A Novel Wireless and Subcellular Device for Neuromodulation

用于神经调节的新型无线和亚细胞设备

• 批准号: 10676270
• 负责人: Deblina Sarkar
• 金额: $ 23.27万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10676270
• 关键词: 3-Dimensional; Acoustics; Action Potentials; Adverse effects; Alzheimer' s Disease; Area; Axon; Behavior; Biological; Brain; Brain Diseases; Cell membrane; Cells; Cephalic; Chronic; Confocal Microscopy; Coupling; Dendrites; Development; Devices; Diffuse; Dimensions; Disadvantaged; Electrodes; Electron Microscopy; Electronics; Engineering; Environment; Equipment Malfunction; Face; Fiber; Film; Foreign-Body Reaction; Future; Generations; Genetic; Goals; Immune system; Implant; Implantation procedure; Individual; Inflammatory Response; Injectable; Learning; Light; Lighting; Magnetism; Membrane; Memory; Microelectrodes; Modality; Modernization; Modification; Molecular; Names; Nerve Regeneration; Neurologic; Neuronal Plasticity; Neurons; Neurosciences; Neurosciences Research; Optics; Outcome; Parkinson Disease; Pattern; Penetration; Performance; Peripheral Nervous System; Physiologic pulse; Polymers; Procedures; Psychological reinforcement; Recovery; Resolution; Source; Stimulus; Structure; Surface; Symbiosis; Synapses; System; Techniques; Technology; Therapeutic; Thick; Thinness; Tissues; Transducers; Tube; azobenzene; biomaterial compatibility; brain machine interface; design; experience; experimental study; extracellular; fabrication; improved; innovation; learning materials; materials science; member; migration; minimally invasive; multi-electrode arrays; nano; nanodevice; nanoelectronics; nanofabrication; nanoparticle; nanopolymer; nervous system disorder; neural; neural implant; neural network; neural stimulation; neuroprosthesis; neuroregulation; neurotoxicity; next generation; non-genetic; novel; novel therapeutics; optogenetics; patch clamp; seal; spatiotemporal; success; synergism; temporal measurement; wireless; wireless electronic

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.

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，并创造突破性的高效神经修复术。 然而，基于多电极阵列的现代植入物存在空间分辨率低、 复杂的植入手术的侵入性，需要长期打开连接线， 另一方面，大量的异物反应，最终导致设备故障。 开发了基于纳米粒子的传感器，可以高精度无线调节神经元 然而，当受到外部刺激时，纳米粒子由于其体积小而存在一些缺点。 尺寸（导致神经毒性、迁移、聚集等）、受限的制造程序和有限的 因此，微创和非基因技术可以实现。 具有高时空分辨率和稳定接口的无线神经调节仍然是一个未实现的目标 到目前为止。 因此，我们建议开发一种创新的基于薄膜的结构，能够无线影响 神经元膜诱导或抑制动作电位沿特定连接路径传播 这些装置将被设计和生产为亚细胞尺寸，以注入到神经元中。 神经组织，扩散并包裹轴突和树突（创建顺应且稳定的神经 接口）；因此，它们被命名为 nanoCUFFs nanoCUFFs 将由两种类型的聚合物组成： i) 一种偶氮苯聚合物，用于卷成微管的薄膜的光诱导重构， 适应单个轴突；和 ii) 用于将光脉冲转换成刺激的半导体聚合物 用于神经光调制 聚合物可以创建柔软、生物相容且舒适的结构。 一旦纳米CUFFs被生产出来，就会与生物组织实现最小的不匹配和最大的耦合。 并进行表征，我们将验证它们围绕轴突和树突的包裹能力，神经调节 效率以及影响不同选定的神经元亚群的能力（使用微图案 光）在神经培养中。 能够设计 nanoCUFF 的材料成分和薄膜上的光诱导效应 该平台有利于未来集成纳米电子元件以实现附加功能。 例如，可以开发用于智能闭环神经调节的多路复用和传感设备。 技术可同时实现超低侵入性、高时空精度、选择性 以及与细胞的稳定连接，因此，不仅对于基础神经科学而且对于 新疗法。