Abstract
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.
Highlights
Peripheral nerves are anisotropic and heterogeneous neural tissues
Using our nerve-on-a-chip platform, we evaluated the efficiency of this thin-film polymer to block neural conduction in peripheral nerves
The nerveon-a-chip platform consists of two aligned microchannel electrodes prepared on a glass carrier through which a nerve rootlet is threaded (Fig. 1a)
Summary
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. In vitro extracellular recording interfaces are manufactured using microfabrication to ensure repeatability and enable statistically relevant sample sizes[14,15,16,17,18,19] They consist of planar microelectrode arrays (MEAs)[14,15,16] or microchannel electrodes[26,28,29,30,31] that combine axonal guidance with high signal-to-noise ratio (SNR) recordings. Seeding neurons in 3D scaffolds can lead to the formation of aligned fibers mimicking nerve structure[17,19] In this configuration, neural activity, usually compound action potentials (CAPs), is visualized using Ca2+ imaging[18,19] or acquired with electrodes positioned by hand with micromanipulators[17]. The resulting SNR typically allow the detection of multiple SFPA composing CAP21 and conduction velocity computation but these experimental techniques are cumbersome and time consuming
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