Reconfigurable 3D Origami Probes for Multi-modal Neural Interface

项目摘要 几十年来，各种神经技术取得了重大进展，以实现《大脑2025报告》中列举的最高优先目标。然而，每一种工具的开发都是由目标大脑区域、细胞类型和有限实验中的某种特定模式驱动的，并且集中在狭窄领域的扩展。虽然这些工具的效用只服务于一种模式，但神经科学实验本质上受到可用观察范围的限制。众所周知，大脑的活动和状态受到生物生理参数的影响，如新陈代谢，激素，神经递质，温度调节等，然而，迄今为止，神经技术工具还没有结合起来，在一个单一的实验中同时测量多个信号。该拨款申请提出了一种可重新配置的神经接口平台，在该平台上，多模态探针可以无缝集成在同一柔性基板上，以大幅提高观测广度。所提出的工具通过将生理-生物-化学传感器模块添加到高密度神经记录和神经元的目标特异性调制的基本关键电生理功能来提供多模态能力。每个传感器模块都可以作为“附加”选项轻松集成到现有模式中，而不是“替换”替代方案。拟议的平台具有高度可重构性，可以通过挑选目标研究和实验所需的模式来满足需求。该方案通过对单模态柔性探头的模块化和组合，为多模态在同一平台上的综合集成提供了一种高效的解决方案。初步数据：先前的工作已经证明了神经元大小的μ LED（15 μm x 10 μm）单片集成在硅记录探针上的可行性，相对于记录位点精确定位。原型探针包含256个记录位点和128 μ LED。最近，我们将μ LED集成在柔性聚合物衬底上，并将它们与记录探针堆叠在一起。初步的可行性被证明用于从柔性探针在体内感测多巴胺和局部脑温度。具体目标：在目标1中，将开发自对准柔性3D折纸探针，用于具有多种模态的各种神经接口。将开发两个原型平台：一个是具有所有电气接口的平面堆叠多模态探头，另一个是缠绕在光纤周围的3D折纸探头，该光纤将提供额外的光学模态，如光度测量。在目标2中，将开发一种模块化的紧凑型云台，采用创新的可适应性芯片上电缆组件，并将定制IC作为插入器。在目标3中，将在慢性啮齿动物实验中对所提出的多模态折纸探针进行验证。

Project Summary Over the decades, various neurotechnologies have made significant advancements to meet the highest priority goals enumerated in the BRAIN 2025 Report. However, each tool development has been driven by a certain type of specific modalities in the target brain region, cell type, and limited experiments and has focused on scaling in a narrow domain. While the utility of such tools has uniquely served one modality, neuroscience experiments are inherently limited by the breadth of observations available. It is known that brain activities and status are affected by biophysiological parameters such as metabolism, hormones, neurotransmitters, temperature regulation, etc. However, as of yet, neurotechnology tools have not been combined to simultaneously measure multiple signals in a single experiment. This grant application proposes a reconfigurable neural interface platform on which multi-modal probes can be seamlessly integrated on the same flexible substrate to substantially enhance observational breadth. The proposed tool offers multi-modal capabilities by adding physio-bio-chemical sensor modules to the basic key electrophysiological functions of high-density neural recording and target-specific modulation of neurons. Each sensor module can be easily integrated into the existing modalities as an “additive” option, not a “replacing” alternative. The proposed platform is highly reconfigurable to meet the needs by pick-and-choose the desired modality for target studies and experiments. By modularizing and combing single-modality flexible probes, the proposed scheme can provide a highly efficient solution to the challenges in the comprehensive integration of multi-modality on the same platform. Preliminary Data: The previous work has demonstrated the feasibility of neuron-sized μLEDs (15 μm x 10 μm) monolithically integrated on silicon recording probes, precisely positioned relative to the recording sites. Prototype probes incorporated 256 recording sites and 128 μLEDs. Recently, we integrated the μLEDs on a flexible polymer substrate and stacked them with a recording probe. Initial feasibility was demonstrated for sensing dopamine and local brain temperature in-vivo from the flexible probes. Specific Aims: In aim 1, self-aligned flexible 3D origami probes will be developed for diverse neural interfaces with multiple modalities. Two prototype platforms will be developed: One is planar, stacked multi-modal probes with all electrical interfaces, and the other is 3D origami probes wrapped around an optical fiber that will give additional opto-modality such as photometry. In aim 2, a modular, compact headstage will be developed utilizing an innovative adaptable cable-on-chip assembly with custom ICs as an interposer. In aim 3, validation of the proposed multi-modal origami probes will be conducted in chronic rodent experiments.