Microfabricated all-diamond microelectrode arrays for neurotransmitter sensing and extracellular recording

项目摘要 对大脑功能的完整理解需要可靠和全面的大规模大脑绘图 具有高时空分辨率和最小侵入性的网络。实现这种映射的工具必须 克服现有任何一个组织都没有充分或同时解决的无数挑战， 技术.因此，本提案的总体目标是开发一种新的基于金刚石的神经接口系统 它由多达256个记录点组成，体积为mm 3， 在活的神经组织中检测神经元活动。拟议的创新工具将具有以下特点 与现有技术相比，具有显著优势。首先，高导电BDD电极将同时 增强神经感测的灵敏度、选择性和稳定性。他们也将有更大的潜力 比目前的电极材料的操作范围。第二，通过使用未掺杂的PCD作为密封材料， 生物相容性和低污染的封装材料，新设备将有可能具有更长的寿命， 长期稳定的长期应用。第三，紧凑的双模云台将更好地实现 控制电生理学和快速扫描循环伏安法（FSCV）测量，具有高精度和 高信噪比，同时最大限度地减少串扰。第四，新的微加工技术将 允许晶片级大规模生产具有各种几何形状、精细空间分辨率 （亚微米至微米级）和高产率（>90%）。采用成熟的半导体 制造技术，所提出的制造方法更可靠，一致，可扩展， 与目前广泛用于制造碳纤维电极的手工组装方法相比，该方法具有更高的劳动力/成本效率。 最后但并非最不重要的是，高度填充的电极的3D阵列将显著增强横向和深度 新的电化学检测工具的覆盖范围与当前的化学传感工具相比。项目 将由一个多学科的合作研究小组进行。该团队将利用其广泛的 具有金刚石纤维电极开发、材料合成和器件制造的经验 将金刚石电极的空间分辨率从几十微米提高到亚微米的技术 (via电子束光刻）和微米（通过紫外光刻）（目标1）。与电极并联 该团队将设计解决方案，以实现小型化头戴式电生理学， FSCV电子学，并将头台与金刚石电极阵列集成，以实现完整的系统 (Aim 2）。然后将离体评估集成系统的功能性、生物相容性和稳定性 和在体内使用互补分析技术（目的3）。拟议的工作意义重大，因为它将 产生一个革命性的神经接口工具，可以很容易地传播给其他研究人员使用， 神经科学和临床研究，以揭示许多大脑紊乱和疾病的潜在机制。

PROJECT SUMMARY Complete understanding of brain function requires reliable and comprehensive mapping of large-scale brain networks with high spatiotemporal resolution and minimum invasiveness. Tools to achieve such mapping must overcome a myriad of challenges that are not adequately or simultaneously addressed by any existing technology. Hence the overall goal of this proposal is to develop a new diamond-based neural interface system that consists of up to 256 recording sites in mm3-sized volumes for combined electrical and chemical detection of neuronal activity in living nerve tissues. The proposed innovative tool will have the following significant advantages over existing technologies. First, highly-conductive BDD electrodes will simultaneously enhance the sensitivity, selectivity, and stability of neurological sensing. They will also have a greater potential range of operation than current electrode materials. Second, by using undoped PCD as a hermetic, biocompatible, and low-fouling encapsulation material, the new device will potentially have greater longevity and long-term stability for chronic applications. Third, a compact, dual-mode headstage will better enable the control of electrophysiology and fast-scan cyclic voltammetric (FSCV) measurements with high precision and a strong signal-to-noise ratio, while minimizing crosstalk. Fourth, the novel micromachining technique will permit wafer-level, mass production of diamond electrodes with various geometries, fine spatial resolution (submicrometer to micrometer scale), and high yields (>90%). Adopted from well-established semiconductor manufacturing techniques, the proposed fabrication approach is more reliable, consistent, scalable, and labor/cost-efficient than the hand assembly approach that is widely used today for making carbon fiber electrodes. Last but not least, 3D arrays of highly packed electrodes will significantly enhance the lateral and depth coverage of the new electrochemical detection tools compared to current chemical sensing tools. The project will be conducted by a multidisciplinary, collaborative team of researchers. The team will leverage their extensive experience in developing diamond fiber electrodes and in refining material synthesis and device fabrication techniques to push the spatial resolution of diamond electrodes from several tens of microns to submicrometer (via electron-beam lithography) and to micrometer (via ultraviolet lithography) (Aim 1). In parallel with electrode development, the team will engineer solutions to implement miniaturized head-mounted electrophysiology and FSCV electronics, and integrate the headstage with diamond electrode arrays to achieve a complete system (Aim 2). The functionality, biocompatibility, and stability of the integrated system will then be assessed ex vivo and in vivo using complementary analysis techniques (Aim 3). The proposed work is significant because it will yield a revolutionary neural interface tool that can be readily disseminated to other researchers for use in neuroscience and clinical studies to reveal the mechanisms underlying many brain disorders and diseases.