Molecular analysis of exhaled breath aerosol (EBA) with simple procedures represents a key step in clinical and point-of-care applications. Due to the crucial health role, a face mask now is a safety device that helps protect the wearer from breathing in hazardous particles such as bacteria and viruses in the air; thus exhaled breath is also blocked to congregate in the small space inside of the face mask. Therefore, direct sampling and analysis of trace constituents in EBA using a face mask can rapidly provide useful insights into human physiologic and pathological information. Herein, we introduce a simple approach to collect and analyze human EBA by combining a face mask with solid-phase microextraction (SPME) fiber. SPME fiber was inserted into a face mask to form SPME-in-mask that covered nose and mouth for in vivo sampling of EBA, and SPME fiber was then coupled with direct analysis in real-time mass spectrometry (DART-MS) to directly analyze the molecular compositions of EBA under ambient conditions. The applicability of SPME-in-mask was demonstrated by direct analysis of drugs and metabolites in oral and nasal EBA. The unique features of SPME-in-mask were also discussed. Our results showed that this method is enabled to analyze volatile and nonvolatile analytes in EBA and is expected to have a significant impact on human EBA analysis in clinical applications. We also hope this method will inspire biomarker screening of some respiratory diseases that usually required wearing of a face mask in daily life.

Rapid and sensitive detection of metabolites and chemical residues in human tears is highly beneficial for understanding eye health. In this study, Schirmer paper was used for noninvasive microsampling of human tears, and then paper spray mass spectrometry (PSMS) was performed for direct analysis of human tears. Schirmer PSMS was successfully used for rapid diagnosis of dry-eye syndrome by detecting the volume and metabolites of human tears. Drugs of abuse, therapeutic drugs, and pharmacodynamics in human tears were also investigated by Schirmer PSMS. Furthermore, specific markers of environmental exposures in the air to human eyes, including volatile organic compounds, aerosol, and smoke, were unambiguously sampled and detected in human tears using Schirmer PSMS. Excellent analytical performances were achieved, including single-use, low-sample consumption (1.0 μL), rapid analysis (the whole analytical procedure completed within 3 min), high sensitivity (absolute limit of detection less than or equal to 0.5 pg, signal-to-noise ratio greater than or equal to 3), good reproducibility (relative standard deviation less than 10%, n = 3), and accurate quantitation (average deviation less than 3%, n = 3). Overall, our results showed that Schirmer PSMS is a highly effective method for direct tear analysis and is expected to be a convenient tool for human tear analysis in significant clinical applications.

COVID-19 is a highly contagious respiratory disease that can be infected through human exhaled breath. Human breath analysis is an attractive strategy for rapid diagnosis of COVID-19 in a non-invasive way by monitoring breath biomarkers. Mass spectrometry (MS)-based approaches offer a promising analytical platform for human breath analysis due to their high speed, specificity, sensitivity, reproducibility, and broad coverage, as well as its versatile coupling methods with different chromatographic separation, and thus can lead to a better understanding of the clinical and biochemical processes of COVID-19. Herein, we try to review the developments and applications of MS-based approaches for multidimensional analysis of COVID-19 breath samples, including metabolites, proteins, microorganisms, and elements. New features of breath sampling and analysis are highlighted. Prospects and challenges on MS-based breath analysis related to COVID-19 diagnosis and study are discussed.

Facemasks are considered safe and wearable devices that cover the human mouth and nose for filtering exhaled aerosols and inhaled environmental exposures; various chemical and environmental residues thus can remain in facemasks. Therefore, direct analysis of residues in facemasks can be used to investigate the wearer's health and behavior. Here, we developed a simple paper-infacemask sampling method for adsorbing a wearer's respiratory aerosol and environmental exposures by fixing paper strips at the outside and inside surfaces of facemasks, and the paper strips were then analyzed by paper spray mass spectrometry (PSMS) for directly detecting adsorbed analytes without any sample pretreatment. The applicability of this device was demonstrated by directly analyzing exhaled aerosolized saliva, breath metabolites, and inhalable environmental exposures. The technical aspects, including sampling time, sampling position, paper property, and spray solvent, were investigated. The sampling process was revealed to involve a continuous-flow adsorptive mechanism. These findings motivated us to extend this work and build a wearable sampling device that is capable of simultaneously monitoring both exhaled and inhaled biomarkers in situ to investigate human health and environmental exposure. This work highlights that facemasks are promising platforms for aerosol collection and direct MS analysis, which is expected to be a promising method for monitoring human health, diseases, and behaviors.

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