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Amperometric NO(g) Sensors with Improved Selectivity/Sensitivity for Biomedical Measurements

用于生物医学测量的具有更高选择性/灵敏度的电流型 NO(g) 传感器

基本信息

批准号：
9068096
负责人：
MARK E MEYERHOFF
金额：
$ 18.75万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-01 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9068096
关键词：
Antiviral Agents Area Asthma Buffers Carbon Dioxide Carbon Monoxide Cells Chemiluminescence assay Chronic Complex Deposition Detection Devices Diagnosis Disease Electrodes Electrolytes Epithelial Epithelial Cells Exhalation Exhibits Film Gases Goals Gold Health Housing Human Infection Inflammatory Institutional Review Boards Life Lung Maintenance Mass Spectrum Analysis Measurement Measures Medical Membrane Methods Microbial Biofilms Monitor Nafion Nitrates Nitric Oxide Nose Oral Oxides Patient Monitoring Patients Performance Phase Platinum Population Procedures Production Protocols documentation Reaction Time Research Respiratory Tract Infections Risk Risk Assessment Sampling Side Silicone Elastomers Sinus Solid Steroids Stream Surface System Teflon Testing Therapeutic Intervention Thick Time Tissues Work antimicrobial base chronic rhinosinusitis cost design healthy volunteer human subject improved instrument macrophage meetings metal oxide oxidation prevent sensor

项目摘要

DESCRIPTION (provided by applicant): Measurement of gas phase nitric oxide (NO) concentrations in exhaled breath, originating from both the oral and nasal passages, can be useful in the diagnosis of several disease states (e.g., asthma) and in the assessment of the risk of frequent infections of the upper airways. Higher levels of NO exist in exhaled nasal breath vs. oral breath, and it is believed that these increased levels of NO originate from NO production in healthy sinus tissues (epithelial cells) that serve to prevent sinus and lung infections, owing to NO's potent antimicrobial/antibiofilm/antiviral activity. Hence, patients with lower levels of exhaled nasal NO are at risk for increased rates of infection and chronic rhinosinusitis (CRS). It is estimated that up to 13% of the US population suffers from CRS. Existing methods to accurately monitor gas phase NO that could aid in identifying patients prone to CRS are complex and costly (e.g., chemiluminescence and mass spectrometry) and not easily adapted for near patient testing. Available electrochemical NO sensors, especially amperometric devices, are relatively simple and inexpensive, but lack of selectivity for NO over carbon monoxide (CO) is problematic in applying such devices for reliable measurements of exhaled gas phase NO to monitor patients. Further, adapting the devices to a gas phase sensing mode with the low detection limits required to be clinically useful has been challenging. This exploratory project builds on a recent discovery that selectivity for NO over CO can be dramatically enhanced when oxide coatings are present on the surface of working electrodes employed to prepare amperometric NO sensors. Hence, this proposal aims to 1a) optimize the formation of oxide layers on the surface of the working electrodes of NO sensors based on conventional (inner working electrode) configurations (Shibuki) and a newer design in which the working electrode is deposited on a solid-electrolyte polymeric film (for both Pt and Au electrodes) by controlling pH and applied polarization potential; 1b) study the analytical performance (sensitivity and selectivity) of these more selective and sensitive NO sensors in detecting NO in flowing gas phase streams using microcontrollers to carefully control gas phase flow rates; and 2) test the most promising amperometric gas phase NO sensors derived from Aim 1 studies to detect NO in exhaled nasal breath collected from healthy human subjects and correlate levels of NO determined by the new gas phase sensors to values measured by the gold-standard chemiluminescence method. It is anticipated that the results of this exploratory study will provide the basis for creating advanced electrochemical NO sensors that will have wide utility in near patient testing of exhaled NO levels to help in diagnosing and treating patients with CRS or asthma.

说明书(申请人提供)：呼出气中一氧化氮(NO)浓度的测量，来源于口腔和鼻腔，可用于诊断几种疾病状态(例如哮喘)和评估上呼吸道频繁感染的风险。与口腔呼吸相比，鼻呼气中存在更高的NO水平，人们认为这些增加的NO水平源于健康的鼻窦组织(上皮细胞)中NO的产生，这些组织用于预防鼻窦和肺部感染，原因是NO具有强大的抗菌/抗生物膜/抗病毒活性。因此，鼻腔呼出的一氧化氮水平较低的患者有感染和慢性鼻窦炎(CRS)增加的风险。据估计，多达13%的美国人口患有CRS。现有的准确监测可帮助识别易患CRS的患者的气相NO的方法复杂且昂贵(例如，化学发光和质谱仪)，并且不容易适用于近距离患者的测试。现有的电化学NO传感器，特别是安培装置，相对简单和便宜，但在应用此类装置可靠地测量呼出的气相NO以监测患者时，缺乏对一氧化碳(CO)的选择性是有问题的。此外，使这些设备适应临床上使用所需的低检测下限的气相传感模式一直是具有挑战性的。这一探索性项目建立在最近的一项发现基础上，即当用于制备电流型NO传感器的工作电极表面存在氧化物涂层时，NO对CO的选择性可以显著提高。因此，这一建议的目的是：1)基于传统的(内部工作电极)构型(Shibuki)和通过控制pH和外加极化电位将工作电极沉积在固体电解质聚合物膜上(对于铂电极和金电极)，优化NO传感器工作电极表面的氧化层的形成；1b)研究这些更选择性和更灵敏的NO传感器的分析性能(灵敏度和选择性)，使用微控制器仔细地控制气相流速来检测流动的气相流中的NO；2)测试最有前景的电流型气相NO传感器，该传感器来自Aim 1研究，目的是检测从健康受试者呼出的鼻气中的NO，并将新的气相传感器测定的NO水平与金标准化学发光法测量的值相关联。预计这项探索性研究的结果将为创造先进的电化学NO传感器提供基础，该传感器将在近患者呼出的NO水平测试中具有广泛的实用价值，以帮助诊断和治疗CRS或哮喘患者。