronal networks for in vitro material biocompatibility testing

Neural interfaces aim to restore neurological function lost during disease or injury. Novel implantable neural interfaces increasingly capitalize on novel materials to achieve microscale coupling with the nervous system. Like any biomedical device, neural interfaces should consist of materials that exhibit biocompatibility in accordance with the international standard ISO10993-5, which describes in vitro testing involving fibroblasts where cytotoxicity serves as the main endpoint. In the present study, we examine the utility of living neuronal networks as functional assays for in vitro material biocompatibility, particularly for materials that comprise implantable neural interfaces. Embryonic mouse cortical tissue was cultured to form functional networks where spontaneous action potentials, or spikes, can be monitored non-invasively using a substrate-integrated microelectrode array. Taking advantage of such a platform, we exposed established positive and negative control materials to the neuronal networks in a consistent method with ISO 10993-5 guidance. Exposure to the negative controls, gold and polyethylene, did not significantly change the neuronal activity whereas the positive controls, copper and polyvinyl chloride (PVC), resulted in reduction of network spike rate. We also compared the functional assay with an established cytotoxicity measure using L929 fibroblast cells. Our findings indicate that neuronal networks exhibit enhanced sensitivity to positive control materials. In addition, we assessed functional neurotoxicity of tungsten, a common microelectrode material, and two conducting polymer formulations that have been used to modify microelectrode properties for in vivo recording and stimulation. These data suggest that cultured neuronal networks are a useful platform for evaluating the functional toxicity of materials intended for implantation in the nervous system.

High pulsed current density β-Ga2O3 MOSFETs verified by an analytical model corrected for interface charge

We report on Sn-doped β-Ga2O3 MOSFETs grown by molecular beam epitaxy with as-grown carrier concentrations from 0.7 × 1018 to 1.6 × 1018 cm−3 and a fixed channel thickness of 200 nm. A pulsed current density of >450 mA/mm was achieved on the sample with the lowest sheet resistance and a gate length of 2  μm. Our results are explained using a simple analytical model with a measured gate voltage correction factor based on interface charges that accurately predict the electrical performance for all doping variations.

Differential responses to ω-agatoxin IVA in murine frontal cortex and spinal cord derived neuronal networks.

ω-Agatoxin-IVA is a well known P/Q-type Ca(2+) channel blocker and has been shown to affect presynaptic Ca(2+) currents as well postsynaptic potentials. P/Q-type voltage gated Ca(2+) channels play a vital role in presynaptic neurotransmitter release and thus play a role in action potential generation. Monitoring spontaneous activity of neuronal networks on microelectrode arrays (MEAs) provides an important tool for examining this neurotoxin. Changes in extracellular action potentials are readily observed and are dependent on synaptic function. Given the efficacy of murine frontal cortex and spinal cord networks to detect neuroactive substances, we investigated the effects of ω-agatoxin on spontaneous action potential firing within these networks. We found that networks derived from spinal cord are more sensitive to the toxin than those from frontal cortex; a concentration of only 10nM produced statistically significant effects on activity from spinal cord networks whereas 50 nM was required to alter activity in frontal cortex networks. Furthermore, the effects of the toxin on frontal cortex are more complex as unit specific responses were observed. These manifested as either a decrease or increase in action potential firing rate which could be statistically separated as unique clusters. Administration of bicuculline, a GABAA inhibitor, isolated a single response to ω-agatoxin, which was characterized by a reduction in network activity. These data support the notion that the two clusters detected with ω-agatoxin exposure represent differential responses from excitatory and inhibitory neuronal populations.

Correlation of the electrical and intrinsic optical signals in the chicken spreading depression phenomenon

This paper presents some results on the correlation between the electrophysiological and intrinsic optical signals (IOS) of spreading depression waves in chicken retinae. We first show that the peak of the time derivative of the electrophysiological wave occurs precisely when the optical signal reaches the electrode tip. Second, by comparing bath applications of propranolol and glycerol it can be shown that the slow potential shift is not directly correlated to the intrinsic optical signal. Propranolol depresses the amplitude of the electrical wave, although the intrinsic optical signal continues being visible. On the other hand, we observe total absence of the IOS under glycerol, while the electrical wave is always present. Correlations of this kind are relevant for a deeper understanding of the underlying mechanisms of the spreading depression phenomenon.

Chronic intracortical neural recordings using microelectrode arrays coated with PEDOT-TFB.

UNLABELLED Microelectrode arrays have been extensively utilized to record extracellular neuronal activity for brain-machine interface applications. Modifying the microelectrodes with conductive polymers such as poly(3,4-ethylenedioxythiophene) (PEDOT) has been reported to be advantageous because it increases the effective surface area of the microelectrodes, thereby decreasing impedance and enhancing charge transfer capacity. However, the long term stability and integrity of such coatings for chronic recordings remains unclear. Previously, our group has demonstrated that use of the smaller counter ion tetrafluoroborate (TFB) during electrodeposition increased the stability of the PEDOT coatings in vitro compared to the commonly used counter ion poly(styrenesulfonate) (PSS). In the current work, we examined the long-term in vivo performance of PEDOT-TFB coated microelectrodes. To do so, we selectively modified half of the microelectrodes on NeuroNexus single shank probes with PEDOT-TFB while the other half of the microelectrodes were modified with gold as a control. The modified probes were then implanted into the primary motor cortex of rats. Single unit recordings were observed on both PEDOT-TFB and gold control microelectrodes for more than 12 weeks. Compared to the gold-coated microelectrodes, the PEDOT-TFB coated microelectrodes exhibited an overall significantly lower impedance and higher number of units per microelectrode specifically for the first four weeks. The majority of PEDOT-TFB microelectrodes with activity had an impedance magnitude lower than 400 kΩ at 1 kHz. Our equivalent circuit modeling of the impedance data suggests stability in the polymer-related parameters for the duration of the study. In addition, when comparing PEDOT-TFB microelectrodes with and without long-term activity, we observed a distinction in certain circuit parameters for these microelectrodes derived from equivalent circuit modeling prior to implantation. This observation may prove useful in qualifying PEDOT-TFB microelectrodes with a greater likelihood of registering long-term activity. Overall, our findings confirm that PEDOT-TFB is a chronically stable coating for microelectrodes to enable neural recording. STATEMENT OF SIGNIFICANCE Microelectrode arrays have been extensively utilized to record extracellular neuronal activity for brain-machine interface applications. Poly(3,4-ethylenedioxythiophene) (PEDOT) has gained interest because of its unique electrochemical characteristics and its excellent intrinsic electrical conductivity. However, the long-term stability of the PEDOT film, especially for chronic neural applications, is unclear. In this manuscript, we report for the first time the use of highly stable PEDOT doped with tetrafluoroborate (TFB) for long-term neural recordings. We show that PEDOT-TFB coated microelectrodes on average register more units compared to control gold microelectrodes for at least first four weeks post implantation. We collected the in vivo impedance data over a wide frequency spectrum and developed an equivalent circuit model which helped us determine certain parameters to distinguish between PEDOT-TFB microelectrodes with and without long-term activity. Our findings suggest that PEDOT-TFB is a chronically stable coating for neural recording microelectrodes. As such, PEDOT-TFB could facilitate chronic recordings with ultra-small and high-density neural arrays.