Laser spectroscopic instrumentation for isotopic sensing of biogenic Nitric Oxide

描述(由申请人提供)：一氧化氮的检测在许多生物医学应用中非常重要，例如基于呼气分析的非侵入性医疗诊断或对人类和哺乳动物细胞中生物和生理过程调节的研究。目前，没有一种可用的NO传感技术能够在单个、紧凑、便携和用户友好的仪器中同时提供十亿分之一以下的灵敏度、&lt；0.1秒的时间分辨率、选择性测量NO同位素的能力、不需要样品制备以及对其他分子物种的干扰具有高度免疫力。本项目提出的研究将导致一种新型的激光光谱传感仪器的开发，该仪器将提供独特的生物NO定量能力。这项新技术将基于法拉第旋转光谱，它可以为NO提供前所未有的灵敏度和特异性。为了达到系统性能和占地面积小的目标，将实现一种基于超灵敏光外差检测的新型灵敏度增强。一个可广泛调谐的中红外外腔量子级联激光器将被用作光谱源，它将提供用单一仪器定量所有稳定的NO同位素的能力。拟议项目的具体目标是：1.开发和实验室演示一种新型的基于激光的光学外差法拉第旋转光谱系统，用于检测呼气中一氧化氮的所有稳定同位素，具有亚ppb的灵敏度、亚秒分辨率和高特异性，以区分潜在的干扰气体，特别是水和二氧化碳。2.开发、实验室测试和实施可靠的无消耗品校准技术，该技术将提供仪器的自动和免维护操作。3.设计并开发了一种便携式传感仪器，该仪器具有灵敏度、选择性和快速响应时间，可用于单次呼吸和潮气呼吸时呼出NO浓度的测量。在该项目期间开发的技术将广泛应用于呼气分析以及其他生物医学应用。此外，其他间接但显著有助于改善人们健康的非生物医学应用，如大气污染监测、燃烧诊断和汽车尾气监测，将受益于拟议中的基于激光的气体分析仪技术的发展。 与公共卫生相关：项目叙述一氧化氮在许多生物学过程中发挥着重要作用，如指示呼吸道炎症、调节血压、调节基本细胞活动(如细胞存活或死亡)，甚至可以改变大脑的计算能力。因此，更好地了解一氧化氮在过程生物学和生物化学中的作用机制，可以显著提高对许多类型疾病或损伤的了解，并将导致改进检测、预防或治疗方法。这项拟议的研究将为医生和科学家提供一种新型的一氧化氮传感仪器，该仪器的性能将超过目前临床研究中使用的技术，并将允许生物医学科学的重大进步和公共卫生的改善。

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.