Printable microscale interfaces for long-term peripheral nerve mapping and precision control

The nascent field of bioelectronic medicine seeks to decode and modulate peripheral nervous system signals to obtain therapeutic control of targeted end organs and effectors. Current approaches rely heavily on electrode-based devices, but size scalability, material and microfabrication challenges, limited surgical accessibility, and the biomechanically dynamic implantation environment are significant impediments to developing and deploying advanced peripheral interfacing technologies. Here, we present a microscale implantable device – the nanoclip – for chronic interfacing with fine peripheral nerves in small animal models that begins to meet these constraints. We demonstrate the capability to make stable, high-resolution recordings of behaviorally-linked nerve activity over multi-week timescales. In addition, we show that multi-channel, current-steering-based stimulation can achieve a high degree of functionally-relevant modulatory specificity within the small scale of the device. These results highlight the potential of new microscale design and fabrication techniques for the realization of viable implantable devices for long-term peripheral interfacing.https://www.biorxiv.org/node/801468.fullFirst author draf

3D Neuro-electronic interface devices for neuromuscular control: Design studies and realisation steps

In order to design the shape and dimensions of new 3D multi-microelectrode information transducers properly, i. e. adapted to the scale of information delivery to and from peripheral nerve fibres, a number of studies were, and still are, being performed on modelling and simulation of electrical volume conduction inside and outside nerves, on animal experiments on stimulation and recording with single wires and linear arrays, and on new technologies for 3D micro-fabrication. This paper presents a selection of the results of these `Neurotechnology¿ studies at the University of Twente. The experimental and simulation results apply primarily to the peripheral motor nerves of the rat, but are also of interest for neural interfacing with myelinated nerves in man, as fascicles in man are about the same size as in the rat

Endoneural selective stimulating using wire-microelectrode arrays

In acute experiments eight 5- to 24-wire-microelectrode arrays were inserted into the common peroneal nerve of the rat, to investigate whether the electrodes could selectively stimulate motor units of the extensor digitorum longus (EDL) muscle. Twitch-force-recruitment curves were measured from the EDL for each array electrode. The curves were plotted on a double-logarithmic scale and parameterized by the low-force slope (which represents the power p in the power-law relationship of force F versus stimulus current I, or F~Ip) and the threshold current. The slopes and threshold currents measured with array electrodes did not differ significantly from those obtained with randomly inserted single wire-microelectrodes. This indicates that, although involving a more invasive insertion procedure, electrode arrays provide neural contacts with low-force recruitment properties similar to those of single wires. Array results revealed partial blocking of neural conduction, similar to that reported with microneurographic insertion with single needles. The efficiency of the array was defined as the fraction of array electrodes selectively contacting a motor unit and evoking the corresponding threshold force. Efficiency thus expresses the practical value of the used electrode array in terms of the total number of distinct threshold forces that can be stimulated by selecting the appropriate electrodes. The eight arrays were capable of evoking threshold forces selectively with an average efficiency of 0.81 (or 81%

Microwire regenerative peripheral nerve interfaces with wireless recording and stimulation capabilities

A scalable microwire peripheral nerve interface was developed, which interacted with regenerated peripheral nerves in microchannel scaffolds. Neural interface technologies are envisioned to facilitate direct connections between the nervous system and external technologies such as limb prosthetics or data acquisition systems for further processing. Presented here is an animal study using a handcrafted microwire regenerative peripheral nerve interface, a novel neural interface device for communicating with peripheral nerves. The neural interface studies using animal models are crucial in the evaluation of efficacy and safety of implantable medical devices before their use in clinical studies.16-electrode microwire microchannel scaffolds were developed for both peripheral nerve regeneration and peripheral nerve interfacing. The microchannels were used for nerve regeneration pathways as a scaffolding material and the embedded microwires were used as a recording electrode to capture neural signals from the regenerated peripheral nerves. Wireless stimulation and recording capabilities were also incorporated to the developed peripheral nerve interface which gave the freedom of the complex experimental setting of wired data acquisition systems and minimized the potential infection of the animals from the wire connections

Biocompatible microchannel scaffold with microwires for recording regenerative peripheral nerve neural spikes

A new process for the fabrication of a microchannel scaffold with microwires for peripheral nerve applications is presented. This microchannel scaffold implemented between the ends of nerves, the axons of which regenerate through microchannel in scaffold and fixed microelectrodes. This device is entirely handcrafted using commercially available materials such as microwires, PDMS film, liquid PDMS, dental cement, and epoxy glue. This device was implemented in the a Lewis rat sciatic nerve to better analyze the electrical signals of regenerated axons. 64-electrode microchannel scaffolds were developed for both peripheral nerve interfacing and peripheral nerve regeneration. The microwires were used for recording electrode to capture neural signal from the regenerated peripheral nerves. To further differentiate the methodology, the new addition of a ribbon cable will facilitate the transmission of the electrical signals. A total of eight devices have been developed, the nerve regeneration were examined four weeks after device implantation

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

Bioelectronic medicines: a research roadmap

Realizing the vision of a new class of medicines based on modulating the electrical signalling patterns of the peripheral nervous system needs a firm research foundation. Here, an interdisciplinary community puts forward a research roadmap for the next 5 years

Topographic guidance scaffolds for peripheral nerve interfacing

In response to high and rising amputation rates, significant advances have been made in the field of prosthetic limb design. Unfortunately, there exists a lag in the neural interfacing technology required to provide an adequate link between the nervous system and this emerging generation of advanced prosthetic devices. Novel approaches to peripheral nerve interfacing are required to establish the stable, high channel count connections necessary to provide natural, thought driven control of an external prosthesis. Here, a tissue engineering-based approach has been used to create a device capable of interfacing with a regenerated portion of amputated nerve. As part of this work, a nerve guidance channel design, in which small amounts of interior scaffolding material could be precisely positioned, was evaluated. Guidance channels containing a single thin-film sheet of aligned scaffolding were shown to support robust functional nerve regeneration across extended injury gaps by minimally supplementing natural repair mechanisms. Significantly, these "thin-film enhanced nerve guidance channels" also provided the capability to guide the course of axons regenerating from a cut nerve. This capability to control axonal growth was next leveraged to create "regenerative scaffold electrodes (RSEs)" able to interface with axons regenerating from an amputated nerve. In the RSE design, low-profile arrays of interfacing electrodes were embedded within layers of aligned scaffolding material, such that regenerating axons were topographically guided by the scaffolding through the device and directly across the embedded electrodes. Chronically implanted RSEs were successfully used to record evoked neural activity from amputated nerves in an animal model. These results demonstrate that the use of topographic cues within a nerve guidance channel might offer the potential to influence the course of nerve regeneration to the advantage of a peripheral nerve interface suitable for limb amputees.PhDCommittee Chair: Ravi Bellamkonda; Committee Member: Arthur English; Committee Member: Pamela Bhatti; Committee Member: Robert Butera; Committee Member: Robert Le

Tutorial: A guide to techniques for analysing recordings from the peripheral nervous system

The nervous system, through a combination of conscious and automatic processes, enables the regulation of the body and its interactions with the environment. The peripheral nervous system is an excellent target for technologies that seek to modulate, restore or enhance these abilities as it carries sensory and motor information that most directly relates to a target organ or function. However, many applications require a combination of both an effective peripheral nerve interface and effective signal processing techniques to provide selective and stable recordings. While there are many reviews on the design of peripheral nerve interfaces, reviews of data analysis techniques and translational considerations are limited. Thus, this tutorial aims to support new and existing researchers in the understanding of the general guiding principles, and introduces a taxonomy for electrode configurations, techniques and translational models to consider