A Wavelet based Teager Energy Operator for Spike Detection in Microelectrode Array Recordings

Spike detection in neural recordings is the initial step in the creation of brain machine interfaces. The Teager energy operator (TEO) treats a spike as an increase in the `local' energy and detects this increase. The performance of TEO in detecting action potential spikes suffers due to its sensitivity to the frequency of spikes in the presence of noise which is present in microelectrode array (MEA) recordings. The multiresolution TEO (mTEO) method overcomes this shortcoming of the TEO by tuning the parameter k to an optimal value m so as to match to frequency of the spike. In this paper, we present an algorithm for the mTEO using the multiresolution structure of wavelets along with inbuilt lowpass filtering of the subband signals. The algorithm is efficient and can be implemented for real-time processing of neural signals for spike detection. The performance of the algorithm is tested on a simulated neural signal with 10 spike templates obtained from [14]. The background noise is modeled as a colored Gaussian random process. Using the noise standard deviation and autocorrelation functions obtained from recorded data, background noise was simulated by an autoregressive (AR(5)) filter. The simulations show a spike detection accuracy of 90%and above with less than 5% false positives at an SNR of 2.35 dB as compared to 80% accuracy and 10% false positives reported [6] on simulated neural signals.

Evaluation of an elastomer based gold microelectrode array for neural recording applications

We are reporting on the fabrication and electrical characterization of a novel elastomer based micro-cuff neural interface. Electrodes are gold (Au) tracks of sub-100nm thickness and are thermally evaporated on a 0.5 mm thick polydimethylsiloxane (PDMS) substrate. We investigate how electrode area and immersion in phosphate buffered saline (PBS) at 37°C influence electrode impedance. A microfluidic channel is bonded to the electrode array to form the cuff. In an acute, in-vivo, proof-of-principle recording, the device is capable of detecting light stroking and pinch of a hind leg of an anaesthetized rat.

Microelectrode array in mixed alkanethiol self-assembled monolayers: Electrochemical studies

We report an efficient alternative to obtain recessed microelectrodes device on gold electrode surface, in which mixed self-assembled monolayer of long and short carbon alkanethiol chains was used for this purpose. Development of the modified electrodes included the chemical adsorption of 11-mercaptoundecanoic acid and 2-mercaptoethanol solution, as well as their mixtures, on gold surface, resulting in the final mixed self-assembled monolayer configuration. For comparison, the electrochemical performance of self-assembled monolayer of 11-mercaptoundecanoic acid. 3-mercaptopropionic acid, 4-mercapto-1-butanol and 6-mercapto-1-hexanol modified electrodes was also investigated. It was verified that, in the mixed self-assembled monolayer, the 11-mercaptoundecanoic acid acts as a barrier for electron transfer while the short alkanethiol chair is deposited in an island-like shape through which electrons can be freely transferred to ions in solution, allowing electrochemical reactions to occur. The performance of the modified electrodes toward microelectrode behavior was investigated via cyclic voltammetry and electrochemical impedance spectroscopy measurements using [Fe(CN)(6)](3-/4-) redox couple as a probe. In this case, sigmoidal voltammetric responses were obtained, very similar to those observed for microelectrodes. Such behavior reinforces the proposition of electron transfer through the short alkanethiol chain layer and surface blockage by the long chain one. Electrochemical impedance results allowed calculated the mean radius value of each microelectrode disks of 3.8 mu m with about 22 mu m interval between them. The microelectrode environment provided by the mixed self-assembled monolayer can be conveniently used to provide an efficient catalytic conversion in biosensing applications. (C) 2012 Elsevier Ltd. All rights reserved.

Microelectrode Implants for Spinal Cord Stimulation in Rats

Paralysis is a debilitating condition afflicting millions of people across the globe, and is particularly deleterious to quality of life when motor function of the legs is severely impaired or completely absent. Fortunately, spinal cord stimulation has shown great potential for improving motor function after spinal cord injury and other pathological conditions. Many animal studies have shown stimulation of the neural networks in the spinal cord can improve motor ability so dramatically that the animals can even stand and step after a complete spinal cord transaction.

This thesis presents work to successfully provide a chronically implantable device for rats that greatly enhances the ability to control the site of spinal cord stimulation. This is achieved through the use of a parylene-C based microelectrode array, which enables a density of stimulation sites unattainable with conventional wire electrodes. While many microelectrode devices have been proposed in the past, the spinal cord is a particularly challenging environment due to the bending and movement it undergoes in a live animal. The developed microelectrode array is the first to have been implanted in vivo while retaining functionality for over a month. In doing so, different neural pathways can be selectively activated to facilitate standing and stepping in spinalized rats using various electrode combinations, and important differences in responses are observed.

An engineering challenge for the usability of any high density electrode array is connecting the numerous electrodes to a stimulation source. This thesis develops several technologies to address this challenge, beginning with a fully passive implant that uses one wire per electrode to connect to an external stimulation source. The number of wires passing through the body and the skin proved to be a hazard for the health of the animal, so a multiplexed implant was devised in which active electronics reduce the number of wires. Finally, a fully wireless implant was developed. As these implants are tested in vivo, encapsulation is of critical importance to retain functionality in a chronic experiment, especially for the active implants, and it was achieved without the use of costly ceramic or metallic hermetic packaging. Active implants were built that retained functionality 8 weeks after implantation, and achieved stepping in spinalized rats after just 8-10 days, which is far sooner than wire-based electrical stimulation has achieved in prior work.

A Simple and Inexpensive Method for Fabrication of Ultramicroelectrode Array and Its Application for the Detection of Dissolved Oxygen

Herein, we report a simple and inexpensive way for fabrication of ultra microelectrode arrays (UMEAs) and the relative characterization methods. The fabrication of UMEAs involves only a few steps of handwork. Since only metal wires and epoxy are used through the fabrication process, it is supposed to be a quite straightforward method for preparing UMEAs. A dissolved oxygen (DO) sensor based on UMEAs was constructed.

A microelectrode impedance method to measure interaction of cells

An impedance method was developed to determine how immune system cells (hemocyte) interact with intruder cells (parasites). When the hemocyte cells interact with the parasites, they cause a defensive reaction and the parasites start to aggregate in clusters. The level of aggregation is a measure of the host-parasite interaction, and provides information about the efficiency of the immune system response. The cell aggregation is monitored using a set of microelectrodes. The impedance spectrum is measured between each individual microelectrode and a large reference electrode. As the cells starts to aggregate and settle down towards the microelectrode array the impedance of the system is changed. It is shown that the system impedance is very sensitive to the level of cell aggregation and can be used to monitor in real time the interaction between hemocyte cells and parasites.

Concurrent recordings of bladder afferents from multiple nerves using a microfabricated PDMS microchannel electrode array

In this paper we present a compliant neural interface designed to record bladder afferent activity. We developed the implant's microfabrication process using multiple layers of silicone rubber and thin metal so that a gold microelectrode array is embedded within four parallel polydimethylsiloxane (PDMS) microchannels (5 mm long, 100 μm wide, 100 μm deep). Electrode impedance at 1 kHz was optimized using a reactive ion etching (RIE) step, which increased the porosity of the electrode surface. The electrodes did not deteriorate after a 3 month immersion in phosphate buffered saline (PBS) at 37 °C. Due to the unique microscopic topography of the metal film on PDMS, the electrodes are extremely compliant and can withstand handling during implantation (twisting and bending) without electrical failure. The device was transplanted acutely to anaesthetized rats, and strands of the dorsal branch of roots L6 and S1 were surgically teased and inserted in three microchannels under saline immersion to allow for simultaneous in vivo recordings in an acute setting. We utilized a tripole electrode configuration to maintain background noise low and improve the signal to noise ratio. The device could distinguish two types of afferent nerve activity related to increasing bladder filling and contraction. To our knowledge, this is the first report of multichannel recordings of bladder afferent activity.

Fast batch injection analysis of H(2)O(2) using an array of Pt-modified gold microelectrodes obtained from split electronic chips

A fast and robust analytical method for amperometric determination of hydrogen peroxide (H(2)O(2)) based on batch injection analysis (BIA) on an array of gold microelectrodes modified with platinum is proposed. The gold microelectrode array (n = 14) was obtained from electronic chips developed for surface mounted device technology (SMD), whose size offers advantages to adapt them in batch cells. The effect of the dispensing rate, volume injected, distance between the platinum microelectrodes and the pipette tip, as well as the volume of solution in the cell on the analytical response were evaluated. The method allows the H(2)O(2) amperometric determination in the concentration range from 0.8 mu mol L(-1) to 100 mu mol L(-1). The analytical frequency can attain 300 determinations per hour and the detection limit was estimated in 0.34 mu mol L(-1) (3 sigma). The anodic current peaks obtained after a series of 23 successive injections of 50 mu L of 25 mu mol L(-1) H(2)O(2) showed an RSD < 0.9%. To ensure the good selectivity to detect H(2)O(2), its determination was performed in a differential mode, with selective destruction of the H(2)O(2) with catalase in 10 mmol L(-1) phosphate buffer solution. Practical application of the analytical procedure involved H(2)O(2) determination in rainwater of Sao Paulo City. A comparison of the results obtained by the proposed ampermetric method with another one which combines flow injection analysis (FIA) with spectrophotometric detection showed good agreement. (C) 2011 Elsevier B.V. All rights reserved.

Flow-through cell based on an array of gold microelectrodes obtained from modified integrated circuit chips

The construction of a flow-through cell incorporating an array of gold microelectrodes is described and its application to flow injection analysis with amperometric detection is presented, Simple modification of almost any conventional integrated circuit chip, used as an inexpensive source of pre-assembled gold micro-wires, leads to the rapid and successful preparation of arrays of 8-48 elements, the polymeric encapsulation material from the top face of the chip is removed by abrasion until the gold micro-mires (used to interconnect the silicon circuit to the external contact pins of the chip) are disrupted and their transversal (elliptical) sections become exposed. Once polished, the flat and smooth top surface of the gold microelectrode-array chip (MEAC) is provided with a spacer and fitted under pressure against an acrylic block with the reference and auxiliary electrodes, to form the electrochemical (thin-layer) flow cell, while the contact pins are plugged into a standard IC socket, This design ensures autonomous electric contact with each electrode and allows fast dismantling for polishing or substitution, the performance of flow cells with MEACs was investigated utilizing the technique of reverse pulse amperometry without oxygen removal, A method was established for the determination of the copper concentration in sugar cane spirit, regulated by law for beverages, Samples from industrial producers and small-scale (alembic) brewers were compared, With a 24 MEAC, a detection limit of 30 mu g I-l of copper (4.7 x 10(-7) mol l(-1) of Cu-II for 100 mu l injections) was calculated, Routine operation was established at a frequency of 60-90 determinations per hour, Intercomparison with atomic absorption spectrometric determinations resulted in excellent agreement.

High-density electrode array for imaging in vitro electrophysiological activity

The development of a high-density active microelectrode array for in vitro electrophysiology is reported. Based on the Active Pixel Sensor (APS) concept, the array integrates 4096 gold microelectrodes (electrode separation 20 microm) on a surface of 2.5 mmx2.5 mm as well as a high-speed random addressing logic allowing the sequential selection of the measuring pixels. Following the electrical characterization in a phosphate solution, the functional evaluation has been carried out by recording the spontaneous electrical activity of neonatal rat cardiomyocytes. Signals with amplitudes from 130 microVp-p to 300 microVp-p could be recorded from different pixels. The results demonstrate the suitability of the APS concept for developing a new generation of high-resolution extracellular recording devices for in vitro electrophysiology.

A microelectrode impedance method to measure interaction of cells

An impedance method was developed to determine how immune system cells (hemocyte) interact with intruder cells (parasites). When the hemocyte cells interact with the parasites, they cause a defensive reaction and the parasites start to aggregate in clusters. The level of aggregation is a measure of the host-parasite interaction, and provides information about the efficiency of the immune system response. The cell aggregation is monitored using a set of microelectrodes. The impedance spectrum is measured between each individual microelectrode and a large reference electrode. As the cells starts to aggregate and settle down towards the microelectrode array the impedance of the system is changed. It is shown that the system impedance is very sensitive to the level of cell aggregation and can be used to monitor in real time the interaction between hemocyte cells and parasites.

Fast Robust Pattern Classification Algorithms for Real Time Neuro-Motor Prosthetic Applications

In this paper, we give a brief review of pattern classification algorithms based on discriminant analysis. We then apply these algorithms to classify movement direction based on multivariate local field potentials recorded from a microelectrode array in the primary motor cortex of a monkey performing a reaching task. We obtain prediction accuracies between 55% and 90% using different methods which are significantly above the chance level of 12.5%.

A micromachined SiO2/silicon probe for neural signal recordings

The development of an implantable five channel microelectrode array is presented for neural signal recordings. The detailed fabrication process is outlined with four masked used. The SEM images show that the probe shank is 1.2mm long, 100 mu m wide and 30 mu m thick with the recording sites spaced 200 mu m apart for good signal isolation. The plot of the single recording site impedance versus frequency is shown by test in vitro and the ompedence declines with the increasing frequency. Experiment in vivo using this probe is under way.

Fabrication of a Silicon-Based Microprobe for Neural Interface Applications

A two-dimensional (2D) multi-channel silicon-based microelectrode array is developed for recording neural signals. Three photolithographic masks are utilized in the fabrication process. SEM images show that the microprobe is 1. 2mm long,100μm wide,and 30μm thick, with recording sites spaced 200μm apart for good signal isolation. For the individual recording sites, the characteristics of impedance versus frequency are shown by in vitro testing. The impedance declines from 14MΩ to 1.9kv as the frequency changes from 0 to 10MHz. A compatible PCB (print circuit board) aids in the less troublesome implantation and stabilization of the microprobe.