Laser spectroscopic instrumentation for isotopic sensing of biogenic Nitric Oxide

用于生物一氧化氮同位素传感的激光光谱仪器

• 批准号: 7943860
• 负责人: Gerard Wysocki
• 金额: $ 19.17万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7943860
• 关键词: Accident and Emergency department; Accounting; Agreement; American; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Asthma; Biochemical Process; Biological; Biological Markers; Biological Process; Biology; Biopsy; Brain; Breath Tests; Breathing; Bronchodilator Agents; Calibration; Carbon Dioxide; Cardiovascular system; Cells; Chemistry; Chest; Child; Chronic; Clinical Research; Complex; Concentration measurement; Data Reporting; Dependence; Detection; Development; Diagnosis; Diagnostic; Disease; Distal; Enzymes; Epithelial Cells; European; Exhalation; Exhibits; Free Radicals; Gases; Goals; Health; Home environment; Hospitals; Host Defense; Human; Immunity; Individual; Inflammation; Inflammatory; Inflammatory Response; Injury; Investigation; Isotope Labeling; Isotopes; Kinetics; Laboratories; Lasers; Lead; Letters; Life; Lower respiratory tract structure; Lung; Lung Inflammation; Lung diseases; Maintenance; Malignant neoplasm of lung; Mammalian Cell; Measurable; Measurement; Measures; Mediating; Medical; Medicine; Metabolism; Methods; Minor; Molecular; Monitor; Muscle; Nasal cavity; Nitric Oxide; Nobel Prize; Nose; Obstruction; Operative Surgical Procedures; Optics; Organ Transplantation; Outpatients; Oxidants; Pathogenesis; Patients; Perception; Performance; Peroxonitrite; Persons; Pharmaceutical Preparations; Physicians; Physiological Processes; Physiology; Play; Pollution; Preparation; Prevention; Process; Property; Public Health; Publications; Publishing; Pulmonary Hypertension; Pulmonary function tests; Reaction Time; Regulation; Reliance; Reporting; Research; Resolution; Respiration Disorders; Role; Rotation; Sampling; Science; Scientist; Sensitivity and Specificity; Signaling Molecule; Societies; Source; Specificity; Spectrum Analysis; Spirometry; Sudden Death; Swelling; Symptoms; System; Techniques; Technology; Testing; Time; Tube; United States; Visit; Water; airway hyperresponsiveness; airway inflammation; antimicrobial; asthmatic patient; bactericide; base; blood pressure regulation; constriction; cytotoxic; cytotoxicity; design; dosage; effective therapy; exhaust; flexibility; frontier; gas analyzer; heterodyning; improved; instrument; instrumentation; interest; neoplastic cell; new technology; novel; operation; physical conditioning; portability; prototype; public health relevance; quantum; respiratory; stable isotope; user-friendly

DESCRIPTION (provided by applicant): Detection of nitric oxide is of great importance in a number of bio-medical applications such as non-invasive medical diagnostics based on exhaled human breath analysis or study of the regulation of biological and physiological processes in human and mammalian cells. None of currently available NO sensing technologies can simultaneously provide sub-parts-per- billion sensitivity, <0.1-sec time resolution, capability of selective measurements of NO isotopes, no sample preparation, and high immunity to interferences from other molecular species in a single, compact, portable and user-friendly instrument. The research proposed in this project will lead to development of a novel laser spectroscopic sensing instrumentation, which will provide unique capabilities of biogenic NO quantification. The new technology will be based on Faraday rotation spectroscopy, which can provide unprecedented sensitivity and specificity to NO. To achieve the goals for the system performance and a compact footprint a novel sensitivity enhancement based on ultra-sensitive optical heterodyne detection will be implemented. A broadly tunable mid-infrared external cavity quantum cascade laser will be used as a spectroscopic source, which will provide capability of quantification of all stable NO isotopes with a single instrument. The specific aims of the proposed project are: 1. Development and laboratory demonstration of a novel laser based, optical heterodyne Faraday rotation spectroscopic system for detection of all stable isotopes of NO in exhaled human breath with sub-ppb sensitivity, sub-second resolution and high specificity to discriminate against potentially interfering gases, particularly H2O and CO2. 2. Development, laboratory tests and implementation of reliable consumable-free calibration techniques, which will provide automatic and maintenance-free operation of the instrument. 3. Design and prototype development of a portable sensing instrument with sensitivity, selectivity and fast response time required for exhaled NO concentration measurements in both single breath maneuver as well as during tidal breathing. The technology developed during this project will be broadly applicable to breath analysis as well as other bio-medical applications. In addition other non-biomedical applications such as atmospheric pollution monitoring, combustion diagnostics and vehicle exhaust monitoring that indirectly but significantly help improving people's health will benefit from the proposed development of laser based gas analyzer technology. PUBLIC HEALTH RELEVANCE: Project Narrative Nitric oxide plays a major role in a number of biological processes such as indication of airway inflammation, regulation of blood pressure, regulation of fundamental cellular activities such as whether cells live or die, or can even change the computational ability of the brain. Therefore better understanding of the mechanisms by which nitric oxide contributes to the process biology and bio-chemistry can significantly enhance understanding of many types of diseases or injuries and will result in improved detection, prevention or treatment methods. The proposed research will provide doctors and scientists with a novel nitric oxide sensing instrumentation that will outperform technologies currently used in clinical studies, and will allow for significant advancements in bio-medical science and for improvements of public health.

描述（由申请人提供）：在许多生物医学应用中，一氧化氮的检测非常重要，例如基于呼出的人呼吸分析或研究人类和哺乳动物细胞生物学和生理过程调节的非侵入性医学诊断。目前尚无感知技术可以同时提供一个每十亿个敏感性，<0.1-SEC时间分辨率，NO同位素的选择性测量的能力，没有样品制备，并且对来自单个，紧凑的，紧凑的，便携式和用户友好型仪器中其他分子物种的干扰的高度免疫力。该项目中提出的研究将导致新型激光光谱传感仪器的发展，该仪器将提供生物源无定量的独特功能。这项新技术将基于法拉第旋转光谱，该光谱可以提供前所未有的灵敏度和特异性。为了实现系统性能的目标和紧凑的足迹，将实施基于超敏感的光学杂差检测的新型灵敏度增强。一个可广泛的中红外外部空腔量子级联激光器将用作光谱源，该光谱源将提供具有单个仪器的所有稳定NO同位素的量化能力。拟议项目的具体目的是：1。开发和实验室演示基于激光的光学杂种法拉迪旋转光谱系统，用于检测所有在呼出的人类呼吸中的所有稳定同位素，具有子PPPB敏感性，次级敏感性，子秒的分辨率，次级分辨率，高特异性，高特异性，以抗潜在地侵害潜在的干扰气体，尤其是H2O和CO2，尤其是H2O和CO2。 2。开发，实验室测试和实施可靠的无耗尽校准技术，该技术将提供仪器的自动和无维护操作。 3。具有灵敏度，选择性和快速响应时间的便携式感应仪器的设计和原型开发在单呼吸动作以及潮汐呼吸过程中均未浓度测量所需的快速响应时间。该项目期间开发的技术将广泛适用于呼吸分析以及其他生物医学应用。此外，其他非生物医学应用，例如大气污染监测，燃烧诊断和车辆排气监控，这些应用间接但大大有助于改善人们的健康，将受益于拟议的基于激光的气体分析仪技术的开发。 公共卫生相关性：项目叙事一氧化氮在许多生物学过程中起着重要作用，例如气道炎症的指示，血压调节，调节基本细胞活性，例如细胞是否生命或死亡，甚至可以改变大脑的计算能力。因此，更好地理解一氧化氮有助于过程生物学和生物化学的机制可以显着增强对许多类型的疾病或伤害的理解，并会改善检测，预防或治疗方法。拟议的研究将为医生和科学家提供一种新型的一氧化氧化物传感仪器，该仪器将胜过目前在临床研究中使用的技术，并可以在生物医学科学和公共卫生的改善方面取得重大进步。