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

 描述（由申请人提供）：测量源自口腔和鼻腔的呼出气中的气相一氧化氮（NO）浓度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。与经口呼吸相比，呼出的鼻呼吸中存在更高水平的NO，并且据信这些增加的NO水平源自健康窦组织（上皮细胞）中的NO产生，由于NO的有效抗微生物/抗微生物膜/抗病毒活性，健康窦组织（上皮细胞）用于预防窦和肺感染。因此，患者呼出的鼻NO水平较低，感染和慢性鼻窦炎（CRS）的风险增加。据估计，高达13%的美国人口患有CRS。现有的精确监测气相NO的方法可以帮助识别容易患CRS的患者，这些方法复杂且昂贵（例如，化学发光和质谱法），并且不容易适用于近距离患者测试。可用的电化学NO传感器，特别是电流型装置，相对简单和便宜，但是在应用这种装置可靠地测量呼出的气相NO以监测患者时，NO相对于一氧化碳（CO）缺乏选择性是有问题的。此外，使设备适应具有临床上有用所需的低检测限的气相感测模式一直是具有挑战性的。这个探索性的项目建立在最近的一项发现上，即当氧化物涂层存在于用于制备电流型NO传感器的工作电极表面上时，NO对CO的选择性可以显著增强。因此，该提议旨在：1a）基于传统的氧化物层形成方法，优化NO传感器的工作电极表面上的氧化物层形成。（内部工作电极）配置（Shibuki）和其中工作电极沉积在固体电解质聚合物膜上的较新设计（对于Pt和Au电极）通过控制pH和施加的极化电位; 1b）研究分析性能（灵敏度和选择性）的这些更有选择性和灵敏度的NO传感器在检测流动的气相流中的NO时使用微控制器来仔细地控制气相流率;以及2）测试源自Aim 1研究的最有前途的电流型气相NO传感器，以检测从健康人受试者收集的呼出的鼻呼吸中的NO，并将由新的气相传感器确定的NO水平与由金标准化学发光方法测量的值相关联。预计这项探索性研究的结果将为创建先进的电化学NO传感器提供基础，该传感器将在呼出NO水平的近患者测试中具有广泛的实用性，以帮助诊断和治疗CRS或哮喘患者。

 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.