Influence of Extracellular Matrix-Mimicking Gel Electrolyte on Electrode Charge Injection

Damage mechanisms and electrode behavior during electrical stimulation must be better understood to address the demands of new electrode technologies. Here, we studied the influence of gel electrolytes on electrode polarization and charge injection. We show that agar gels do not change electrode behavior significantly

Effect of pH and gel electrolyte on safe charge injection and electrode degradation of platinum electrodes

Platinum (Pt) is a widespread electrode material choice for neural interfaces and electrochemical biosensors, due to its supposed electrochemical inertness. However, faradaic reactions can take place at Pt electrodes, including Pt oxide formation and reduction. Repeated redox cycles of Pt can lead to Pt dissolution, which may harm the tissue and significantly reduce electrode lifetime. In this study, we investigated how the electrolyte may influence Pt dissolution mechanisms during current pulsing. Two electrolyte characteristics were considered: pH and gelation. We confirmed that empirically reported tissue damage thresholds correlate with Pt oxide formation and reduction. Varying electrolyte pH occasioned a shift in recorded potentials, however, damage thresholds correlated with the same mechanisms for all pH values. The similar behaviour observed for pH values in the central range (4 ≤ pH ≤ 10) can be explained by variations of local pH at the electrode surface. Gel electrolytes behaved comparably to solutions, which was confirmed by statistical similarity tests. This study extends the knowledge about platinum electrochemistry and shows the necessity to carefully choose the stimulation protocol and the electrolyte to avoid platinum dissolution and tissue damage

Influence of Aspect Ratio on the Current Density Profile of Recessed Stimulation Electrodes

Introduction: Electrical stimulation is a therapeutic technique aiming at restoring impaired biological functions by injecting a controlled amount of charge in the body. Commonly used planar stimulation electrodes exhibit a non-uniform current density distribution (j) that can lead to locally exceeding the safe stimulation threshold [1]. An electrode can be recessed into an insulating part, which results in a different j [2], thus a different injection of charge, which can induce damage or insufficient stimulation. However, few studies [3] have focused on the influence of the recess parameters on j and how it could be used in electrode design. / Material & Methods: A finite element model was used to calculate j at recessed and non-recessed planar disc platinum electrodes in saline in response to an applied potential (COMSOL 54 Electrochemistry module). Recess shape (tubular and conical) and aspect ratio (AR), defined as recess depth divided by electrode diameter, were varied. Fig. 1 (c) shows a transverse view of a conical (left) and tubular (right) recess with the electrode covering the entire base of the recess. / Results: The tubular recess presents a uniform j at the electrode surface and at most depths throughout the recess, except at the open end of the recess, where the apparent j is more similar to the one of a non-recessed electrode, fig. 1(a, c). The conical recess presents a distribution more similar to a non-recessed electrode at the electrode surface, which becomes more uniform towards the recess end, fig. 1 (b, c). Increasing the AR makes j more uniform, both at the electrode surface and at the end of the recess, fig. 1 (a, b, d). At a given AR, varying the dimensions of the recess does not affect j, with relative standard deviations typically smaller than 0.5% (7 ARs tested, 3 pairs of dimensions per AR). / Discussion: The non-uniformity of j depended only on the recess shape and AR. Understanding this relationship will allow finetuning the current density profile at the electrode surface and at the recess end. For instance, a tubular recess with an AR larger than 2 will yield a uniform distribution at the electrode surface. Similarly, a conical recess of AR = 1/3 will reproduce the current density profile of a non-recessed electrode with less than 6% error, while being straightforward to manufacture. This study used a purely resistive model under steady-state conditions, which is a simple model for charge injection at an electrode-electrolyte interface. Further studies will consider a more realistic charge-transfer model and conditions closer to real dynamic electrical stimulation experiments

Extending the understanding of Shannon's safe stimulation limit for platinum electrodes: biphasic charge-balanced pulse trains in unbuffered saline at pH = 1 to pH = 12

Objective: In neural electrical stimulation, safe stimulation guidelines are essential to deliver efficient treatment by avoiding neural damage and electrode degradation. The widely used Shannon's limit, k, gives conditions on the stimulation parameters to avoid neural damage, however, underlying damage mechanisms are not fully understood. Moreover, the translation from bench testing to in vivo experiments still presents some challenges, including the increased polarisation observed, which may influence charge-injection mechanisms. In this work, we studied the influence on damage mechanisms of two electrolyte parameters that are different in vivo compared to usual bench tests: solution pH and electrolyte gelation. Approach: The potential of a platinum macroelectrode was monitored in a three-electrode setup during current-controlled biphasic charge-balanced cathodic-first pulse trains. Maximum anodic and cathodic potential excursions during pulse trains were projected on cyclic voltammograms to infer possible electrochemical reactions. // Main results: In unbuffered saline of pH ranging from 1 to 12, the maximum anodic potential was systematically located in the oxide formation region, while the cathodic potential was located the molecular oxygen and oxide reduction region when k approached Shannon's damage limit, independent of solution pH. The results support the hypothesis that Shannon's limit corresponds to the beginning of platinum dissolution following repeated cycles of platinum oxidation and reduction, for which the cathodic excursion is a key tipping point. Despite similar potential excursions between solution and gel electrolytes, we found a joint influence of pH and gelation on the cathodic potential alone, while we observed no effect on the anodic potential. We hypothesise that gelation creates a positive feedback loop exacerbating the effects of pH ; however, the extent of that influence needs to be examined further. // Significance: This work supports the hypothesis of charge injection mechanisms associated with stimulation-induced damage at platinum electrodes. The validity of a major hypothesis explaining stimulation-induced damage was tested and supported on a range of electrolytes representing potential electrode environments, calling for further characterisation of platinum dissolution during electrical stimulation in various testing conditions

New postnatal urinary incontinence: obstetric and other risk factors in primparae.

Objective To identify obstetric and other risk factors for urinary incontinence which occurs during pregnancy or after childbirth. Design Questionnaire survey of women. Setting Maternity units in Aberdeen (Scotland), Birmingham (England) and Dunedin (New Zealand). Population 3405 primiparous women with singleton births delivered during one year. Methods Questionnaire responses and obstetric casenote data were analysed using multivariate analysis to identify associations with urinary incontinence. Main outcome measures Urinary incontinence at three months after delivery first starting in pregnancy or after birth. Results The prevalence of urinary incontinence was 29%. New incontinence first beginning after delivery was associated with higher maternal age (oldest versus youngest group, odds ratio, OR 2.02, 95% CI 1.35 to 3.02); and method of delivery (caesarean section versus spontaneous vaginal delivery, OR 0.28, 95% CI 0.19 to 0.41). There were no significant associations with forceps delivery (OR 1.18, 95% CI 0.92 to 1.51) or vacuum delivery (OR 1.16, 95% CI 0.83 to 1.63). Incontinence first occurring during pregnancy and still present at three months was associated with higher maternal body mass index (BMI > 25, OR 1.68, 95% CI 1.16 to 2.43), and heavier babies (birthweight in top quartile, OR 1.56, 95% CI 1.12 to 2.19). In these women, caesarean section was associated with less incontinence (OR 0.39, 95% CI 0.27 to 0.58) but incontinence was not associated with age. Conclusions Women have less urinary incontinence after a first delivery by caesarean section whether or not that first starts during pregnancy. Older maternal age was associated with new postnatal incontinence, and higher body mass index and heavier babies with incontinence first starting during pregnancy. The effect of further deliveries may modify these findings

Microchannel neural interface manufacture by stacking silicone and metal foil laminae

Objective: Microchannel neural interfaces (MNIs) overcome problems with recording from peripheral nerves by amplifying signals independent of Node of Ranvier position. Selective recording and stimulation using an MNI requires good insulation between microchannels and a high electrode density. We propose that stacking microchannel laminae will improve selectivity over single layer MNI designs due to the increase in electrode number and an improvement in microchannel sealing. Approach: This paper describes a manufacturing method for creating MNIs which overcomes limitations on electrode connectivity and microchannel sealing. Laser cut silicone – metal foil laminae were stacked using plasma bonding to create an array of microchannels containing tripolar electrodes. Electrodes were DC etched and electrode impedance and cyclic voltammetry were tested. Main results: MNIs with 100 µm and 200 µm diameter microchannels were manufactured. High electrode density MNIs are achievable with electrodes present in every microchannel. Electrode impedances of 27.2 ± 19.8 kΩ at 1kHz were achieved. Following 2 months of implantation in Lewis rat sciatic nerve, micro-fascicles were observed regenerating through the MNI microchannels. Significance: Selective microchannel neural interfaces with the peripheral nervous system may allow upper limb amputees to control prostheses intuitively

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio