权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Ultrananocrystalline Diamond Microarray Biosensor for Neurochemical Detection

用于神经化学检测的超纳米晶金刚石微阵列生物传感器

基本信息

批准号：
8252825
负责人：
Prabhu U Arumugam
金额：
$ 14.94万
依托单位：
ADVANCED DIAMOND TECHNOLOGIES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-05-15 至 2013-05-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8252825
关键词：
Acute Address Aftercare Antibodies Behavior Biocompatible Biological Markers Biosensor Boron Brain Brain Chemistry Brain region Caliber Characteristics Chemicals Chemistry Chronic Data Deposition Detection Development Diamond Diffusion Disease Dopamine Electric Capacitance Electrodes Engineering Environment Enzymes Epilepsy Ethanol Event Exhibits Fast Electron Film Flow Injection Analysis Glutamates Goals Gold Human Hydrogen Peroxide In Vitro Investigation Kinetics Letters Maps Marketing Measurement Measures Mechanics Mediating Medical Membrane Metals Methods Metric Microelectrodes Microfabrication Mission Monitor Nafion Nanotechnology Neurosciences Neurotransmitters Nitric Oxide Noise Norepinephrine Oligonucleotide Probes Oxidases Performance Phase Physiological Platinum Preparation Price Process Property Rattus Reaction Time Reporting Resistance Resolution Sales Scanning Sensitivity and Specificity Serotonin Signal Transduction Silicon Site Specificity Surface Techniques Technology Testing Thick Time Toxin United States National Institutes of Health alcohol effect alcohol prevention base carbon fiber cost ductile implantation improved in vivo instrumentation interest nano nanofabrication nanometer neurochemistry neurophysiology new technology next generation novel operation parylene prototype research study scale up sensor tool

项目摘要

DESCRIPTION (provided by applicant): There is an acute need for the development of a new class of microarray biosensors that are sufficiently versatile, selective, sensitive and reliable to allow investigation of the time-dependent neurochemical events of ethanol administration in multiple regions of the brain. 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 development of 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 as compared to carbon fibers. The goal is to develop chronically implantable UNCD microarray electrodes for long-term (i.e., months to years) recording of multiple neurochemicals, especially if human compatible. The specific aims of this project are to: (i) develop a reliable, scalable and mass-producible UNCD microarray that exhibits micro or nano electrode electrochemical behavior (i.e. higher signal-to-noise ratio) using cyclic voltammetry and dopamine (the most widely studied neurotransmitter), (ii) demonstrate glutamate detection on a modified UNCD microelectrode and (iii) demonstrate the unique advantages of UNCD microarrays by measuring two neurochemicals (dopamine and glutamate with flow injection analysis and in an anesthetized rat brain) i.e. multiplexing, which is an important step towards multiple neurochemical detection at a single site. As a proof-of-concept, the electrodes will be used to measure the two neurochemicals down to physiological concentrations. The proposed microarray chemical/biosensor could potentially be used for simultaneous measurement of dopamine, glutamate and many other important neurotransmitters in multiple brain regions. If this project is successful, it will accomplish key NIH mission goals, specifically: 1) UNCD's bioinertness, low pseudo capacitance and high selectively due to its surface chemistry will greatly enhance "in vivo voltammetry"; 2) UNCD/parylene passivation is novel and completely "biocompatible" for chronic neurochemical sensing; 3) application of UCND and nanometer thick insulators will greatly advance the way in which probes are fabricated for "nanotechnologies' in general; and 4) UNCD can be easily modified with enzymes, antibodies and oligonucleotide probes through photochemical or electrochemical means for "biosensors". A recent sensor market report suggests that the medical sensing market will reach $10.9 billion in 2012. Based on a letter of support from a leading neurophysiological microelectrodes and instrumentation company, the expected annual sales for this product at FHC Inc., would be "at least $10-15 million" and would be expected to exceed this number many-fold over the broader neuroscience market. 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 sensors for toxins, metabolites and disease biomarkers. PUBLIC HEALTH RELEVANCE: This project will develop a microarray biosensor technology using ultrananocrystalline diamond electrodes to further advance the neuroscience field (brain function and the effects of ethanol administration). 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）：迫切需要开发一类新的微阵列生物传感器，其具有足够的通用性、选择性、灵敏性和可靠性，以允许研究在大脑多个区域中给予乙醇的时间依赖性神经化学事件。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。我们建议开发下一代电极材料，硼掺杂超纳米金刚石（BD-UNCD），与碳纤维相比，它具有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。目标是开发长期可植入的UNCD微阵列电极（即，几个月到几年）记录多种神经化学物质，特别是如果人类兼容。该项目的具体目标是：（i）开发可靠的、可扩展的和可批量生产的UNCD微阵列，其表现出微电极或纳米电极电化学行为，（即较高的信噪比）使用循环伏安法和多巴胺（研究最广泛的神经递质），（ii）证明在修饰的UNCD微电极上的谷氨酸检测，和（iii）通过测量两种神经化学物质（多巴胺和谷氨酸，使用流动注射分析，在麻醉的大鼠脑中），即多路复用，证明了UNCD微阵列的独特优势，这是在单个位点进行多神经化学物质检测的重要一步。作为概念验证，电极将用于测量两种神经化学物质的生理浓度。所提出的微阵列化学/生物传感器可能用于同时测量多巴胺，谷氨酸和许多其他重要的神经递质在多个大脑区域。如果该项目成功，它将实现NIH的关键使命目标，具体地说：1）UNCD的生物惰性、低伪电容和由于其表面化学的高选择性将大大增强“体内伏安法”; 2）UNCD/聚对二甲苯钝化是新颖的并且对于慢性神经化学传感是完全“生物相容的”; 3）UCND和纳米厚绝缘体的应用将极大地推进“纳米技术”探针的制造方式;和4）UNCD可以通过光化学或电化学手段用酶、抗体和寡核苷酸探针轻松修饰，用于“生物传感器”。最近的一份传感器市场报告显示，2012年医疗传感市场将达到109亿美元。根据一家领先的神经生理微电极和仪器公司的支持信，该产品在FHC Inc.的预期年销售额，这将是“至少1000 - 1500万美元”，预计将超过这个数字许多倍，在更广泛的神经科学市场。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，用于毒素，代谢物和疾病生物标志物的便携式传感器。公共卫生相关性：本项目将开发使用超纳米金刚石电极的微阵列生物传感器技术，以进一步推进神经科学领域（大脑功能和乙醇管理的影响）。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。