Using Chronopotentiometry to Better Characterize the Charge Injection Mechanisms of Platinum Electrodes Used in Bionic Devices

The safe charge injection capacity and charge density of neural stimulating electrodes is based on empirical evidence obtained from stimulating feline cortices. Stimulation induced tissue damage may be caused by electrochemical or biological mechanisms. Separating these mechanisms requires greater understanding of charge transfer at the electrode-tissue interface. Clinical devices typically use a biphasic waveform with controlled current. Therefore, the charge injection mechanism and charge injection capacity of platinum was assessed on a commercial potentiostat by chronopotentiometry (controlled current stimulation). Platinum is a non-ideal electrode, charge injection by chronopotentiometry can be passed via capacitive and Faradaic mechanisms. Electrodes were tested under a variety of conditions to assess the impact on charge injection capacity. The change in electrode potential (charge injection capacity) was affected by applied charge density, pulse length, pulse polarity, electrode size, polishing method, electrolyte composition, and oxygen concentration. The safe charge injection capacity and charge density could be increased by changing the electrode-solution composition and stimulation parameters. However, certain conditions (e.g., acid polished electrodes) allowed the electrode to exceed the water electrolysis potential despite the stimulation protocol being deemed safe according to the Shannon plot. Multiple current pulses led to a shift or ratcheting in electrode potential due to changes in the electrode-solution composition. An accurate measure of safe charge injection capacity and charge density of an implantable electrode can only be obtained from suitable conditions (an appropriately degassed electrolyte and clinically relevant electrode structure). Cyclic voltammetric measurement of charge storage capacity can be performed on implantable electrodes, but will not provide information on electrode stability to multiple chronopotentiometric pulses. In contrast, chronopotentiometry will provide details on electrode stability, but the minimum time resolution of typical commercial potentiostats (ms range) is greater than used in a clinical stimulator (μs range) so that extrapolation to short stimulation pulses is required. Finally, an impedance test is typically used to assess clinical electrode performance. The impedance test is also based on a biphasic chronopotentiometic waveform where the measured potential is used to calculate an impedance value. Here it is shown that the measured potential is a function of many parameters (solution composition, electrode area, and surface composition). Subsequently, impedance test results allow electrode comparison and to indicate electrode failure, but use of Ohm’s law to calculate an impedance value is not valid

A round robin approach to the analysis of bisphenol a (BPA) in human blood samples

BACKGROUND: Human exposure to bisphenol A (BPA) is ubiquitous, yet there are concerns about whether BPA can be measured in human blood. This Round Robin was designed to address this concern through three goals: 1) to identify collection materials, reagents and detection apparatuses that do not contribute BPA to serum; 2) to identify sensitive and precise methods to accurately measure unconjugated BPA (uBPA) and BPA-glucuronide (BPA-G), a metabolite, in serum; and 3) to evaluate whether inadvertent hydrolysis of BPA-G occurs during sample handling and processing. METHODS: Four laboratories participated in this Round Robin. Laboratories screened materials to identify BPA contamination in collection and analysis materials. Serum was spiked with concentrations of uBPA and/or BPA-G ranging from 0.09-19.5 (uBPA) and 0.5-32 (BPA-G) ng/mL. Additional samples were preserved unspiked as ‘environmental’ samples. Blinded samples were provided to laboratories that used LC/MSMS to simultaneously quantify uBPA and BPA-G. To determine whether inadvertent hydrolysis of BPA metabolites occurred, samples spiked with only BPA-G were analyzed for the presence of uBPA. Finally, three laboratories compared direct and indirect methods of quantifying BPA-G. RESULTS: We identified collection materials and reagents that did not introduce BPA contamination. In the blinded spiked sample analysis, all laboratories were able to distinguish low from high values of uBPA and BPA-G, for the whole spiked sample range and for those samples spiked with the three lowest concentrations (0.5-3.1 ng/ml). By completion of the Round Robin, three laboratories had verified methods for the analysis of uBPA and two verified for the analysis of BPA-G (verification determined by: 4 of 5 samples within 20% of spiked concentrations). In the analysis of BPA-G only spiked samples, all laboratories reported BPA-G was the majority of BPA detected (92.2 – 100%). Finally, laboratories were more likely to be verified using direct methods than indirect ones using enzymatic hydrolysis. CONCLUSIONS: Sensitive and accurate methods for the direct quantification of uBPA and BPA-G were developed in multiple laboratories and can be used for the analysis of human serum samples. BPA contamination can be controlled during sample collection and inadvertent hydrolysis of BPA conjugates can be avoided during sample handling

Electrode-tissue interface: development and findings of an in vitro model

© 2006 Dr.Carrie NewboldIn the period immediately following the implantation of a cochlear implant electrode array within the cochlear environment, the power required to stimulate the auditory nerve at preset current levels increases. This rise is due to increases in electrode impedance which in turn is suggested to be a result of tissue growth around the electrode array. The foreign body response initiated by the immune system encapsulates the array in a matrix of fibrous tissue, separating the electrode array from the rest of the body. A second change in electrode impedance occurs with the onset of electrical stimulation. A transitory reduction in impedance has been recorded in animals and humans after stimulation of electrodes. Impedance returns to pre-stimulation levels following the cessation of stimulation. It was suggested that these changes in impedance with stimulation were also related to the tissue growth around the electrode array. A more thorough understanding of the interface was required to ascertain these concepts

Insights into the Electron Transfer Kinetics, Capacitance and Resistance Effects of Implantable Electrodes Using Fourier Transform AC Voltammetry on Platinum

The charge transfer mechanism at the electrode-solution interface was assessed by Fourier transform AC voltammetry (FTACV). The faradaic reactions that occur within the safe potential window on platinum had slow electron transfer kinetics. The charge transfer mechanisms during short chronopotentiometric stimulation of cells, is most likely dominated by capacitance. Impedance was modelled with a single time constant. FTACV was fit with a 2-component equivalent circuit comprising a series capacitor and resistor. Capacitance and resistance varied with electrode potential, area, topography, surface functionality and solution composition. Capacitance correlated with charge storage capacity measured by voltammetry. Increased capacitance reduced the change in potential during chronopotentiometry. Increased resistance resulted in uncompensated resistance, and a larger change in potential during chronopotentiometry. Uncompensated resistance in tissue may lead to the measured potential of an electrode being considerably higher than its true potential, leading to a conservative estimate of the safe operating potential window. An impedance test is used to assess electrode performance in vivo. The impedance test is a function of capacitance, faradaic charge and resistance. Impedance test results allow electrode comparison, indicating changes in electrode-tissue interface, electrode failure and power usage, however use of Ohm\u27s law to calculate an impedance value is not valid

Charge Injection from Chronoamperometry of Platinum Electrodes for Bionic Devices

The chronoamperometric response of platinum under biologically relevant conditions was investigated to understand how charge transfer across the electrode-tissue interface occurs during potential pulsing. Platinum behaves as a non-ideal electrode, passing capacitance and faradaic charge. The faradaic reactions are associated with oxide formation and removal, hydrogen and anion adsorption. The capacitance charge decayed within μs while the faradaic charge decay occurred over longer times. The total charge and the ratio of faradaic to capacitance charge was seen to vary with time, potential, electrode size, oxygen concentration, electrolyte and surface cleaning method. The charge transfer mechanisms result in an accumulation of charge during multiple potential pulses, mostly reductive charge under the conditions presented here. This modifies the composition of the electrode/solution interface. An accurate understanding of charge transfer at the electrode/tissue interface must subsequently be obtained under biologically relevant conditions (an artificial perilymph with low oxygen concentration for cochlear implants electrodes and artificial cerebrospinal fluid for neural implants) and with appropriate clinical electrodes

Using chronopotentiometry to better characterize the charge injection mechanisms of platinum electrodes used in bionic devices

The safe charge injection capacity and charge density of neural stimulating electrodes is based on empirical evidence obtained from stimulating feline cortices. Stimulation induced tissue damage may be caused by electrochemical or biological mechanisms. Separating these mechanisms requires greater understanding of charge transfer at the electrode-tissue interface. Clinical devices typically use a biphasic waveform with controlled current. Therefore, the charge injection mechanism and charge injection capacity of platinum was assessed on a commercial potentiostat by chronopotentiometry (controlled current stimulation). Platinum is a non-ideal electrode, charge injection by chronopotentiometry can be passed via capacitive and Faradaic mechanisms. Electrodes were tested under a variety of conditions to assess the impact on charge injection capacity. The change in electrode potential (charge injection capacity) was affected by applied charge density, pulse length, pulse polarity, electrode size, polishing method, electrolyte composition, and oxygen concentration. The safe charge injection capacity and charge density could be increased by changing the electrode-solution composition and stimulation parameters. However, certain conditions (e.g., acid polished electrodes) allowed the electrode to exceed the water electrolysis potential despite the stimulation protocol being deemed safe according to the Shannon plot. Multiple current pulses led to a shift or ratcheting in electrode potential due to changes in the electrode-solution composition. An accurate measure of safe charge injection capacity and charge density of an implantable electrode can only be obtained from suitable conditions (an appropriately degassed electrolyte and clinically relevant electrode structure). Cyclic voltammetric measurement of charge storage capacity can be performed on implantable electrodes, but will not provide information on electrode stability to multiple chronopotentiometric pulses. In contrast, chronopotentiometry will provide details on electrode stability, but the minimum time resolution of typical commercial potentiostats (ms range) is greater than used in a clinical stimulator (μs range) so that extrapolation to short stimulation pulses is required. Finally, an impedance test is typically used to assess clinical electrode performance. The impedance test is also based on a biphasic chronopotentiometic waveform where the measured potential is used to calculate an impedance value. Here it is shown that the measured potential is a function of many parameters (solution composition, electrode area, and surface composition). Subsequently, impedance test results allow electrode comparison and to indicate electrode failure, but use of Ohm\u27s law to calculate an impedance value is not valid

Photoresist-less patterning of silicone substrates for thick film deposition

Traditionally, fabrication processes to produce microelectrode arrays for neural stimulating electrodes have employed photolithography and a photoresist layer to produce a pattern on a substrate which subsequently has a metal layer deposited. The deposited metal layer is then used to create stimulating electrodes that will ultimately be in close contact with neural tissue. While the process enables accurate fabrication at a reasonable cost, the use of photoresist in the process presents a number of issues. Photoresist is a contamination risk with the potential for chemicals to be absorbed into the silicone, which will then subsequently be in close proximity to neural structures, introducing a risk of toxicity. In addition, due to the use of flexible substrates such as silicone elastomer, patterning of films greater than 1 μm thick can be difficult. Whilst an obvious solution would be to avoid using photoresist in the fabrication process, few alternatives have been systematically investigated. We investigated use of shadow masks fabricated from glass, brass and silicone elastomer, and exploitation of the natural tackiness of the silicone substrate for mask adhesion. All three mask materials attached well to silicone, but each presented differing degrees of difficulty during alignment and mask removal. Subsequently, thin gold films (∼20 nm) and thick platinum films (∼8 μm) were deposited on the silicone substrates using the shadow masks. We discuss the mask fabrication, pattern definition, the difficulties which arose, and the benefits of using shadow masks for the fabrication of medical devices.5 page(s

Comparison of the In Vitro and In Vivo Electrochemical Performance of Bionic Electrodes

The electrochemical performance of platinum electrodes was assessed in vitro and in vivo to determine the impact of electrode implantation and the relevance of in vitro testing in predicting in vivo behaviour. A significant change in electrochemical response was seen after electrode polarisation. As a result, initial in vitro measurements were poor predictors of subsequent measurements performed in vitro or in vivo. Charge storage capacity and charge density measurements from initial voltammetric measurements were not correlated with subsequent measurements. Electrode implantation also affected the electrochemical impedance. The typically reported impedance at 1 kHz was a very poor predictor of electrode performance. Lower frequencies were significantly more dependent on electrode properties, while higher frequencies were dependent on solution properties. Stronger correlations in impedance at low frequencies were seen between in vitro and in vivo measurements after electrode activation had occurred. Implanting the electrode increased the resistance of the electrochemical circuit, with bone having a higher resistivity than soft tissue. In contrast, protein fouling and fibrous tissue formation had a minimal impact on electrochemical response. In vivo electrochemical measurements also typically use a quasi-reference electrode, may operate in a 2-electrode system, and suffer from uncompensated resistance. The impact of these experimental conditions on electrochemical performance and the relevance of in vitro electrode assessment is discussed. Recommended in vitro testing protocols for assessing bionic electrodes are presented

Long-term electrode impedance changes and failure prevalence in cochlear implants

<div><p></p><p><i>Objective:</i> This study assessed the prevalence of electrode failures and electrode impedance measures in Nucleus cochlear implants around initial activation (an average of 16 days after surgery) and after 8 to 12 years of device use. <i>Design:</i> Retrospective data from the Melbourne Cochlear Implant Clinic was collated and analysed. <i>Study sample:</i> Included in this study were 232 adults, all of whom were implanted at the clinic between March 1998 and August 2005. <i>Results:</i> Overall 0.5% of electrodes failed over the entire test period, with 5.6% of devices showing one or more electrode failure. The majority of these failures were recorded by initial activation. The numbers of electrode failures have decreased over time with array type, such that no failures were recorded with the currently available Contour Advance array. Array type was shown to affect electrode impedance at both time points, with the Contour and Contour Advance arrays having significantly higher absolute values than the Banded array. However, the Banded array had significantly higher area-normalized impedances at initial and final measures than the Contour and Contour Advance array. <i>Conclusions:</i> A relatively low incidence of electrode failures were recorded for the Nucleus devices of these recipients. Electrode impedance dropped for all array types after 8 to 12 years of device use.</p></div