Towards Clinical Translation of Penetrating Multisite Device for Cochlear Nucleus

 描述(申请人提供)：听神经严重受损的患者不能从人工耳蜗术中受益。该项目的目标是加速翻译 硅基，多点，穿透性微电极阵列到耳蜗核听觉假体。我们最近在CAT模型中的设备方面取得了重大技术进步，再加上高数量的电缆和馈通，将提供一个独特的机会来开发适合临床使用的多部位微电极阵列。这 该项目将展示将具有少量微刺激部位的多部位微电极阵列连接到植入式脉冲发生器(IPG)的可行性，为随后的临床试验做准备。临床使用的耳蜗核植入物的验证也将推动其他配置的硅衬底多点微电极阵列走向临床使用。这包括听神经和听觉中脑(下丘)，甚至初级听觉皮质。我们建议根据国际标准化组织的两个指南进行适当的测试：(1)目标1中的ISO 10933，用于验证电极阵列和相关电缆的生物兼容性；(2)目标2中的ISO 14708，用于将阵列和电缆连接到神经刺激器。在目标2中，我们将开发到IPG的接口，并根据国际标准化组织规定的可靠接口到神经刺激器的要求来确定该系统在体外的依从性。这些测试是优化我们的设备以获得FDA未来研究设备豁免的关键重要一步。该项目的成功成果将是新一代多部位穿透性硅微电极阵列的平移，这些微电极阵列将被植入人类耳蜗核，使人们能够前所未有地接触到耳蜗核的立位组织。最后，这些多部位硅设备可以针对其他神经疾病进行改造，包括脊髓和脑深部刺激。

 DESCRIPTION (provided by applicant): Patients with severely damaged auditory nerves cannot benefit from cochlear implants. The goal of this project is to accelerate the translation of silicon-based, multisite, penetrating microelectrode arrays to a cochlear nucleus auditory prosthesis. We have recently made significant technological advances with our devices in the cat model, which together with high-count cables and feedthroughs will provide a unique opportunity to develop arrays of multisite microelectrodes that are suitable for clinical use. This project will demonstrate the feasibility of interfacing a multisite microelectrode array with a lare number of microstimualting sites to an implantable pulse generator (IPG), in preparation for a subsequent clinical trial. Validation of the cochlear nucleus implant for clinical use will also advance other configurations of silicon- substrate multisite microelectrode arrays toward clinical use. These include the auditory nerve and the auditory midbrain (inferior colliculus), and perhaps even the primary auditory cortex. We are proposing to conduct appropriate tests under two ISO (International Organization for Standardization) guidelines: (1) ISO 10933 in Aim 1 to validate the biocompatibility of the electrode array and associated cables, and (2) ISO 14708 in Aim 2 for interfacing the array and cable to a neurostimulator. In Aim 2, we will develop the interface to an IPG, and determine the compliance of the system in-vitro per ISO 14708 which specifies requirements for reliable interfaces to neurostimulators. These tests are a critical majo step to optimizing our devices for a future investigational device exemption by the FDA. The successful outcome of the project will be the translation of a new generation of multisite, penetrating silicon microelectrode arrays that will be implanted in a human cochlear nucleus, allowing for unprecedented access to the tonotopic organization of the nucleus. Finally, these multisite silicon devices can be modified for other neurological conditions including spinal cord and deep brain stimulation.