Enhanced Neural Stimulation System using Localized Surface Plasmon Resonance of Gold Nanorods

Abstract

Modulating neural activity is essential to clinical treatment of neurological disorder and to the study of neural function. In particular, there has been growing interest in the development of a contact-free and high spatial selective infrared neural stimulation (INS) technique for use in clinics as well as research area. Despite a potential of INS for modulating neural activities, INS suffers from limited light confinement and tissue damage due to bulk heating. This dissertation provides fundamental information on the development of enhanced INS that could circumvent the limitations of conventional INS. The first part of this dissertation demonstrates for the first time that localized surface plasmon resonance of gold nanorods (GNRs) could induce neural depolarization with safe manner by lowering the stimulation threshold. To perform optical stimulation of neural tissue with GNRs, controllable fiber-coupled laser diode system, GNRs complex and neural cells are prepared. Pulsed near-infrared (NIR) light to efficiently absorbed to GNRs rather than bulk tissue and converted into localized heat which finally triggers neural activation. In the second part of this dissertation, surface-modified GNRs are used to bind to neuronal membrane to achieve washout resistance and to locally heat the neuronal membrane for which neural activation is responsible. INS using cell-targeted GNRs are employed in other types of cells, which is discussed in third part of this dissertation. Transient intracellular calcium waves are evoked in the astrocyte cells revealing GNRs-mediated INS stimulation can be applied in variety of cells. In the last part of this dissertation, the mechanism underlying GNRs-mediated INS is discussed. Illumination of NIR light to the GNRs at their resonant wavelength leads to local electromagnetic field enhancement and the generation localized heat. Local heat diffuses to the nearby plasma membrane which result transient temperature elevation. Transient temperature increase lead to capacitance change and/or opening of the temperature sensitive ion-channel (e.g. transient receptor potential vanilloid 1 (TRPV1) channel) which both trigger the neural depolarization. A neuron model is developed to theoretically and mathematically demonstrate on the mechanism underlying GNRs-mediated INS. These experimental and theoretical findings are expected to open up new possibilities for applications to non-invasive investigations of diverse excitable tissues and treatments of neurological disorders.