NIH SBIR Phase I: Development of a Novel Boron-doped Ultrananocrystalline Diamond

NIH SBIR 第一阶段：新型掺硼超纳米晶金刚石的开发

• 批准号: 8125356
• 负责人: Prabhu U Arumugam
• 金额: $ 14.81万
• 依托单位: ADVANCED DIAMOND TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-05 至 2012-05-04
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8125356
• 关键词: Address; Adhesions; Aftercare; Antibodies; Basic Behavioral Science; Behavior; Biocompatible; Biocompatible Materials; Biological Markers; Biosensor; Boron; Brain; Brain Chemistry; Caliber; Characteristics; Chemicals; Chemistry; Chronic; Communities; Deposition; Detection; Development; Diamond; Diffusion; Disease; Dopamine; Electric Capacitance; Electrodes; Engineering; Environment; Exhibits; Fast Electron; Film; Flow Injection Analysis; Glutamates; Goals; Gold; Human; In Vitro; Investigation; Kinetics; Maps; Marketing; Measurement; Measures; Mechanics; Medical; Methods; Metric; Microelectrodes; Microfabrication; Mission; Modeling; Modification; Monitor; Nanotechnology; Natural regeneration; Neurosciences; Neurotransmitters; Nitric Oxide; Noise; Norepinephrine; Oligonucleotide Probes; Oxidation-Reduction; Pathology; Pattern; Performance; Phase; Physiological; Preparation; Price; Process; Property; Rattus; Reaction Time; Reporting; Resistance; Resolution; Scanning; Sensitivity and Specificity; Serotonin; Signal Transduction; Small Business Innovation Research Grant; Solutions; Specificity; Surface; Symptoms; Tantalum; Techniques; Technology; Testing; Thick; Time; Toxin; United States National Institutes of Health; Work; carbon fiber; cost; ductile; implantation; improved; in vivo; nanofabrication; nanometer; neurobiological mechanism; neurochemistry; new technology; next generation; novel; operation; parylene; potassium ferrocyanide; research study; sensor; tool

DESCRIPTION (provided by applicant): There is an enormous need for the development of a new class of chemical microsensors that are versatile, selective, sensitive and reliable to allow investigation of the neurobiological mechanisms of behavior and disease symptoms. Currently, the preferred method for monitoring neurotransmitters in vivo real time is fast- scan cyclic voltammetry (FSCV) and the preferred microelectrode material is carbon fiber. We propose here the next generation electrode material, boron-doped ultrananocrystalline diamond (BD UNCD) that offers superior sensitivity and specificity, fast response time, low background currents, long-term stability and resistance to fouling compared to carbon fibers. The goal is to develop a chronically implantable UNCD microsensor for long-term (i.e., months to years) neurochemical recording, especially if human compatible. The specific aims of this project are, (i) to develop a reliable UNCD film deposition process on a tantalum (Ta) wire substrate that is scalable and mass-producible, (ii) to demonstrate microelectrode electrochemical behavior (i.e. higher signal-to-noise ratio) of a patterned UNCD-Ta microsensor using cyclic voltammetry and potassium ferrocyanide solution and (iii) to demonstrate the unique advantages of UNCD microelectrodes by measuring dopamine with flow injection analysis and in the anesthetized rat brain. Some of the planned improvements include modifications to the Ta surface preparation process to increase film adhesion and selective patterning of insulators to produce "windows" of BD UNCD that should allow consistent microelectrode behavior. As a proof-of-concept, the electrodes will be used to measure dopamine (the most widely studied neurotransmitter) down to 10 nM physiological concentration. The proposed sensor could potentially be used for simultaneous measurement of dopamine and many other important neurotransmitters. If this project is successful, it will readily accomplish many NIH mission goals for the Division of Neuroscience and Basic Behavioral Science, specifically: 1) for "in vivo voltammetry" - the UNCD is bioinert and highly selective due to its surface chemistry and small pseudo capacitance; 2) for "biocompatible biomaterials" - UNCD/parylene passivation is novel and completely biocompatible for chronic neurochemical sensing; 3) for "nanotechnologies'" - application of UCND and nanometer thick insulators greatly advance the way in which probes are fabricated; and 4) for "biosensors"- UNCD can be easily modified with antibodies and oligonucleotide probes through photochemical or electrochemical means. A recent report suggests that the medical sensing market will reach $10.9 billion in 2012. If only 0.1% ($10.9 million) of that market is accessible by UNCD microelectrode technology, it would still be sufficient justification for the proposed work. Also, a greater understanding of real-time sensing of neurotransmitters from this project would enable alternative applications for the technology, including: low-cost, point-of-use, portable, implantable sensors for toxins, metabolites and disease biomarkers. PUBLIC HEALTH RELEVANCE: This project will develop a microsensor technology using Ultrananocrystalline diamond electrodes to further advance the neuroscience field (brain function and disease symptoms). Its versatility, sensitivity and reliability are ideally suited for real-time, chronic measurement of multiple neurochemicals and brain activity mapping.

描述（由申请人提供）：非常需要开发一种新型的化学微传感器，其是通用的、选择性的、灵敏的和可靠的，以允许研究行为和疾病症状的神经生物学机制。目前，用于在体内真实的时间监测神经递质的优选方法是快速扫描循环伏安法（FSCV），并且优选的微电极材料是碳纤维。我们在这里提出的下一代电极材料，硼掺杂超纳米金刚石（BD UNCD），提供上级灵敏度和特异性，快速响应时间，低背景电流，长期稳定性和抗污染性相比，碳纤维。目标是开发一种长期可植入的UNCD微传感器（即，几个月到几年）的神经化学记录，特别是如果人类兼容。该项目的具体目标是，（一）开发一种可靠的UNCD膜沉积工艺在钽（Ta）线基板上，是可扩展和大规模生产，（ii）展示微电极电化学行为（iii）使用循环伏安法和亚铁氰化钾溶液的图案化UNCD-Ta微传感器的信噪比（即更高的信噪比）用流动注射分析法和麻醉大鼠脑内多巴胺的含量，证明了UNCD微电极的独特优势。一些计划的改进包括修改Ta表面制备工艺，以增加膜粘附力和绝缘体的选择性图案化，以产生BD UNCD的“窗口”，这应该允许一致的微电极行为。作为概念验证，电极将用于测量多巴胺（研究最广泛的神经递质），最低可达10 nM生理浓度。所提出的传感器可能用于同时测量多巴胺和许多其他重要的神经递质。如果该项目成功，它将很容易地完成神经科学和基础行为科学部的许多NIH使命目标，特别是：1）“体内伏安法”-UNCD由于其表面化学和小的伪电容而具有生物惰性和高度选择性; 2）“生物相容性生物材料”- UNCD/聚对二甲苯钝化对于慢性神经化学传感是新颖的和完全生物相容的; 3）对于“纳米技术”-UCND和纳米厚绝缘体的应用极大地推进了探针制造的方式;和4）对于“生物传感器”- UNCD可以通过光化学或电化学手段容易地用抗体和寡核苷酸探针修饰。最近的一份报告显示，2012年医疗传感市场将达到109亿美元。即使只有0.1%（1，090万美元）的市场可通过联合国防治荒漠化公约微电极技术进入，也足以证明拟议的工作是合理的。此外，从该项目中对神经递质实时传感的更深入了解将使该技术的替代应用成为可能，包括：低成本、使用点、便携式、可植入的毒素、代谢物和疾病生物标志物传感器。 公共卫生相关性： 该项目将开发一种使用超纳米金刚石电极的微传感器技术，以进一步推进神经科学领域（大脑功能和疾病症状）。它的多功能性、灵敏度和可靠性非常适合实时、长期测量多种神经化学物质和大脑活动绘图。