Determination of the two-compartment model parameters of exhaled HCN by fast negative photoionization mass spectrometry.

Breath exhaled hydrogen cyanide (HCN) has been identified to be associated with several respiratory diseases. Accurately distinguishing the concentration and release rate of different HCN sources is of great value in clinical research. However, there are still significant challenges due to the high adsorption and low concentration characteristics of exhaled HCN. In this study, a two-compartment kinetic model method based on negative photoionization mass spectrometry was developed to simultaneously determine the kinetic parameters including concentrations and release rates in the airways and alveoli. The influences of the sampling line diameter, length, and temperature on the response time of the sampling system were studied and optimized, achieving a response time of 0.2 s. The negative influence of oral cavity-released HCN was reduced by employing a strategy based on anatomical lung volume calculation. The calibration for HCN in the dynamic range of 0.5-100 ppbv and limit of detection (LOD) at 0.3 ppbv were achieved. Subsequently, the experiments of smoking, short-term passive smoking, and intake of bitter almonds were performed to examine the influences of endogenous and exogenous factors on the dynamic parameters of the model method. The results indicate that compared with steady-state concentration measurements, the kinetic parameters obtained using this model method can accurately and significantly reflect the changes in different HCN sources, highlighting its potential for HCN-related disease research.

Antigen-loaded flagellate bacteria for enhanced adaptive immune response by intradermal injection.

Since the skin limits the distribution of intradermal vaccines, a large number of dendritic cells in the skin cannot be fully utilized to elicit a more effective immune response. Here, we loaded the antigen to the surface of the flagellate bacteria that was modified by cationic polymer, thus creating antigen-loaded flagellate bacteria (denoted as 'FB-Ag') to overcome the skin barrier and perform the active delivery of antigen in the skin. The FB-Ag showed fast speed (∼0.2 µm s-1) and strong dendritic cell activation capabilities in the skin model in vitro. In vivo, the FB-Ag promoted the spread of antigen in the skin through active movement, increased the contact between Intradermal dendritic cells and antigen, and effectively activated the internal dendritic cells in the skin. In a mouse of pulmonary metastatic melanoma and in mice bearing subcutaneous melanoma tumor, the FB-Ag effectively increased antigen-specific therapeutic efficacy and produced long-lasting immune memory. More importantly, the FB-Ag also enhanced the level of COVID-19 specific antibodies in the serum and the number of memory B cells in the spleen of mice. The movement of antigen-loaded flagellate bacteria to overcome intradermal constraints may enhance the activation of intradermal dendritic cells, providing new ideas for developing intradermal vaccines.

Online Detection of HCN in Humid Exhaled Air by Gas Flow-Assisted Negative Photoionization Mass Spectrometry.

Hydrogen cyanide (HCN) is a well-known toxic compound in many fields. The trace amount of endogenous HCN in human exhalation has been associated with the presence of Pseudomonas aeruginosa (PA) infection in cystic fibrosis (CF) patients. Online monitoring of HCN profile is promising to screen PA infection rapidly and accurately. In this study, a gas flow-assisted negative photoionization (NPI) mass spectrometry method was developed for monitoring the single-exhalation HCN profile. The sensitivity could be optimized by introducing helium to eliminate the humidity influence and reduce the low mass cutoff effect, with improvements of a factor 150 observed. By employing a purging gas procedure and minimizing the length of the sample line, the residual and response time were greatly reduced. The limit of detection (LOD) of 0.3 ppbv and time resolution of 0.5 s were achieved. HCN profiles of exhalations from different volunteers before or after gargling with water were detected to show the performance of the method. All profiles showed a sharp peak and a stable end-tidal plateau, representing the concentration of oral cavity and end-tidal gas, respectively. The HCN concentration based on the plateau of the profile showed better reproducibility and accuracy, which indicates this method has potential application in the detection of PA infection in CF patients.

Rapid Determination of Ethyl Carbamate in Chinese Liquor via a Direct Injection Mass Spectrometry with Time-Resolved Flash-Thermal-Vaporization and Acetone-Assisted High-Pressure Photoionization Strategy.

Ethyl carbamate (EC), a carcinogenic compound, is naturally produced in fermented foods and alcoholic beverages. Rapid and accurate measurement of EC is necessary and important for quality control and safety evaluation of Chinese liquor, a traditionally distilled spirit with the highest consumption in China, but it remains a great challenge. In this work, a direct injection mass spectrometry (DIMS) with time-resolved flash-thermal-vaporization (TRFTV) and acetone-assisted high-pressure photoionization (HPPI) strategy has been developed. EC was rapidly separated from the main matrix components, ethyl acetate (EA) and ethanol, by the TRFTV sampling strategy due to the retention time difference of these three compounds with large boiling point differences on the inner wall of a poly(tetrafluoroethylene) (PTFE) tube. Therefore, the matrix effect of EA and ethanol was effectively eliminated. The acetone-assisted HPPI source was developed for efficient ionization of EC through a photoionization-induced proton transfer reaction between EC molecules and protonated acetone ions. The accurate quantitative analysis of EC in liquor was achieved by introducing an internal standard method (ISM) using deuterated EC (d5-EC). As a result, the limit of detection (LOD) for EC was 8.88 µg/L with the analysis time of only 2 min, and the recoveries ranged from 92.3 to 113.1%. Finally, the prominent capability of the developed system was demonstrated by rapid determination of trace EC in Chinese liquors with different flavor types, exhibiting wide potential applications in online quality control and safety evaluation of not only Chinese liquors but also other liquor and alcoholic beverages.

Rapid and highly sensitive measurement of trimethylamine in seawater using dynamic purge-release and dopant-assisted atmospheric pressure photoionization mass spectrometry.

Trimethylamine (TMA) is ubiquitous in the marine systems and may affect atmospheric chemistry as a precursor and strong stabilizer of atmospheric secondary aerosol, influencing cloud formation. Rapid and accurate measurement of the concentration of TMA in seawater is challenging due to their polarity, aqueous solubility, volatility and existence at low concentrations in marine environments. In this study, a dopant-assisted atmospheric pressure photoionization time-of-flight mass spectrometry (DA-APPI-TOFMS) coupled with a dynamic purge-release method was developed for rapid and sensitive analysis of TMA in seawater. A novel three-zones ionization source has been developed for improving the ionization efficiency of analyte molecules and minimizing the influence of high-humidity of the sample gas, which allowed direct analysis of high-humidity (RH> 90%) gas samples from microbubble purging process by the mass spectrometer. At atmospheric pressure, the three-zones ionization source allows the use of high-speed purge gas to quickly purge all organic amines dissolved in the water into the gas phase, ensuring quantitative accuracy. The limit of quantification (LOQ) for TMA down to 0.1 µg L-1 was obtained in less than 2 min by consuming only 2 mL seawater sample. This method was applied for the determination of the concentrations of TMA in the coastal seawater to validate its practicability and reliability for analysis of trace amines in marine environments.