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

Interfacing peripheral nerve with macro-sieve electrodes following spinal cord injury

Macro-sieve electrodes were implanted in the sciatic nerve of five adult male Lewis rats following spinal cord injury to assess the ability of the macro-sieve electrode to interface regenerated peripheral nerve fibers post-spinal cord injury. Each spinal cord injury was performed via right lateral hemisection of the cord at the T9–10 site. Five months post-implantation, the ability of the macro-sieve electrode to interface the regenerated nerve was assessed by stimulating through the macro-sieve electrode and recording both electromyography signals and evoked muscle force from distal musculature. Electromyography measurements were recorded from the tibialis anterior and gastrocnemius muscles, while evoked muscle force measurements were recorded from the tibialis anterior, extensor digitorum longus, and gastrocnemius muscles. The macro-sieve electrode and regenerated sciatic nerve were then explanted for histological evaluation. Successful sciatic nerve regeneration across the macro-sieve electrode interface following spinal cord injury was seen in all five animals. Recorded electromyography signals and muscle force recordings obtained through macro-sieve electrode stimulation confirm the ability of the macro-sieve electrode to successfully recruit distal musculature in this injury model. Taken together, these results demonstrate the macro-sieve electrode as a viable interface for peripheral nerve stimulation in the context of spinal cord injury

An Energy-Efficient, Dynamic Voltage Scaling Neural Stimulator for a Proprioceptive Prosthesis

Accepted versio

Neuro-electronic technology in medicine and beyond

This dissertation looks at the technology and social issues involved with interfacing electronics directly to the human nervous system, in particular the methods for both reading and stimulating nerves. The development and use of cochlea implants is discussed, and is compared with recent developments in artificial vision. The final sections consider a future for non-medicinal applications of neuro-electronic technology. Social attitudes towards use for both medicinal and non-medicinal purposes are discussed, and the viability of use in the latter case assessed

Organic electrode coatings for next-generation neural interfaces

Traditional neuronal interfaces utilize metallic electrodes which in recent years have reached a plateau in terms of the ability to provide safe stimulation at high resolution or rather with high densities of microelectrodes with improved spatial selectivity. To achieve higher resolution it has become clear that reducing the size of electrodes is required to enable higher electrode counts from the implant device. The limitations of interfacing electrodes including low charge injection limits, mechanical mismatch and foreign body response can be addressed through the use of organic electrode coatings which typically provide a softer, more roughened surface to enable both improved charge transfer and lower mechanical mismatch with neural tissue. Coating electrodes with conductive polymers or carbon nanotubes offers a substantial increase in charge transfer area compared to conventional platinum electrodes. These organic conductors provide safe electrical stimulation of tissue while avoiding undesirable chemical reactions and cell damage. However, the mechanical properties of conductive polymers are not ideal, as they are quite brittle. Hydrogel polymers present a versatile coating option for electrodes as they can be chemically modified to provide a soft and conductive scaffold. However, the in vivo chronic inflammatory response of these conductive hydrogels remains unknown. A more recent approach proposes tissue engineering the electrode interface through the use of encapsulated neurons within hydrogel coatings. This approach may provide a method for activating tissue at the cellular scale, however, several technological challenges must be addressed to demonstrate feasibility of this innovative idea. The review focuses on the various organic coatings which have been investigated to improve neural interface electrodes

Master of Science

thesisSeveral neural interfaces have been designed in order to improve access to peripheral nerve fibers and more accurately monitor or evoke various functions. Currently, such devices are more successful in larger nerves, but are limited in potential applications involving smaller target nerves. For example, the restoration of micturition (urination) to spinal cord injured patients requires the ability to monitor the changes in bladder pressure, to gauge bladder fullness as well as detect hyper-reflexive contractions. The pudendal nerve has been shown to be an appropriate site for monitoring bladder status. However, its small diameter, particularly in animal models, and the need for multiple access points required the development and fabrication of a novel high density electrode array. The research presented here describes the validation of such a device in small diameter nerve applications, as well as its use in the pudendal nerve to provide information about bladder pressure, showing the potential expansion of neural interfaces to new applications in both research and clinical fields

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