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

用于神经递质传感和细胞外记录的微加工全金刚石微电极阵列

• 批准号: 10563205
• 负责人: Wen Li
• 金额: $ 57.67万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10563205
• 关键词: 3-Dimensional; Address; Adopted; Adult; Amplifiers; Behavior; Biocompatible Materials; Blood - brain barrier anatomy; Brain; Brain Diseases; Brain region; Cell Death; Chemicals; Chemistry; Chronic; Cicatrix; Clinical; Clinical Research; Communities; Complex; Computer software; Corpus striatum structure; Data Analyses; Detection; Development; Device Designs; Devices; Diamond; Dimensions; Dopamine; Drug Addiction; Electrochemistry; Electrodes; Electronics; Electrophysiology (science); Encapsulated; Engineering; Fiber; Film; Future; Geometry; Goals; Hand; Head; Hybrids; Immunohistochemistry; Implant; Implanted Electrodes; Individual; Inflammation; Lateral; Light; Longevity; Maps; Measurement; Mechanics; Microelectrodes; Miniaturization; Mission; Monitor; Morphology; Nerve Tissue; Neurologic; Neurons; Neurosciences; Neurotransmitters; Noise; North Carolina; Parkinson Disease; Performance; Periodicity; Property; Public Health; Rattus; Research Personnel; Resolution; Safety; Scanning; Schizophrenia; Semiconductors; Signal Transduction; Site; Specificity; Surface; System; Systems Integration; Techniques; Technology; Time; United States National Institutes of Health; Universities; Work; biomaterial compatibility; carbon fiber; cost efficient; data acquisition; data integration; density; design; detection limit; electric impedance; electron beam lithography; experience; extracellular; fabrication; flexibility; fundamental research; implantation; in vivo; innovation; instrument; large scale production; lithography; manufacture; mechanical properties; meter; millisecond; miniaturize; minimally invasive; multidisciplinary; nanofabrication; neural; neural implant; neurochemistry; neurophysiology; novel; operation; response; sensor technology; spatiotemporal; study characteristics; submicron; technological innovation; tool; two-dimensional; ultraviolet

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.

项目概要 完整了解大脑功能需要可靠且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。实现此类映射的工具必须 克服任何现有技术都无法充分或同时解决的无数挑战 技术。因此，该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 由多达 256 个 mm3 大小的记录点组成，用于结合电气和化学 检测活体神经组织中的神经元活动。拟议的创新工具将具有以下特点 与现有技术相比具有显着优势。首先，高导电BDD电极将同时 增强神经传感的灵敏度、选择性和稳定性。他们也将拥有更大的潜力 比目前的电极材料的操作范围。其次，通过使用未掺杂的 PCD 作为密封件， 生物相容性和低污染封装材料，新设备将有可能具有更长的使用寿命和 长期应用的长期稳定性。第三，紧凑的双模前置放大器将更好地实现 高精度和快速扫描循环伏安 (FSCV) 测量的控制 强大的信噪比，同时最大限度地减少串扰。第四，新型微加工技术将 允许晶圆级大规模生产具有各种几何形状、精细空间分辨率的金刚石电极 （亚微米到微米尺度）和高产率（>90%）。采用成熟半导体 制造技术，所提出的制造方法更加可靠、一致、可扩展，并且 比当今广泛用于制造碳纤维电极的手工组装方法更具劳动力/成本效益。 最后但并非最不重要的一点是，高度堆积的电极 3D 阵列将显着增强横向和深度 与当前化学传感工具相比，新型电化学检测工具的覆盖范围。项目 将由多学科的研究人员协作团队进行。该团队将利用其广泛的 具有开发金刚石纤维电极以及精炼材料合成和设备制造的经验 将金刚石电极的空间分辨率从几十微米提升到亚微米的技术 （通过电子束光刻）和微米（通过紫外光刻）（目标 1）。与电极并联 开发过程中，该团队将设计解决方案来实施小型化头戴式电生理学和 FSCV 电子器件，并将探头与金刚石电极阵列集成以实现完整的系统 （目标 2）。然后将对集成系统的功能、生物相容性和稳定性进行离体评估 以及体内使用补充分析技术（目标 3）。拟议的工作意义重大，因为它将 产生了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揭示了许多大脑紊乱和疾病的机制。