Revolutionizing Utah Array using Nanotechnology to Enhance Efficacy and Longevity

利用纳米技术革新犹他阵列以提高功效和寿命

• 批准号: 8523542
• 负责人: Rajmohan Bhandari
• 金额: $ 35万
• 依托单位: BLACKROCK MICROSYSTEMS
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8523542
• 关键词: Action Potentials; Address; Adhesions; Astrocytes; Biocompatible; Brain; Cardiac; Characteristics; Charge; Chronic; Clinical; Data; Deep Brain Stimulation; Deposition; Devices; Documentation; Electrodes; Evaluation; Family Felidae; Felis catus; Film; Forensic Medicine; Frequencies; Glial Cell Proliferation; Histology; Immune response; Implant; In Vitro; Individual; Injection of therapeutic agent; Lead; Literature; Longevity; Methods; Microelectrodes; Modification; Motor Cortex; Nanotechnology; Neurons; Neurosciences Research; Pain management; Performance; Physiologic pulse; Physiological; Platinum; Property; Protocols documentation; Rattus; Reporting; Research; Research Personnel; Signal Transduction; Site; Stimulus; Structure; Surface; Techniques; Technology; Technology Transfer; Testing; Time; Tissues; Utah; Water; Width; biomaterial compatibility; cohort; comparative; density; electric impedance; implantation; improved; in vivo; injured; innovation; iridium oxide; macrophage; nerve injury; neuron loss; novel; public health relevance; relating to nervous system; research study

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.

描述(申请人提供)：为了成功地在慢性植入中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。刺激的效果主要是指向目标组织注入足够的电荷以引发动作电位。然而，在这样做的过程中，电极本身不能(1)降解，(2)产生有害物质，(3)引发显著的免疫反应。达到规定的要求仍然是一个挑战，因为研究表明，可区分的单单位动作电位损失在几周、几个月的数量级，或者在罕见的研究中，几年。适当的电极材料或策略允许长时间地对神经元进行长时间的兴奋，而不会损伤组织或破坏电极，目前还没有开发和证明。对于刺激电极的有效性，需要大的电荷注入容量(CIC)。CIC依赖于电极-组织界面，是所用电极材料的特征。尽管在过去的30年里，许多微电极的研究都是针对各种材料关于个体刺激电荷密度极限的评估，但到目前为止，在科学文献中还没有一种单一的材料可以避免过度刺激，即神经损伤。在这一应用中，我们提出了一种新的表面修饰技术，以解决慢性实验中微电极的寿命和有效性问题。我们提出的目标的三个明显特征是：(1)新颖的表面修饰技术，其产生的电化学特性远远优于迄今文献中报道的任何材料/技术。利用表面修饰电极，我们在1 kHz下获得了188的电极阻抗和24 mC/cm2的CIC。较高的CIC将降低刺激所需的电位，从而减少神经损伤以及电极材料和有毒残留物溶解的机会。即使有神经胶质鞘的存在，也不需要走出水窗，从而减少了刺激部位组织受到伤害的机会。(2)生物相容性电极-组织界面。它有 研究人员推测，通过在微尺度上操纵电极的表面结构，可以减少星形胶质细胞在微电极周围的黏附，包括减少胶质细胞的增殖，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，而不是任何当前的薄膜沉积方法。本研究的目的是开发、验证、检验(体外、体内和组织学)微电极表面修饰技术，并将其商业化。我们提出的研究的具体目的是证明(1)用于微电极阵列的表面修饰的可制造性；(2)优异的电化学性质；(3)改善生理功效；(4)生物相容的电极-组织界面，即减少胶质细胞的增殖和减少生物-非生物界面上的神经元丢失。据设想， 随着所提出的神经微电极阵列具有优异的电化学特性，神经科学的研究和应用将发生范式转变。这项使能创新在皮质刺激和记录、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好处，因此具有巨大的商业潜力。