Sub-millimeter precision wireless neuromodulation using a microwave split ring resonator

项目摘要 亚毫米空间分辨率的微创神经调制仍然是一个关键但尚未满足的问题 生物医学需求。研究人员探索了广泛的电磁波频谱，并开发出 无线神经调节方法。由于其波长较长，经颅磁刺激不能 提供足够的空间分辨率以瞄准功能单元，例如 视皮层或病变的周围神经。另一方面，具有短波长的光子提供了 微米级的空间精度，但只能勉强穿透几百微米进入组织，而不是 提到人类的头骨。频率在300 MHz到300 GHz之间的微波(MW)填补了这一空白 在光波和磁波之间，对于神经调节的研究还很少。我们提出了一个 利用微波开环谐振器(SRR)的微创神经调节装置 设计。SRR具有大约一半兆瓦波长的周长，因此充当谐振器 天线。它以无线方式耦合微波，并将微波集中在缝隙处，产生 空间局域电场为~100μm。我们的科学前提是基于非热神经 微波的抑制效应和SRR的共振效应。SRR生产浓缩的 微波并允许神经调制超过微波衍射限制，达到~100μm空间 精确度。在这项拟议的工作中，我们将设计和制造一种可植入的钛SRR，以满足其优越的性能 生物兼容性。然后我们将使用体外培养的原代神经元来验证SRR在神经抑制方面的潜力 一种小鼠体内癫痫模型。通过完成拟议的研究，我们将制定一个 生物相容性和植入性神经调节装置。提供的厘米级穿透深度 微波和SRR提供的亚毫米空间精度具有广阔的生物医学应用前景。 对于中枢神经系统，我们的技术允许对神经进行微创的经颅调制 脑内活动和癫痫的临床治疗。一支多学科互补的团队 汇集了专门知识，以执行拟议的活动。

Project Summary Minimally invasive neural modulation at sub-millimeter spatial resolution remains a critical yet unmet biomedical need. Researchers have explored a broad spectrum of electromagnetic wave and developed wireless neuromodulation methods. Due to its long wavelength, transcranial magnetic stimulation does not provide sufficient spatial resolution to target a functional unit such as a single ocular dominance column in the visual cortex or a diseased peripheral nerve. On the other hand, photons, with their short wavelength, offer micrometer-scale spatial precision but can barely penetrate couple hundred micrometers into the tissue, not to mention the human skull. Microwave (MW), with frequencies between 300 MHz and 300 GHz, fills the gap between optical wave and magnetic wave, yet, has rarely been explored for neuromodulation. We propose a minimally invasive neuromodulation device by taking advantage of a microwave split ring resonator (SRR) design. The SRR has a perimeter of approximately one half of MW wavelength, thus acting as a resonant antenna. It couples the microwave wirelessly and concentrates the microwave at the gap, producing a localized electrical field of ~100 μm in space. Our scientific premise is based on the nonthermal neural inhibitory effect of microwave and the resonance effect of the SRR. The SRR produces concentrated microwave and allows for neuromodulation beyond the microwave diffraction limit, reaching ~100 μm spatial precision. In the proposed work, we will design and fabricate an implantable SRR with titanium for its superior biocompatibility. We will then validate the SRR’s potential in neural inhibition using primary neurons in vitro and a mouse epilepsy model in vivo. By accomplishing the proposed studies, we will have developed a biocompatible and implantable neuromodulation device. The centimeter-scale penetration depth provided by microwave and the sub-millimeter spatial precision provided by SRR promises broad biomedical applications. For central nervous system, our technology allows minimally invasive transcranial modulation of neural activities inside brain and for clinical treatment of epilepsy. A multi-disciplinary team with complementary expertise is assembled to implement the proposed activities.