A Novel Wireless and Subcellular Device for Neuromodulation

用于神经调节的可植入接口对于推进基础神经科学研究是必要的， 开发治疗神经疾病的新疗法，创造高效的突破性神经假体。 然而，基于多电极阵列的现代植入物存在空间分辨率低、高分辨率 通过复杂的植入程序进行侵入性，需要用于连接电线的慢性开口， 和大量的异物反应，最终导致设备故障。另一方面，各种群体 已经开发出基于纳米颗粒的换能器，可以高精度地无线调制神经元 当受到外部刺激时。然而，由于纳米颗粒很小，所以它们有几个缺点。 尺寸(导致神经毒性、迁移、聚集等)、受限的制造程序和受限的 设计或集成机会。因此，微创和非基因技术可以使 具有高时空分辨率和稳定界面的无线神经调制仍然是一个未实现的目标 到日期为止。 因此，我们建议开发一种创新的薄膜结构，能够无线影响 神经元膜诱导或抑制动作电位沿特定的连接路径传播 神经元。这些设备的设计和生产将具有亚细胞维度，以注入到 神经组织，扩散并包裹轴突和树突(创建整合和稳定的神经 接口)；因此，它们被命名为纳米CUF。纳米CuFf将由两种类型的聚合物组成： I)用于卷入微管的薄膜的光诱导重构的偶氮苯聚合物， 容纳单个轴突；以及ii)用于将光脉冲转换为刺激的半导体聚合物 用于神经元的光调制。聚合物允许创建柔软的、生物兼容的和可整合的结构 与生物组织的最小失配和最大耦合。一旦生产出纳米CuFf 我们将验证它们包裹轴突和树突、神经调节的能力 效率以及影响不同的选定神经元亚群的能力(使用微图案 光)在神经培养中。 设计纳米CuFf材料组成和光诱导薄膜效应的能力 Platform支持未来集成纳米电子元件以实现更多功能。为 例如，可以开发用于智能闭环神经调节的多路传输和传感设备。这 技术可以同时实现超低侵入性、高时空精度、选择性 并与细胞稳定连接，因此，不仅在基础神经科学方面，而且在 新的治疗方法。

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.