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

摘要 内脏器官对功能生理学和神经控制的研究提出了独特的挑战。内脏器官 通常被神经丛包围，神经丛沿着器官表面提供分布的神经，并包含 能局部调节功能的自主神经节。鉴于这种复杂性，创建内脏的功能图 器官的神经支配是具有挑战性的。另一个挑战是测量器官状态本身。这一点意义重大 这些器官中的许多都是柔软的、有弹性的，并经历了大量的体积变化，这一事实加剧了这种情况。 在这项提案中，我们将开发与这些独特挑战兼容的软硅胶电极网，并 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。 这种方法是基于3D打印硅胶电极技术。这些电极网将被加强 用应变计传感器和电阻抗断层扫描电极监测生理器官状态。 归根结底，这类新设备将1)本质上是柔软和有弹性的，以便与内脏保持一致 经历较大体积变化的器官，2)基于应变计的集成器官状态传感器和 电阻抗断层扫描，3)防止通常与其他薄膜相关的分层问题 电极制造工艺，以及4)允许快速定制以经济高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中有使用历史的材料 因此可能适合于进行神经标测和电生理研究 活体内的人体器官。 由于具有挑战性的接口，我们将使用膀胱和尿路作为模型来评估设备的性能 要求(例如，大容量变化)和潜在的临床相关性。膀胱和尿路过度活跃 大小便失禁影响全球数百万人，每年造成超过600亿美元的损失 并导致生活质量显著下降。电极网将在急性猫身上进行测试 我们将在实验中确定电极-组织的机械稳定性，评估嵌入式传感器 并开发出膀胱和尿路表面的功能神经图谱。我们还将验证 一系列慢性动物实验中的设备性能，其中设备性能将被监控 植入后长达四个月。这种使能技术和相关制造的一个重要特征 过程是，这些设备将能够快速和经济地重新设计，以研究其他内脏 包括胃、肠和结肠在内的器官系统在一系列动物模型和人类中都是如此。

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.