Flexible fMRI-Compatible Neural Probes with Organic Semiconductor based Multi-modal Sensors for Closed Loop Neuromodulation

神经探针传感和调制已被证明是诊断和治疗许多神经系统疾病以及理解神经元回路复杂连接和功能的有效工具。为了促进对神经回路动力学和闭环神经调节的理解，有必要利用功能磁共振成像（fMRI）、电生理学、光学传感和刺激以及神经化学等技术的组合来研究脑回路的综合功能过程。在一个探针内容纳所有这些多模态功能，并且与fMRI兼容是一个非常重要但具有挑战性的研究问题。该项目将开发的具有多模态功能的新型柔性fMRI兼容神经探针解决了现有神经探针系统的局限性，并有可能彻底改变基础脑研究和神经系统疾病治疗的许多应用。此外，通过整合研究和教育，该项目将把研究成果与未来劳动力参与者的活动联系起来，以满足现代工业对生物传感器、神经探针制造和医疗仪器的需求。该项目的目标是研究一种灵活的神经探针，具有多模态传感和调制功能，可与fMRI兼容，用于先进的个性化神经学研究和治疗。利用高分子材料设计和制造柔性多柄神经探针，在功能磁共振成像下提供深部脑传感和调制，从而实现对神经系统的全面理解和闭环控制。多模态功能，包括基于有机电解质门控晶体管（OEGTs）的神经电位记录，基于聚合物波导的光遗传学和基于光电二极管的光度测定，以及基于有机电化学晶体管（OECTs）的神经化学传感器，将被定制集成到探针中。与传统基于电极的神经探针相比，该探针采用多种基于有机半导体（OSC）的传感器进行电学、光学和化学传感，显著提高了当前神经传感和调制技术的灵敏度和选择性。为了证明该平台在治疗神经系统疾病方面的潜力，新型多模态神经探针将在动物模型体内应用，在闭环中动态控制目标脑神经回路的活动，同时使用相邻通道监测其活动模式。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。

Neural probe sensing and modulation have been demonstrated as effective tools for diagnosing and treating numerous neurological disorders as well as for understanding sophisticated connections and functions of neuron circuits. To advance the understanding of neural circuit dynamics and closed-loop neuromodulation, it is essential to investigate the integrated functional processes of the brain circuits using a combination of techniques, including functional Magnetic Resonance Imaging (fMRI), electrophysiology, optical sensing and stimulation, and neurochemistry. Accommodating all these multi-modal functions within a single probe that is also fMRI compatible is a critically important but challenging research problem. The novel flexible fMRI compatible neural probe with multi-modal functions that will be developed in this project addresses the limitations of existing neural probe systems and has the potential to revolutionize a host of applications for fundamental brain research and neurological disorders treatment. Moreover, by integrating research and education, this project will link the research outcomes and the activities of future workforce participants to satisfy the needs of the modern industry for biosensors, neural probe fabrication, and medical instrumentation.The objective of this project is to investigate a flexible neural probe with multi-modal sensing and modulation functions compatible with fMRI for advanced personalized neurological research and treatments. A flexible multi-shank neural probe will be designed and fabricated using polymeric materials to provide deep brain sensing and modulation under fMRI, which enables comprehensive understanding and closed-loop control of the nervous system. The multi-modal functions, including organic electrolyte-gated transistors (OEGTs) based neural potential recording, polymer waveguide-enabled optogenetics and photodiode-based photometry, and organic electrochemical transistors (OECTs) based neurochemical sensors, will be custom integrated into the probe. Compared with traditional electrode-based neural probes, the proposed probe adopts a variety of organic semiconductor (OSC) based sensors for electrical, optical, and chemical sensing, significantly improving the sensitivity and selectivity of the current neural sensing and modulation techniques. To demonstrate the platform’s potential for treating neurological disorders, the novel multi-modal neural probes will be applied in vivo in animal models to dynamically control the activity of target brain neural circuits in a closed loop while simultaneously monitoring their activity pattern using adjacent channels.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.