Conformable, Expandable Neural Interface Device for the developing brain

项目摘要/摘要 识别导致认知功能出现的神经网络机制的一个主要障碍是 在大脑成熟过程中获取大规模电生理信号的能力不足。 迫切需要开发技术和实验方案来获取大规模的、慢性的神经细胞。 通过微创可植入设备从小的、脆弱的、未成熟的大脑中发出生理信号。我们的 长期目标是使这种大规模神经网络的微创记录和操作成为可能 在关键的发育时间框架内发展生物体。我们的总体目标是建立一种神经 一种可以完全植入小鼠体内并能适应组织生长的接口装置，使 在不破坏环境实验的情况下对多个皮质区域进行慢性神经生理记录- 正常发育所需的智力。我们的中心假设是，整合导电聚合物电子- 电极、可扩展的衬底和可整合的离子回路将允许创建可整合、可扩展的 大脑发育中的神经接口(CENID)将帮助我们阐明神经活动的协调 随着大脑的成长和成熟。这一假设是在初步数据的基础上提出的 有机电子学可以有效地获取和处理神经生理信号。支持的理由是- 所提出的研究是，这些材料和设备部件的集成使我们的设备能够获取数据 这是以前无法访问的。为了实现我们的目标，我们追求以下两个具体目标： (I)建立可扩展的、可整合的和生物兼容的集成组件，以实现高时空分辨率- 脑内灌流信号的获取和传递；(Ii)体内慢性植入 CENID能够在自由活动的小鼠幼鼠身上获取和传递神经生理信号 成熟。我们认为，拟议的研究是创新的，因为它在很大程度上偏离了 金属基电极和硅基电子器件的研究现状 导电聚合物组件，以创建与以下兼容的完全可植入的神经接口设备 监测自然行为啮齿动物发育过程中的大规模皮质网络。这项工作是前- 被认为意义重大，因为它将为随着时间的推移监控神经网络提供基础 与大脑成熟和复杂大脑功能出现相关的时期。它将产生积极的影响- 就发展以前无法实现的实验范式达成协议，并更广泛地促进国际合作。 在设计安全、长期、微创的生物电子器件方面的证明。

PROJECT SUMMARY/ABSTRACT A major obstacle to identifying neural network mechanisms responsible for emergence of cognitive function is insufficient capability to acquire large-scale electrophysiologic signals across the course of brain maturation. There is urgent need to develop the technology and experimental protocols to acquire large-scale, chronic neu- rophysiological signals from small, fragile, immature brains via minimally invasive implantable devices. Our long-term goal is to enable such minimally invasive recording and manipulation of large-scale neural networks in developing organisms across critical developmental timeframes. Our overall objective is to establish a neural interface device that can be fully implanted in a mouse pup and can accommodate tissue growth, enabling chronic neurophysiological recording of multiple cortical regions without disrupting the environmental experi- ences required for normal development. Our central hypothesis is that integrating conducting polymer elec- trodes, expandable substrates, and conformable ionic circuits will allow creation of a Conformable, Expandable Neural Interface for the Developing Brain (CENID) that will help us elucidate the coordination of neural activity as the brain grows and matures. This hypothesis was formulated on the basis of preliminary data suggesting that organic electronics can efficiently acquire and process neurophysiologic signals. The rationale for the pro- posed research is that integration of these materials and device components enable our device to acquire data that was previously inaccessible. In order to achieve our objectives, we pursue the following two specific aims: (i) establish expandable, conformable and biocompatible integrated components for high spatiotemporal reso- lution signal acquisition and transmission of the developing brain; (ii) perform in vivo chronic implantation of CENID capable of acquiring and transmitting neurophysiological signals in freely moving mouse pups across maturation. The proposed research is innovative, in our opinion, because it substantially departs from the sta- tus quo of metal-based electrodes and silicon-based electronics by using conformable, fully biocompatible, conducting polymer-based components to create a fully implantable neural interface device compatible with monitoring large-scale cortical networks across development in naturally behaving rodents. This work is ex- pected to be significant because it will provide the groundwork for monitoring of neural networks across time periods associated with brain maturation and emergence of complex brain functions. It will have positive im- pact on development of previous unattainable experimental paradigms and contribute more broadly to im- provement in design of safe, long-term, minimally invasive bioelectronic devices.