SBIR-STTR Award

Ethanol is one of the most widely consumed drugs with resultant profound consequences to individuals and society. The current methodology used to measure ethanol concentration in breath relies on decades old technology and may limit development of breath analysis to detect not only ethanol with great specificity, but also a number of other compounds that appear in breath. Therefore, the overall goal of the present grant is to prepare the scientific foundations and an actual prototype of a new generation of breath-analysis equipment and software to address the public health needs of the twenty-first century. This proposal describes the current and proposed activities of a multi-disciplinary team of physical and medical scientists who are evaluating use of a mini-gas chromatograph (mini-GC) device and exhaled breath condensate (EBC) collected using active breath management as alternative matrices for real-time, point-of-use measurement of ethanol concentration with preservation of samples for later analysis, if necessary. The applicants have constructed a mini-GC modified to detect ethanol in a real-time manner with excellent specificity that can accurately discriminate between ethanol and other molecules (e.g., acetone, methanol, toluene) that may interfere with alternative technologies used to detect ethanol in breath. Using novel breath handling techniques that gate breath collection to end-tidal carbon dioxide concentrations, we show that ethanol appears in the EBC, at concentrations similar to those measured in blood, following oral consumption of alcohol (3-5 ounces). The appearance of DNA in EBC alludes to the possibility of a "self-identifying tag" to reliably and accurately link an EBC sample to an individual subject source. The goal of this proposal is to expand these findings to refine, construct, and examine the performance characteristics of a mini-GC coupled to an EBC collector. To that end, the following specific aims will be achieved: Specific Aim 1: Design and build a mini-GC device coupled to an EBC collector with active breath management that reliably measures ethanol concentrations in real-time collects and preserves EBC for later analysis. (Milestone: Availability of device by 10/15/2007). Specific Aim 2: Correlate gaseous and EBC ethanol concentrations measured by this device in human subjects with concentrations found in venous blood and document the absence of oral fluid contamination during several different temperatures, normal or hyperventilating breathing patterns, and with/without active breath management. (Milestone: Completion of performance data by 12/31/2007). The short term objective of Xhale Diagnostics, Inc. is to develop these devices to a market of $70 million. The long term objectives of the investigators are to develop breath-based detection technology to enable medical diagnostics as sheltered by intellectual property licensed from the University of Florida.

Thesaurus Terms:
biomedical equipment development, breath test, drug detection, ethanol, gas chromatography, miniature biomedical equipment clinical biomedical equipment, diagnosis design /evaluation, hyperpnea, portable biomedical equipment, temperature blood test, clinical research, human subject

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

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