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

项目总结 对大脑功能的完整理解需要可靠而全面的大规模脑图谱 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 克服大量挑战，这些挑战不是任何现有的 技术因此，这项提议的总体目标是开发一种新的基于钻石的神经接口系统 它包括多达256个记录点，以毫米为大小的体积，用于电气和化学的组合 活体神经组织中神经元活性的检测。拟议的创新工具将具有以下功能 与现有技术相比具有显著优势。首先，高导电性的BDD电极将同时 提高神经传感的灵敏度、选择性和稳定性。他们也将拥有更大的潜力 操作范围比目前的电极材料。其次，通过使用未掺杂的PCD作为密封件， 生物相容和低污染的封装材料，这种新的设备可能会有更长的寿命和 长期稳定适用于慢性应用。第三，紧凑的双模前台将更好地支持 电生理和快速扫描循环伏安(FSCV)测量的高精度和高精度控制 强大的信噪比，同时最大限度地减少串扰。第四，新的微机械加工技术将 允许晶片级、批量生产各种几何形状、高空间分辨率的金刚石电极 (亚微米到微米级)和高产量(&gt；90%)。采用来自久负盛名的半导体 制造技术，建议的制造方法更可靠、一致、可扩展和 比目前广泛用于制造碳纤维电极的手工组装方法更节省劳动力/成本。 最后但并非最不重要的是，高填充电极的3D阵列将显著增强横向和深度 将新的电化学检测工具与当前的化学传感工具进行比较。该项目 将由一个多学科、协作的研究团队进行。该团队将利用其广泛的 开发金刚石纤维电极和精炼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 (通过电子束光刻)和微米(通过紫外线光刻)(目标1)。与电极并联 在开发过程中，该团队将设计解决方案，以实现微型化的头盔电生理和 FSCV电子，并将头台与金刚石电极阵列集成在一起，实现了一个完整的系统 (目标2)。然后将对集成系统的功能、生物兼容性和稳定性进行体外评估 并在体内使用互补分析技术(目标3)。拟议的工作意义重大，因为它将 产生一种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，用于 神经科学和临床研究，以揭示许多大脑疾病和疾病的潜在机制。

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.