A Novel Wireless and Subcellular Device for Neuromodulation

用于神经调节的植入式接口对于推进基础神经科学研究是必要的， 开发神经系统疾病的新疗法，并创造有效的突破性神经修复术。 然而，基于多电极阵列的现代植入物遭受低空间分辨率、高分辨率、高分辨率和高分辨率的缺点。 复杂的可植入手术的侵入性，需要长期开口用于连接导线， 以及大量的异物反应，最终导致装置失效。另一方面，各种团体 已经开发出基于纳米颗粒的传感器，可以高精度地无线调制神经元 当受到外部刺激时。然而，纳米颗粒由于它们的小尺寸而具有若干缺点。 尺寸（导致神经毒性、迁移、聚集等），有限的制造程序和有限的 设计或整合机会。因此，微创和非基因技术，可以使 具有高时空分辨率和稳定接口的无线神经调制仍然是未满足的目标 直到约会。 因此，我们建议开发一种创新的基于薄膜的结构，能够无线地影响 沿着特定的连接路径诱导或抑制动作电位传播 神经元这些装置将被设计和生产为具有亚细胞尺寸，以被注射到 神经组织，扩散，并包裹轴突和树突（产生整合和稳定的神经 接口）;因此，它们被命名为nanoCUFF。nanoCUFF将由两种类型的聚合物组成： i）用于卷绕成微管的薄膜的光诱导重构的偶氮苯聚合物， 容纳单个轴突;和ii）用于将光脉冲转换成刺激的半导体聚合物 用于神经元光调制。聚合物允许产生柔软的、生物相容的和适形的结构， 与生物组织的最小失配和最大耦合。一旦生产出nanoCUFF， 并进行表征，我们将验证它们在轴突和树突周围的包裹能力，神经调节， 效率以及影响不同选择的神经元亚群的能力（使用微图案化的 光）在神经培养物中。 设计nanoCUFF材料成分和薄膜光致效应的能力 该平台有利于未来集成纳米电子组件以实现附加功能。为 例如，可以开发多路复用和传感设备用于智能闭环神经调节。这 技术可以同时实现超低侵入性、高时空精度、选择性 和稳定的细胞连接，因此，不仅对基础神经科学， 新疗法。

Implantable interfaces for neuromodulation is necessary to advance fundamental neuroscience research, develop new treatments for neurological disorders, and create efficient breakthrough neuroprosthetics. However, modern implants based on multi-electrode arrays suffer from low spatial resolution, high invasiveness with complicated implantable procedures, the need for a chronic opening for connecting wires, and substantial foreign body reaction, eventually leading to device failure. On the other hand, various groups have developed nanoparticles-based transducers that can wirelessly modulate neurons with high precision when actuated with external stimuli. Nevertheless, nanoparticles hold several disadvantages due to their small size (resulting in neurotoxicity, migration, aggregation, etc.), restricted fabrication procedures, and limited design or integration opportunities. Hence, minimally invasive and non-genetic technology that can enable wireless neuromodulation with high spatio-temporal resolution and stable interface remains an unmet goal till date. Therefore, we propose to develop an innovative thin-film-based structure able to wirelessly influence the neuronal membrane to induce or inhibit action potential propagation along a specific path of connected neurons. These devices will be designed and produced with subcellular dimensions to be injected into the neural tissue, diffuse, and wrap around axons and dendrites (creating conformable and stable neural interface); hence, they are named nanoCUFFs. The nanoCUFFs will be composed of two types of polymers: i) an azobenzene polymer for photo-induced reconfiguration of thin films rolled into microtubes, accommodating single axons; and ii) a semiconducting polymer for transduction of light pulses into stimuli for neuronal opto-modulation. Polymers allow creating soft, biocompatible, and conformable structures for a minimal mismatch and maximal coupling with the biological tissue. Once the nanoCUFFs are produced and characterized, we will verify their wrapping capabilities around axons and dendrites, neuromodulation efficiencies as well as ability to influence distinct selected subpopulations of neurons (using micro-patterned light) in neural cultures. The ability to engineer the nanoCUFFs’ material composition and photo-induced effects on a thin-film platform favors the future integration of nanoelectronics components for additional functionalities. For instance, multiplexing and sensing devices could be developed for smart closed-loop neuromodulation. This technology can simultaneously achieve ultra-low invasiveness, high-spatio-temporal precision, selectivity and stable junction with cells and thus, is highly promising for not only fundamental neuroscience but also novel therapeutics.