Electrochemical Modulation of Peripheral Nerves Using Ion-Selective Electrodes

Abstract

New methods of locally delivering chemicals to biological systems have emerged in recent years, but nearly all are limited by their reliance on finite capacities of therapeutic stock which require physical access for restoration or replacement. In this thesis, I examine the ion-selective membrane (ISM), a filter that discriminately transports single ions within mixed electrolytes, whose operation in ion delivery platforms does not suffer from the fundamental restriction of finite capacity. Specifically, I discuss the optimal design of the ISM and its operating conditions, as well as its implementation for peripheral neuro-modulation. Up to this point, limitations in available characterization methods, both theoretical and practical, have severely restricted its technical development and the exploration of in vivo applications. In this thesis, I (1) began by revisiting the operation of ISM systems from a first-principles perspective, constructing a highly detailed physicochemical transport model to describe intra-membrane processes, (2) developed a new experimental technique for direct, real-time monitoring of ion concentration polarization which allowed me to evaluate those processes under relevant conditions, (3) established a rapid-manufacturing process for fabricating nerve cuff electrodes compatible with ISM coating and tested it in vivo, and (4) built off this foundational work to fabricate a Ca²⁺-selective nerve cuff electrode suitable for electrochemical operations, implanted in vivo on the sciatic nerve of a rat. I discovered over-limiting phenomena that arise in ISM systems under electrical polarization, which have broad implications for all of its ion filtering applications. Finally, from my electrophysiological studies, I found evidence that Ca²⁺ depletion with the nerve cuff had a discriminatory effect on distinct fascicles within the rat sciatic nerve, potentially offering a new strategy for the selective activation of therapeutic targets.