Breath-by-breath measurement of exhaled ammonia by acetone-modifier positive photoionization ion mobility spectrometry via online dilution and purging sampling.

Exhaled ammonia (NH3) is an essential noninvasive biomarker for disease diagnosis. In this study, an acetone-modifier positive photoionization ion mobility spectrometry (AM-PIMS) method was developed for accurate qualitative and quantitative analysis of exhaled NH3 with high selectivity and sensitivity. Acetone was introduced into the drift tube along with the drift gas as a modifier, and the characteristic NH3 product ion peak of (C3H6O)4NH4+ (K0 = 1.45 cm2/V·s) was obtained through the ion-molecule reaction with acetone reactant ions (C3H6O)2H+ (K0 = 1.87 cm2/V·s), which significantly increased the peak-to-peak resolution and improved the accuracy of exhaled NH3 qualitative identification. Moreover, the interference of high humidity and the memory effect of NH3 molecules were significantly reduced via online dilution and purging sampling, thus realizing breath-by-breath measurement. As a result, a wide quantitative range of 5.87-140.92 µmol/L with a response time of 40 ms was achieved, and the exhaled NH3 profile could be synchronized with the concentration curve of exhaled CO2. Finally, the analytical capacity of AM-PIMS was demonstrated by measuring the exhaled NH3 of healthy subjects, demonstrating its great potential for clinical disease diagnosis.

Breath-by-breath measurement of exhaled ammonia by acetone-modifier positive photoionization ion mobility spectrometry via online dilution and purging sampling / 药物分析学报

Exhaled ammonia(NH3)is an essential noninvasive biomarker for disease diagnosis.In this study,an acetone-modifier positive photoionization ion mobility spectrometry(AM-PIMS)method was developed for accurate qualitative and quantitative analysis of exhaled NH3 with high selectivity and sensitivity.Acetone was introduced into the drift tube along with the drift gas as a modifier,and the characteristic NH3 product ion peak of(C3H6O)4NH4+(K0=1.45 cm2/V·s)was obtained through the ion-molecule reaction with acetone reactant ions(C3H6O)2H+(K0=1.87 cm2/V·s),which significantly increased the peak-to-peak resolution and improved the accuracy of exhaled NH3 qualitative identification.Moreover,the interference of high humidity and the memory effect of NH3 molecules were significantly reduced via online dilution and purging sampling,thus realizing breath-by-breath measurement.As a result,a wide quantitative range of 5.87-140.92 μmol/L with a response time of 40 ms was achieved,and the exhaled NH3 profile could be synchronized with the concentration curve of exhaled CO2.Finally,the analytical capacity of AM-PIMS was demonstrated by measuring the exhaled NH3 of healthy subjects,demon-strating its great potential for clinical disease diagnosis.

A Low-Cost Device for Measurement of Exhaled Breath for the Detection of Obstructive Lung Disease.

Breath sensor technology can be used in medical diagnostics. This study aimed to build a device to measure the level of hydrogen sulfide, ammonia, acetone and alcohol in exhaled breath of patients as well as healthy individuals. The purpose was to determine the efficacy of these gases for detection of obstructive lung disease. This study was conducted on a total of 105 subjects, where 60 subjects were patients of obstructive lung disease and 45 subjects were healthy individuals. Patients were screened by means of the Pulmonary Function Test (PFT) by a pulmonologist. The gases present in the exhaled breath of all subjects were measured. The level of ammonia (32.29 ± 20.83 ppb), (68.83 ± 35.25 ppb), hydrogen sulfide (0.50 ± 0.26 ppm), (62.71 ± 22.20 ppb), and acetone (103.49 ± 35.01 ppb), (0.66 ± 0.31 ppm) in exhaled breath were significantly different (p < 0.05) between obstructive lung disease patients and healthy individuals, except alcohol, with a p-value greater than 0.05. Positive correlation was found between ammonia w.r.t Forced Expiratory Volume in 1 s (FEV1) (r = 0.74), Forced Vital Capacity (FVC) (r = 0.61) and Forced Expiratory Flow (FEF) (r = 0.63) and hydrogen sulfide w.r.t FEV1 (r = 0.54), FVC (r = 0.41) and FEF (r = 0.37). Whereas, weak correlation was found for acetone and alcohol w.r.t FEV1, FVC and PEF. Therefore, the level of ammonia and hydrogen sulfide are useful breath markers for detection of obstructive lung disease.

Quartz-enhanced photoacoustic NH3 sensor exploiting a large-prong-spacing quartz tuning fork and an optical fiber amplifier for biomedical applications.

A sensor system for exhaled ammonia (NH3) monitoring exploiting quartz-enhanced photoacoustic spectroscopy (QEPAS) was demonstrated. An erbium-doped fiber amplifier (EDFA) with an operating frequency band targeting an NH3 absorption line falling at 1531.68 nm and capable to emit up to 3 W of optical power was employed. A custom T-shaped grooved QTF with prong spacing of 1 mm was designed and realized to allow a proper focusing of the high-power optical beam exiting the EDFA between the prongs. The performance of the realized sensor system was optimized in terms of spectrophone parameters, laser power and modulation current, resulting in a NH3 minimum detectable concentration of 14 ppb at 1 s averaging time, corresponding to a normalized noise equivalent absorption coefficient (NNEA) of 8.15 × 10-9 cm-1 W/√Hz. Continuous measurements of the NH3 level exhaled by 3 healthy volunteers was carried out to demonstrate the potentiality of the developed sensor for breath analysis applications.

Breath Ammonia Is a Useful Biomarker Predicting Kidney Function in Chronic Kidney Disease Patients.

Chronic kidney disease (CKD) is a public health problem and its prevalence has increased worldwide; patients are commonly unaware of the condition. The present study aimed to investigate whether exhaled breath ammonia via vertical-channel organic semiconductor (V-OSC) sensor measurement could be used for rapid CKD screening. We enrolled 121 CKD stage 1-5 patients, including 19 stage 1 patients, 26 stage 2 patients, 38 stage 3 patients, 21 stage 4 patients, and 17 stage 5 patients, from July 2019 to January 2020. Demographic and laboratory data were recorded. The exhaled ammonia was collected and rapidly measured by the V-OSC sensor to correlate with kidney function. Results showed no significant difference in age, sex, body weight, hemoglobin, albumin level, and comorbidities in different CKD stage patients. Correlation analysis demonstrated a good correlation between breath ammonia and blood urea nitrogen levels, serum creatinine levels, and estimated glomerular filtration rate (eGFR). Breath ammonia concentration was significantly elevated with increased CKD stage compared with the previous stage (CKD stage 1/2/3/4/5: 636 ± 94; 1020 ± 120; 1943 ± 326; 4421 ± 1042; 12781 ± 1807 ppb, p < 0.05). The receiver operating characteristic curve analysis showed an area under the curve (AUC) of 0.835 (p < 0.0001) for distinguishing CKD stage 1 from other CKD stages at 974 ppb (sensitivity, 69%; specificity, 95%). The AUC was 0.831 (p < 0.0001) for distinguishing between patients with/without eGFR < 60 mL/min/1.73 m2 (cutoff 1187 ppb: sensitivity, 71%; specificity, 78%). At 886 ppb, the sensitivity increased to 80% but the specificity decreased to 69%. This value is suitable for kidney function screening. Breath ammonia detection with V-OSC is a real time, inexpensive, and easy to administer measurement device for screening CKD with reliable diagnostic accuracy.