Peripheral nerve interface | EPFL Graph Search

A peripheral nerve interface is the bridge between the peripheral nervous system and a computer interface which serves as a bi‐directional information transducer recording and sending signals between the human body and a machine processor. Interfaces to the nervous system usually take the form of electrodes for stimulation and recording, though chemical stimulation and sensing are possible. Research in this area is focused on developing peripheral nerve interfaces for the restoration of function following disease or injury to minimize associated losses. Peripheral nerve interfaces also enable electrical stimulation and recording of the peripheral nervous system to study the form and function of the peripheral nervous system. For example, recent animal studies have demonstrated high accuracy in tracking physiological meaningful measures, like joint angle. Many researchers also focus in the area of neuroprosthesis, linking the human nervous system to bionics in order to mimic natural sen

Microchannel-based technologies for nerve interfacing

Sandra Gribi

Biomedical technologies in neuroprosthetics are made to restore or replace functions from the nervous system, as well as alleviate pathological conditions. Peripheral nerve interfaces use neuromodulatory techniques to inhibit pain or depression, prevent epileptic strokes, or connect amputee patients to an artificial limb. Man-made neural interfaces are, however, far from matching the complexity of the nerves, leaving patients with low-resolution interfaces. To engineer peripheral neuroprostheses, scientists and clinicians investigate neuromodulatory strategies using in vitro neuron culture, explanted nerves, in vivo and in silico experiments using simulation, patch-clamp or extracellular recordings, and neural classification/learning algorithms. However, the available models can not replicate the complex morphology of the nerves, thereby limiting the resolution and selective recording of axonal activity. While nerve fibers respond differently to a neuromodulation paradigm depending on their size and degree of myelination, studies often fail to deal with the whole variety of axon characteristics present in the body. Therefore, in this thesis, I developed a nerve-on-a-chip platform that uniquely integrates the following features: stimulation and recording of single myelinated nerve fibers, controlled single-fiber action potential propagation with respect to electrodes position, and signal amp- lification leading to recorded signals in the 20 - 300 ÎŒV range. Nerve fibers diameter can further be deduced from propagation velocity to include the effect of nerve heterogeneity and function in the implementation of neuromodulatory strategies. I first present a versatile nerve-on-a-chip platform, aiming at offering robust standards to eval- uate neuromodulation strategies and selectivity of neuroprostheses. In order to conduct rapid, high resolution and systematic recording of peripheral nerve activity, microchannel electrodes are used to achieve stimulation and recording of single myelinated nerve fibers ex vivo. I demonstrate the platform versatility through three case studies: (i) Optimising the design of microchannel regenerative implants to detect the velocity and direction of neural signal propagation. I implemented and experimentally validated a mathematical model predicting how the reliability of velocity calculation depends on the implant geometry and neural signal waveform. (ii) Demonstrating how heat-induced neuroinhibition upon P3HT:PCBM (blend polymer) illumination selectively and reversibly silenced thinner fibers, but did not affect larger fibers. (iii) To improve artificial sensory feedback, new patterns of electrical stimulation were investigated in silico. In this study, the platform is used to show that high frequency modulated stimulation elicits more biomimetic nerve activity. This novel nerve-on-a-chip platform enables rapid prototyping using standard microfabrication methods, simultaneous probing of myelinated fibers of various diameters, data library collection for computational modelling and multi-factorial analysis. Subsequently, I have applied the results from (i) to develop a microfabrication process of a microchannel regenerative implant, further exploiting the use of microchannel electrodes to improve neural interfaces. The nerve-on-a-chip platform is an efficient tool for designing and evaluating new implantable neuroprosthetic devices, using time and cost-efficient techniques. We foresee that this simple and broad

EPFL2019

A microfabricated nerve-on-a-chip platform for rapid assessment of neural conduction in explanted peripheral nerve fibers

Sophie du Bois de Dunilac, Diego Ghezzi, Sandra Gribi, Stéphanie Lacour

Peripheral nerves are anisotropic and heterogeneous neural tissues. Their complex physiology restricts realistic in vitro models, and high resolution and selective probing of axonal activity. Here, we present a nerve-on-a-chip platform that enables rapid extracellular recording and axonal tracking of action potentials collected from tens of myelinated fibers. The platform consists of microfabricated stimulation and recording microchannel electrode arrays. First, we identify conduction velocities of action potentials traveling through the microchannel and propose a robust data-sorting algorithm using velocity selective recording. We optimize channel geometry and electrode spacing to enhance the algorithm reliability. Second, we demonstrate selective heat-induced neuro-inhibition of peripheral nerve activity upon local illumination of a conjugated polymer (P3HT) blended with a fullerene derivative (PCBM) coated on the floor of the microchannel. We demonstrate the nerve-on-a-chip platform is a versatile tool to optimize the design of implantable peripheral nerve interfaces and test selective neuromodulation techniques ex vivo.

2018

A Nerve-on-a-Chip Platform to Facilitate the Design of Peripheral Nerve Interfaces

Diego Ghezzi, Sandra Gribi, Stéphanie Lacour

Peripheral nerves are often interfaced with cuff-based and microchannel-based nerve implants so that neural activity may be stimulated, inhibited and/or recorded. In vivo evaluation of these interfaces is mandatory but often time-consuming, and focused on single implant design. In vitro studies can provide further design freedom to the bioelectronic engineer, but neuron cultures do not replicate accurately in vivo, in-nerve conditions. In order to overcome these restrictions, we developed a microchannel electrode platform for stimulating and recording from explanted nerve roots in a dish. The fabrication method of the platform enables to easily vary electrodes’ design parameters and materials, while the use of explanted nerve roots leads to immediate recording from bundles of axons and from a large number of samples. Furthermore the microchannel electrode design enables high signal-to-noise ratio recording of individual single-fiber action potential (SFAP). The nerve-on-a-chip platform is prepared as follows: 8 platinum thin film electrodes are patterned on glass (pitch: 1mm) and encapsulated in a PDMS microchannel (100 x 100 µm2 cross-section, 10 mm length) thereby defining 100 x 300 µm2 electrode contacts. The chip is immersed in Hanks’ balanced salt solution kept at 37°C. Nerve roots are explanted from adult rats, and dissected to obtain strands of diameter in the 100 µm to 500 µm range. The microelectrodes are wired to standard electrophysiology hardware for stimulation and recordings. The platform allows for the tracking of SFAP propagation with varying amplitude (15 to 140 µV) as well as back propagating SFAP. By slowly increasing the current, we obtained SFAPs, multi-unit and compound action potentials, leading to a diversity of signals close to in vivo nerve activity. We successfully implemented the nerve-on-a-chip platform to detect the velocity and direction of propagation of SFAPs. We developed a velocity calculation algorithm and evaluated its performance using recordings of 22 different SFAPs. The algorithm successfully detected all the SFAPs as well as their direction of propagation. Velocities were obtained in the 0 to 80 m/s range and correlated with SFAP amplitudes. Next we used the platform to evaluate the inhibition of neural activity using a conjugated polymer (P3HT:PCBM). The polymer was coated inside the microchannel and locally heated using a narrow light beam. Upon green light illumination, we observed clear silencing of nerve compound action potentials. The nerve-on-a-chip platform provides a straightforward interface with nerve strands, and offers an exciting avenue for improved nerve neuroprosthesis.

2017