The underlying cause of electrical stimulation-induced tissue trauma is debated. Our focus has been to study effects of generating electrochemical by-products at the electrode-electrolyte interface, using the pulse-clamp technique coupled with voltammetry to analyze charge transfer. The platinum-H(2)SO(4) system has been a standard for analyzing electrochemistry on platinum-stimulating electrodes, even though the chemical differences between H(2)SO(4) and the living body are obvious. Experiments were designed to determine whether phosphate-buffered saline (PBS) could serve as a more accurate emulation of living tissue. It had been rumored that platinum's performance in PBS deviates from that in H(2)SO(4) at larger potentials. Voltammetry in PBS was performed in two potential ranges. In a conventional potential range (-0.6 V to +0.9 V versus Ag/AgCl), characteristic peaks appear very similar to published voltammograms of platinum in H(2)SO(4). However, in an extended range (-1.0 V to +1.7 V versus Ag/AgCl), platinum exhibited additional electrochemical activity: one oxidation peak and two reduction peaks. Therefore, voltammetry was performed in NaCl and a sodium phosphate mixture (i.e. PBS components) to separate their activity. The altered electrochemical performance of platinum in PBS suggests that certain reactions on platinum at potentials outside the water window will not reflect what happens in vivo.

Objective Neural prostheses employing platinum electrodes are often constrained by a charge/charge-density parameter known as the Shannon limit. In examining the relationship between charge injection and observed tissue damage, the electrochemistry at the electrode-tissue interface should be considered. The charge-storage capacity (CSC) is often used as a predictor of how much charge an electrode can inject during stimulation, but calculating charge from a steady-state i-E curve (cyclic voltammogram) over the water window misrepresents how electrodes operate during stimulation. We aim to gain insight into why CSC predictions from classic i-E curves overestimate the amount of charge that can be injected during neural stimulation pulsing. Approach In this study, we use a standard electrochemical technique to investigate how platinum electrochemistry depends on the potentials accessed by the electrode and on the electrolyte composition. Main Results The experiments indicate: 1) platinum electrodes must be subjected to a “cleaning” procedure in order to expose the maximum number of surface platinum sites for hydrogen adsorption; 2) the “cleaned” platinum surface will likely revert to an obstructed condition under typical neural stimulation conditions; 3) irreversible oxygen reduction may occur under neural stimulation conditions, so the consequences of this reaction should be considered; and 4) the presence of the chloride ion (Cl−) or proteins (bovine serum albumin) inhibits oxide formation and alters H adsorption. Significance These observations help explain why traditional CSC calculations overestimate the charge that can be injected during neural stimulation. The results underscore how careful electrochemical examination of the electrode-electrolyte interface can result in more accurate expectations of electrode performance during applied stimulation.

The aim of this tutorial is to encourage members of the neuroprosthesis community to incorporate electron transfer processes into their thinking and provide them with the tools to do so when they design and work with neurostimulating devices. The focus of this article is on platinum because it is the most used electrode metal for devices in commercial use. The i(V e) profile or cyclic voltammogram contains information about electron transfer processes that can occur when the electrode-electrolyte interface, V e, is at a specific potential, and assumed to be near steady-state conditions. For the engineer/designer this means that if the potential is not in the range of a specific electron transfer process, that process cannot occur. An i(V e) profile, recorded at sweep rates greater than 0.1 mVs(-1), approximates steady-state conditions. Rapid transient potential excursions, like that seen with neural stimulation pulses, may be too fast for the reaction to occur, however, this means that if the potential is in the range of a specific electron transfer process it may occur and should be considered. The approach described here can be used to describe the thermodynamic electron transfer processes on other candidate electrode metals, e.g. stainless steel, iridium, carbon-based, etc.

The application of a train of cathodic-first/charge-balanced/biphasic pulses applied to a platinum electrode resulted in a positive creep of the anodic phase potential that increases with increasing charge injection but reaches a steady-state value before 1000 pulses have been delivered. The increase follows from the fact that charge going into irreversible reactions occurring during the anodic phase must equal the charge going into irreversible reactions during the cathodic phase for charge-balanced pulses. In an oxygenated electrolyte the drift of the measured positive potential moved into the platinum oxidation region of the i(V e) profile when the charge injection level exceeds k = 1.75. Platinum dissolution may occur in this region and k = 1.75 defines a boundary between damaging and non-damaging levels on the Shannon Plot. In a very low oxygen environment, the positive potential remained below the platinum oxidation region for the highest charge injection values studied, k = 2.3. The results support the hypothesis that platinum dissolution is the defining factor for the Shannon limit, k = 1.75. Numerous instrumentation issues were encountered in the course of making measurements. The solutions to these issues are provided.

A high surface area, Pt-Ir coating was electrodeposited onto the contacts of Advanced Bionics HiFocus 1j electrode arrays. The coating was imaged using optical and scanning electron microscopy (SEM) and the impedance was directly measured using clinically relevant voltage transients of biphasic pulses as short as 17 μs. The coating, which SEM showed to completely cover the underlying substrate, decreased the polarization impedance of 17 μs and 32 μs pulses by 91% and 93%, respectively.

Objective Electrical neurostimulation has traditionally been limited to the use of charge-balanced waveforms. Charge-imbalanced and monophasic waveforms are not used to deliver clinical therapy, because it is believed that these stimulation paradigms may generate noxious electrochemical species that cause tissue damage. Approach In this study, we investigated the dissolution of platinum as one of such irreversible reactions over a range of charge densities up to 160 µC cm−2 with current-controlled first phase, capacitive discharge second phase waveforms of both cathodic-first and anodic-first polarity. We monitored the concentration of platinum in solution under different stimulation delivery conditions including charge-balanced, charge-imbalanced, and monophasic pulses. Main results We observed that platinum dissolution decreased during charge-imbalanced and monophasic stimulation when compared to charge-balanced waveforms. Significance This observation provides an opportunity to re-evaluate the charge-balanced waveform as the primary option for sustainable neural stimulation.

We hypothesize that the k  =  1.75 Shannon limit for safe stimulation designates a charge-injection boundary above which platinum toxicity becomes a relevant consideration for living cells around an electrode, a possibility that can be directly tested, and is a vital step forward in mission (1).

Objective The Shannon model is often used to define an expected boundary between non-damaging and damaging modes of electrical neurostimulation. Numerous preclinical studies have been performed by manufacturers of neuromodulation devices using different animal models and a broad range of stimulation parameters while developing devices for clinical use. These studies are mostly absent from peer-reviewed literature, which may lead to this information being overlooked by the scientific community. We aimed to locate summaries of these studies accessible via public regulatory databases and to add them to a body of knowledge available to a broad scientific community. Methods We employed web search terms describing device type, intended use, neural target, therapeutic application, company name, and submission number to identify summaries for premarket approval (PMA) devices and 510(k) devices. We filtered these records to a subset of entries that have sufficient technical information relevant to safety of neurostimulation. Results We identified 13 product codes for 8 types of neuromodulation devices. These led us to devices that have 22 PMAs and 154 510(k)s and six transcripts of public panel meetings. We found one PMA for a brain, peripheral nerve, and spinal cord stimulator and five 510(k) spinal cord stimulators with enough information to plot in Shannon coordinates of charge and charge density per phase. Conclusions Analysis of relevant entries from public regulatory databases reveals use of pig, sheep, monkey, dog, and goat animal models with deep brain, peripheral nerve, muscle and spinal cord electrode placement with a variety of stimulation durations (hours to years); frequencies (10–10,000 Hz) and magnitudes (Shannon k from below zero to 4.47). Data from located entries indicate that a feline cortical model that employs acute stimulation might have limitations for assessing tissue damage in diverse anatomical locations, particularly for peripheral nerve and spinal cord simulation.