and this high charge capacity is obtained from a reversible Ir 3+/Ir 4+ valence transition that takes place within the film [8, 35] as depicted in Fig. 11.2. By restricting the redox reactions within the film, and utilizing a known high-charge capacity reaction, an increase in the injectable charge capacity and significantly improved safety and consistency of neural stimulation can be obtained. For cathodal-first stimulation pulses, the ability of AIROF to inject charge can be further be increased by applying a positive bias of 0.4–0.8 V (vs. Ag|AgCl) prior to the stimulation pulse [6]. The bias acts to convert the AIROF from a mixed Ir 3+/Ir 4+ valence state to the Ir 4+ valence state, not only making the film significantly more electronically conductive, but also richer in the Ir 4+ needed for reduction during the cathodal phase. In some cases, the use of bias allows for as much as a factor of three increase in charge capacity [16].

It is not surprising that iridium oxide films have emerged as the preferred coatings for intracortical, and other neural prosthesis, electrodes. AIROF has been shown, in vitro, to allow for about 10–20 times the maximum injectable charge, when compared to bare Pt, achieving a charge density limit of up to 3.5 mC/cm2 for anodally-biased cathodal-first pulses [6]. However, the use of AIROF, rather than bare metal, is fraught with some additional peril. AIROF is susceptible to damage if the electrode polarization moves outside of the water window. Initiating water decomposition reactions can cause the AIROF to delaminate from the underlying metal surface, thus rendering the electrode non-usable for continued charge injection. While it is generally regarded that it is not viable, for any electrode, to inject charge outside of the water window, there is often uncertainty about the voltage and current conditions for which the electrode polarization exceeds the water window limits. If using a Pt electrode, a momentary transgression of the water window limits may cause highly undesirable reactions and residual by-products that enter the tissue. Yet the surface of the electrode may remain relatively unharmed. For the AIROF electrode, the films acts as a buffer zone that protects the tissue, and therefore reactions outside of the water window can potentially damage the AIROF in an irreversible manner.

11.5  Characterization of Intracortical Electrodes

11.5.1  Cyclic Voltammetry

Since the faradaic reactions used for electrode/tissue charge transfer are initiated by polarization of the electrode-electrolyte interface, it is useful to use an analytical method for examining how this interface behaves within, and outside of, the water window. Cyclic voltammetry (CV) is a commonly-utilized method for accessing the nature and behavior of stimulating electrodes. As derived from standard electrochemical methods, CV uses three-electrodes within an electrolyte. The potential of the intracortical electrode, with respect to a reference electrode, is periodically swept between two predetermined potential limits, usually at the water window

boundaries, while measuring the current that flows between the intracortical electrode and a larger counter electrode. The potential sweep shifts the electrode-electroyte interface through the full range of reversible redox reactions while the measured current provides an indication of the capacity and rate of these reactions. Integration of the CV current waveform is often used to calculate a total charge storage capacity (CSC), for both anodic-(CSCA) or cathodic-(CSCC) first stimulation. Typically, CV electrode measurements are made at sweep rates that are much slower than the voltage changes which the electrode-electrolyte interface experiences during a typical stimulation pulse, with CV sweeps typically on the order of 50 mV/s. Since the charge injection redox reactions are rate dependent, it is important to understand that CSC values are always larger than maximum charge injection values for any given electrode. Typically, less than 20% of the CSC can be utilized during a stimulus pulse. In this regard, review of the literature can often become confusing when comparing reported values of CSC to reported values of charge injected in vitro and in vivo. In other words, only a fraction of the CSC can be accessed during a short duration stimulus pulse. The CV measurement is highly sensitive to the condition of the electrode-electrolyte interface, the morphology the electrode coating, the electrode surface roughness, the geometric shape of the electrode tip, and the nature of the electrolyte. For any electrode metal, or coating, the shape of the CV can vary dramatically, depending upon how the electrode is fabricated and in what electrolyte the measurement is performed, even though the nature of the redox reactions themselves remains the same.

11.5.2  Electrode Stimulation Voltage Waveforms

Stimulation of cortical neural tissue is most commonly accomplished by driving the electrode with a two-phase waveform that consists of a first neural-stimulation phase and a second charge-recovery phase. Typically, each of these phases are generated by constant-current electronic circuits producing rectangular pulses. Often the first phase consists of a cathodal (negative) constant current pulse, followed by a second phase anodal (positive) constant current pulse as depicted in Fig. 11.3. In Fig. 11.3, a highly simplified model for an intracortical electrode is presented consisting of a series resistive-capacitive network. While simplistic, this model does allow for a first-order understanding of the relationship between the electrodeelectrolyte interface and the voltage/current waveforms. The resistive component is commonly called: the access resistance, and the capacitive component is commonly called: the electrode pseudocapacitance. These are, of course, merely lumpedmodel approximations for the electrical and electrochemical processes that take place during a stimulation pulse.

Referring to Fig. 11.3, during the first cathodal phase, constant current is forced through the electrode for the purpose of activating near-by cortical neurons. At the leading edge of the current pulse, an immediate voltage drop across

11.5.3  Non-ideal Access Resistance Behavior

Historically, the leading edge voltage drop was attributed to the electrolyte resistance caused by limitations in ionic conductivity of the electrolyte. Thus it was common practice to subtract the entire leading edge drop from the total electrode voltage excursion, during the first phase, as a means of determining the electrode polarization. However, the leading edge drop can include other effects besides simple electrolyte resistance, specifically, concentration polarization near the electrode-electrolyte interface. Concentration polarization is essentially caused by a depletion in electrolyte charge carriers (counter ions) at the onset of the current pulse. For coated metal electrodes, such as AIROF, near instantaneous changes in film conductivity at the leading edge of the current can be a secondary contribution to the access voltage drop.

11.5.4  Non-linear Electrode Polarization

Based upon the earlier discussion, it is obvious that the dynamics of charge injection via redox reactions cannot be directly compared to the charging and discharging of an ideal capacitor. Owing to the complex geometric shape of the electrode tip, and the highly non-uniform current densities, as well as the range of possible of redox reactions that might be experienced, the behavior of the electrode-electrolyte interface might be better explained by a set of distributed RC networks, however even this remains an oversimplification. Rather, the behavior of the electrode during what is often called the electrode polarization phase, or the capacitive charging phase, is driven by the rates of one or more reactions, the changes in interfacial and film conductivity, and the closeness of the electrode voltage to the edge of the water window. Strictly speaking, the electrode polarization is comprised of the reaction activation overpotential and a shift in the electrode equilibrium potential. However, these components cannot be easily derived from the stimulus voltage excursion waveform.

11.5.5  Determining Electrode Safety

The uncertainties in determining the components, and magnitude, of the leading-edge access voltage drop make the estimation and prediction of electrode polarization, during any given stimulus pulse, difficult. Often the leading edge drop is by far the largest component of the total voltage excursion experienced by an electrode during a stimulation pulse. Simply subtracting the measured access voltage from the total voltage excursion is most often inadequate for estimating whether the electrode polarization is within the water window. It is unclear how much of the leading edge access voltage drop is truly caused by a benign resistive drop, and how much is caused by an interfacial process that might contribute to undesirable redox reactions.