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

A Fully Implantable Opto-Electro Closed-Loop Neural Interface for Motor Neuron Disease Studies

This paper presents a fully implantable closed-loop device for use in freely moving rodents to investigate new treatments for motor neuron disease. The 0.18 µm CMOS integrated circuit comprises 4 stimulators, each featuring 16 channels for optical and electrical stimulation using arbitrary current waveforms at frequencies from 1.5 Hz to 50 kHz, and a bandwidth programmable front-end for neural recording. The implant uses a Qi wireless inductive link which can deliver >100 mW power at a maximum distance of 2 cm for a freely moving rodent. A backup rechargeable battery can support 10 mA continuous stimulation currents for 2.5 hours in the absence of an inductive power link. The implant is controlled by a graphic user interface with broad programmable parameters via a Bluetooth low energy bidirectional data telemetry link. The encapsulated implant is 40 mm × 20 mm × 10 mm. Measured results are presented showing the electrical performance of the electronics and the packaging method

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

Methods of poly (3,4)-ethylenedioxithiophene (PEDOT) electrodeposition on metal electrodes for neural stimulation and recording

Conductive polymers are of great interest in the field of neural electrodes because of their potential to improve the interfacial properties of electrodes. In particular, the conductive polymer poly (3,4)-ethylenedioxithiophene (PEDOT) has been widely studied for neural applications. This review compares methods for electrodeposition of PEDOT on metal neural electrodes, and analyses the effects of deposition methods on morphology and electrochemical performance. The findings of this review show that: coating thickness and charge storage capacity are positively correlated with PEDOT electrodeposition charge density. We also show that PEDOT coated electrode impedance at 1 kHz, the only consistently reported impedance quantity, is strongly dependent upon electrode radius across a wide range of studies, because PEDOT coatings reduces the reactance of the complex impedance, conferring a more resistive behavior to electrodes (at 1 kHz) dominated by the solution resistance and electrode geometry. This review also summarises how PEDOT co-ion choice affects coating structure and morphology and shows that co-ions notably influence the charge injection limit but have a limited influence on charge storage capacity and impedance. Finally we discuss the possible influence of characterisation methods to assess the robustness of comparisons between published results using different methods of characterisation

A Versatile Hermetically Sealed Microelectronic Implant for Peripheral Nerve Stimulation Applications

This article presents a versatile neurostimulation platform featuring a fully implantable multi-channel neural stimulator for chronic experimental studies with freely moving large animal models involving peripheral nerves. The implant is hermetically sealed in a ceramic enclosure and encapsulated in medical grade silicone rubber, and then underwent active tests at accelerated aging conditions at 100°C for 15 consecutive days. The stimulator microelectronics are implemented in a 0.6-μm CMOS technology, with a crosstalk reduction scheme to minimize cross-channel interference, and high-speed power and data telemetry for battery-less operation. A wearable transmitter equipped with a Bluetooth Low Energy radio link, and a custom graphical user interface provide real-time, remotely controlled stimulation. Three parallel stimulators provide independent stimulation on three channels, where each stimulator supports six stimulating sites and two return sites through multiplexing, hence the implant can facilitate stimulation at up to 36 different electrode pairs. The design of the electronics, method of hermetic packaging and electrical performance as well as in vitro testing with electrodes in saline are presented