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PubMed2001

Theoretical simulation of oxygen tension measurement in tissues using a microelectrode: I. The response function of the electrode.

The aim of this article is to determine the correlation between the actual oxygen distribution in tissues and the distribution of oxygen measured by microelectrodes. This correlation is determined by the response function of the electrode, which depends on the oxygen consumed by the electrode. In tissue it is necessary to consider the gradients resulting from cellular respiration. A computer program has been used to simulate the vascular structure of various tissues and also the measurements of oxygen tension using a polarographic electrode. The electrode absorption process is described using a theoretical model. The gradient of oxygen in tissue is described by a mathematical model that takes into consideration both diffusion and cellular consumption of oxygen. We have compared the results obtained using the response function of the electrode and some simplifications of it. The results of these comparisons show that there are some differences in the 'observed' distributions of the oxygen tension in tissues predicted using different formulae for the electrode response function. Also, there are considerable differences between the input oxygen distribution and the measured values in all cases. All the results of the simulations of the oxygen tension 'observed' by a 12 microm polarographic electrode, using different response functions of the electrode, show that the electrode averages the values from many cells. Care should be taken in using a simplification for the response function of the electrode, especially if the results are going to be used as input values in modelling the tumour response to new treatments and/or as a basis of selecting patients for treatments. A computer simulation of measurement of oxygen tensions in regions of steep pO2 gradients shows that extremely high and extremely low pO2 values will not be detected.

Algorithms↗

PubMed2004

Resistivity probing of multi-layered tissue phantoms using microelectrodes.

We present the use of an array of rectangular microelectrodes to discriminate between different resistivities in a thin, layered sample. Each electrode was 8 mm long and 200 nm thick. The electrode widths ranged from 20 to 500 microm. The electrodes were designed such that all pairs of consecutive electrodes had the same relative geometry, and therefore identical cell constants. A hydrogel-based tissue phantom, made by photopolymerization of 2-hydroxyethyl methacrylate (HEMA), was developed. By changing the hydrogel composition and the ionic strength of the storage medium, the resistivity of the hydrogels could be tuned between 100 omegam and 100 komegam. Using bipolar measurements, the tissue phantoms were characterized in the frequency range from 100 Hz to 30 MHz. The relative resistivity distribution of a three-layered structure composed of 120 microm sheets could be calculated and was shown to agree to within 7% of the bulk measurements. Potential clinical applications for this technique include probing of epithelial tissue and skin cancer screening.

Connective Tissue↗

PubMed2005

Comparison of electrically evoked cortical potential thresholds generated with subretinal or suprachoroidal placement of a microelectrode array in the rabbit.

The aim of the study was to directly compare the threshold electrical charge density of the retina (retinal threshold) in rabbits for the generation of electrical evoked potentials (EEP) by delivering electrical stimulation with a custom-made microelectrode array (MEA) implanted into either the subretinal or suprachoroidal space. Nine eyes of seven Dutch-belted rabbits were studied. The electroretinogram (ERG), visual evoked potentials (VEP) and EEP were recorded. Electrodes for the VEP and EEP were placed on the dura mater overlying the visual cortex. The EEP was recorded following electrical stimulation of the MEA placed either subretinally beneath the visual streak of the retina or in the suprachoroidal space in the rabbit eye. An ab externo approach was used for placement of the MEA. Liquid perfluorodecaline (PFCL; 0.4 ml) was placed within the vitreous cavity to flatten the neurosensory retina on the MEA after subretinal implantation. The retinal threshold for generation of an EEP was determined for each MEA placement by three consecutive measurements consisting of 100 computer-averaged recordings. Animals were sacrificed at the conclusion of the experiment and the eyes were enucleated for histological examination. The retinal threshold to generate an EEP was 9 +/- 7 nC (0.023 +/- 0.016 mC cm(-2)) within the subretinal space and 150 +/- 122 nC (0.375 +/- 0.306 mC cm(-2)) within the suprachoroidal space. Histology showed disruption of the outer retina with subretinal but not suprachoroidal placement. The retinal threshold to elicit an EEP is significantly lower with subretinal placement of the MEA compared to suprachoroidal placement (P < 0.05). The retinal threshold charge density with a subretinal MEA is well below the published charge limit of 1 mC cm(-2), which is the level below which chronic stimulation of the retina is considered necessary to avoid tissue damage (Shannon 1992 IEEE Trans. Biomed. Eng. 39 424-6).

Animals↗

PubMed2005

Fabrication of implantable microelectrode arrays by laser cutting of silicone rubber and platinum foil.

A new method for fabrication of microelectrode arrays comprised of traditional implant materials is presented. The main construction principle is the use of spun-on medical grade silicone rubber as insulating substrate material and platinum foil as conductor (tracks, pads and electrodes). The silicone rubber and the platinum foil are patterned by laser cutting using an Nd:YAG laser and a microcontroller-driven, stepper-motor operated x-y table. The method does not require expensive clean room facilities and offers an extremely short design-to-prototype time of below 1 day. First prototypes demonstrate a minimal achievable feature size of about 30 microm.

Biocompatible Materials↗

PubMed2006

Chronic neural recordings using silicon microelectrode arrays electrochemically deposited with a poly(3,4-ethylenedioxythiophene) (PEDOT) film.

Conductive polymer coatings can be used to modify traditional electrode recording sites with the intent of improving the long-term performance of cortical microelectrodes. Conductive polymers can drastically decrease recording site impedance, which in turn is hypothesized to reduce thermal noise and signal loss through shunt pathways. Moreover, conductive polymers can be seeded with agents aimed at promoting neural growth toward the recording sites or minimizing the inherent immune response. The end goal of these efforts is to generate an ideal long-term interface between the recording electrode and surrounding tissue. The goal of this study was to refine a method to electrochemically deposit surfactant-templated ordered poly(3,4-ethylenedioxythiophene) (PEDOT) films on the recording sites of standard 'Michigan' probes and to evaluate the efficacy of these modified sites in recording chronic neural activity. PEDOT-coated site performance was compared to control sites over a six-week evaluation period in terms of impedance spectroscopy, signal-to-noise ratio, number of viable unit potentials recorded and local field potential recordings. PEDOT sites were found to outperform control sites with respect to signal-to-noise ratio and number of viable unit potentials. The benefit of reduced initial impedance, however, was mitigated by the impedance contribution of typical silicon electrode encapsulation. Coating sites with PEDOT also reduced the amount of low-frequency drift evident in local field potential recordings. These findings indicate that electrode sites electrochemically deposited with PEDOT films are suitable for recording neural activity in vivo for extended periods. This study also provided a unique opportunity to monitor how neural recording characteristics develop over the six weeks following implantation.

Action Potentials↗

PubMed1999

Relationship of lesion location to clinical outcome following microelectrode-guided pallidotomy for Parkinson's disease.

The purpose of this study was to examine the relationship between lesion location and clinical outcome following globus pallidus internus (GPi) pallidotomy for advanced Parkinson's disease. Thirty-three patients were prospectively studied with extensive neurological examinations before and at 6 and 12 months following microelectrode-guided pallidotomy. Lesion location was characterized using volumetric MRI. The position of lesions within the posteroventral region of the GPi was measured, from anteromedial to posterolateral along an axis parallel to the internal capsule. To relate lesion position to clinical outcome, hierarchical multiple regression analysis was used. The variance in outcome measures that was related to preoperative scores and lesion volume was first calculated, and then the remaining variance attributable to lesion location was determined. Lesion location along the anteromedial-to-posterolateral axis within the GPi influenced the variance in total score on the Unified Parkinson's Disease Rating Scale in the postoperative 'off' period, and in 'on' period dyskinesia scores. Within the posteroventral GPi, anteromedial lesions were associated with greater improvement in 'off' period contralateral rigidity and 'on' period dyskinesia, whereas more centrally located lesions correlated with better postoperative scores of contralateral akinesia and postural instability/gait disturbance. Improvement in contralateral tremor was weakly related to lesion location, being greater with posterolateral lesions. We conclude that improvement in specific motor signs in Parkinson's disease following pallidotomy is related to lesion position within the posteroventral GPi. These findings are consistent with the known segregated but parallel organization of specific motor circuits in the basal ganglia, and may explain the variability in clinical outcome after pallidotomy and therefore have important therapeutic implications.

Aged↗

PubMed2006

Transient ST-segment-elevation during pulmonary vein ablation using circumferential coiled microelectrodes in a prospective multi-centre study.

AIMS: Paroxysmal atrial fibrillation (PAF) is predominantly triggered by focal ectopies located within the pulmonary veins (PV). The BITMAP Study (Breakthrough and Isolation Trial: Mapping and Ablation of Pulmonary Veins) investigated prospectively the safety and efficacy of a catheter design with circumferential mapping and ablation electrodes. We report the phenomenon of ST-segment-elevation during catheter placement in the left atrium (LA) and superior PVs in this multi-centre study. METHODS AND RESULTS: Forty-three patients (57+/-10 years) with PAF were included in this study. Radiofrequency catheter (RFC) ablation supported by the 4F REVELATION Helix microcatheter (Cardima Inc., Freemont, CA, USA) with eight distal-coiled microelectrodes for bipolar mapping and ablation. RFC was applied at the ostial region of PV (30 W, 45-50 degrees C) with a maximum of four RFC applications per electrode. In four of the 43 patients from three centres, we recorded the occurrence of ST-segment-elevation greater than 0.2 mV and accompanying left thoracic discomfort. The ECG changes and the symptoms started abruptly and lasted for 4.2+/-2.2 min. Pericardial effusion could instantaneously be excluded by echocardiography in all cases. Coronary angiograms were performed in three patients with the longest episodes; no thrombotic material or air emboli were present. The symptoms and the ECG changes resolved completely in all patients. CONCLUSION: The phenomenon of ST-segment-elevation during LA- and PV-mapping in patients with PAF may be a common occurrence. In this prospective multi-centre trial, we demonstrated the reversibility of this phenomenon; no cardiovascular or cerebral damage was reported during both the procedure and the follow-up. Although the mechanism is still unclear, vasospasm may contribute to this phenomenon because of autonomic dysregulation.

Adult↗

PubMed2003

Sepal color variation of Hydrangea macrophylla and vacuolar pH measured with a proton-selective microelectrode.

Sepal color of hydrangea varies with the environmental conditions. Although chemical and biological studies on this color variation have a long history, little correct knowledge has been generated about color development. All colored sepals contain the same anthocyanin, delphinidin 3-glucoside. Thus, there must be some other system for developing the wide variety of colors. In hydrangea sepals the cells of the epidermis are colorless and only the second layer of cells contain pigment. We prepared protoplasts without any color change during enzyme treatment of sepals and measured the vacuolar pH of each of the colored cells. We could correlate the color of a single hydrangea cell with its vacuolar pH using a combination of micro-spectrophotometry and a proton-selective microelectrode. Values for the vacuolar pH of blue (lambda vismax: 589 nm) and red cells (lambda vismax: 537 nm) were 4.1 and 3.3, respectively, the vacuolar pH of blue cells being significantly higher.

Anthocyanins↗

PubMed1999

Microelectrode recording during posteroventral pallidotomy: impact on target selection and complications.

OBJECTIVE: To assess the practical usefulness of single-cell microelectrode recording (MER) when performing posteroventral pallidotomy. METHODS: A retrospective comparison of the initial, magnetic resonance imaging-derived coordinates of the pallidotomy target to the final, MER-refined lesion coordinates in 132 consecutive pallidotomies was conducted. The time required to perform the procedure and the surgical complications are reported. RESULTS: MER led to targeting changes in 98% of the cases. In 12%, the MER-refined target was more than 4 mm from the original, image-guided site, which is a targeting error that could adversely affect outcome. Although all components of targeting were affected by MER, laterality and depth were impacted most. The ventral border of the globus pallidus pars interna was located within 1 mm of the magnetic resonance imaging-selected target in only 40% of the cases. On average, only 2.2 MER trajectories were required to perform pallidotomy. During the last 3 years of our study, 85% of the procedures were performed with one or two trajectories. The mean operating time of the operations performed during the last 3 years was 2 hours and 12 minutes. The incidence of intracerebral hemorrhage in our series (1.5%) was no higher than that reported for other large series of stereotactic procedures. No patient suffered an optic tract injury. CONCLUSION: MER provides important targeting information for performing pallidotomy. In particular, the micrometric delineation of the ventral border of the globus pallidus pars interna permits safe lesioning of the posteroventral region of the globus pallidus pars interna with little risk of visual field deficit. These data can be obtained efficiently and without increased surgical risk.

Cerebral Hemorrhage↗

PubMed2000

Use of a modified oxygen microelectrode and laser-Doppler flowmetry to monitor changes in oxygen tension and microcirculation in a flap.

Flap failure is a clinical problem in free tissue transfer, and there is no reliable device for monitoring the tissue. Differentiating between an arterial occlusion and venous congestion is also a problem. A study was undertaken to monitor viability in a pedicled groin flap and to compare two different monitoring methods. The oxygen tension in the flap, measured with a modified Clark-type microelectrode (tip diameter = 3 to 8 microm; 90 percent response within 2.6 +/- 0.5 seconds), was compared with changes in blood flow in the flap, measured with a laser-Doppler probe. In 11 Sprague-Dawley rats, the changes in oxygen tension and blood flow in the pedicled groin flap were studied after clamping and subsequent reperfusion of the artery or vein. After occlusion of the artery to the flap, oxygen tension decreased to a stable value (i.e., the recording level remained unchanged for 30 seconds), from 19.7 +/- 1.8 to 0.3 +/- 0.1 mmHg, after 193 +/-25 seconds; blood flow decreased to a stable value, from 117 +/- 21 to 54 +/- 18 perfusion units, after 26 +/- 6 seconds. Clamping of the vein resulted in a decrease in oxygen tension, from 17.1 +/- 1.8 to 1.4 +/- 0.7 mmHg, after 416 +/- 67 seconds, and blood flow decreased to a stable value, from 90 +/- 14 to 35 +/- 6 perfusion units, after 107 +/- 27 seconds. The results of this study show that there is a difference in oxygen tension and blood flow responses between arterial and venous occlusion and that it may be possible with both methods to distinguish arterial from venous occlusion. However, although oxygen tension measurements are slightly slower in response than laser-Doppler measurements, the values are more reliable as a diagnostic tool for interpretation of a vessel occlusion.

Animals↗

PubMed1999

Successful long-term implantation of electrically inactive epiretinal microelectrode arrays in rabbits.

BACKGROUND: In the ongoing discussion concerning the realization of an epiretinal prosthesis for electric stimulation of retinal ganglion cells, long-term fixation of such a device is a crucial question. We evaluated surgical techniques for implantation and fixation of electrically inactive microelectrode arrays (MA) into the retinas of rabbits and secondary tissue reactions to the implant. METHODS: Vitrectomy and laser coagulation of the prospective fixation area were performed in rabbits. Implantation of MAs was performed 3 weeks later in 10 animals. The MA was fixated using retinal tacks. The follow-up included ophthalmoscopy and electrophysiology. At the end of the follow-up, the enucleated eyes were processed for light microscopy using standard procedures and grinding techniques. RESULTS: Nine of 10 rabbits were implanted without serious complications. Clinical and electrophysiologic data through 6 months of follow-up did not indicate any adverse effect of the surgery, the implant, or the tack itself. No change in retinal architecture underneath the implant was found by light microscopy. In these cases, the implant was stable at its original fixation area. In three cases, mild cataract formation was observed, and in one case, a total retinal detachment was found. CONCLUSION: Tack fixation of electrode arrays for electric stimulation of the inner retinal surface seems to be a useful approach in long-term implantation of an epiretinal prosthesis.

Animals↗

PubMed1982

Measurement of GABA-evoked conductance changes of lobster muscle fibres by a three-microelectrode voltage clamp technique.

The effective membrane conductance and capacity of lobster muscle fibres was measured by a three-intracellular-microelectrode voltage clamp technique. Conductance values agreed well with those determined under current clamp, by means of the 'short' cable equations. Reversible increases in conductance evoked by gamma-aminobutyric acid (GABA) were reflected by differences (delta V) in electrotonic potential amplitude recorded at the centre, and midway between the centre and fibre end respectively. GABA dose--conductance curves derived from cable theory or from delta V measurements were virtually identical. The effective capacity (ceff), determined from the area beneath the 'on' delta V capacity transient, yielded values of the membrane time constant consistently lower than those obtained by the graphical method of E. Stefani & A.B. Steinbach (J. Physiol., London. 203, 383-401 (1969)); one possible explanation for this discrepancy is discussed. In the presence of GABA, the effective capacity was reduced in a dose-related manner. The results were interpreted in terms of an equivalent circuit in which surface membrane was arranged in parallel with cleft-tubular membrane of finite conductance, charged through an access resistance. GABA was though to be decreasing ceff by selectively increasing the conductance of the cleft-tubular membranes.

Animals↗

PubMed1992

A flexible perforated microelectrode array for extended neural recordings.

A flexible and perforated 32-element planar microelectrode array has been fabricated and used to measure evoked potentials in brain slices. Electrodes are spaced 200 microns apart in a 4 x 8 array and are sandwiched between layers of insulating polyimide. The polyimide sandwich is lifted off its substrate, making it flexible so that it could shape to contoured tissues. Prior to lift off, holes are etched to expose recording sites 15 microns in diameter and to create perforations which allow increased circulation of artificial cerebrospinal fluid to the recording surface of the tissue and, hence, increased viability. Comparisons of evoked potentials measured over time showed an average increase of 10 h to the viability of the slice while using the perforated versus nonperforated arrays.

Animals↗

PubMed1994

Silicon ribbon cables for chronically implantable microelectrode arrays.

This paper describes the design, fabrication, and testing of miniature ultraflexible ribbon cables for use with micromachined silicon microprobes capable of chronic recording and/or stimulation in the central nervous system (CNS). These interconnects are of critical importance in reliably linking these microelectrodes to the external world through a percutaneous connector. The silicon cables allow the realization of multilead, multistrand shielded local interconnects that are extremely flexible and yet strong enough to withstand normal handling and surgical manipulation. Cables 5 microns thick, 1-5 cm long, and from 60 to 250 microns wide have been fabricated with up to eight leads. The series lead resistance is typically 4 k omega/cm for polysilicon and 500 omega/cm for tantalum, with shunt capacitance values of 5-10 pF/cm and an interlead capacitance below 10 fF/cm. Soak tests in buffered saline performed under electrical and mechanical stress have been underway for over three years and show subpicoampere leakage levels. Silicon microprobes with built-in ribbon cables have remained functional for up to one year in the guinea pig CNS, recording driven single-unit activity and maintaining impedance levels in the 1-7 M omega range.

Animals↗

PubMed1994

A three-dimensional microelectrode array for chronic neural recording.

This paper describes a 3-D microelectrode array for the chronic recording of single-unit activity in the central nervous system. The array is formed by a microassembly of planar silicon multishank microprobes, which are precisely positioned in a micromachined platform that resides on the surface of the cortex. Interconnects between the probes and the platform are formed using electroplated nickel lead transfers, implemented using automated computer control. All dimensions are controlled to +/- 1 micron and sank/probe separations as small as 100 microns are possible. Four-probe 16-shank prototype arrays have been tested chronically in guinea pig cortex. After three months in vivo, no significant tissue reaction has been observed surrounding these structures when they remain free to move with the brain, with normal appearing tissue between shanks spaced at 150 microns to 200 microns intervals. The array structure is compatible with the use of signal processing circuitry both on the probes and on the platform. A platform-based signal processing system has been designed to interface with several active probes, providing direct analog access to the recording sites, performing on-chip analog-to-digital conversion of neural activity, and providing simple binary-output recognition of single-unit spike events using a user-input threshold voltage.

Animals↗

PubMed1997

Microelectrode arrays for electrophysiological monitoring of hippocampal organotypic slice cultures.

A three-dimensional platinum (Pt) microelectrode array embedded on a micromachined silicon (Si) substrate (porosity of 13%, via hole diameter of 40 microns) has been developed. Electrodes are 35-micron wide and 20-microns high, spaced 200 microns apart and arranged in an elliptic geometry. Integrated within a microperfusion chamber, the devices were used for stimulation and recording experiments of hippocampal slice cultures over a period of several days.

Animals↗

PubMed1991

A low-noise demultiplexing system for active multichannel microelectrode arrays.

This paper reports a low-noise demultiplexing system capable of reconstructing multichannel single-unit neural signals derived from multiplexed microelectrode arrays. The overall multiplexing-demultiplexing system realizes ten channels, a per-channel gain of 68 dB, a bandwidth from 100 Hz to 6 kHz, and an equivalent noise level (referred to the probe input) of 13 microV rms. It provides for signaling over the power supply to allow control of on-chip probe functions such as self-testing. The interchannel crosstalk is less than 3%, and switching noise is suppressed by blanking the transition intervals. The 200 kHz probe sample clock is tracked automatically over a range from 150 to 250 kHz. Neural signals as low as 20 microV (typically 640 microV at the demultiplexing system input) can be reconstructed. The overall system organization is compatible with the demultiplexing of as many as 40 time-multiplexed electrode channels from a single probe data line.

Electric Conductivity↗

PubMed1991

A deconvolution technique for improved estimation of rapid changes in ion concentration recorded with ion-selective microelectrodes.

In biological preparations, measurements of rapid, stimulus-evoked changes in ion concentration by ion-selective microelectrodes can be distorted by the limited bandwidth of these sensors. Techniques were developed to reconstruct the actual change in ion concentration using deconvolution of the electrode's output signal and the electrode's transfer function. In the vertebrate retina, a knowledge of the actual time course of a light-evoked increase in extracellular K+ concentration was used to provide a rigorous test of a hypothesis regarding the electrical origin of a clinically important component of the electroretinogram.

Animals↗