EAGER: A novel parallel extracellular and intracellular nanoelectrode and nanoelectrode probe array for high throughput electrophysiological recording.

传统的神经接口由微电极阵列(MEA)组成，微电极阵列与神经元密切接触以记录细胞外电位或刺激电活动。然而，由于微电极尺寸相对较大，这些MEA不能提取细胞内信号，这在恢复脊髓损伤或中风患者肢体控制的功能丧失方面特别有意义。MEAS电生理记录仍然面临着两大挑战：固有的数据噪声和有限的空间分辨率。这些问题尤其限制了运动参数的准确性和可靠性，因为长时间的尖峰记录不可靠。本研究的目的是制备和表征可独立寻址的纳米电极阵列(NEAs)和纳米电极探针阵列(NEPA)，用于高通量记录神经活动的细胞外和细胞内电生理测量。目的：通过以下具体目标实现这一目标：a)开发金纳米电极阵列平台，用于同时表征多个神经元的神经活动；b)开发直接方法，利用金属催化的化学气相沉积在256-金纳米针尖上生长碳纳米管(CNTs)；以及c)验证高通量检测神经活动的有效性。智力优势：提出的研究具有创新性和变革性，因为将首次开发利用细间距NEA和NEPA技术同时表征细胞外和细胞内的大量神经元，同时保持高空间分辨率、高信噪比和良好的神经界面选择性。由于可以潜在连接的神经元数量非常多，因此产生的NEA和NEPA系统将为并行表征神经元的细胞外和细胞内提供开创性的能力。广泛的影响：拟议的NEA和NEPA系统代表了电生理记录技术的前沿挑战。这种高通量的方法将通过同时研究多个神经元，同时控制其他刺激条件，使脊髓损伤或中风后神经元之间复杂的连接得以重建，从而促进电生理特征的研究。拟议研究的结果将通过为K-12和即将入学的大学转校生发展暑期研究经验，以及为本科生发展研究经验，纳入教育推广活动。

Conventional neural interfaces consist of microelectrode arrays (MEAs) that are in close contactwith neurons to record extracellular potential or stimulate electrical activity. However,due to the relative large microelectrode size, these MEAs are not capable of extracting intracellular signals, which is of particular interest in restoring functional loss of limb control of individuals with spinal cord injury or stroke. MEAs electrophysiological recordings still faces two major challenges, the inherent noisy data and the limited spatial resolution. These problems especially limit the accuracy and reliability of the movement parameter due to the unreliable spike recording for long durations. The objective of this research is the fabrication and characterization of independently addressable nanoelectrode arrays (NEAs) and nanoelectrode probe arrays (NEPAs) for high-throughput recording of extracellular and intracellular electrophysiological measurements of neural activity. Objective: This objective will be achieved through the following specific aims: a) To develop gold nanoelectrode array platforms for simultaneous characterization of neural activity in multiple neurons, b) to develop direct methods for growing carbon nanotubes (CNTs) on the 256-gold nanotips using metal-catalyzed chemical vapor deposition, and c) to validate high throughput detection of neural activities.Intellectual Merit: The proposed research is innovative and transformative because for the first time, simultaneous extracellular and intracellular characterization using fine pitch NEA and NEPA technology will be developed to probe large numbers of neurons, while maintaining high spatial resolution, high signal-to-noise ratio, and excellent selectivity of neural interfaces. Because of the very large number of neurons that can be potentially interfaced, the resulting NEA and NEPA system will provide ground-breaking capabilities for parallel extracellular and intracellular characterization of neurons.Broader Impacts: The proposed NEA and NEPA system represents the frontier challenge for electrophysiological recording technology. This high throughput approach will advance electrophysiological characterization by enabling multiple neurons to be studied simultaneously while controlling other stimulation conditions to enable the reestablishment of the intricate connections between neurons after spinal injury or stroke. Results of the proposed research will be integrated into educational outreach activities by developing summer research experiences for K-12 and incoming university transfer students and by developing research experience for undergraduates.