CAREER: Bioelectronics-embedded hybrid brain tissues

该职业奖旨在探索通过嵌入式生物电子设备监测和控制的实验室培养的脑组织。体外脑组织模型在神经科学中扮演着重要的角色，因为它们使无法在活人身上进行的研究成为可能，例如年轻的大脑如何发育或受到损伤或疾病的影响。然而，这些模型是有限的。大脑是由通过电脉冲交流的神经元网络组成的，但目前的技术还不能与这些信号相互作用。该项目将开发一个脑机接口，提供来自脑组织多个位置的生物电子输出和输入。输出将提供关于大脑如何发展或对刺激作出反应的见解，而输入将提供关于如何处理感官信号的见解。除了产生有关神经科学和材料科学的知识外，该项目产生的工具还可以提供对大脑功能障碍的见解，包括影响全球六分之一人口的神经系统疾病。该项目还将利用神经科学作为一种工具，通过高中外展、资助的暑期实习和旨在吸引不同受众的课程，招募和留住代表性不足的少数民族进入科学、技术、工程和数学领域。该职业奖旨在开发一种工程混合脑组织模型，该模型将功能神经网络与3D配置的生物电子设备融合在一起。这项工作的核心将是一个生物电子网格（BioEM），它将支持多路刺激和/或记录元素及其相互连接；并与周围组织无缝结合。中心假设是，在工程神经网络中存储和传输的信息可以通过这种双向生物电子接口解码或重新编程。该项目将包括材料、设备和组织尺度的研究。第一个目标是开发一种适合神经元整合的生物电子显微镜。将探索基于化学和纳米材料的方法来实现促进电子耦合的生物活性界面。第二个目标是研究如何使用输出来获得有关网络结构的信息，以及它们如何响应化学扰动。将开发网络分析和机器学习技术来分析产生的数据量并推导预测框架。第三个目标是结合刺激装置来实现感觉输入，并研究它们如何影响神经元功能，包括突触可塑性或“记忆”形成。最终目标是结合纳米电子探针进入细胞质并测量细胞内信号。除了丰富我们对神经科学的理解之外，所产生的工具和知识将加强体外脑功能障碍模型的实用性，包括影响全球六分之一人口的神经系统疾病。这项研究也可能对其他领域产生革命性的影响，包括混合生物/固态计算、生物电子医学、发育生物学和再生医学。此外，该计划还将纳入一个教育组成部分，旨在提高在科学、技术、工程和数学领域中代表性不足的少数民族的参与度和留任率。它将建立一个高中外展项目，资助暑期实习机会，以及结合文化可持续教学法的课程。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This CAREER award aims to explore lab-grown brain tissues that are monitored and controlled through embedded bioelectronic devices. In vitro brain tissue models play an important role in neuroscience because they enable studies that cannot be performed in living humans, for example how the young brain develops or is affected by injury or disease. These models, however, are limited. Brains are composed of networks of neurons that communicate through electrical impulses, yet current technologies cannot interact with these signals. This project will develop a brain-machine interface that will provide bioelectronic outputs and inputs from multiple locations throughout the brain tissue. The outputs will provide insights into how the brain develops or responds to stimuli, while the inputs will provide insight into how sensory signals are processed. In addition to generating knowledge about neuroscience and materials science, the tools generated in this project could provide insights into brain dysfunction, including neurological disorders which affect one in six people globally. This project will also use neuroscience as a tool to recruit and retain underrepresented minorities into Science, Technology Engineering and Math fields through high school outreach, funded summer internships, and coursework designed to engage a diverse audience.This CAREER award aims to develop an engineered hybrid brain tissue model that merges functional neuronal networks with bioelectronic devices in 3D configurations. Central to the work will be a BioElectronic Mesh (BioEM) that will support multiplexed stimulation and/or recording elements and their interconnections; and will seamlessly integrate with the surrounding tissue. The central hypothesis is that information stored and transmitted in engineered neural networks can be decoded or reprogrammed via this two-way bioelectronic interface. The project will incorporate investigations at the materials, device, and tissue scales. The first goal is to develop a BioEM suitable for neuronal integration. Chemical and nanomaterials-based approaches will be explored to achieve bioactive interfaces that promote electronic coupling. The second goal is to investigate how outputs can be used to derive information about the structure of the networks and how they respond to chemical perturbations. Network analysis and machine learning techniques will be developed to analyze the volumes of data produced and derive predictive frameworks. The third goal is to incorporate stimulation devices to achieve sensory-like inputs and study how they affect neuronal function including synaptic plasticity or “memory” formation. The final goal is to incorporate nanoelectronic probes that enter the cytosol and measure intracellular signals. In addition to enriching our understanding of neuroscience, the tools and knowledge generated will bolster the utility of in vitro models for brain dysfunction, including neurological disorders which affect one in six people globally. The research could also be transformative for other fields, including hybrid biological/solid-state computation, bioelectronic medicine, developmental biology and regenerative medicine. In addition, the program will incorporate an education component aimed at increasing participation and retention among underrepresented minorities in Science, Technology, Engineering and Math fields. It will establish a high school outreach program, funded summer internship opportunities, and coursework that incorporates culturally sustained pedagogies.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.