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.

项目摘要 对大脑功能的完全了解需要对大型大脑的可靠和全面的映射 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 克服无数挑战，这些挑战未充分或同时由任何现有的挑战 技术。因此，该提案的总体目标是开发新的基于钻石的神经接口系统 这包括MM3大小的量的多达256个记录位点，用于混合电气和化学 在活神经组织中检测神经元活性。拟议的创新工具将具有以下 与现有技术相比，具有重要优势。首先，高电导性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 运行范围比当前电极材料。其次，通过使用未掺杂的PCD作为密封 新设备的生物相容性和低污染封装材料可能会具有更大的寿命，并且 长期用于慢性应用的稳定性。第三，紧凑的双模式媒体将更好地启用 用高精度和A 强烈的信噪比，同时最大程度地减少串扰。第四，新颖的微加工技术将 允许晶圆级，具有各种几何形状的钻石电极的质量生产，精细的空间分辨率 （微米尺度的亚微米计）和高产量（> 90％）。从公认的半导体采用 制造技术，提议的制造方法更可靠，一致，可扩展，并且 人工/成本效益比当今广泛用于制造碳纤维电极的手装配方法。 最后但并非最不重要的一点是，高度填充电极的3D阵列将显着增强横向和深度 与当前的化学传感工具相比，新的电化学检测工具的覆盖范围。项目 将由多学科的研究人员团队进行。团队将利用他们的广泛 有开发钻石纤维电极以及精炼材料合成和装置制造的经验 将钻石电极空间分辨率从几十微米推到亚微米计的技术 （通过电子束光刻）和千分尺（通过紫外线光刻）（AIM 1）。与电极并行 开发，该团队将设计解决方案，以实施微型的头部载体电生理学和 FSCV电子设备，并将媒体与钻石电极阵列整合在一起，以实现完整的系统 （目标2）。然后将评估集成系统的功能，生物相容性和稳定性 并使用互补分析技术进行体内（AIM 3）。拟议的工作很重要，因为它将 产生一种革命性的神经接口工具，可以很容易地将其传播给其他研究人员 神经科学和临床研究揭示了许多脑部疾病和疾病的机制。