ERI: Microscale Implants for Closed-loop Neuromodulation

生物电子医学具有改变个性化医学的潜力。生物电子药物是一种植入设备，可以读取并调节人体神经系统的电活动，以治疗常规疗法无法治疗的疾病和状况。尺寸小于一粒米的下一代生物电子药物的医疗保健将能够持续监测患者的状态，并自主提供按需治疗，以显著减轻临床医生的负担，提高患者的依从性，并减少药物不良反应和滥用。然而，目前的生物电子医学依赖于大型、笨重的设备，这些设备具有高度侵入性，使用的电子设备无法感知微弱的神经信号，同时也无法提供刺激治疗。为了克服这些障碍，迈向下一代生物电子医学的愿景，该项目寻求在电路设计方面取得关键技术进步，使生物电子医学微型化，并实现闭环治疗的同时感知和刺激。该项目将开发能够无线记录和刺激同时进行闭环实验的微型周围神经接口。为此，拟议的工作将开发一个新的跨域模拟框架，以实现对关键物理参数(如无线能量采集和电极特性)的准确联合模拟，并利用集成电路设计来优化微尺度神经接口系统的设计。接下来，将开发用于神经刺激和记录的小面积、低功耗的电路设计技术。通过自适应地监测和控制电极接口，刺激电路将在没有芯片外组件的情况下确保长期安全运行。记录电路将使用精确定时的无记忆采样，以对来自神经刺激的饱和干扰具有弹性。最后，原型神经接口将在啮齿动物模型中进行验证，并用于动态控制周围神经，作为闭环生物电子医学的概念验证演示。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Bioelectronic medicine has the potential to transform personalized medicine. Bioelectronic medicines are implanted devices that read and modulate the electrical activity of the body’s nervous system to treat diseases and conditions that are resistant to conventional therapy. Medical care with next generation bioelectronic medicine of size smaller than a grain of rice will be able to continuously monitor a patient’s state and autonomously deliver on-demand therapy to significantly reduce clinician burden, improve patient compliance, and reduce adverse drug reactions and abuse. However, current bioelectronic medicine relies on large, bulky devices that are highly invasive and use electronics that cannot sense weak neural signals and deliver stimulation therapy at the same time. To overcome these barriers and move toward this vision for next generation bioelectronic medicine, this project seeks to make key technological advances in circuit design to miniaturize bioelectronic medicine and enable simultaneous sensing and stimulation for closed-loop therapy.This project will develop miniaturized peripheral nerve interfaces that can wirelessly record and stimulate at the same time to enable closed-loop experimentation. To do so, the proposed work will develop a new cross-domain simulation framework to enable accurate co-simulation of key physical parameters, such as wireless power harvesting and electrode properties, with integrated circuit design to optimize the design of microscale neural interface systems. Next, small-area, low-power circuit design techniques for neural stimulation and recording will be developed. The stimulation circuitry will guarantee chronically safe operation without off-chip components by adaptively monitoring and controlling the electrode interface. The recording circuitry will employ precisely-timed memoryless sampling to be resilient to saturating interference from neural stimulation. Lastly, the prototype nerve interface will be validated in a rodent model and be used to dynamically control a peripheral nerve as a proof-of-concept demonstration of closed-loop bioelectronic medicine.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.