Human Breath Analysis Research Articles

Co3O4/CQDs composite for selective ammonia detection in exhaled human breath analysis

Co3O4 was synthesized using electrospinning method and different amounts of carbon quantum dots (CQDs) were subsequently doped into the Co3O4 matrix via grinding, resulting in Co3O4/CQDs composite materials with various ratios. Gas sensing tests revealed that the resulting composite Co3O4/CQDs sensors exhibited excellent performance at a low temperature of 50°C, with outstanding selectivity towards ammonia gas and rapid response and recovery characteristics. Specifically, response and recovery time for 50 ppm ammonia gas were 14 s and 164 s, respectively. The outcomes of the exhalation simulation test utilizing sensors composed of this material demonstrate that the sensor's response to simulated chronic kidney disease breath closely approximates that of pure biological samples (1.08), exceeding the average response value of healthy exhaled breath samples (1.0). This demonstrates the sensor's capability to differentiate between healthy individuals and chronic kidney disease patients despite significant water vapor and carbon dioxide interference. This study provides valuable insights for the development of more efficient ammonia sensors and their role in the early detection of chronic kidney disease.

Portable and Hand-Held Ammonia Gas Sensor Enables Noninvasive Prediagnosis of Helicobacter pylori Infection.

Disease diagnosis of Helicobacter pylori (Hp) through human exhaled breath analysis has attracted considerable attention. However, conventional methods, such as carbon 13 (13C) breath test and infrared spectrometers, are facing the challenge of achieving portability and reliability synchronously. Herein, we report a portable and hand-held Hp analyzer using a bimetallic PtRu@SnO2-based gas sensor for the prediagnosis of Hp infection, which is based on detecting ammonia (NH3) as a potential biomarker in exhaled breath. Owing to the surface functionalization through highly catalytically active bimetallic PtRu nanoparticles (NPs) prepared by a photochemical reduction strategy, the PtRu@SnO2-based sensor exhibits high sensitivity and selectivity toward trace-level (200 ppb) NH3 even at high-humidity surroundings (80% RH). Consequently, the designed portable and hand-held Hp analyzer makes the accurate determination of NH3 at 800 ppb in exhaled breath. The tuning of energy band structure and electrical characteristics and the catalytic modulation of NH3 oxidation by PtRu NPs are proposed to be the reasons behind the enhanced NH3 gas-sensing performance, as confirmed by in situ analysis using an online MKS MultiGas 2030 FTIR gas analyzer. This work paves the way for the prediagnosis of Hp infection using a metal oxide gas sensor.

Hollow Porous Structures for Improving the Sensitivity of Colorimetric Array Gas Sensors

AbstractDetecting volatile organic compounds (VOCs) in exhaled breath is a promising research area for disease diagnosis. Mass transfer behavior plays a crucial role in determining the detection performance of VOCs. However, the high mobility of exhaled breath poses a substantial challenge for the mass transfer process. Here, the distinct mass transfer behavior of mobile gaseous molecules is discovered by employing the schlieren imaging technique to visualize gas flow. The results demonstrate that hollow porous structures exhibit a higher gas flow flux than solid film and microporous structures, thereby generating a sufficient probability of contact reactions for mobile gaseous molecules. The proposed colorimetric array sensors offer enhanced sensitivity and stability for detecting mobile gaseous molecules. The discovery will serve as a foundational milestone is anticipated in elucidating the behavior of gas mass transfer and promoting its potential application in disease detection through the analysis of human exhaled breath.

Quantum mechanisms for selective detection in complex gas mixtures using conductive sensors

In this paper, we consider new quantum mechanisms for selective detection in complex gaseous media which provide the highest possible efficiency of quantum sensors and for the first time analyze their nature. On the basis of these quantum mechanisms, the concepts of quantum detection and innovative methods of analysis are developed, which are virtually impossible to implement in the conventional conductive sensors and nanosensors. Examples of original solutions to problems in the field of detection and analysis of human breath using point-contact sensors are considered. A new method of analysis based on detection of metastable quantum states of the "point-contact sensor—breath" system in dynamic mode is proposed. The conductance histogram of dendritic Yanson point contacts recorded for this system is a unique energy signature of breath which allows differentiation between the states of human body. We demonstrate that nanosized Yanson point contacts, which, thanks to their quantum properties, can replace a massive spectrometer, open up wide opportunities for solving complex problems in the field of breath analysis using a new generation of portable high-tech quantum sensor devices.

Room-Temperature NH3 Gas Surface Acoustic Wave (SAW) Sensors Based on Graphene/PPy Composite Films Decorated by Au Nanoparticles with ppb Detection Ability.

Exhaled human breath analysis has great potential for the diagnosis of diseases in non-invasive way. The 13C-Urea breath test for the diagnosis of Helicobacter pylori infection indicates the ammonia concentration of 50-400 ppb in the breath. This work successfully developed a surface acoustic wave (SAW) resonator based on graphene/polypyrrole composite films decorated by gold nanoparticles (AuNPs-G/PPy) with sensitivity and selectivity to detect ammonia in parts-per-billion concentrations, which is promising for the accurate diagnosis of H. pylori infection. XRD, EDS, and SEM characterized the AuNPs-G/PPy nanocomposites, providing comprehensive insights into their structural, compositional, and morphological properties. The gas-sensing capabilities of the fabricated SAW sensors were extensively investigated, focusing on their response to NH3 gas at ambient temperature. The concentration of ammonia gas was effectively quantified by monitoring the frequency shift of the SAW device. Notably, our developed SAW sensor demonstrated outstanding sensitivity, selectivity, repeatability, and reproducibility for 50-1000 ppb NH3 in dry air. The excellent sensing performance of the AuNPs-G/PPy hybrid composite film can be attributed to the synergistic effects of graphene's superior conductivity, the catalytic properties of gold nanoparticles, and the conductivity sensitization facilitated by electron-hole recombination on the polypyrrole surface.

Direct mass spectrometry analysis of exhaled human breath in real-time.

The molecular composition of exhaled human breath can reflect various physiological and pathological conditions. Considerable progress has been achieved over the past decade in real-time analysis of exhaled human breath using direct mass spectrometry methods, including selected ion flow tube mass spectrometry, proton transfer reaction mass spectrometry, extractive electrospray ionization mass spectrometry, secondary electrospray ionization mass spectrometry, acetone-assisted negative photoionization mass spectrometry, atmospheric pressure photoionization mass spectrometry, and low-pressure photoionization mass spectrometry. Here, recent developments in direct mass spectrometry analysis of exhaled human breath are reviewed with regard to analytical performance (chemical sensitivity, selectivity, quantitative capabilities) and applications of the developed methods in disease diagnosis, targeted molecular detection, and real-time metabolic monitoring.

Diode laser absorption spectroscopy for real-time detection of breath oxygen

In this paper, a high-resolution laser absorption spectrometer is developed using a distributed feedback (DFB) diode laser in the spectral region near 760 nm, which is designed for the highly sensitive detection of oxygen (O2) in breathing gas. To investigate the spectrometer performance, O2 absorption line at 13146.580 cm−1 was selected, and detailed experiments on air-broadening coefficient, self-broadening coefficient and spectral line intensity were conducted. Compared to the corresponding data listed in the HITRAN2020 database, the results show that the errors for air-broadening coefficient, self-broadening coefficient and line intensity, were −6.832%, 4.082% and 4.667%, respectively. Finally, the developed laser absorption spectrometer was primarily evaluated for real-time analysis of O2 content in human breath analysis. The results indicate that the measured O2 concentrations in several volunteers range from 16% to 16.5%, which is in agreement with the levels reported in the literature for healthy humans.

Characterization of Breath Sensor at Different Frequencies in Outdoor Condition

This paper investigates a breath sensor device that is designed to detect the moisture in human bulk matrix in outdoor conditions. The human bulk matrix is rich in moisture and carbon dioxide apart from the 872 volatile organic compounds emanating from the human breath. Human breathing effort is a respiration process that involves inhalation and exhalation modes. The human bulk matrix is a product of the latter. Most research in human breath analysis is concentrating on both human bulk matrix and breathing pattern. The aim of this study is to characterize the fabricated breath sensor at different input wave frequencies in the outdoor environment. In this study, an outdoor experiment was carried out using the breath sensor device that is connected to the input waveform from the frequency generator and the output reading is captured using the oscilloscope. A single exhaled breath originated from the human subject is required to activate the breath sensor. This method is easier and simpler, and the output wave result is generated by an oscilloscope in real-time. The result indicates that the investigated breath sensor is suitable for clinical and healthcare monitoring. Early studies indicate that the breath sensor can diagnose diseases related to breathing problems such as sleep apnoea, asthma, and strokes.

Janus PdSTe nanosheet as promising contender for detection of volatile organic compounds (VOCs) in human breath: A first principles investigation

Using the density functional theory and nonequilibrium Green’s function formalism, recent work report brings the interaction between the two-dimensional (2D) Janus PdSTe nanosheet and volatile organic compounds (VOCs) (i.e., acetone, ethanol, methanol, and propanol) to investigate the latent application of Janus PdSTe for excellent performance of VOCs sensors used for human breath analysis. The pristine Janus PdSTe monolayer is semiconducting with band gap of 0.32 eV, having the valence band maxima (VBM) at the Γ-point while, conduction band minima (CBM) at k-point in the Brillouin zone. The adsorption energies are revealed that all the targeted VOCs molecule are physiosorbed on the Janus PdSTe monolayer. We found that the acetone has greater sensitivity compare to other considered VOCs. To check the sensing mechanism of VOCs, the Mulliken charge transfer (CT), interaction distance and type of adsorption were analyzed. The calculated Mulliken charge is also reveals that the stronger electron exchange interation between ethanol and Janus PdSTe monolayer. Simultaneously, the I-V relation for before and after adsorption of VOCs molecules were also obtained using the Green’s function (NEGF) for experimental set up. Finally, our outcome indicates that Janus PdSTe monolayer is a potential and feasible candidate for aformentioned VOCs sensors for applications in room temperature breath analysis of VOCs.

Detection of abused drugs in human exhaled breath using mass spectrometry: A review.

Human breath analysis has been attracting increasing interest in the detection of abused drugs in forensic and clinical applications because of its noninvasive sampling and distinctive molecular information. Mass spectrometry (MS)-based approaches have been proven to be powerful tools for accurately analyzing exhaled abused drugs. The major advantages of MS-based approaches include high sensitivity, high specificity, and versatile couplings with various breath sampling methods. Recent advances in the methodological development of MS analysis of exhaled abused drugs are discussed. Breath collection and sample pretreatment methods for MS analysis are also introduced. Recent advances in technical aspects of breath sampling methods are summarized, highlighting active and passive sampling. MS methods for detecting different exhaled abused drugs are reviewed, emphasizing their features, advantages, and limitations. The future trends and challenges in MS-based breath analysis of exhaled abused drugs are also discussed. The coupling of breath sampling methods with MS approaches has been proven to be a powerful tool for the detection of exhaled abused drugs, offering highly attractive results in forensic investigations. MS-based detection of exhaled abused drugs in exhaled breath is a relatively new field and is still in the early stages of methodological development. New MS technologies promise a substantial benefit for future forensic analysis.

MoS2 monolayers functionalized with gold nanoparticles using microwave absorption for FET-type NO2 gas sensors in ppb-levels

Molybdenum disulfide (MoS2) monolayers functionalized with nanometals using microwave absorption are developed in this study to realize high-performance field-effect transistor (FET)-type gas sensors detecting NO2 molecules in ppb-levels for health monitoring bioelectronics. The optimized microwave-induced functionalization of chemical vapor deposition-grown MoS2 monolayer films with gold nanoparticles (Au NPs) solution-processed at low temperatures (∼120 °C) for a short time periods (∼1 min), is investigated. The FET-type gas sensor exhibited a threshold voltage shift of ∼0.5 V and a sensing response of ∼10 % with a theoretical detection limit of 0.183 ppb when exposed to 200 ppb of NO2 gas at 30 °C for 15 s, as compared to that reported in the literature. In addition, the functionalization mechanism of Au NPs in the developed NO2 gas sensors is investigated to reveal high selectivity toward different gas species in exhaled breath and excellent stability against environmental factors, such as humidity and temperature, which are crucial for the practical analysis of human breath. Finally, the effect of ultraviolet irradiation on the photo-induced surface reactions is demonstrated to enhance the recovery characteristics of the FET-type gas sensors with recovery times spanning a few seconds.

High-Sensitivity and -Selectivity Gas Sensors with Nanoparticles, Nanostructures, and Thin Films

Advanced gas sensors fabricated with nanoparticles and thin films of semiconductor metal oxides have been widely used for the detection of toxic, hazardous, and combustible gases and as biomarkers for the safety of human beings, environmental control, and breath analysis [...]

SnO2-Based Ultra-Flexible Humidity/Respiratory Sensor for Analysis of Human Breath.

Developing ultraflexible sensors using metal oxides is challenging due to the high-temperature annealing step in the fabrication process. Here, we demonstrate the ultraflexible relative humidity (RH) sensor on food plastic wrap by using 808 nm near-infrared (NIR) laser annealing for 1 min at a low temperature (26.2-40.8 °C). The wettability of plastic wraps coated with sol-gel solution is modulated to obtain uniform films. The surface morphology, local temperature, and electrical properties of the SnO2 resistor under NIR laser irradiation with a power of 16, 33, and 84 W/cm2 are investigated. The optimal device can detect wide-range RH from 15% to 70% with small incremental changes (0.1-2.2%). X-ray photoelectron spectroscopy reveals the relation between the surface binding condition and sensing response. Finally, the proposed sensor is attached onto the face mask to analyze the real-time human breath pattern in slow, normal, and fast modes, showing potential in wearable electronics or respiration monitoring.

The IOMT-Based Risk-Free Approach to Lung Disorders Detection from Exhaled Breath Examination

The lungs are the main fundamental part of the human respiratory system and are among the major organs of the human body. Lung disorders, including Coronavirus (Covid-19), are among the world’s deadliest and most life-threatening diseases. Early and social distance-based detection and treatment can save lives as well as protect the rest of humanity. Even though X-rays or Computed Tomography (CT) scans are the imaging techniques to analyze lung-related disorders, medical practitioners still find it challenging to analyze and identify lung cancer from scanned images. unless COVID-19 reaches the lungs, it is unable to be diagnosed. through these modalities. So, the Internet of Medical Things (IoMT) and machine learning-based computer-assisted approaches have been developed and applied to automate these diagnostic procedures. This study also aims at investigating an automated approach for the detection of COVID-19 and lung disorders other than COVID-19 infection in a non-invasive manner at their early stages through the analysis of human breath. Human breath contains several volatile organic compounds, i.e., water vapor (5.0%–6.3%), nitrogen (79%), oxygen (13.6%–16.0%), carbon dioxide (4.0%–5.3%), argon (1%), hydrogen (1 ppm) (parts per million), carbon monoxide (1%), proteins (1%), isoprene (1%), acetone (1%), and ammonia (1%). Beyond these limits, the presence of a certain volatile organic compound (VOC) may indicate a disease. The proposed research not only aims to increase the accuracy of lung disorder detection from breath analysis but also to deploy the model in a real-time environment as a home appliance. Different sensors detect VOC; microcontrollers and machine learning models have been used to detect these lung disorders. Overall, the suggested methodology is accurate, efficient, and non-invasive. The proposed method obtained an accuracy of 93.59%, a sensitivity of 89.59%, a specificity of 94.87%, and an AUC-Value of 0.96.

Resonant Inertial Mass Sensing for VOCs—CMOS-Compatible SoC Integration Advantages and Challenges: A Review

Volatile organic compounds (VOCs) have gained the biomedical community’s attention given their relevance in exhaled human breath analysis for noninvasive disease diagnosis. Today, only bulky, expensive, and high-skill bench-top equipment is commercially available to reach the outstanding resolution and selectivity required for their detection. However, these solutions fail to meet the society demands of portable and low-cost devices required for point-of-care diagnosis and e-health. In this line, resonant inertial mass sensing has emerged as a promising technique to achieve high-resolution VOCs’ identification, fulfilling the portability requirements. Their excellent distributed mass sensitivity and integration capabilities within standard CMOS microfabrication techniques constitute excellent candidates for building lab-on-chip applications in line with current technological trends. The capability of operating as self-sustained oscillators provides an inherent real-time tracking system with quasi-digital output. Resonator coating using novel sensing films for specific analyte caption is required to boost the mass loading effect and improve sensing selectivity. This article reviews and analyzes the resonator topologies proposed in the literature together with the techniques used for electromechanical transduction, as well as coating materials and procedures. The ultimate goal is to discuss the advantages achieved for CMOS fully integrated solutions, analyzing the state of the art in the field and providing specific design guidelines while foreseeing upcoming trends.

Carbon fiber paper spray ionization mass spectrometry

Carbon fiber paper (CFP) is commonly used as a proton exchange membrane in fuel cells due to its prominent areal electrosorption capacity, exceptional conductivity and excellent chemical stability. In this paper, we first explored the feasibility of carbon fiber paper as a specific paper substrate in paper spray ionization mass spectrometry (PSI-MS). The results demonstrated that CFPSI-MS combines the merits of PSI and carbon fiber ionization (CFI) and exhibits better performance of various compound analyses than either of these techniques alone. The application of CFP can highly enhance the signal stability and detection sensitivity of a diverse array of analytes, especially in negative ionization mode. The ion intensity of target analytes such as saccharides and flavonoids was improved 2-90-fold. Many nonpolar/low-polarity analytes, such as polycyclic aromatic hydrocarbons, which are difficult to ionize by traditional PSI-MS, were successfully detected by CFPSI-MS with a 2.5 kV high voltage. Moreover, CFPSI-MS presents high sensitivity in semiquantitative analysis, and the limits of detection (LODs) of cyclic adenosine monophosphate (CAMP), naringin and tivantinib in whole blood were improved 2-100-fold compared to those in traditional PSI-MS. In real sample analysis, CFPSI-MS also exhibits excellent capability in human breath analysis and blood metabolomic profiling.

Solid phase microextraction for human breath analysis of environmental and occupational exposures: A review

Human exhaled breath contains various molecules that relate to human health and environmental exposures. There has been increasing interest in human breath analysis for exposure monitoring. This review focuses on the utilization of solid phase microextraction (SPME) for breath analysis of environmental and occupational exposures. Breath analysis of different types of exposures are summarized. The developments of SPME methods for breath analysis are highlighted. The limitations of the current studies and the prospects of breath analysis in exposure monitoring are discussed.

Numerical methods of spectral analysis of multicomponent gas mixtures and human exhaled breath

In this paper, the application of machine learning and deep learning in the spectral analysis of multicomponent gas mixtures is considered. The experimental setup consists of a quantum cascade laser with a tuning range of 5.3–12.8 µm, a peak power of up to 150 mW, and an astigmatic Herriott gas cell with an optical path length of up to 76 m. Acetone, ethanol, methanol, and their mixtures are used as test substances. For the detection and clustering of substances, including molecular biomarkers, methods of machine learning, such as stochastic embedding of neighbors with a t-distribution, principal component analysis and classification methods, such as random forest, gradient boosting, and logistic regression, are proposed. A shallow convolutional neural network based on TensorFlow (Google) and Keras is used for the spectral analysis of gas mixtures. Model spectra of substances are used as a training sample, and model and experimental spectra are used as a test sample. It is shown that neural networks trained on model spectra (NIST database) can recognize substances in experimental gas mixtures. We propose using machine learning methods for clustering and classification of pure substances and gas mixtures and neural networks for the identification of gas mixture components. Using the experimental setup described, the experimentally obtained concentration limits are 80 ppb for acetone and 100–120 ppb for ethanol and methanol. The possibility of using the proposed methods for analyzing spectra of human exhaled air is shown, which is significant for biomedical applications.

Millimeter-wave gas spectroscopy for breath analysis of COPD patients in comparison to GC-MS

The analysis of human breath is a very active area of research, driven by the vision of a fast, easy, and non-invasive tool for medical diagnoses at the point of care. Millimeter-wave gas spectroscopy (MMWGS) is a novel, well-suited technique for this application as it provides high sensitivity, specificity and selectivity. Most of all, it offers the perspective of compact low-cost systems to be used in doctors’ offices or hospitals. In this work, we demonstrate the analysis of breath samples acquired in a medical environment using MMWGS and evaluate validity, reliability, as well as limitations and perspectives of the method. To this end, we investigated 28 duplicate samples from chronic obstructive lung disease patients and compared the results to gas chromatography-mass spectrometry (GC-MS). The quantification of the data was conducted using a calibration-free fit model, which describes the data precisely and delivers absolute quantities. For ethanol, acetone, and acetonitrile, the results agree well with the GC-MS measurements and are as reliable as GC-MS. The duplicate samples deviate from the mean values by only 6% to 18%. Detection limits of MMWGS depend strongly on the molecular species. For example, acetonitrile can be traced down to 1.8 × 10−12 mol by the MMWGS system, which is comparable to the GC-MS system. We observed correlations of abundances between formaldehyde and acetaldehyde as well as between acetonitrile and acetaldehyde, which demonstrates the potential of MMWGS for breath research.

Spectroscopic trace gas detection in air-based gas mixtures: Some methods and applications for breath analysis and environmental monitoring

Laser absorption spectroscopy as a powerful tool for detecting trace gases has been widely used in the monitoring of atmospheric greenhouse gases, pollutions, and respiration processes, including human breath analysis. The detection is based on the light absorption when it propagates through a medium. Most inorganic and organic molecules have characteristic absorption lines in the mid-infrared (mid-IR), which correspond to fundamental vibrational modes and in the near-IR (first overtones) presenting their absorption fingerprints. Here, we summarize the recent developments of the three techniques, namely, wavelength modulation spectroscopy (WMS), cavity ringdown spectroscopy (CRDS), and frequency comb spectroscopy (FCS), and describe their main features as well as possible applications, illustrated by recent experimental results. Emphasis is made on methane detection as applied to breath analysis and atmospheric monitoring. For the WMS technique, we consider local measurements with a multipass cell and also kilometer long open-path configurations for the near-IR and mid-IR spectral regions. The results of measurements of methane in exhaled breath with the CRDS technique in the near-IR are presented for a group of subjects of different ages. We consider various schemes of the FCS that enable fast broadband detection, including direct spectroscopy, dual FCS, and Vernier FCS, and review numerous applications of this approach that revolutionized the field of absorption spectroscopy. The current trends and possible future developments and applications are also discussed.