Revolutionizing Utah Array using Nanotechnology to Enhance Efficacy and Longevity

描述（由申请人提供）：为了在慢性植入中成功使用微电极阵列进行刺激，神经电极必须具有寿命和有效性。刺激的有效性主要是指向目标组织注入足够的电荷以引起动作电位。然而，在这样做时，电极本身不能(1)降解，(2)产生有害物质，(3)引起显著的免疫反应。达到所述的要求仍然是一个挑战，因为研究表明，在数周、数月或罕见的研究中，单个单位动作电位的可辨别性损失为数年。合适的电极材料或策略，允许长时间延长神经元的兴奋，而不伤害组织或损害电极尚未开发和证明。为了保证刺激电极的有效性，需要较大的电荷注入容量。CIC取决于电极-组织界面，是所使用电极材料的特征。尽管在过去的30年里，许多微电极研究都是针对不同类型材料的单独刺激电荷密度限制进行评估，但到目前为止，在科学文献中，还没有一种材料可以避免过度刺激，即神经损伤。在这个应用中，我们提出了一种新的表面修饰技术，解决了微电极在慢性实验中的寿命和功效。我们提出的目标有三个明显的特点：(1)新型表面改性技术，其产生的电化学特性远远优于迄今为止文献中报道的任何材料/技术。使用表面修饰电极，我们能够在1 kHz时实现188的电极阻抗和24 mC/cm2的CIC。高CIC会降低刺激所需的电位，从而减少神经损伤、电极材料溶解和有毒残留物的机会。即使有神经胶质鞘的存在，也没有必要走出水窗，从而减少了刺激部位组织“损伤”的机会。(2)生物相容性电极-组织界面。它已经

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 have shown 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 or damaging 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.