electrode termed the reference electrode required for measuring precisely controlled electrical potentials. At equilibrium (no current), the potential of the system remains constant and is typically referred to as the open-circuit potential. Net electrochemical processes begin to take place as soon as the potential is forced away from equilibrium and resulting current begins to flow through the system. Charge transfer across the interface takes place through two primary mechanisms viz., Faradaic and non-Faradaic reactions.

Faradaic and non-faradaic reactions:  Non-Faradaic processes include redistribution of the charge at the electrode–electrolyte interface and do not involve any net transfer of charge species across the interface. If charge injection is achieved through only non-Faradaic reactions, i.e. charging and discharging the double-layer capacitance, then the electrode–electrolyte interface can be modeled as a simple capacitor, viz. the double-layer capacitor Cdl. If the total amount of charge transferred is small then the transferred charge can be recovered by simply reversing the polarity of the applied pulse or by discharging the capacitor. In addition to chargingdischarging of the double layer capacitance, charge injection can also be achieved by Faradaic processes such as oxidation–reduction reactions. These reactions involve the transfer of electrons between the two phases of the reaction and unlike the capacitive mechanism, may or may not be completely reversible in nature. In case of reactions in which at least one of the chemical species is surface bound, the reaction is completely reversible under steady state conditions. Such reactions are limited by the available surface area of electrode and the amount of species adsorbed onto the interface. However, reactions that do not involve at least one surface bound species, have no mechanism to force the reaction to be reversible in the steady state. Charge balancing in the Faradaic regimen is most often achieved via multiple partially reversible reactions that result in the release of one or more possibly cytotoxic chemical substances in the surrounding tissue.

6.3  Electrode Material

In order to depolarize neurons or to record biological potentials, an interface is required between the body and the electronic apparatus. This interface is called the biopotential electrode. Biopotential electrodes deal with challenges different from electrodes used in other systems. First the electrode material has to be biocompatible, i.e. non-toxic to the body and second it has to have the ability to serve as a transducer. This is because as we saw in the preceding section, current in the electrode is carried by electrons while in the electrolyte it is carried by ions.

Electrode potential:  When a metal is brought into contact with a solution, a net rearrangement of charge occurs at the interface leading to a loss of neutrality of charge at the interface. As a result, the electrolyte in the immediate vicinity of the electrode is at a potential different from the rest of the solution. This difference in potential is called the half-cell potential and is determined by many different parameters such as the type of metal, the type and concentration of ions in the solution,

temperature, etc. This half-cell potential is also referred to as the electrode interfacial potential. It is not possible to measure this potential without utilizing a second electrode. However, the second electrode would then create an interface of its own with the electrolyte thus making it impossible to separate the two resulting potentials from each other. To overcome this, electrochemical cells are evaluated in their entirety, generally composed of a working electrode and a reference electrode separated by the electrolyte. Thus a cell’s potential is defined as the potential of the working electrode vs. the reference electrode.

Consider the reaction between a metal electrode and a redox couple in the electrolyte:

O+ne− ↔ R

The equilibrium potential for any electrochemical cell can be calculated using the Nernst equation:

where, [X ]o and [X ]i are the concentrations of the species, R is the gas constant, T is the absolute temperature (Kelvin), F is Faraday’s constant and n is the number of electrons transferred. For the electrochemical cell above, if the concentration of both species in solution is equal then the potential of the cell will equilibrate to its formal potential E0. For unequal concentrations, using the Nernst equation, the equilibrium potential for the electrochemical cell is:

In the absence of any net current, the measured cell potential is called the opencircuit potential, which again is the sum of the two interfacial potentials. Now if instead a current is present, then the observed potential is different from the equilibrium potential. This is due to the polarization of the electrode and the difference between the observed potential and the equilibrium potential is known as the overpotential h.

Three basic mechanisms contribute to overpotential: ohmic, concentration and activation overpotentials. Ohmic overpotential is due to the electrolyte resistance which leads to a voltage drop across the solution during the passage of current between the electrodes. Concentration overpotential occurs due to changes in the distribution of ions at the electrode–electrolyte interface. Activation overpotential occurs due to charge transfer processes involved during oxidation–reduction reactions that are not completely reversible. The net overpotential is simply a sum of three mechanisms.

Polarizable and non-polarizable electrodes:  For ideally polarizable electrodes, no actual charge crosses the electrode–electrolyte interface during current flow. Instead, during current flow, redistribution of ions occurs at the interface thus exhibiting capacitor like properties. As a result the overpotential is dominated by the concentration overpotential. One example is titanium nitride electrode where charge injection takes place through capacitive charging–discharging processes. Noble metals such as platinum also behave as polarizable electrodes but over a limited range of voltages. Ideally non-polarizable electrodes on the other hand are the ones in which current passes freely between the electrode–electrolyte interface and hence causes no overpotential. Electrodes such as silver–silver chloride and saturated calomel come closest to behaving as non-polarizable electrodes. These electrodes are best used as reference electrodes during measurement of electrode potential as there is no change in voltage across their interface during current flow. However, it is essential to note that in reality no electrode behaves either as ideally polarizable or ideally non-polarizable. Electrodes come closest to ideal characteristics only over a limited range of voltages.

6.3.1  Electrode Characterization

Measurement of impedance:  Electrochemical impedance spectroscopy [17] has been used successfully to characterize the electrode–electrolyte interface. Specifically for neuroprostheses employing current stimulation, impedance measurement techniques have been employed to test the efficacy of neural stimulation. Studies in the past have shown that for all stimulation strategies to efficiently inject charge across the electrode-tissue interface, an optimal relationship exists between the threshold of excitation and the distance between the electrode and tissue. For the auditory brainstem implants [31], measurements of threshold of excitation as a function of the distance of the electrodes from the target neurons have shown a strong correlation between the two [42]. The reason behind this is that in order to cause neuronal excitation a minimum amount of current density is required. If the interface impedance were high, it would lead to a higher applied voltage, which could then become a limiting factor in the power capabilities of the device. As shall be discussed in Sect. 6.5, in some cases, this high voltage can also lead to undesirable electrochemical reactions to take place at the interface thereby causing tissue damage.

As it is not possible to control the tissue properties of the target system, efforts are made instead to control the electrode design in order to allow safe and effective stimulation. To achieve this, equivalent circuit models of the electrode–electrolyte interface have been developed which along with impedance measurements, provide an estimate of optimal parameters for the electrode. The first ever model was proposed by Warburg in 1899 who modeled the interface as a polarization resistance in series with a polarization capacitance. This would produce a straight vertical line on the complex plane plots (Z imaginary vs. Z real). However, for solid electrodes it was often observed that the straight vertical line had an angle less than 90°. Thus, the

experiments, measurement is started at the highest frequency and stepped down to progressively lower values until enough data has been collected to determine the impedance of the system as a function of frequency. This is done to ensure minimal sample perturbation, and to explore non-Faradaic before Faradaic charge transfer.

The impedance profiles of microelectrodes assist in developing electronic models analogous to the electrode–electrolyte interface such as the Randles model described in the preceding paragraphs. Values of the different circuit elements can be estimated from the impedance measurements. This aids in designing improved versions of the electrode in order to achieve optimal charge-injection situations. The profiles are viewed either through the ‘Nyquist plot’ or the ‘Bode plot’ and corresponding model parameters can be estimated. At high frequencies, the impedance of the Randles cell becomes almost entirely dominated by the solution resistance Rs while at low frequencies the resistance of the electrochemical reaction Re also comes into play. The solution resistance has long been shown to have an inverse relationship with the radius of a disc electrode. However, recent work by Ahuja et al. suggests that this dependence may not hold for all frequencies [1]. Their work showed that the electrode impedance does scale with radius but only in the high frequency regime (~100 kHz), whereas at lower frequencies (~10 Hz) it scales with the area of the electrode. Thus, only the electrode edge contributes at higher frequencies due to the primary current distribution while at lower frequencies, a secondary current distribution comes into play that drives the current to the centre of the disk leading to an area dependence. They also showed that for microelectrodes of radii less than 50 mm, the area dependence is exhibited even at relatively higher frequencies due to the decreased RC time constant and double layer charging of the electrodes at these frequencies.

Surface reactions and potential limits:  Cyclic voltammetry (CV) falls under the class of voltammetric methods where the electrode potential is controlled and the resulting current is measured. In voltammetric methods, solutes in contact with the electrode undergo oxidation or reduction reactions producing current at the electrode surface that is measured. In case of cyclic voltammetry, the applied potential is linearly varied with time (cycled) while the resulting current is measured. The applied potential has a triangular waveform with negative and positive turn-around potentials. Since, in a cyclic voltammogram, the range of applied potential is quite large, the measured current aids in understanding the reaction mechanisms available during stimulation. CV can characterize the potential at which the reaction ­proceeds maximally, the reaction kinetics, and the reversibility of the reaction, all of which are critical to determining if this reaction can be safely used to transfer charge to tissue. Platinum by far has been the most well studied electrode material (Fig. 6.2) but with increasing demands of neural stimulation treatment strategies, focus has shifted towards analyzing and characterizing other candidate electrode materials as reflected in the next section.

For microelectrode characterization in neural stimulation applications, CV plots are used to study a number of important parameters associated with the safe and effective charge-injection at the electrode-tissue interface.

Fig. 6.2  Cyclic voltammogram of poly crystalline platinum in 1 M KOH at scan rate of 100 mV/s exhibits all the different processes involved during the cathodic and anodic direction. The potential scale is referred to a reversible hydrogen electrode (RHE) in the same solution. Reprinted from [28], with permission

1. Voltage limits. All electrodes must operate within the “water window,” the term given for the potential range between hydrogen evolution potential (negative) and oxygen evolution potential (positive).

Cyclic voltammetry is used to determine these voltage limits, which are material and solution dependent. As will be discussed in Sect. 6.5, during neural stimulation only reversible reactions are employed for charge injection, to avoid causing damage to either the electrode or tissue. For example, from cyclic voltammograms of IrOx and TiN done by Weiland et al., it is observed that the water window of TiN is in the voltage range of −0.6 to 0.8 V in phosphate-buffered saline solution (PBS). For IrOx, the water window has been estimated to be −0.7 to 0.8 V in PBS [55]. Note that the water window does not change in width, but can shift depending on the reference potential.

2. Charge-Injection mechanism. In a CV plot, the presence of peaks indicates electrochemical reactions occurring at the electrode–electrolyte interface along with the charging–discharging of the double layer capacitance. As an example,

the CV plot of platinum exhibits distinct peaks associated with the different surface­ reactions such as hydrogen-atom plating. Also, from the voltammograms of Weiland et al., IrOx CV traces exhibited distinct peaks indicating reduction– oxidation reactions involving transfer of electrons across the interface, along with current flow due to capacitive charging–discharging. On the other hand, the CV traces of TiN show no distinct peaks indicating that the current flow is dominated by the capacitive charging–discharging mechanism [55]. Also, from the nature of peaks, the type of reaction that is occurring can be determined. For example along with the oxidation–reduction peaks of water with the electrode metal, the presence of additional peaks indicates existence of other electro-active substances.

3. Charge-storage capacity. An important parameter for neural stimulation is the charge-storage capacity of the electrode. This is determined by integrating the area under either the cathodic or anodic sweep in the CV plot within the water window. The value obtained indicates the maximum charge that can be injected via reversible surface processes by an electrode. This is usually expressed in terms of charge density limit of the electrode. As an example, the charge storage capacity of activated iridium oxide has been reported to range from 10 to 240 mC/ cm2 depending upon the thickness of the film [52]. However, it should be noted that this is only capacity measured with cyclic voltammetry. The actual amount of charge injection that can be achieved during neural stimulation is usually only a fraction of the charge storage capacity and depends upon factors such as the thickness and morphology of the film, specific reactions of the redox material, pulse duration, etc.

4. Reversibility of reaction. Whether the electrochemical reaction occurring is reversible or irreversible in nature can be determined from the cyclic voltammogram of the electrode. All chemical reactions, including reactions occurring at the electrode–electrolyte interface, proceed at a finite rate. The reversibility of a reaction is thus governed by the rate of electron transfer and surface concentrations. In a reversible reaction, the cathodic peak height is equal to the anodic peak height and the reversible half-wave potential will lie exactly midway between the peaks. However, as the reaction becomes more and more irreversible, the cathodic peak height no longer remains equal to the anodic peak height and the separation between the peaks increase (Fig. 6.3). This situation can occur at high scan rates where due to slow reaction kinetics, the voltammogram changes from reversible to irreversible shape.

Voltage response:  While charge storage estimates acquired from CVs give the maximum charge value that the electrode in question can store without causing hydrolysis, the actual amount that is injected during current stimulation is quite different. Hence, in order to get a comprehensive picture of how the electrode will behave during active stimulation, one must study the voltage response developed during stimulation. Whenever a current pulse is applied across the electrode–­ electrolyte or electrode–tissue interface, a resulting voltage response develops across the interface. This voltage waveform is characterized by an initial drop