Microbial Platform for Accessing Plant Alkaloids

DESCRIPTION (provided by applicant): In order to successfully use microelectrode arrays for stimulation in chronic implantation, the neural electrode must have longevity and efficacy. Efficacy of stimulation primarily means injecting enough charge to the targeted tissue to elicit action potentials. However, in doing so, the electrode itself must not (1) degrade, (2) generate harmful substances and (3) provoke significant immune response. Attaining the stated requirements remains a challenge as studies haveshown loss of discriminable single unit action potentials on the order of weeks, months, or in rare studies, years. Suitable electrode material or strategies that permit prolonged excitation of neurons for long period of time without injuring the tissue ordamaging the electrodes are yet to be developed and demonstrated. For the efficacy of the stimulating electrodes, large charge injection capacity (CIC) is desired. CIC depends on the electrode-tissue interface and is characteristic of electrode material used. Though, much of the microelectrode research during the past 30 years has been directed toward the evaluation of various types of materials with regard to individual stimulus charge density limits, till date, in the scientific literature, there is no single material which can avoi over-stimulation i.e. neural damage. In this application, we present a novel surface modification technique that addresses the longevity and efficacy of the microelectrodes in chronic experiments. The three distinct features of our proposed objectives are (1) novel surface modification technique that produces electrochemical characteristics which are by far superior to any material/technology reported in the literature till date. With the surface modified electrodes we were able to achieve electrode impedance of 188 at 1 kHz and CIC of 24 mC/cm2. The high CIC would lower the potential required for stimulation thereby reducing the chances of neural injury and dissolution of electrode material and toxic remnants. Even with the presence of glial sheath, it would not be necessary to go outside the water window thereby reducing the chances of tissue insult at the site of stimulation. (2) Biocompatible electrode-tissue interface. It has been postulated by researchers that by manipulating the surface structure of the electrode at micro scale one can reduce astrocyte adhesion around the microelectrode, including reducing the proliferation of glial cells, reduced macrophages and preferential neuron sparing at the site of implant. (3) Simple and inexpensive method of obtaining desired electrode characteristics as opposed to any current thin film deposition method. The objective of this research is to develop, validate, examine (in-vitro, in-vivo and histology) and commercialize the proposed surface modification technology for microelectrodes in chronic experiments. The specific aim of our proposed research is to demonstrate (1) manufacturability of the proposed surface modification for use in a microelectrode array; (2) superior electrochemical properties; (3) improved physiological efficacy; and (4) biocompatible electrode-tissue interface i.e. reduced glial proliferation and reduction in neuronal loss at the biotic-abiotic interface. It is envisioned that with the availability of proposed superior electrochemical characteristics in the neural microelectrode arrays there would be a paradigm shift in the neuroscience research and applications. The enabling innovation has clear clinical benefits in such applications as cortical stimulation and recording, deep brain stimulation, cardiac pacing and pain management and therefore has a significant commercial potential. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: In this application, we present a novel surface modification technology that addresses the efficacy and longevity of microelectrodes in chronic studies. The proposed technology is very simple and inexpensive method of obtaining superior electrochemical characteristics as opposed to currently employed thin film deposition techniques. The distinct features of our proposed objectives are (1) exceptionally low impedance (188) and high CIC (24 mC/cm2). The electrochemical characteristics achieved are by far superior among any other material reported in the literature till date. The high CIC would lower the potential required for stimulation thereby reducing the chances of neural injury and dissolution of electrode material and toxic remnants. (2) Biocompatible electrode-tissue interface. The surface modified electrode would lead to reduction of glial proliferation and preferential neuron sparing at the site of implant. The enabling innovation has clear clinical benefits in such applications as cortical stimulation and recording, deep brain stimulation, cardiac pacing and pain management and therefore has a significant commercial potential.