Detection of Ethanol and Interferents in Breath: Validation of a Novel Technology

检测呼吸中的乙醇和干扰物：新技术的验证

基本信息

批准号：
8131584
负责人：
RICHARD J MELKER
金额：
$ 91.29万
依托单位：
XHALE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-20 至 2013-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8131584
关键词：
Acetaminophen Acetone Address Air Alcohol abuse Alcohols Alzheimer&apos s Disease Amphetamines Automobile Driving Aviation Biological Breath Tests Businesses Caffeine Central Nervous System Depressants Characteristics Clinical Research Clinical Trials Cocaine Cognitive Data Quality Data Set Detection Development Devices Diagnostic Dose Drug Kinetics Drug Monitoring Engineering Environment Enzymes Ethanol Exhalation Florida Forensic Medicine Future Gas Chromatography Gases Generations Goals Growth Hand Human Illicit Drugs Individual Industry Intellectual Property Law Enforcement Legal Marketing Measures Medical Methanol Methods Military Personnel Mining Naltrexone National Institute on Alcohol Abuse and Alcoholism Performance Pharmaceutical Preparations Pharmacodynamics Pharmacologic Substance Phase Physicians Principal Investigator Propofol Public Health Research Research Personnel Schizophrenia Sensitivity and Specificity Shelter facility Small Business Innovation Research Grant Societies Specificity System Technology Testing Therapeutic Time United States Universities Validation Work Workplace addiction base breath alcohol measurement clinical practice cognitive function combat commercialization cost court design design and construction drug of abuse human subject improved instrumentation interest medication compliance meetings metal oxide new technology next generation novel patient population programs public health relevance sensor social success tool

项目摘要

DESCRIPTION (provided by applicant): Among drugs that cause widespread human suffering, none is more destructive than ethanol. The estimated annual cost of ethanol abuse in the United States is $185B. A new breath-based toxicological tool with superior capabilities dedicated to understanding the pharmacokinetics (PK) and pharmacodynamics (PD) of ethanol is needed to combat alcohol abuse and understand its origins. Current devices used to measure ethanol in human breath rely on technologies that are several decades old, which limit the sensitivity and specificity of ethanol detection and poorly separate ethanol from confounding analytes in breath. We propose to develop a new generation of "evidential" (generates high quality data that is directly introduced into courts as legal evidence) breath-based ethanol sensors to combat ethanol abuse in the 21st century. A multi-disciplinary team (physicians, engineers, chemists, addiction experts, and forensic toxicologists) will collectively develop a miniature gas chromatograph metal oxide sensor (mGC-MOS) device for real-time, point-of-use detection of ethanol and other analytes. NIAAA SBIR Phase I support was used to 1) design and construct a mGC-MOS to detect ethanol in real-time, 2) demonstrate the mGC-MOS has outstanding specificity and accuracy, and can readily discriminated between ethanol and other analytes (e.g., acetone, methanol), which commonly interfere with the function of present sensor technologies, and 3) establish mGC-MOS accuracy in humans intoxicated with ethanol in the University of Florida (UF) General Clinical Research Center (GCRC). We now propose to expand this work to refine, construct, and examine the performance characteristics of the next generation breath ethanol analyzer, an evidential mGC-MOS. To that end, the following 3 specific aims will be achieved: Specific Aim 1: Design and build an improved mGC-MOS device with a single GC column (vis-`-vis current dual column configuration) that accurately and precisely measures ethanol concentrations in real-time. (Milestone: 10/31/2010). Specific Aim 2: Demonstrate that the mGC-MOS meets or exceeds evidential breath analyzer performance using established industry standards as enumerated by the Organisation Internationale de Metrologie Legale. (Milestone: 12/31/2010). Specific Aim 3: Validate and use the mGC-MOS as a research tool to investigate the pharmacokinetic/dynamic and cognitive effects of a moderate dose of alcohol in older and younger social drinkers. (Milestone: 03/31/2012). The mGC-MOS being developed will not only 1) provide a superior dataset from ethanol PK/PD clinical studies, but also 2) improve testing in law enforcement and workplace settings by bringing the power of evidential ethanol breath analysis to point-of-use environments, while markedly lowering the cost of evidential testing (<$1,000 mGC-MOS system versus >$100,000 current units). Our long term goal is to expand the utility of this novel mGC-MOS technology in order to effectively address other major medical problems, including drugs of abuse, medication adherence, and functional interrogation of CYP-450 enzyme competency. PUBLIC HEALTH RELEVANCE: Current devices used to measure ethanol in human breath rely on technologies that are several decades old, which limit the sensitivity and specificity of ethanol detection and poorly separate ethanol from confounding analytes in human breath. We propose to develop a new generation of portable, "evidential" breath-based ethanol sensors with superior capabilities to understand the pharmacokinetics and pharmacodynamics of ethanol and to combat ethanol abuse in the 21st century. PHS 398/2590 (Rev. 11/07) Page Continuation Format Page

描述（由申请人提供）：在造成广泛人类痛苦的药物中，没有一种药物比乙醇更具破坏性。美国每年因滥用乙醇造成的成本估计为 $185B。需要一种新的基于呼吸的毒理学工具，具有卓越的能力，致力于了解乙醇的药代动力学 (PK) 和药效学 (PD)，以对抗酒精滥用并了解其起源。目前用于测量人类呼吸中乙醇的设备依赖于几十年前的技术，这限制了乙醇检测的灵敏度和特异性，并且很难将乙醇与呼吸中的混杂分析物分离。我们建议开发新一代“证据”（生成高质量数据，直接作为法律证据提交给法庭）基于呼吸的乙醇传感器，以打击 21 世纪的乙醇滥用。多学科团队（医生、工程师、化学家、成瘾专家和法医毒理学家）将共同开发微型气相色谱金属氧化物传感器 (mGC-MOS) 设备，用于实时、使用点检测乙醇和其他物质分析物。 NIAAA SBIR 第一阶段支持用于 1) 设计和构建 mGC-MOS 以实时检测乙醇，2) 证明 mGC-MOS 具有出色的特异性和准确性，并且可以轻松区分乙醇和其他分析物（例如，丙酮、甲醇），这些物质通常会干扰现有传感器技术的功能，以及 3）在佛罗里达大学 (UF) 一般临床研究中心确定乙醇中毒人体的 mGC-MOS 准确性（GCRC）。我们现在建议扩展这项工作，以完善、构建和检查下一代呼气乙醇分析仪（证据性 mGC-MOS）的性能特征。为此，将实现以下 3 个具体目标：具体目标 1：设计和构建改进的 mGC-MOS 装置，具有单个 GC 色谱柱（相对于当前的双色谱柱配置），可准确、精确地测量乙醇浓度即时的。（里程碑：2010 年 10 月 31 日）。具体目标 2：使用国际法律计量组织列举的既定行业标准，证明 mGC-MOS 达到或超过证据呼吸分析仪性能。（里程碑：2010 年 12 月 31 日）。具体目标 3：验证并使用 mGC-MOS 作为研究工具，研究中等剂量酒精对老年和年轻社交饮酒者的药代动力学/动力学和认知影响。（里程碑：2012 年 3 月 31 日）。正在开发的 mGC-MOS 不仅 1) 提供来自乙醇 PK/PD 临床研究的优质数据集，而且 2) 通过将证据性乙醇呼吸分析的力量引入使用点，改进执法和工作场所环境中的测试环境，同时显着降低证据测试的成本（<1,000 美元的 mGC-MOS 系统与 >100,000 美元的当前装置相比）。我们的长期目标是扩大这种新型 mGC-MOS 技术的实用性，以有效解决其他主要医疗问题，包括药物滥用、药物依从性和 CYP-450 酶能力的功能询问。公共健康相关性：目前用于测量人类呼吸中乙醇的设备依赖于几十年前的技术，这限制了乙醇检测的灵敏度和特异性，并且很难将乙醇与人类呼吸中的混杂分析物分离。我们建议开发新一代便携式、“证据”呼吸乙醇传感器，其具有卓越的能力，可以了解乙醇的药代动力学和药效学，并在 21 世纪打击乙醇滥用。 PHS 398/2590（修订版 11/07）页面延续格式页面