Polymer Bioelectronics: A Solution for Both Stimulating and Recording Electrodes.

The advent of closed-loop bionics has created a demand for electrode materials that are ideal for both stimulating and recording applications. The growing complexity and diminishing size of implantable devices for neural interfaces have moved beyond what can be achieved with conventional metallic electrode materials. Polymeric electrode materials are a recent development based on polymer composites of organic conductors such as conductive polymers. These materials present exciting new opportunities in the design and fabrication of next-generation electrode arrays which can overcome the electrochemical and mechanical limitations of conventional electrode materials. This review will examine the recent developments in polymeric electrode materials, their application as stimulating and recording electrodes in bionic devices, and their impact on the development of soft, conformal, and high-density neural interfaces.

A Pilot In Vivo Study of Flexible Fully Polymeric Nerve Cuff Electrodes.

Recent trends in the field of bioelectronics have been focused on the development of electrodes that facilitate safe and efficient stimulation of nervous tissues. Novel conducting polymer (CP) based materials, such as flexible and fully polymeric conductive elastomers (CEs), constitute a promising alternative to improve on the limitations of current metallic devices. This pilot study demonstrates the performance of tripolar CE-based peripheral nerve cuffs compared to current commercial tripolar platinum-iridium (PtIr) nerve cuffs in vivo. CE and metallic cuff devices were implanted onto rodent sciatic nerves for a period of 8 weeks. Throughout the entire study, the CE device demonstrated improved charge transfer and electrochemical safety compared to the PtIr cuff, able to safely inject 2 to 3 times more charge. In comparison to the commercial control, the CE cuff was able to record in the in vivo setting with reduced noise and produced smaller voltages at all simulation levels. CE technologies provide a promising alternative to metallic devices for the development of bioelectronics with enhanced chronic device functionality.

Controlled electroactive release from solid-state conductive elastomer electrodes.

This work highlights the development of a conductive elastomer (CE) based electrophoretic platform that enables the transfer of charged molecules from a solid-state CE electrode directly to targeted tissues. Using an elastomer-based electrode containing poly (3,4-ethylenedioxythiophene) nanowires, controlled electrophoretic delivery of methylene blue (MB) and fluorescein (FLSC) was achieved with applied voltage. Electroactive release of positively charged MB and negatively charged FLSC achieved 33.19 ± 6.47 µg release of MB and 22.36 ± 3.05 µg release of FLSC, a 24 and 20-fold increase in comparison to inhibitory voltages over 1 h. Additionally, selective, and sequential release of the two oppositely charged molecules from a single CE device was demonstrated, showing the potential of this device to be used in multi-drug treatments.

Surface electromyography using dry polymeric electrodes.

Conventional wet Ag/AgCl electrodes are widely used in electrocardiography, electromyography (EMG), and electroencephalography (EEG) and are considered the gold standard for biopotential measurements. However, these electrodes require substantial skin preparation, are single use, and cannot be used for continuous monitoring (>24 h). For these reasons, dry electrodes are preferable during surface electromyography (sEMG) due to their convenience, durability, and longevity. Dry conductive elastomers (CEs) combine conductivity, flexibility, and stretchability. In this study, CEs combining poly(3,4-ehtylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS) in polyurethane are explored as dry, skin contacting EMG electrodes. This study compares these CE electrodes to commercial wet Ag/AgCl electrodes in five subjects, classifying four movements: open hand, fist, wrist extension, and wrist flexion. Classification accuracy is tested using a backpropagation artificial neural network. The control Ag/AgCl electrodes have a 98.7% classification accuracy, while the dry conductive elastomer electrodes have a classification accuracy of 99.5%. As a conclusion, PEDOT based dry CEs were shown to successfully function as on-skin electrodes for EMG recording, matching the performance of Ag/AgCl electrodes, while addressing the need for minimal skin prep, no gel, and wearable technology.

Preparation of Rat Sciatic Nerve for Ex Vivo Neurophysiology.

Ex vivo preparations enable the study of many neurophysiological processes in isolation from the rest of the body while preserving local tissue structure. This work describes the preparation of rat sciatic nerves for ex vivo neurophysiology, including buffer preparation, animal procedures, equipment setup and neurophysiological recording. This work provides an overview of the different types of experiments possible with this method. The outlined method aims to provide 6 h of stimulation and recording on extracted peripheral nerve tissue in tightly controlled conditions for optimal consistency in results. Results obtained using this method are A-fibre compound action potentials (CAP) with peak-to-peak amplitudes in the millivolt range over the entire duration of the experiment. CAP amplitudes and shapes are consistent and reliable, making them useful to test and compare new electrodes to existing models, or the effects of interventions on the tissue, such as the use of chemicals, surgical alterations, or neuromodulatory stimulation techniques. Both conventional commercially available cuff electrodes with platinum-iridium contacts and custom-made conductive elastomer electrodes were tested and gave similar results in terms of nerve stimulus strength-duration response.

Stretchable, Fully Polymeric Electrode Arrays for Peripheral Nerve Stimulation.

There is a critical need to transition research level flexible polymer bioelectronics toward the clinic by demonstrating both reliability in fabrication and stable device performance. Conductive elastomers (CEs) are composites of conductive polymers in elastomeric matrices that provide both flexibility and enhanced electrochemical properties compared to conventional metallic electrodes. This work focuses on the development of nerve cuff devices and the assessment of the device functionality at each development stage, from CE material to fully polymeric electrode arrays. Two device types are fabricated by laser machining of a thick and thin CE sheet variant on an insulative polydimethylsiloxane substrate and lamination into tubing to produce pre-curled cuffs. Device performance and stability following sterilization and mechanical loading are compared to a state-of-the-art stretchable metallic nerve cuff. The CE cuffs are found to be electrically and mechanically stable with improved charge transfer properties compared to the commercial cuff. All devices are applied to an ex vivo whole sciatic nerve and shown to be functional, with the CE cuffs demonstrating superior charge transfer and electrochemical safety in the biological environment.

Flexible Nanowire Conductive Elastomers for Applications in Fully Polymeric Bioelectronic Devices.

Soft, flexible polymer-based bioelectronics are a promising approach to minimize the chronic inflammatory reactions associated with metallic devices, impairing long-term device reliability and functionality. This work demonstrates the fabrication of conductive elastomers (CEs) consisting of chemically synthesized poly(3,4-ethylenedioxythiophene) (PEDOT) nanowires embedded within a polyurethane (PU) elastomeric matrix, resulting in soft and flexible, fully polymeric electrode materials. Increasing PEDOT nanowire loadings resulted in an improvement in electrochemical properties and conductivity, an increased Young's modulus and reduced strain at failure. Nanowire CEs were also found to have significantly improved electrochemical performance compared to one of the standard electrode materials, platinum (Pt). Indirect in vitro cytocompatibility test was carried out to investigate the effect of leachable substances from the CE on primary rodent cells. Nanowire CEs provide a promising alternative to metals for the fabrication of soft bioelectronics.

Multifocal stimulation of the cerebro-cerebellar loop during the acquisition of a novel motor skill.

Transcranial direct current stimulation (tDCS)-based interventions for augmenting motor learning are gaining interest in systems neuroscience and clinical research. Current approaches focus largely on monofocal motorcortical stimulation. Innovative stimulation protocols, accounting for motor learning related brain network interactions also, may further enhance effect sizes. Here, we tested different stimulation approaches targeting the cerebro-cerebellar loop. Forty young, healthy participants trained a fine motor skill with concurrent tDCS in four sessions over two days, testing the following conditions: (1) monofocal motorcortical, (2) sham, (3) monofocal cerebellar, or (4) sequential multifocal motorcortico-cerebellar stimulation in a double-blind, parallel design. Skill retention was assessed after circa 10 and 20 days. Furthermore, potential underlying mechanisms were studied, applying paired-pulse transcranial magnetic stimulation and multimodal magnetic resonance imaging-based techniques. Multisession motorcortical stimulation facilitated skill acquisition, when compared with sham. The data failed to reveal beneficial effects of monofocal cerebellar or additive effects of sequential multifocal motorcortico-cerebellar stimulation. Multimodal multiple linear regression modelling identified baseline task performance and structural integrity of the bilateral superior cerebellar peduncle as the most influential predictors for training success. Multisession application of motorcortical tDCS in several daily sessions may further boost motor training efficiency. This has potential implications for future rehabilitation trials.

Conductive elastomer composites for fully polymeric, flexible bioelectronics.

Flexible polymeric bioelectronics have the potential to address the limitations of metallic electrode arrays by minimizing the mechanical mismatch at the device-tissue interface for neuroprosthetic applications. This work demonstrates the straightforward fabrication of fully organic electrode arrays based on conductive elastomers (CEs) as a soft, flexible and stretchable electroactive composite material. CEs were designed as hybrids of polyurethane elastomers (PU) and poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS), with the aim of combining the electrical properties of PEDOT:PSS with the mechanical compliance of elastomers. CE composites were fabricated by solvent casting of PEDOT:PSS dispersed in dissolved PU at different conductive polymer (CP) loadings, from 5 wt% to 25 wt%. The formation of PEDOT:PSS networks within the PU matrix and the resultant composite material properties were examined as a function of CP loading. Increased PEDOT:PSS loading was found to result in a more connected network within the PU matrix, resulting in increased conductivity and charge storage capacity. Increased CP loading was also determined to increase the Young's modulus and reduce the strain at failure. Biological assessment of CE composites showed them to mediate ReNcell VM human neural precursor cell adhesion. The increased stiffness of CE films was also found to promote neurite outgrowth. CE sheets were directly laser micromachined into a functional array and shown to deliver biphasic waveforms with comparable voltage transients to Pt arrays in in vitro testing.

Development and Characterization of PEDOT:PSS/Alginate Soft Microelectrodes for Application in Neuroprosthetics.

Reducing the mechanical mismatch between the stiffness of a neural implant and the softness of the neural tissue is still an open challenge in neuroprosthetics. The emergence of conductive hydrogels in the last few years has considerably widened the spectrum of possibilities to tackle this issue. Nevertheless, despite the advancements in this field, further improvements in the fabrication of conductive hydrogel-based electrodes are still required. In this work, we report the fabrication of a conductive hydrogel-based microelectrode array for neural recording using a hybrid material composed of poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate), and alginate. The mechanical properties of the conductive hydrogel have been investigated using imaging techniques, while the electrode arrays have been electrochemically characterized at each fabrication step, and successfully validated both in vitro and in vivo. The presence of the conductive hydrogel, selectively electrodeposited onto the platinum microelectrodes, allowed achieving superior electrochemical characteristics, leading to a lower electrical noise during recordings. These findings represent an advancement in the design of soft conductive electrodes for neuroprosthetic applications.