Sustainability inspired fabrication of next generation neurostimulation and cardiac rhythm management electrodes via reactive hierarchical surface restructuring.

Over the last two decades, platinum group metals (PGMs) and their alloys have dominated as the materials of choice for electrodes in long-term implantable neurostimulation and cardiac rhythm management devices due to their superior conductivity, mechanical and chemical stability, biocompatibility, corrosion resistance, radiopacity, and electrochemical performance. Despite these benefits, PGM manufacturing processes are extremely costly, complex, and challenging with potential health hazards. Additionally, the volatility in PGM prices and their high supply risk, combined with their scarce concentration of approximately 0.01 ppm in the earth's upper crust and limited mining geographical areas, underscores their classification as critical raw materials, thus, their effective recovery or substitution worldwide is of paramount importance. Since postmortem recovery from deceased patients and/or refining of PGMs that are used in the manufacturing of the electrodes and microelectrode arrays is extremely rare, challenging, and highly costly, therefore, substitution of PGM-based electrodes with other biocompatible materials that can yield electrochemical performance values equal or greater than PGMs is the only viable and sustainable solution to reduce and ultimately substitute the use of PGMs in long-term implantable neurostimulation and cardiac rhythm management devices. In this article, we demonstrate for the first time how the novel technique of "reactive hierarchical surface restructuring" can be utilized on titanium-that is widely used in many non-stimulation medical device and implant applications-to manufacture biocompatible, low-cost, sustainable, and high-performing neurostimulation and cardiac rhythm management electrodes. We have shown how the surface of titanium electrodes with extremely poor electrochemical performance undergoes compositional and topographical transformations that result in electrodes with outstanding electrochemical performance.

Development of antibacterial neural stimulation electrodes via hierarchical surface restructuring and atomic layer deposition.

Miniaturization and electrochemical performance enhancement of electrodes and microelectrode arrays in emerging long-term implantable neural stimulation devices improves specificity, functionality, and performance of these devices. However, surgical site and post-implantation infections are amongst the most devastating complications after surgical procedures and implantations. Additionally, with the increased use of antibiotics, the threat of antibiotic resistance is significant and is increasingly being recognized as a global problem. Therefore, the need for alternative strategies to eliminate post-implantation infections and reduce antibiotic use has led to the development of medical devices with antibacterial properties. In this work, we report on the development of electrochemically active antibacterial platinum-iridium electrodes targeted for use in neural stimulation and sensing applications. A two-step development process was used. Electrodes were first restructured using femtosecond laser hierarchical surface restructuring. In the second step of the process, atomic layer deposition was utilized to deposit conformal antibacterial copper oxide thin films on the hierarchical surface structure of the electrodes to impart antibacterial properties to the electrodes with minimal impact on electrochemical performance of the electrodes. Morphological, compositional, and structural properties of the electrodes were studied using multiple modalities of microscopy and spectroscopy. Antibacterial properties of the electrodes were also studied, particularly, the killing effect of the hierarchically restructured antibacterial electrodes on Escherichia coli and Staphylococcus aureus-two common types of bacteria responsible for implant infections.

Stimulation and Recording of the Hippocampus Using the Same Pt-Ir Coated Microelectrodes.

Same-electrode stimulation and recording with high spatial resolution, signal quality, and power efficiency is highly desirable in neuroscience and neural engineering. High spatial resolution and signal-to-noise ratio is necessary for obtaining unitary activities and delivering focal stimulations. Power efficiency is critical for battery-operated implantable neural interfaces. This study demonstrates the capability of recording single units as well as evoked potentials in response to a wide range of electrochemically safe stimulation pulses through high-resolution microelectrodes coated with co-deposition of Pt-Ir. It also compares signal-to-noise ratio, single unit activity, and power efficiencies between Pt-Ir coated and uncoated microelectrodes. To enable stimulation and recording with the same microelectrodes, microelectrode arrays were treated with electrodeposited platinum-iridium coating (EPIC) and tested in the CA1 cell body layer of rat hippocampi. The electrodes' ability to (1) inject a large range of electrochemically reversable stimulation pulses to the tissue, and (2) record evoked potentials and single unit activities were quantitively assessed over an acute time period. Compared to uncoated electrodes, EPIC electrodes recorded signals with higher signal-to-noise ratios (coated: 9.77 ± 1.95 dB; uncoated: 1.95 ± 0.40 dB) and generated lower voltages (coated: 100 mV; uncoated: 650 mV) for a given stimulus (5 µA). The improved performance corresponded to lower energy consumptions and electrochemically safe stimulation above 5 µA (>0.38 mC/cm2), which enabled elicitation of field excitatory post synaptic potentials and population spikes. Spontaneous single unit activities were also modulated by varying stimulation intensities and monitored through the same electrodes. This work represents an example of stimulation and recording single unit activities from the same microelectrode, which provides a powerful tool for monitoring and manipulating neural circuits at the single neuron level.

Acute in vivo testing of a polymer cuff electrode with integrated microfluidic channels for stimulation, recording, and drug delivery on rat sciatic nerve.

BACKGROUND: Extraneural cuffs are among the least invasive peripheral nerve interfaces as they remain outside the nerve. However, compared with more invasive interfaces, these electrodes may suffer from lower selectivity and sensitivity since the targeted nerve fibers are more distanced from the electrodes. NEW METHOD: A lyse-and-attract cuff electrode (LACE) was enabled by microfabrication and developed to improve selectivity and sensitivity while maintaining a cuff format. Its engineering design was described in previous work. LACE is a hybrid cuff that integrates both microelectrodes and microfluidic channels. The ultimate goal is to increase fascicular selectivity and sensitivity by focal delivery via the microchannels of (1) lysing agent to remove connective tissue separating electrodes from nerve fibers, and (2) neurotrophic factors to promote axonal sprouting of the exposed nerve fibers into microfluidic channels where electrodes are embedded. Here, we focus on demonstrating in vivo function of microfluidics and microelectrodes in an acute preparation in which we evaluate the ability to focally remove connective tissue and record and stimulate with microchannel-embedded microelectrodes neural activity in rat sciatic nerves. COMPARISON WITH EXISTING METHODS: While extraneural interfaces prioritize nerve health and intraneural interfaces prioritize functionality, LACE represents a new extraneural approach which could potentially excel at both aims. RESULTS: Surgical implantation demonstrate preservation of LACE function following careful and minimal handling. In vivo electrical evaluation demonstrates the ability of microelectrodes placed within microfluidic channels to successfully stimulate and record compound action potentials from rat sciatic nerve. Furthermore, collagen-rich epineurium was focally removed following infusion of collagenase via microchannels and confirmed via microscopy. CONCLUSION: The feasibility of using a cuff having integrated microelectrodes and microfluidics to stimulate, record, and deliver drug to focally lyse away the epineurium layer was demonstrated in acute experiments on rat sciatic nerve.

A Multi-Channel Asynchronous Neurostimulator With Artifact Suppression for Neural Code-Based Stimulations.

A novel neurostimulator for generating neural code-based, precise, asynchronous electrical stimulation pulses is designed, fabricated, and characterized. Through multiplexing, this system can deliver constant current biphasic pulses, with arbitrary temporal patterns, and pulse parameters to 32 electrodes using one pulse generator. The design also features a stimulus artifact suppression (SAS) technique that can be integrated with commercial amplifiers. Using an array of CMOS switches, electrodes are disconnected from recording amplifiers during stimulation, while the input of the recording system is shorted to ground through another CMOS switch to suppress ringing in the recording system. The timing of the switches used to block and suppress the stimulus artifact are crucial and are determined by the electrochemical properties of the electrode. This system allows stimulation and recording from the same electrodes to monitor local field potentials with short latencies from the region of stimulation for achieving feedback control of neural stimulation. In this way, timing between each pulse is controlled by inputs from an external source and stimulus magnitude is controlled by feed-back from neural response from the stimulated tissue. The system was implemented with low-power and compact packaged microchips to constitute an effective, cost-efficient, and miniaturized neurostimulator. The device has been first evaluated in phantom preparations and then tested in hippocampi of behaving rats. Benchtop results demonstrate the capability of the stimulator to generate arbitrary spatio-temporal pattern of stimulation pulses dictated by random number generators (RNGs) to control magnitude and timing between each individual biphasic pulse. In vivo results show that evoked potentials elicited by the neurostimulator can be recorded ∼2 ms after the termination of stimulus pulses from the same electrodes where stimulation pulses are delivered, whereas commercial amplifiers without such an artifact suppression typically result in tens to hundreds of milliseconds recovery period. This neurostimulator design is desirable in a variety of neural interface applications, particularly hippocampal memory prosthesis aiming to restore cognitive functions by reinstating neural code transmissions in the brain.

A Closed-Loop Multi-Channel Asynchronous Neurostimulator to Mimic Neural Code for Cognitive Prosthesis.

We describe a novel hardware and embedded system design of a closed loop neurostimulator for generating precise neural code-like, multi-channel, asynchronous electrical stimulation pulses. Such stimulator will be used as the output unit of the cortical prosthesis that aims to restore cognitive functions by reinstating the neural signal transmission.