Paper-in-Facemask Device for Direct Mass Spectrometry Analysis of Human Respiratory Aerosols and Environmental Exposures via Wearable Continuous-Flow Adsorptive Sampling: A Proof-of-Concept Study.

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-in-facemask 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.

Mass Spectrometry-Based Human Breath Analysis: Towards COVID-19 Diagnosis and Research.

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.

In vivo solid-phase microextraction swab-mass spectrometry for multidimensional analysis of human saliva.

Solid phase microextraction (SPME) is one of the most powerful sample preparation techniques for analyte extraction and enrichment from complex matrices. SPME fibers are commonly used to extract analytes from collected samples. Following our recent work on development of in vivo SPME swab that integrates an SPME fiber and a medical swab (Anal Chim Acta, 2020, 1124, 71-77), the multiple SPME fibers inserted into a medical swab (multiple-SPME swab) is further developed to couple with different mass spectrometry (MS) approaches for multidimensional analysis of human saliva in this work. The new features of cotton ball and SPME fiber of multiple-SPME swab are investigated. Biomarker discovery and disease diagnosis using multiple-SPME swab are also demonstrated. The present study shows that direct coupling multiple-SPME swab with different MS-based approaches could be simple and versatile in vivo method to expand the classes of analytes extracted simultaneously from human saliva.

Solid-Phase Microextraction Fiber in Face Mask for in Vivo Sampling and Direct Mass Spectrometry Analysis of Exhaled Breath Aerosol.

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.

In vivo solid-phase microextraction swab sampling of environmental pollutants and drugs in human body for nano-electrospray ionization mass spectrometry analysis.

In vivo sampling and sensitive detection of environmental pollutants and drugs in human body play a crucial role in understanding human health. In this study, in vivo solid-phase microextraction (SPME) swab was fabricated using a SPME fiber and a medical cotton swab for noninvasive sampling and extraction of environmental pollutants and drugs in human oral cavity, nasal cavity and on skin surface. After sampling, SPME was coupled with nano-electrospray ionization mass spectrometry (nanoESI-MS) for desorption, ionization, and detection of the extracted analytes. As a result, limit of detection (LOD) and limit of quantification (LOQ) of nicotine in oral fluid were found to be 1.0 pg/mL (S/N ≥ 3) and 4.0 pg/mL (S/N ≥ 10), respectively. Linear dynamic signal responses of nicotine exhibited excellent linearity (R2 = 0.9996) in human oral fluid ranging from 0.1 to 50 ng/mL. The coefficient of variation (CV) values of SPME swab for five measurements from sample vials and human body were 5.1-6.7% and 22.7-32.6%, respectively. Rapid analysis of a single sample could be completed within 10 min. Overall, our results demonstrated that SPME swab-MS is a promising noninvasive method for enhanced detection of analytes in human body.

Schirmer Paper Noninvasive Microsampling for Direct Mass Spectrometry Analysis of Human Tears.

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.

Direct Detection of Lysozyme in Viscous Raw Hen Egg White Binding to Sodium Dodecyl Sulfonate by Reactive Wooden-tip Electrospray Ionization Mass Spectrometry.

Direct characterization of native protein binding to ligands in raw biological samples is a challenging task, because the ligand solution might induce proteins to aggregation, flocculation and denaturation. In this work, we developed a reactive wooden-tip electrospray ionization mass spectrometry (ESI-MS) for formation and characterization of protein-ligand complexes upon rapid mixing in electrospray droplets. Raw viscous hen egg white (HEW) was directly loaded onto a wooden tip to induce spray ionization, and sodium dodecyl sulfonate (SDS) solution was directly loaded into the HEW spray by a pipette tip, and thus lysozyme-DS complexes were then formed in the electrospray droplets and were detected subsequently by mass spectrometry. The new approach was successfully applied to investigate interaction of SDS and native lysozyme in electrospray droplets of standard solution and raw egg white. Our results showed that wooden-tip ESI-MS is a promising method to form and characterize protein-ligand complexes.

Fast-switching high-voltage porous-tip electrospray ionization mass spectrometry for rapid detection of antirheumatic drugs in adulterated herbal dietary supplements.

RATIONALE: Herbal dietary supplements (HDSs) adulterated with undeclared synthetic drugs can lead to serious health problems METHODS: A fast-switching positive/negative high-voltage (+/- HV) was developed to apply on electrospray ionization mass spectrometry (ESI-MS) with porous tips for rapid screening of five antirheumatic drugs in antirheumatic HDSs. The fast-switching (switch-time: 100 ms) negative and positive ions were alternately generated to perform full-MS and tandem-MS analysis, providing an effective method for rapid detection of analytes in whichever mode of detection was most suitable (negative or positive ion mode). The use of different tips and solvents was also optimized in this work. RESULTS: The limits of detection of the five antirheumatic drugs were found to be less than 0.1 ng/g (S/N > 3). The reproducibility of the five drugs was measured to be 10.0-23.3% (n = 5). A single sample analysis could be completed within 1 min. Rapid screening of a total of 28 real HDS samples collected from the market was examined by the fast-switching HV substrate-tip ESI-MS method, and the screening result was further validated by conventional liquid chromatography/mass spectrometry. CONCLUSIONS: Overall, our results demonstrated that fast-switching HV substrate-tip ESI-MS is a rapid, reliable, and effective method for simultaneous screening of various analytes in complex samples.

Vibrating tip spray ionization mass spectrometry for direct sample analysis.

In this work, a vibrating tip spray ionization source was developed for direct mass spectrometric analysis of raw samples under voltage-free condition. A solid tip was mounted on a vibrator, and the solid tip was placed on the front of MS inlet. Liquid, viscous, and bulk solid samples could be directly loaded on the tip-end surface, and then a drop of solvent at microliter level was subsequently loaded on the tip for dissolution and extraction of analytes, and a vibrator was then started to atomize and ionize the analytes under ambient condition. We demonstrated vibrating tip spray mass spectrometry in various applications, including food safety, pharmaceutical analysis, and forensic science. Furthermore, in situ analysis of biological tissues and in vivo analysis of living plants were conveniently performed, due to voltage-free. Different vibration frequencies and solvent compositions were investigated. The analytical performances, including sensitivity, reproducibility, and linear range, were investigated. The ionization process and mechanism were also discussed in this work.