Electron transfer processes occurring on platinum neural stimulating electrodes: pulsing experiments for cathodic-first, charge-imbalanced, biphasic pulses for 0.566 ⩽ k ⩽ 2.3 in rat subcutaneous tissues.

OBJECTIVE: Charge injection through platinum neural stimulation electrodes is often constrained by the Shannon limit (Shannon 1992 IEEE Trans. Biomed. Eng. 39 424-6) of k = 1.75. By leveraging the tools of electrochemistry to better understand the reactions at electrode-tissue interface, we endeavor to find a way to safely inject more charge than allowed if the traditional Shannon limit were followed. APPROACH: In previous studies on platinum electrodes using charge-balanced, cathodic-first, biphasic pulses, we noted that during the secondary anodic phase, the electrode potential moves into a range where platinum dissolution is possible when charge injection is greater than k = 1.75. Platinum dissolution products are known to be toxic to brain tissues. We hypothesize that by injecting less charge in the anodic phase than the cathodic phase, the anodic potential excursions will decrease, thereby avoiding potentials where platinum dissolution is more likely. MAIN RESULTS: Our findings show that using these charge-imbalanced pulses decreases the anodic potential excursions to a level where platinum oxidation and dissolution are less likely, and aligns the anodic potentials with those observed with charge-balanced stimulation at k < 1.75-a range widely accepted as safe for stimulation with platinum. SIGNIFICANCE: From these results, we further hypothesize that charge-imbalanced biphasic stimulation would permit more charge to be safely injected through platinum electrodes than would be permitted if the dogma of charge-balanced biphasic stimuli were followed. Testing this hypothesis in cat brain in the same manner as the experiments that formed the basis for the Shannon plot could open the door for safe charge injection through platinum electrodes at levels greater than k = 1.75.

Electron transfer processes occurring on platinum neural stimulating electrodes: pulsing experiments for cathodic-first, charge-balanced, biphasic pulses for 0.566 ⩽ k ⩽ 2.3 in rat subcutaneous tissues.

OBJECTIVE: Our mission is twofold: (1) find a way to safely inject more charge through platinum electrodes than the Shannon limit (k = 1.75) permits and (2) nurture an interest in the neural stimulation community to understand the electron transfer process occurring on neural stimulating electrodes. APPROACH: We report here on measurements of the electrode potential, performed on platinum neural stimulating electrodes in the subcutaneous space of an anesthetized rat under neural stimulation conditions. MAIN RESULTS: The results for six platinum electrodes with areas ranging from 0.2 mm2 to 12.7 mm2 were similar to prior results in sulfuric acid, except that the measured potentials were shifted negative 0.36 V because of the pH difference between the two media. The anodic 'end' potential, measured at t = 20 ms after the onset of the biphasic current pulse, was the primary focus of the data collected because previous results had shown that as charge injection crosses the Shannon limit (k = 1.75), this potential moves into a range where platinum surface oxidation and dissolution is likely to occur. The behavior of V e(t = 20 ms) over a range of electrode surface areas studied was consistent with our sulfuric acid study. Implicit, but little noticed, in Shannon's formulation is that small and large platinum electrodes behave the same in terms of k value; our data supports this idea. SIGNIFICANCE: 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).

Electron transfer processes occurring on platinum neural stimulating electrodes: calculated charge-storage capacities are inaccessible during applied stimulation.

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.

High-throughput in vitro assay to evaluate the cytotoxicity of liberated platinum compounds for stimulating neural electrodes.

BACKGROUND: It is currently unclear how the platinum (Pt) species released from platinum-containing stimulating electrodes may affect the health of the surrounding tissue. This study develops an effective system to assess the cytotoxicity of any electrode-liberated Pt over a short duration, to screen systems before future in vivo testing. NEW METHOD: A platinum electrode was stimulated for two hours under physiologically relevant conditions to induce the liberation of Pt species. The total concentration of liberated Pt species was quantified and the concentration found was used to develop a range of Pt species for our model system comprised of microglia and neuron-like cells. RESULTS: Under our stimulation conditions (k=2.3, charge density of 57.7µC/cm2), Pt was liberated to a concentration of 1ppm. Interestingly, after 24h of Pt exposure, the dose-dependent cytotoxicity plots revealed that cell death became statistically significant at 10ppm for microglia and 20ppm for neuronal cells. However, in neuron-like cell cultures, concentrations above 1ppm resulted in significant neurite loss after 24h. COMPARISON WITH EXISTING METHODS: To our knowledge, there does not exist a simple, in vitro assay system for assessing the cytotoxicity of Pt liberated from stimulating neural electrodes. CONCLUSIONS: This work describes a simple model assay that is designed to be applicable to almost any electrode and stimulation system where the electrode is directly juxtaposed to the neural target. Based on the application, the duration of stimulation and Pt exposure may be varied.

Electron transfer processes occurring on platinum neural stimulating electrodes: a tutorial on the i(V e) profile.

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.

Electron transfer processes occurring on platinum neural stimulating electrodes: pulsing experiments for cathodic-first/charge-balanced/biphasic pulses for 0.566 ≤ k ≤ 2.3 in oxygenated and deoxygenated sulfuric acid.

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.