Online Measurement of Exhaled NO Concentration and Its Production Sites by Fast Non-equilibrium Dilution Ion Mobility Spectrometry

Abstract

Exhaled nitric oxide (NO) is one of the most promising breath markers for respiratory diseases. Its profile for exhalation and the respiratory NO production sites can provide useful information for medical disease diagnosis and therapeutic procedures. However, the high-level moisture in exhaled gas always leads to the poor selectivity and sensitivity for ion spectrometric techniques. Herein, a method based on fast non-equilibrium dilution ion mobility spectrometry (NED-IMS) was firstly proposed to directly monitor the exhaled NO profile on line. The moisture interference was eliminated by turbulently diluting the original moisture to 21% of the original with the drift gas and dilution gas. Weak enhancement was observed for humid NO response and its limit of detection at 100% relative humidity was down to 0.58 ppb. The NO concentrations at multiple exhalation flow rates were measured, while its respiratory production sites were determined by using two-compartment model (2CM) and Högman and Meriläinen algorithm (HMA). Last but not the least, the NO production sites were analyzed hourly to tentatively investigate the daily physiological process of NO. The results demonstrated the capacity of NED-IMS in the real-time analysis of exhaled NO and its production sites for clinical diagnosis and assessment.

Fractional exhaled nitric oxide-measuring devices: technology update

“…Recently, a novel method based on fast nonequilibrium dilution ion mobility spectrometry was proposed to capture the exhaled NO profile in real time with response time of 75 ms, while its profiles at different flow rates were obtained. 51 …”

Fitting of single-exhalation profiles using a pulmonary gas exchange model—application to carbon monoxide

“…Since the data acquisition rate and exhaled volume were kept constant, the relative amount of data points in each exhalation phase was the same regardless of exhalation flow rate and time. The TMAD fitting parameters, J awCO , D awCO , J ACO and D ACO , were free to vary in the range of 100-500 pl s −1 , 1.0-1.6 pl s −1 ppb −1 , 5×10 5 -2×10 8 pl s −1 , and 300-5×10 5 pl s −1 ppb −1 , respectively.…”

“…In general, compounds with low water/blood solubility will exchange in the alveolar region, whereas highly watersoluble molecules will exchange in the airways. For example, both carbon monoxide (CO) and nitric oxide (NO) have a low water solubility, but exhaled CO originates mainly from the alveoli, leading to high end-tidal values [4], while exhaled NO to a large extent stems from ambient air and nasal/airway production, resulting in a characteristic maximum in the beginning of the exhalation [3,5]. High initial concentrations can also be expected for ammonia (NH 3 ), which mostly originates from the oral cavity, but the exceptionally high water solubility and the propensity to adsorption hamper quantitative detection and have so far prevented the reliable measurement of NH 3 exhalation profiles [6].…”

“…However, more sophisticated analytical techniques are needed for real-time analysis of the less abundant molecules. These methods include softionization mass spectrometry (MS), such as selectedion flow tube and proton transfer reaction MS [1], electrospray ionization MS [8], non-equilibrium dilution ion mobility spectrometry [5] and laser absorption spectroscopy (LAS) [2,9].…”

A Novel Microwave-Induced Plasma Ionization Source for Ion Mobility Spectrometry

“…Since then, the applications of IMS were proposed in numerous fields because of low expenditure, fast response time (a few seconds), good portability, relatively low detection limits, etc. These applications include the detection of organic explosives 3 and inorganic explosives 4 , chemical warfare agents 5 , illegal drugs 6 , food and feed analyses 7 , clinical analysis 8 9 , pharmaceutical applications 10 , environmental monitoring 11 , and process and bioprocess monitoring 12 .…”