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

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.