Xue Zou

Exhaled gases online measurements for esophageal cancer patients and healthy people by proton transfer reaction mass spectrometry

Esophageal cancer is a prevalent malignancy. There is a considerable demand for developing a fast and noninvasive method to screen out the suspect esophageal cancer patients who may undergo further clinical diagnosis.

Spray Inlet Proton Transfer Reaction Mass Spectrometry (SI-PTR-MS) for Rapid and Sensitive Online Monitoring of Benzene in Water

Rapid and sensitive monitoring of benzene in water is very important to the health of people and for environmental protection. A novel and online detection method of spray inlet proton transfer reaction mass spectrometry (SI-PTR-MS) was introduced for rapid and sensitive monitoring of trace benzene in water. A spraying extraction system was coupled with the self-developed PTR-MS. The benzene was extracted from the water sample in the spraying extraction system and continuously detected with PTR-MS. The flow of carrier gas and salt concentration in water were optimized to be 50 sccm and 20% (w/v), respectively. The response time and the limit of detection of the SI-PTR-MS for detection of benzene in water were 55 s and 0.14 μg/L at 10 s integration time, respectively. The repeatability of the SI-PTR-MS was evaluated, and the relative standard deviation of five replicate determinations was 4.3%. The SI-PTR-MS system was employed for monitoring benzene in different water matrices, such as tap water, lake water, and wastewater. The results indicated that the online SI-PTR-MS can be used for rapid and sensitive monitoring of trace benzene in water.

Detection of Ketones by a Novel Technology: Dipolar Proton Transfer Reaction Mass Spectrometry (DP-PTR-MS)

AbstractProton transfer reaction mass spectrometry (PTR-MS) has played an important role in the field of real-time monitoring of trace volatile organic compounds (VOCs) due to its advantages such as low limit of detection (LOD) and fast time response. Recently, a new technology of proton extraction reaction mass spectrometry (PER-MS) with negative ions OH– as the reagent ions has also been presented, which can be applied to the detection of VOCs and even inorganic compounds. In this work, we combined the functions of PTR-MS and PER-MS in one instrument, thereby developing a novel technology called dipolar proton transfer reaction mass spectrometry (DP-PTR-MS). The selection of PTR-MS mode and PER-MS mode was achieved in DP-PTR-MS using only water vapor in the ion source and switching the polarity. In this experiment, ketones (denoted by M) were selected as analytes. The ketone (molecular weight denoted by m) was ionized as protonated ketone [M + H]+ [mass-to-charge ratio (m/z) m + 1] in PTR-MS mode and deprotonated ketone [M – H]– (m/z m – 1) in PER-MS mode. By comparing the m/z value of the product ions in the two modes, the molecular weight of the ketone can be positively identified as m. Results showed that whether it is a single ketone sample or a mixed sample of eight kinds of ketones, the molecular weights can be detected with DP-PTR-MS. The newly developed DP-PTR-MS not only maintains the original advantages of PTR-MS and PER-MS in sensitive and rapid detection of ketones, but also can estimate molecular weight of ketones. Graphical Abstractᅟ

Application of a self-developed proton transfer reaction-mass spectrometer to on-line monitoring trace volatile organic compounds in ambient air

Real-time and on-line monitoring volatile organic compounds(VOCs) are valuable for real-time evaluating air quality and monitoring the key source of pollution. A self-developed proton transfer reaction-mass spectrometer( PTR-MS) was constructed and applied to on-line monitoring trace VOCs in ambient air in Hefei. With the help of a self-developed catalytic converter, the background signal of the instrument was detected and the stability of the instrument was evaluated. The relative standard deviation of signal at m/z 21 was only 0.74% and the detection limit of PTR-MS was 97 part per trillion(97×10–12, volume ratio). As a case of the air monitoring in Hefei, the ambient air at Dongpu reservoir spot was on-line monitored for 13 d with our self-developed PTR-MS. Meanwhile, a solid-phase micro-extraction(SPME) technique coupled to gas chromatography-mass spectrometry/mass spectrometry (GC-MS/MS) was also used for the off-line detection of the air. The results show that our self-developed PTR-MS can be used for the on-line and long-term monitoring of VOCs in air at part per trillion level, and the change trend of VOCs concentration monitored with PTR-MS was consistent with that detected with the conventional SPME-GC-MS. This self-developed PTR-MS can fully satisfy the requirements of air quality monitoring and real-time monitoring of the key pollution sources.

Detection of Volatile Organic Compounds in a Drop of Urine by Ultrasonic Nebulization Extraction Proton Transfer Reaction Mass Spectrometry

Detection of volatile organic compounds (VOCs) in human urine has potential application value in screening for disease and toxin exposure. However, the current technologies are too slow to detect the concentration of VOCs in fresh urine. In this study, we developed a novel ultrasonic nebulization extraction proton transfer reaction mass spectrometry (UNE-PTR-MS) technology. The urinary VOCs can be rapidly extracted to gaseous VOCs using the UNE system and then delivered using a carrier gas to the PTR-MS instrument for rapid detection. The carrier gas flow and sample size were optimized to 100 mL/min and 100 μL, respectively. The limits of detection (LODs) and response time of the UNE-PTR-MS were evaluated by detecting three VOCs that are common in human urine: methanol, acetaldehyde, and acetone. The LODs determined for methanol (4.47 μg/L), acetaldehyde (1.98 μg/L), and acetone (3.47 μg/L) are 2-3 orders of magnitude lower than the mean concentrations of that in healthy human urine. The response time of the UNE-PTR-MS is 34 s and only 0.66 mL of urine is required for a full scan. The repeatability of this UNE-PTR-MS was evaluated, and the relative standard deviations of 5 independent determinations were between 4.62% and 5.21%. Lastly, the UNE-PTR-MS was applied for detection of methanol, acetaldehyde, and acetone in real human urine to test matrix effects, yielding relative recoveries of between 88.39% and 94.54%. These results indicate the UNE-PTR-MS can be used for the rapid detection of VOCs in a drop of urine and has practical potential for diagnosing disease or toxin exposure.

Glass bottle sampling solid phase microextraction gas chromatography mass spectrometry for breath analysis of drug metabolites

Breath analysis is a non-invasive approach which may be applied to disease diagnosis and pharmacokinetic study. In the case of offline analysis, the exhaled gas needs to be collected and the sampling bag is often used as the storage vessel. However, the sampling bag usually releases some extra compounds, which may interfere with the result of the breath test. In this study, a novel breath sampling glass bottle was developed with a syringe needle sampling port for solid phase microextraction (SPME). Such a glass bottle scarcely liberates compounds and can be used to collect exhaled gas for ensuing analysis by gas chromatography-mass spectrometry (GC-MS). The glass bottle sampling SPME-GC-MS analysis was carried out to investigate the breath metabolites of myrtol, a multicompound drug normally used in the treatment of bronchitis and sinusitis. Four compounds, α-pinene, 2,3-dehydro-1,8-cineole, d-limonene and 1,8-cineole were found in the exhaled breath of all eight volunteers who had taken the myrtol. While for other ten subjects who had not used the myrtol, these compounds were undetectable. In the SPME-GC-MS analysis of the headspace of myrtol, three compounds were detected including α-pinene, d-limonene and 1,8-cineole. Comparing the results of breath and headspace analysis, it indicates that 2,3-dehydro-1,8-cineole in the breath is the metabolite of 1,8-cineole. It is the first time that this metabolite was identified in human breath. The study demonstrates that the glass bottle sampling SPME-GC-MS method is applicable to exhaled gas analysis including breath metabolites investigation of drugs like myrtol.

Online exhaled gas measurements for radiotherapy patients by proton transfer reaction mass spectrometry

The present study assessed whether exhaled breath analysis using proton transfer reaction mass spectrometry (PTR-MS) could screen for radiation exposure. As the intensity of proton transfer reaction reagent ion H3(16)O(+) can be calculated with the intensity of H3(18)O(+), the intensity of H3(18)O(+) was monitored to observe the stability of the PTR-MS instrument during the experiment. The PTR-MS was applied for detecting the volatile organic compounds (VOCs) in the exhaled breath from 42 radiotherapy patients and other 61 patients who had not received radiotherapy. All patients were enrolled in the local cancer hospital. In the experiment, the subjects breathe slowly to the PTR-MS through a direct inlet system without any sampling bag or tube. The breath mass spectrometric data was statistically analyzed using Mann-Whitney U test and stepwise discriminant analysis to find the characteristic ions of radiation exposure. Receiver operating characteristics (ROC) analysis was applied for a combination of the characteristic ions. The PTR-MS instrument was stable as the intensity of reaction ion H3(16)O(+) was maintained in 1.1%. Through statistically analysis, we found 6 kinds of characteristic ions of radiation exposure, specifically mass-to-charge ratio (m/z) 93, m/z 41, m/z 102, m/z 79, m/z 131, and m/z 143. The sensitivity (true positive rate) and specificity (true negative rate) were 78.6% and 82.0% respectively. The integrated area under the ROC curve (AUC) was 0.869. The results in our study demonstrated the potential of the online breath tester PTR-MS as a non-invasive screening for radiation exposure.

Exhaled breath online measurement for cervical cancer patients and healthy subjects by proton transfer reaction mass spectrometry

Cervical cancer is a common cancer among women and has a high morbidity and mortality. The traditional clinical methods for cervical cancer screening are invasive and limited in terms of cost and time. There is an unmet clinical need for new methods to aid clinicians in the rapid screening and auxiliary diagnosis of cervical precancer. Recently, breath analysis has become an attractive approach for investigation of cancer biomarkers and shows great potential in cancer screening owing to its high sensitivity, quickness, and non-invasive nature. In this pilot study, breath analysis by proton transfer reaction mass spectrometry (PTR-MS) was utilized for online analysis of the exhaled breath of 13 cervical cancer patients and 34 female healthy volunteers. The Mann–Whitney U test and stepwise forward linear discriminant analysis were performed for data statistics. On the basis of the statistical analysis, four characteristic ions at m/z 76, 87, 93, and 121 were found for discriminating cervical cancer. The sensitivity and specificity were calculated to be 92.3% and 88.2%, respectively, using the stepwise discriminant analysis. The possible identities of characteristic ions were also discussed in detail. Although there are some uncertainties in the identification of these characteristic ions and more participants (including cervical cancer patients and healthy volunteers) are needed to further confirm the results, the results in this study demonstrate that the online breath test using PTR-MS is a promising approach for cervical cancer screening.