Soft Silicone Electrode Nets: implantable technology for visceral organ neural interfacing and functional evaluation

摘要 内脏器官对研究功能生理学和神经控制提出了独特的挑战。内脏器官 通常被神经丛包围，所述神经丛沿着器官表面提供分布的神经支配， 自主神经节可以局部调节功能。鉴于这种复杂性，创建内脏功能图 器官神经支配是一个挑战另一个挑战是测量器官状态本身。这明显 由于这些器官中的许多是柔软的、有弹性的并且经历大的体积变化的事实而加剧。 在本提案中，我们将开发与这些独特挑战兼容的软硅胶电极网， 可以包裹内脏器官，并将高分辨率电极部署到器官表面的任意位置。 这种方法基于3D打印的硅胶电极技术。这些电极网将被扩大 利用应变仪传感器和电阻抗断层扫描电极来监测生理器官状态。 最终，这类新的装置将1）本质上是柔软和弹性的，以允许与内脏的顺应性。 经历大体积变化的器官，2）集成基于应变仪的器官状态传感器， 电阻抗断层成像，3）防止通常与其它薄膜相关的分层问题 电极制造过程，以及4）允许快速定制，以成本有效地过渡到任何器官 动物或人类的系统。这项技术是基于在生物医学领域有使用历史的材料。 植入物，因此可能适用于进行神经映射和电生理学研究， 人体内器官 由于接口具有挑战性，我们将使用膀胱和尿道作为模型来评价器械性能 要求（例如，大体积变化）和潜在临床相关性。膀胱过度活动症 尿失禁影响着全世界数百万人，每年与超过600亿美元的成本相关， 美国，并导致生活质量显着下降。将在急性猫中测试电极网 我们将确定电极-组织机械稳定性，评估嵌入式传感器 性能，并开发膀胱和尿道表面的功能神经地图。我们还将验证 在一系列慢性动物实验中，器械性能将被监测， 植入后4个月内。这种使能技术和相关制造的一个重要特征是 这一过程的关键是，这些设备将能够快速、经济地重新设计，以研究其他内脏器官。 器官系统，包括胃、肠和结肠，在一系列动物模型以及人类中。

Abstract Visceral organs present unique challenges to studying functional physiology and neural control. Visceral organs are often surrounded by a nerve plexus that provides distributed innervation along the organ surface and contain autonomic ganglia that can modulate function locally. Given this complexity, creating functional maps of visceral organ innervation is challenging. Another challenge is measuring organ state itself. This is significantly exacerbated by the fact that many of these organs are soft, elastic, and undergo large volume changes. In this proposal, we will develop soft silicone electrode nets compatible with these unique challenges and that can envelop visceral organs and deploy high-resolution electrodes to arbitrary positions on the organ surface. This approach is based on a 3D printed silicone electrode technology. These electrode nets will be augmented with strain gauge sensors and electrical impedance tomography electrodes to monitor physiological organ state. Ultimately, this new class of devices will 1) be intrinsically soft and elastic to allow conformation with visceral organs that undergo large volume changes, 2) integrate organ state sensors based on strain gauges and electrical impedance tomography, 3) prevent delamination issues typically associated with other thin film electrode manufacturing processes, and 4) allow rapid customization to cost-effectively transition to any organ system in animals or humans. This technology is based on materials that have a history of use in biomedical implants and are therefore potentially suitable for conducting neural mapping and electrophysiological studies of human organs in vivo. We will evaluate device performance using the bladder and urethra as a model due to the challenging interface requirements (e.g. large volume changes) and potential clinical relevance. Overactive bladder and urinary incontinence affects millions of people worldwide, is associated with costs upwards of $60 billion each year in the United States, and leads to significant decreases in quality of life. Electrode nets will be tested in acute cat experiments where we will determine the electrode-tissue mechanical stability, evaluate embedded sensor performance, and develop functional neural maps of the surface of the bladder and urethra. We will also validate device performance in a series of chronic animal experiments where device performance will be monitored for up to four months post-implant. An important feature of this enabling technology and associated manufacturing process is that these devices will be able to be quickly and cost-effectively redesigned to study other visceral organ systems including the stomach, intestines, and colon across a range of animal models as well as humans.