Silicon-based microelectrode arrays for neuroprosthetic control of micturition

描述（由研究者提供）：本研究的长期目标是为无法自主控制膀胱的脊髓损伤患者开发神经假体。我们的方法是设计一个最佳的穿透多位点多柄硅探针阵列，用于在完整和脊髓横断的猫的骶脊髓中慢性植入，以选择性刺激参与排尿反射的神经元群。这种方法是基于我们最近竞争的NIH合同的结果，在该合同中，我们使用了一组离散的微丝电极长期植入S1-S2脊髓，其中包含膀胱激活和外尿道括约肌抑制神经回路。虽然我们能够在一些完整的和脊髓横断的猫中诱导近乎完全的膀胱排空，但靶向效率不足以在所有植入的动物中可靠地诱导排尿。在本提案中，我们将利用先进的硅微加工技术，特别是硅晶圆的深度反应离子蚀刻，这比我们目前基于微线的制造技术更具可重复性，可扩展性，成本效益和临床可翻译性。该技术允许在每个柄上放置多个电极位置，完全控制探针的几何形状，并且增加了阵列设计的灵活性，所有这些都将提高我们针对骶骨脊髓中少量神经元的精度和可靠性。本研究项目是设计驱动的，旨在优化硅探针的几何形状和刺激部位的密度，以实现脊髓损伤前后可靠的神经义肢排尿。公共卫生相关性：本研究的长期目标是为不能自主控制膀胱的脊髓损伤患者开发神经假体。在体外和体内测试中提出的新技术的使用将允许精确靶向脊髓中控制膀胱排尿的小群神经元。如果这个项目成功，它将允许瘫痪的动物（以及后来的人类）通过脊髓内刺激来控制他们的膀胱，这比目前使用的骶神经和神经根刺激有更好的选择性和更少的副作用。

DESCRIPTION (provided by investigator): The long-term objective of this study is to develop neuroprostheses for persons with spinal cord injury who are unable to voluntarily control their bladder. Our approach is to design an optimal array with penetrating multi-site multi-shank silicon probes for chronic implantation in the sacral spinal cord of intact and spinally transected cats for selective stimulation of neuronal populations involved in micturition reflexes. This approach is based on results of our recently competed NIH contract, where we used an array of discrete microwire electrodes chronically implanted in the S1-S2 spinal cord containing bladder-activating and external urethral sphincter-inhibiting neuronal circuitry. While we were able to induce near-complete bladder emptying in some intact and spinal cord transected cats, the targeting efficiency was insufficient for reliable induction of micturition in every implanted animal. In this proposal, we will utilize advanced silicon microfabrication technology, and particularly the deep-reactive ion etching of silicon wafers, that is more reproducible, scalable, cost-efficient, and clinically-translatable than our current microwire-based fabrication technology. This technology allows placement of multiple electrode sites per shank, full control of probe geometry, and increased flexibility in the array design, all of which would improve our precision and reliability in targeting small populations of neurons in the sacral spinal cord. This research project is design-driven and aims to optimize the silicon probe geometry and density of stimulating sites to achieve reliable neuroprosthetic micturition before as well as after the spinal cord injury. PUBLIC HEALTH RELEVANCE: The long-term objective of this study is to develop neuroprostheses for persons with spinal cord injury who are unable to voluntarily control their bladder. Proposed use of novel technologies in fabricating and in vitro and in vivo testing will allow precise targeting of small populations of neurons in the spinal cord controlling bladder voiding. If this project is successful, it will allow paralyzed animals (and later humans) to control their bladder by intraspinal stimulation, which has better selectivity and fewer side- effects than currently used sacral nerve and root stimulation.