The impedance of stimulating electrodes used in cochlear implants and other neural prostheses often increases post-implantation, and is thought to be due to fibrous tissue encapsulation of the electrode array. Increased impedance results in higher power requirements to stimulate target neurons at set charge densities. We developed an in vitro model to investigate the electrode-tissue interface in a highly controlled environment. This model was tested using three cell types, with and without charge-balanced biphasic electrical stimulation. Under standard tissue culture conditions, a monolayer of cells was grown over the electrode surface. Electrode impedance increased in proportion to the extent of cell coverage of the electrode. Cell type was a significant factor in the amount of impedance increase, with kidney epithelial cells (MDCK) creating the greatest impedance, followed by dissociated rat skin fibroblasts and then macrophages (J774). The application of electrical stimulation to cell-covered electrodes caused impedance fluctuations similar to that seen in vivo, with a lowering of impedance immediately following stimulation, and a recovery to pre-stimulation levels during inactive periods. Examination of these electrodes suggests that the stimulation-induced impedance changes were due to the amount of cell cover over the electrodes. This in vitro technique accurately models the changes in impedance observed with neural prostheses in vivo, and shows the close relationship between impedance and tissue coverage adjacent to the electrode surface. We believe that this in vitro approach holds great promise to further our knowledge of the mechanisms contributing to electrode impedance.

Neural prostheses use charge recovery mechanisms to ensure the electrical stimulus is charge balanced. Nucleus cochlear implants short all stimulating electrodes between pulses in order to achieve charge balance, resulting in a small residual direct current (DC). In the present study we sought to characterize the variation of this residual DC with different charge recovery mechanisms, stimulation modes, and stimulation parameters, and by modeling, to gain insight into the underlying mechanisms. In an acute study with anaesthetised guinea pigs, DC was measured in four platinum intracochlear electrodes stimulated using a Nucleus C124M cochlear implant at moderate to high pulse rates (1200-14,500 pulses/s) and stimulus intensities (0.2-1.75 mA at 26-200 microseconds/phase). Both monopolar and bipolar stimulation modes were used, and the effects of shorting or combining a capacitor with shorting for charge recovery were investigated. Residual DC increased as a function of stimulus rate, stimulus intensity, and pulse width. DC was lower for monopolar than bipolar stimulation, and lower still with capacitively coupled monopolar stimulation. Our model suggests that residual DC is a consequence of Faradaic reactions which allow charge to leak through the electrode tissue interface. Such reactions and charge leakage are still present when capacitors are used to achieve charge recovery, but anodic and cathodic reactions are balanced in such a way that the net charge leakage is zero.

This study was undertaken to assess the contribution of protein adsorption and cell growth to increases in electrode impedance that occur immediately following implantation of cochlear implant electrodes and other neural stimulation devices. An in vitro model of the electrode-tissue interface was used. Radiolabelled albumin in phosphate buffered saline was added to planar gold electrodes and electrode impedance measured using a charge-balanced biphasic current pulse. The polarisation impedance component increased with protein adsorption, while no change to access resistance was observed. The maximum level of protein adsorbed was measured at 0.5 μg/cm2, indicating a tightly packed monolayer of albumin molecules on the gold electrode and resin substrate. Three cell types were grown over the electrodes, macrophage cell line J774, dissociated fibroblasts and epithelial cell line MDCK, all of which created a significant increase in electrode impedance. As cell cover over electrodes increased, there was a corresponding increase in the initial rise in voltage, suggesting cell cover mainly contributes to the access resistance of the electrodes. Only a small increase in the polarisation component of impedance was seen with cell cover.

Large pH changes have been shown to be potentially harmful to tissue. The present study was designed to examine stimulus induced changes in pH for a variety of stimulus parameters both in vitro and in vivo, in order to ensure that stimulation strategies for neural prostheses result in minimal pH change. Stimulation using charge balanced biphasic pulses at intensities both within and well above maximum clinical levels for cochlear implants (0.025-0.68 microC per phase), were delivered to platinum electrodes in vitro [saline, phosphate buffered saline (PBS), or saline with human serum albumin (HSA)], and in vivo (scala tympani). Stimulus rates were typically varied from 62.5 to 1000 pulses per second (pps), although rates of up to 14,500 pps were used in some experiments. The pH level was recorded using a pH indicator (Phenol red) or pH microelectrodes. While electrical stimulation at intensities and rates used clinically showed no evidence of a pH shift, intensities significantly above these levels induced pH changes both in vitro and in vivo. The extent of pH change was related to stimulus rate and intensity. In addition, pH change was closely associated with the residual direct current (dc) level. As expected, stimulation with capacitive coupling induced little dc and a minimal pH shift. Moreover, no pH shift was observed using alternating leading phase pulse trains at intensities up to 0.68 microC per phase and 1000 pps. Saline with HSA or buffered solutions dramatically reduced the extent of pH shift observed following stimulation in unbuffered inorganic saline. Reduced pH shift was also observed following in vivo stimulation. These findings provide an insight into mechanisms of safe change injection in neural prostheses.