ASCENT: BioNet: A distributed network of bioelectronic devices for closed-loop control of physiological processes

生物电子学有望以个性化和高度可控的方式感知和影响局部组织和器官功能，从而显著改善人类健康和表现，这是传统材料和药物无法做到的。此外，人体生物系统的交流方式需要在物理上分离的位置进行传感和/或刺激，这就需要一个生物电子元件的“分布式”网络。为了实现这一愿景，必须克服一些关键障碍，包括与植入设备通过组织进行不可靠的无线通信、人体对工程设备的排斥以及集成。该项目将实现一个分布式生物电子网络，或“BioNet”，微型，独立设备来克服这些挑战，并将展示其在修复神经损伤方面的实用性。BioNet将开发新的导电生物材料，以及用于无线供电和传输数据的小型化工具。该项目将通过提高生活质量和福祉来满足社会需求，并将减少疼痛，更快地从周围神经损伤中恢复功能，并减少因损伤而导致的生产力损失。除了组织再生和功能修复之外，BioNet还可以在其他医学领域做出更广泛的贡献，例如，神经系统疾病的长期治疗和治疗。本提案将开发一个生物混合生物电子分布式网络，桥接尺度（材料、器件、电路和系统）和学科。具有毫米级磁电微粒（MagMotes）的BioNet将无缝集成到再生组织中，提供功能性生物标志物和治疗性刺激，以影响生理状态。因此，该项目通过将不同学科汇集在一个融合研究框架中，为生物电子系统创造了新的知识和技术。协同设计策略使材料迭代/发现变得合理，平衡物理和实际限制与硬件/软件限制，并协调设计约束与应用程序/最终用户需求。该项目将推进组织集成导电聚合物同种异体接枝复合材料的材料和方法。它将提供一种使用磁电和定制CMOS电路的无线电源和低功耗数据传输的新方法。这些超低功耗CMOS电路和系统将增强鲁棒性和稳定性，减少校准工作，并提高制造成品率。共同设计的BioNet将产生一个周围神经损伤生物电子系统，能够进行生物混合刺激和神经再生进展的实时诊断，以形成闭环系统的基础。对科学和工程界的更广泛影响是建立一个平台，可以用作研究疾病和功能障碍背后的生物机制的工具。通过开发分布式传感器和执行器的硬件平台，该项目将为生理控制创造一个新的范例，这将为开发和测试分布式控制理论的概念提供新的机会。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。

Bioelectronics promises to dramatically improve human health and performance by sensing and affecting local tissue and organ function in a personalized and highly controlled manner which is not possible with traditional materials and medications. Furthermore, the way that biological systems of the body communicate requires sensing and/or stimulation at physically separated locations, necessitating a “distributed” network of bioelectronic components. To achieve this vision key barriers must be overcome, including unreliable wireless communication with implanted devices through tissue, rejection of engineered devices by the body, and integration. This project will realize a distributed bioelectronic network, or “BioNet”, of miniature, free-standing devices to overcome these challenges, and will demonstrate its utility for repairing nerve injuries. BioNet will develop new electrically conducting biomaterials, and miniaturized tools for powering and transmitting data wirelessly. This project will contribute to societal needs through improved quality of life and well-being and will result in reduced pain, faster functional recovery from peripheral nerve injury, and reduced loss in productivity due to injury. Beyond tissue regeneration and functional restoration, BioNet could contribute more broadly to other areas of medicine, for example, the long-term treatment and therapy of neurological disorders. This proposal will develop a biohybrid bioelectronic distributed network bridging scales (materials, devices, circuits, and systems) and disciplines. The BioNet, with millimeter-scale magneto-electric motes (MagMotes), will seamlessly integrate into regenerating tissues to provide functional biomarkers and therapeutic stimuli in order to affect physiological states. This project thus creates new knowledge and technology towards the bioelectronic system by bringing together diverse disciplines in a convergence research framework. A co-design strategy enables rational for material iteration/discovery, balances physical and practical limitations with hardware/software limitations and reconciles design constraints with application/end user needs. The project will advance materials and methods for tissue-integrated conducting polymer allograft composites. It will deliver a novel approach towards wireless power and low-power data transfer using magnetoelectrics and custom CMOS circuits. These ultra-low-power CMOS circuits and systems will enhance robustness and stability, reduce calibration efforts, and improve fabrication yield. The co-designed BioNet will result in a peripheral nerve injury bioelectronic system capable of biohybrid stimulation and real time diagnostics of nerve regeneration progress, needed in order to form the basis of a closed loop system. The broader impacts for the scientific and engineering community are the establishment of a platform that can be used as a tool to study biological mechanisms underlying disease and dysfunction. By developing the hardware platform for distributed sensors and actuators the project will create a new paradigm for physiological control which will open new opportunities to develop and test concepts for distributed control theory.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.