Revolutionizing Utah Array using Nanotechnology to Enhance Efficacy and Longevity

描述（由申请人提供）：为了在长期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。刺激的功效主要是指向靶组织注入足够的电荷以引发动作电位。然而，在这样做时，电极本身必须（1）不降解，（2）不产生有害物质，（3）不引起显著的免疫反应。达到规定的要求仍然是一个挑战，因为研究表明，可辨别的单个单位动作电位的损失约为数周，数月，或在罕见的研究中，数年。允许神经元长时间的延长激发而不损伤组织或损坏电极的合适的电极材料或策略还有待开发和证明。为了刺激电极的功效，需要大的电荷注入容量（CIC）。CIC取决于电极-组织界面，并且是所用电极材料的特征。尽管在过去的30年中，许多微电极研究都是针对各种类型材料的个体刺激电荷密度限值进行评估，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。在此应用中，我们提出了一种新的表面改性技术，解决了在慢性实验中的微电极的寿命和功效。我们提出的目标的三个不同的特点是（1）新的表面改性技术，产生的电化学特性，这是迄今为止在文献中报道的任何材料/技术优于上级。使用表面改性的电极，我们能够在1 kHz下实现188的电极阻抗和24 mC/cm 2的CIC。高CIC将降低刺激所需的电位，从而减少神经损伤和电极材料和有毒残留物溶解的机会。即使存在神经胶质鞘，也不需要到水窗之外，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。它有 研究人员假设，通过在微观尺度上操纵电极的表面结构，可以减少微电极周围的星形胶质细胞粘附，包括减少神经胶质细胞的增殖，减少巨噬细胞和优先保留植入部位的神经元。(3)获得所需电极特性的简单且廉价的方法，与任何当前的薄膜沉积方法相反。本研究的目的是开发，验证，检查（在体外，在体内和组织学）和商业化提出的表面改性技术的微电极在慢性实验。我们提出的研究的具体目的是证明（1）用于微电极阵列的所提出的表面改性的可制造性;（2）上级电化学性质;（3）改善的生理功效;和（4）生物相容性电极-组织界面，即减少生物-非生物界面处的神经胶质增殖和神经元损失。可以设想 随着所提出的神经微电极阵列中的上级电化学特性的可用性，在神经科学研究和应用中将有范式转变。这一创新在皮层刺激和记录、脑深部刺激、心脏起搏和疼痛管理等应用中具有明显的临床效益，因此具有巨大的商业潜力。

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.