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Significance Bioelectronic medicine relies on electrical stimulation for most applications in the peripheral nervous system. It faces persistent challenges in selectively activating bundled nerve fibers. Here, we investigated ion-concentration modulation with ion-selective membranes and whether this modality may enhance the functional selectivity of peripheral nerve stimulation. We designed a multimodal stimulator that could control Ca 2+ concentrations within a focused volume. Acutely implanting it on the sciatic nerve of a rat, we demonstrated that Ca 2+ depletion could increase the sensitivity of the nerve to electrical stimulation in vivo. We provided evidence that it selectively influenced individual fascicles of the nerve, allowing selective activation by electrical current. Improved functional selectivity may improve outcomes for important therapeutic modalities.

© Copyright © 2021 Flavin, Paul, Lim, Abdulhamed, Lissandrello, Ajemian, Lin and Han. For many peripheral neuro-modulation applications, the cuff electrode has become a preferred technology for delivering electrical current into targeted volumes of tissue. While basic cuffs with low spatial selectivity, having longitudinally arranged contacts, can be produced from relatively straightforward processes, the fabrication of more complex electrode configurations typically requires iterative design and clean-room fabrication with skilled technicians. Although facile methods for fabricating cuff electrodes exist, their inconsistent products have limited their adoption for rapid manufacturing. In this article, we report a fast, low-cost fabrication process for patterning of electrode contacts in an implantable peripheral nerve cuff. Using a laser cutter as we have prescribed, the designer can render precise contact geometries that are consistent between batches. This method is enabled by the use of silicone/carbon black (CB) composite electrodes, which integrate with the patterned surface of its substrate—tubular silicone insulation. The size and features of its products can be adapted to fit a wide range of nerve diameters and applications. In this study, we specifically documented the manufacturing and evaluation of circumpolar cuffs with radial arrays of three contacts for acute implantation on the rat sciatic nerve. As part of this method, we also detail protocols for verification—electrochemical characterization—and validation—electrophysiological evaluation—of implantable cuff electrodes. Applied to our circumpolar cuff electrode, we report favorable electrical characteristics. In addition, we report that it reproduces expected electrophysiological behaviors described in prior literature. No specialized equipment or fabrication experience was required in our production, and we encountered negligible costs relative to commercially available solutions. Since, as we demo

Thesis: S.M., Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2017., Cataloged from PDF version of thesis., Includes bibliographical references (pages 96-107)., Developing precise and effective means of modulating the human nervous system is an aspiration of the fields of neuroscience and neurotechnology. Our research group is approaching this challenge by constructing a prosthetic device that can perform focal chemical modulation of selected ions in the interstitial space of neural tissue. Its principle of operation is based on ion-concentration polarization (ICP) generated by polarization of electrodes covered with ion-selective membranes (ISMs). In order to optimize this modality in terms of clinical effect and safety, we require a more fundamental understanding of the physical processes that give rise to ICP of the selected ion. Broadly, the goal of this thesis is to: (1) present and validate mathematical models for the description and prediction of polarized ISM systems, and (2) characterize transport phenomena that are uniquely captured using these models. To start, we used a semi-empirical equilibrium model to compare the integral transference of several common membrane formulations in a physiological electrolyte. Then, we introduced a 1-D model of Nernst-Planck-Poisson (NPP) with kinetic ion-ionophore reaction that could be solved using the finite element method (FEM). Our analysis of this model focused on four key features: the interfacial transition regions at the contact planes between the aqueous and membrane phases, the intra-membrane reaction boundary layer (RBL), ICP arising in the aqueous phase, and ICP arising in the membrane phase. Lastly, we presented several multidimensional models of ion transport in the aqueous phase. This was used to examine processes that limit the lengthscale of aqueous ICP, such as forced convection and non-planar diffusion. Once fully realized, an ISM-based device could be used to manipulate extracellular ions in neural tissue to produce therapeutic effects. In the peripheral nervous system, this operation could potentially be used to lower the stimulus energy required to elicit m, by Matthew T. Flavin., S.M.