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1.
Sci Rep ; 14(1): 11943, 2024 05 24.
Article En | MEDLINE | ID: mdl-38789449

The volatile particles and molecules in our dry exhaled breath can reveal enormous information about the health of any person, such as the person's respiratory and metabolic functioning. Beyond the carbon dioxide level is an indicator of life, it provides important health-related data like people's metabolic rate. This study considers periodic open and closed resonators for measuring carbon dioxide concentration in dry exhaled breath. Transfer matrix and green methods are used to simulate the interaction between acoustic waves and the proposed sensor. The band gaps using the green method coincide with the transmittance spectra by the transfer matrix. The suggested sensor recorded a sensitivity of 5.3 H z . m - 1 . s , a figure of merit of 10,254 m - 1 . s , a detection limit of 5 × 10 - 6 m . s - 1 , and a quality factor of 3 × 10 6 . Furthermore, the efficiency shows that the proposed design is appropriate as a diagnostic sensor for different diseases such as chronic obstructive pulmonary. Besides, cylindrical-adapted sensors are urgently needed in medicine, industry, and biology because they can simultaneously be used for fluid transport and detection.


Biosensing Techniques , Breath Tests , Carbon Dioxide , Biosensing Techniques/methods , Biosensing Techniques/instrumentation , Humans , Carbon Dioxide/analysis , Breath Tests/methods , Breath Tests/instrumentation , Exhalation
2.
J Breath Res ; 18(3)2024 May 17.
Article En | MEDLINE | ID: mdl-38701772

The analysis of volatile organic compounds (VOCs) in exhaled air has attracted the interest of the scientific community because it provides the possibility of monitoring physiological and metabolic processes and non-invasive diagnostics of various diseases. However, this method remains underused in clinical practice as well as in research because of the lack of standardized procedures for the collection, storage and transport of breath samples, which would guarantee good reproducibility and comparability of results. The method of sampling, as well as the storage time of the breath samples in the polymer bags used for sample storage and transport, affect the composition and concentration of VOCs present in the breath samples. The aim of our study was to compare breath samples obtained using two methods with fully disposable equipment: a Haldane sampling tube intended for direct breath collection and breath samples exhaled into a transparent Tedlar bag. The second task was to monitor the stability of selected compounds of real breath samples stored in a Tedlar bag for 6 h. Gas chromatography coupled with ion mobility spectrometry (GC-IMS) implemented in the BreathSpec®device was used to analyse exhaled breath. Our results showed a significant difference in the signal intensity of some volatiles when taking a breath sample with a Haldane tube and a Tedlar bag. Due to its endogenous origin, acetone levels were significantly higher when the Haldane tube sampler was used while elevated levels of 2-propanol and unidentified VOC (designated as VOC 3) in the Tedlar bag samples likely originated from contamination of the Tedlar bags. The VOC stability study revealed compound-specific signal intensity changes of the selected VOCs with storage time in the Tedlar bags, with some volatiles showing increasing signal intensity during storage in Tedlar bags. This limits the use of Tedlar bags only for very limited time and carefully selected purpose. Our results highlight the importance of careful design and implementation of experiments and clinical protocols to obtain relevant and reliable results.


Breath Tests , Specimen Handling , Volatile Organic Compounds , Humans , Breath Tests/instrumentation , Breath Tests/methods , Volatile Organic Compounds/analysis , Specimen Handling/instrumentation , Specimen Handling/methods , Ion Mobility Spectrometry/methods , Ion Mobility Spectrometry/instrumentation , Male , Female , Reproducibility of Results , Adult , Gas Chromatography-Mass Spectrometry/methods , Gas Chromatography-Mass Spectrometry/instrumentation , Exhalation , Middle Aged , Time Factors
3.
Adv Sci (Weinh) ; 11(19): e2309481, 2024 May.
Article En | MEDLINE | ID: mdl-38477429

Diabetic ketoacidosis (DKA) is a life-threatening acute complication of diabetes characterized by the accumulation of ketone bodies in the blood. Breath acetone, a ketone, directly correlates with blood ketones. Therefore, monitoring breath acetone can significantly enhance the safety and efficacy of diabetes care. In this work, the design and fabrication of an InP/Pt/chitosan nanowire array-based chemiresistive acetone sensor is reported. By incorporation of chitosan as a surface-functional layer and a Pt Schottky contact for efficient charge transfer processes and photovoltaic effect, self-powered, highly selective acetone sensing is achieved. The sensor has exhibited an ultra-wide acetone detection range from sub-ppb to >100 000 ppm level at room temperature, covering those in the exhaled breath from healthy individuals (300-800 ppb) to people at high risk of DKA (>75 ppm). The nanowire sensor has also been successfully integrated into a handheld breath testing prototype, the Ketowhistle, which can successfully detect different ranges of acetone concentrations in simulated breath samples. The Ketowhistle demonstrates the immediate potential for non-invasive ketone monitoring for people living with diabetes, in particular for DKA prevention.


Acetone , Breath Tests , Nanowires , Acetone/analysis , Humans , Breath Tests/methods , Breath Tests/instrumentation , Diabetic Ketoacidosis/diagnosis , Biosensing Techniques/methods , Biosensing Techniques/instrumentation , Chitosan/chemistry , Equipment Design , Diabetes Mellitus/diagnosis , Diabetes Mellitus/blood
4.
Nanotechnology ; 33(20)2022 Feb 21.
Article En | MEDLINE | ID: mdl-35042201

Breathomics is the future of non-invasive point-of-care devices. The field of breathomics can be split into the isolation of disease-specific volatile organic compounds (VOCs) and their detection. In the present work, an array of five quartz tuning fork (QTF)-based sensors modified by polymer with nanomaterial additive has been utilized. The array has been used to detect samples of human breath spiked with ∼0.5 ppm of known VOCs namely, acetone, acetaldehyde, octane, decane, ethanol, methanol, styrene, propylbenzene, cyclohexanone, butanediol, and isopropyl alcohol which are bio-markers for certain diseases. Polystyrene was used as the base polymer and it was functionalized with 4 different fillers namely, silver nanoparticles-reduced graphene oxide composite, titanium dioxide nanoparticles, zinc ferrite nanoparticles-reduced graphene oxide composite, and cellulose acetate. Each of these fillers enhanced the selectivity of a particular sensor towards a certain VOC compared to the pristine polystyrene-modified sensor. Their interaction with the VOCs in changing the mechanical properties of polymer giving rise to change in the resonant frequency of QTF is used as sensor response for detection. The interaction of functionalized polymers with VOCs was analyzed by FTIR and UV-vis spectroscopy. The collective sensor response of five sensors is used to identify VOCs using an ensemble classifier with 92.8% accuracy of prediction. The accuracy of prediction improved to 96% when isopropyl alcohol, ethanol, and methanol were considered as one class.


Breath Tests/methods , Volatile Organic Compounds/analysis , Biomarkers/analysis , Breath Tests/instrumentation , Cellulose/analogs & derivatives , Cellulose/chemistry , Ferric Compounds/chemistry , Graphite/chemistry , Humans , Metal Nanoparticles/chemistry , Nickel/chemistry , Point-of-Care Testing , Polystyrenes/chemistry , Quartz Crystal Microbalance Techniques , Silver/chemistry , Titanium/chemistry , Volatile Organic Compounds/chemistry , Volatile Organic Compounds/classification , Zinc/chemistry
5.
ACS Appl Mater Interfaces ; 14(5): 7301-7310, 2022 Feb 09.
Article En | MEDLINE | ID: mdl-35076218

The high moisture level of exhaled gases unavoidably limits the sensitivity of breath analysis via wearable bioelectronics. Inspired by pulmonary lobe expansion/contraction observed during respiration, a respiration-driven triboelectric sensor (RTS) was devised for simultaneous respiratory biomechanical monitoring and exhaled acetone concentration analysis. A tin oxide-doped polyethyleneimine membrane was devised to play a dual role as both a triboelectric layer and an acetone sensing material. The prepared RTS exhibited excellent ability in measuring respiratory flow rate (2-8 L/min) and breath frequency (0.33-0.8 Hz). Furthermore, the RTS presented good performance in biochemical acetone sensing (2-10 ppm range at high moisture levels), which was validated via finite element analysis. This work has led to the development of a novel real-time active respiratory monitoring system and strengthened triboelectric-chemisorption coupling sensing mechanism.


Acetone/analysis , Breath Tests/methods , Respiratory Rate/physiology , Breath Tests/instrumentation , Electronics , Humans , Nanostructures/chemistry , Polyethyleneimine/chemistry , Reproducibility of Results , Tin Compounds/chemistry , Wearable Electronic Devices
6.
Biosensors (Basel) ; 11(11)2021 Nov 17.
Article En | MEDLINE | ID: mdl-34821677

A surface-plasmon-resonance-based fiber device is proposed for highly sensitive relative humidity (RH) sensing and human breath monitoring. The device is fabricated by using a polyvinyl alcohol (PVA) film and gold coating on the flat surface of a side-polished polymer optical fiber. The thickness and refractive index of the PVA coating are sensitive to environmental humidity, and thus the resonant wavelength of the proposed device exhibits a redshift as the RH increases. Experimental results demonstrate an average sensitivity of 4.98 nm/RH% across an ambient RH ranging from 40% to 90%. In particular, the sensor exhibits a linear response between 75% and 90% RH, with a sensitivity of 10.15 nm/RH%. The device is suitable for human breath tests and shows an average wavelength shift of up to 228.20 nm, which is 10 times larger than that of a silica-fiber-based humidity sensor. The corresponding response and recovery times are determined to be 0.44 s and 0.86 s, respectively. The proposed sensor has significant potential for a variety of practical applications, such as intensive care and human health analysis.


Optical Fibers , Surface Plasmon Resonance , Breath Tests/instrumentation , Equipment Design , Humans , Humidity , Polyvinyl Alcohol
7.
Appl Opt ; 60(23): 7036-7042, 2021 Aug 10.
Article En | MEDLINE | ID: mdl-34613187

A precise and fast optical thermometer based on a tunable diode laser absorption spectroscopy is developed for breath diagnostics with relevance to noncontact body temperature measurement. As water vapor (H2O) is the major component in human breath, two optimal absorption lines of H2O at 1392 nm and 1371 nm are selected for sensitive body temperature measurement by systematically investigating the near-infrared spectral database. The optical thermometer is developed using two distributed feedback diode lasers with the time-division multiplexing technique to achieve real-time measurement. The sensor performance such as accuracy, repeatability, and time response is tested in a custom-designed gas cell with its temperature controlled in the range of 20°C-50°C. By measuring the test air with different water concentrations, the sensor consistently shows a quadratic response to temperature with an R-squared value of 0.9998. Under the readout rate of 1 s, the sensor achieves a measurement precision of 0.16°C, suggesting its potential applications to fast, accurate, and noncontact body temperature measurements.


Body Temperature/physiology , Body Water/chemistry , Breath Tests/instrumentation , Lasers, Semiconductor , Thermometers , Thermometry/instrumentation , Equipment Design , Humans , Spectrum Analysis
8.
J Diabetes Complications ; 35(11): 108030, 2021 11.
Article En | MEDLINE | ID: mdl-34481712

OBJECTIVE: To assess the accuracy of a breath ketone analyzer to detect ketosis in adults and children with type 1 diabetes. RESEARCH DESIGN AND METHODS: This is a proof-of-concept, prospective study comparing breath ketone analyzer and blood ketone meter to detect ketosis. RESULTS: A total of 500 measurements from 19 adults and children with type 1 diabetes were analyzed. There was a significant association between the breath ketone analyzer and blood ketone meter results in non-fasting adults (p = 0.0066), but not in children (p = 0.4579). In adults, a cut-off of 3.9 PPM on the breath ketone analyzer maximized the Youden Index with an AUC of 0.73. This cut-off for the breath ketone analyzer had 94.7% sensitivity and 54.2% specificity to detect ketosis (≥0.6 mmol/L in blood ketone meter). CONCLUSIONS: The breath ketone analyzer may be considered as a non-invasive screening tool to rule out ketosis in adults with type 1 diabetes.


Diabetes Mellitus, Type 1 , Diabetic Ketoacidosis , Ketosis , 3-Hydroxybutyric Acid , Adult , Breath Tests/instrumentation , Child , Diabetes Mellitus, Type 1/complications , Diabetic Ketoacidosis/diagnosis , Humans , Ketone Bodies , Ketones/analysis , Ketosis/diagnosis , Prospective Studies
9.
ACS Appl Mater Interfaces ; 13(35): 41445-41453, 2021 Sep 08.
Article En | MEDLINE | ID: mdl-34428374

Airborne transmission of exhaled virus can rapidly spread, thereby increasing disease progression from local incidents to pandemics. Due to the COVID-19 pandemic, states and local governments have enforced the use of protective masks in public and work areas to minimize the disease spread. Here, we have leveraged the function of protective face coverings toward COVID-19 diagnosis. We developed a user-friendly, affordable, and wearable collector. This noninvasive platform is integrated into protective masks toward collecting airborne virus in the exhaled breath over the wearing period. A viral sample was sprayed into the collector to model airborne dispersion, and then the enriched pathogen was extracted from the collector for further analytical evaluation. To validate this design, qualitative colorimetric loop-mediated isothermal amplification, quantitative reverse transcription polymerase chain reaction, and antibody-based dot blot assays were performed to detect the presence of SARS-CoV-2. We envision that this platform will facilitate sampling of current SARS-CoV-2 and is potentially broadly applicable to other airborne diseases for future emerging pandemics.


Breath Tests/instrumentation , COVID-19 Testing/instrumentation , Masks , SARS-CoV-2/isolation & purification , Air Microbiology , Antibodies, Viral/immunology , Breath Tests/methods , COVID-19 Testing/methods , Collodion/chemistry , Colorimetry/methods , Molecular Diagnostic Techniques/methods , Nucleic Acid Amplification Techniques/methods , Polycarboxylate Cement/chemistry , Porosity , Proof of Concept Study , RNA, Viral/analysis , Real-Time Polymerase Chain Reaction/methods , SARS-CoV-2/chemistry , Viral Proteins/analysis , Viral Proteins/immunology
10.
Mikrochim Acta ; 188(9): 306, 2021 Aug 27.
Article En | MEDLINE | ID: mdl-34453195

A portable smartphone device is reported that uses 3D printing technology for the primary diagnosis of diseases by detecting acetone. The key part of the device consists of red carbon dots (RCDs), which are used as internal standards, and a sensing reagent (3-N,N-(diacethydrazide)-9-ethylcarbazole (2-HCA)) for acetone. With an excitation wavelength of 360 nm, the emission wavelengths of 2-HCA and RCDs are 443 nm and 619 nm, respectively. 2-HCA effectively captures acetone to form a nonfluorescent acylhydrazone via a condensation reaction occurring in aqueous solution, resulting in obvious color changes from blue-violet to dark red. The detection limit for acetone is 2.62 µM (~ 0.24 ppm). This is far lower than the ketone content in normal human blood (≤ 0.50 mM) and the acetone content in human respiratory gas (≤ 1.80 ppm). The device has good recovery rates for acetone detection in blood and exhaled breath, which are 90.56-109.98% (RSD ≤ 5.48) and 92.80-108.00% (RSD ≤ 5.07), respectively. The method designed here provides a reliable way to provide health warnings by visually detecting markers of ketosis/diabetes in blood or exhaled breath. The portable smart phone device visually detects ketosis/diabetes markers in the blood or exhaled breath through the nucleophilic addition reaction, which effectively captures acetone to form nonfluorescent acyl groups. This will be a reliable tool to warn human health.


Acetone/blood , Hydrazines/chemistry , Ketosis/diagnosis , Quantum Dots/chemistry , Smartphone , Acetone/chemistry , Biomarkers/blood , Biomarkers/chemistry , Breath Tests/instrumentation , Breath Tests/methods , Carbon/chemistry , Exhalation , Humans , Ketosis/blood , Limit of Detection , Printing, Three-Dimensional , Spectrometry, Fluorescence/instrumentation , Spectrometry, Fluorescence/methods
11.
Eur J Cancer ; 152: 60-67, 2021 07.
Article En | MEDLINE | ID: mdl-34087572

INTRODUCTION: Recent clinical trials with immune checkpoint inhibitors (ICIs) have shown that a subgroup of patients with malignant pleural mesothelioma (MPM) could benefit from these agents. However, there are no accurate biomarkers to predict who will respond. The aim of this study was to assess the accuracy of exhaled breath analysis using electronic technology (eNose) for discriminating between responders to ICI and non-responders. METHODS: This proof-of-concept prospective observational study was part of an intervention study (INITIATE) in patients with recurrent MPM who were treated with nivolumab (anti-PD-1) plus ipilimumab (anti-CTLA-4). At baseline and after six weeks of treatment, breath profiles were collected by an eNose. Modified Response Evaluation Criteria in Solid Tumors were used to assess efficacy at 6-month follow-up. For data processing and statistics, we used independent t-test analyses followed by linear discriminant and receiver-operating characteristic (ROC) analysis. RESULTS: Exhaled breath data of 31 MPM patients who received nivolumab plus ipilimumab were available at baseline. There were 16 with and 15 without a response after 6 months of treatment. At baseline, breath profiles significantly differed between responders and non-responders, with a cross validation value of 71%. The ROC-AUC after internal cross-validation was 0.90 (confidence interval: 0.80-1.00). CONCLUSION: An eNose is able to discriminate at baseline between responders and non-responders to nivolumab plus ipilimumab in MPM, thereby potentially identifying a subgroup of patients that will benefit from ICI treatment.


Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Immune Checkpoint Inhibitors/administration & dosage , Mesothelioma, Malignant/drug therapy , Neoplasm Recurrence, Local/drug therapy , Pleural Neoplasms/drug therapy , Adult , Aged , Breath Tests/instrumentation , Female , Follow-Up Studies , Humans , Male , Mesothelioma, Malignant/immunology , Middle Aged , Neoplasm Recurrence, Local/immunology , Pleural Neoplasms/immunology , Prognosis , Prospective Studies , Response Evaluation Criteria in Solid Tumors , Treatment Outcome
12.
J Forensic Leg Med ; 80: 102175, 2021 May.
Article En | MEDLINE | ID: mdl-33962211

The EvidenzerIRL instrument has been in use as an evidential breath analyser in the application of drink driving laws in the Republic of Ireland since 2011. The result of the analysis is used as evidence in prosecutions before the Courts in per se offences of driving under the influence of alcohol as distinct from screening results at the roadside. This study aims to assist doctors, lawyers and judges in assessing drivers' failure to provide valid evidential breath specimens. Since the introduction of the EvidenzerIRL, approximately 10% of evidential breath tests annually result in failure or refusal to provide a successful breath specimen, this is an offence under Irish road traffic laws. The presence of lung disease has been given as a reason for the driver failing to provide evidential breath specimens. The aim of this study is to assess the ability of subjects with lung disease to provide breath specimens using the EvidenzerIRL. Pulmonary function tests (PFT) were carried out on volunteers from outpatients of the pulmonary laboratory in St Vincent's University Hospital, Dublin (n = 58) and a control group with no underlying lung disease (n = 19). After the PFTs all volunteers were asked to provide breath specimens using the EvidenzerIRL. Fourteen (24%) out of 58 lung disease volunteers failed to provide a breath specimen, no one from the control group was unsuccessful. Thirteen females and one male volunteer could not successfully provide. Female volunteers were more likely to fail to provide than male volunteers. A significant difference was found between the median age of successful (62.2 years) and unsuccessful (69.2 years) lung disease volunteers. Only one PFT, percentage predicted of Forced Expiratory Volume in 1 second (FEV1), had a significant difference between the mean of successful (86.6%) and unsuccessful (66.5%) lung disease volunteers. A subject with lung disease was more likely to be successful than unsuccessful. Drivers' effort and operators' guidance through the process were found to be crucial parts to a successful outcome.


Breath Tests/instrumentation , Driving Under the Influence , Lung Diseases/complications , Aged , Case-Control Studies , Central Nervous System Depressants/analysis , Ethanol/analysis , Female , Humans , Male , Middle Aged , Respiratory Function Tests , Substance Abuse Detection/instrumentation
13.
Nat Protoc ; 16(6): 2968-2990, 2021 06.
Article En | MEDLINE | ID: mdl-34012107

Chemiresistors that are based on monolayer-capped metal nanoparticles (MCNPs) have been used in a wide variety of innovative sensing applications, including detection and monitoring of diagnostic markers in body fluids, explosive materials, environmental contaminations and food quality control. The sensing mechanism is based on reversible swelling or aggregation and/or changes in dielectric constant of the MCNPs. In this protocol, we describe a procedure for producing MCNP-based chemiresistive sensors that is reproducible from device to device and from batch to batch. The approach relies on three main steps: (i) controlled synthesis of gold MCNPs, (ii) fabrication of electrodes that are surrounded with a microbarrier ring to confine the deposited MCNP solution and (iii) a tailor-made drying process to enable evaporation of solvent residues from the MCNP sensing layer to prevent a coffee-ring effect. Application of this approach has been shown to produce devices with ±1.5% variance-a value consistent with the criterion for commercial sensors-as well as long shelf life and stability. Fabrication of chemical sensors based on dodecanethiol- or 2-ethylhexanethiol-capped MCNPs with this approach provides high sensitivity and accuracy in the detection of volatile organic compounds (e.g., octane and decane), toxic gaseous species (e.g., HCl and NH3) in air and simulated mixtures of lung and gastric cancer from exhaled breath.


Metal Nanoparticles , Microtechnology/methods , Printing , Breath Tests/instrumentation , Electrodes , Gold
14.
Alcohol Clin Exp Res ; 45(5): 1091-1099, 2021 05.
Article En | MEDLINE | ID: mdl-33966283

BACKGROUND: Although alcohol breath testing devices that pair with smartphones are promoted for the prevention of alcohol-impaired driving, their accuracy has not been established. METHODS: In a within-subjects laboratory study, we administered weight-based doses of ethanol to two groups of 10 healthy, moderate drinkers aiming to achieve a target peak blood alcohol concentration (BAC) of 0.10%. We obtained a peak phlebotomy BAC and measured breath alcohol concentration (BrAC) with a police-grade device (Intoxilyzer 240) and two randomly ordered series of 3 consumer smartphone-paired devices (6 total devices) with measurements every 20 min until the BrAC reached <0.02% on the police device. Ten participants tested the first 3 devices, and the other 10 participants tested the other 3 devices. We measured mean paired differences in BrAC with 95% confidence intervals between the police-grade device and consumer devices. RESULTS: The enrolled sample (N = 20) included 11 females; 15 white, 3 Asian, and 2 Black participants; with a mean age of 27 and mean BMI of 24.6. Peak BACs ranged from 0.06-0.14%. All 7 devices underestimated BAC by >0.01%, though the BACtrack Mobile Pro and police-grade device were consistently more accurate than the Drinkmate and Evoc. Compared with the police-grade device measurements, the BACtrack Mobile Pro readings were consistently higher, the BACtrack Vio and Alcohoot measurements similar, and the Floome, Drinkmake, and Evoc consistently lower. The BACtrack Mobile Pro and Alcohoot were most sensitive in detecting BAC driving limit thresholds, while the Drinkmate and Evoc devices failed to detect BAC limit thresholds more than 50% of the time relative to the police-grade device. CONCLUSIONS: The accuracy of smartphone-paired devices varied widely in this laboratory study of healthy participants. Although some devices are suitable for clinical and research purposes, others underestimated BAC, creating the potential to mislead intoxicated users into thinking that they are fit to drive.


Blood Alcohol Content , Breath Tests/instrumentation , Direct-To-Consumer Screening and Testing , Smartphone , Adult , Female , Humans , Male , Reproducibility of Results , Young Adult
15.
J Am Soc Mass Spectrom ; 32(5): 1215-1223, 2021 May 05.
Article En | MEDLINE | ID: mdl-33831301

Volatile breath metabolites serve as potential disease biomarkers. Online mass spectrometry (MS) presents real-time quantification of breath volatile organic compounds (VOCs). The study aims to assess the relationship between two online analytical mass spectrometry techniques in the quantification of target breath metabolites: selected ion flow tube mass spectrometry (SIFT-MS) and proton-transfer-reaction time-of-flight mass spectrometry (PTR-ToF-MS). The two following techniques were employed: (i) direct injection with bag sampling using SIFT-MS and PTR-ToF-MS and (ii) direct injection and thermal desorption (TD) tube comparison using PTR-ToF-MS. The concentration of abundant breath metabolites, acetone and isoprene, demonstrated a strong positive linear correlation between both mass spectrometry techniques (r = 0.97, r = 0.89, respectively; p < 0.001) and between direct injection and TD tube (r = 0.97, r = 0.92, respectively; p < 0.001) breath sampling techniques. This was reflected for the majority of short chain fatty acids and alcohols tested (r > 0.80, p < 0.001). Analyte concentrations were notably higher with the direct injection of a sampling bag compared to the TD method. All metabolites produced a high degree of agreement in the detection range of VOCs between SIFT-MS and PTR-ToF-MS, with the majority of compounds falling within 95% of the limits of agreement with Bland-Altman analysis. The cross platform analysis of exhaled breath demonstrates strong positive correlation coefficients, linear regression, and agreement in target metabolite detection rates between both breath sampling techniques. The study demonstrates the transferability of using data outputs between SIFT-MS and PTR-ToF-MS. It supports the implementation of a TD platform in multi-site studies for breath biomarker research in order to facilitate sample transport between clinics and the laboratory.


Breath Tests/methods , Mass Spectrometry/methods , Volatile Organic Compounds/analysis , Acetone/analysis , Adult , Breath Tests/instrumentation , Butadienes/analysis , Female , Hemiterpenes/analysis , Humans , Male , Mass Spectrometry/instrumentation
16.
Appl Opt ; 60(10): 2907-2911, 2021 Apr 01.
Article En | MEDLINE | ID: mdl-33798172

There is a great need for cost-efficient non-invasive medical diagnostic tools for analyzing humanly exhaled air. Compared to present day methods, photoacoustic spectroscopy (PAS) can provide a compact and portable (bedside), sensitive and inexpensive solution. We demonstrate a novel portable photoacoustic spectroscopic platform for isotopic measurements of methane (CH4). We identify and discriminate the 12CH4- and 13CH4 isotopologues and determine their mixing ratio. An Allan deviation analysis shows that the noise equivalent concentration for CH4 is 200 ppt (pmol/mol) at 100 s of integration time, corresponding to a normalized noise equivalent absorption coefficient of 5.1×10-9Wcm-1Hz-1/2, potentially making the PAS sensor a truly disruptive instrument for bedside monitoring using isotope tracers by providing real-time metabolism data to clinical personnel.


Breath Tests/methods , Carbon Isotopes/chemistry , Methane/analysis , Photoacoustic Techniques/methods , Biosensing Techniques , Breath Tests/instrumentation , Equipment Design , Exhalation , Humans , Photoacoustic Techniques/instrumentation , Spectrophotometry, Infrared
17.
J Breath Res ; 15(3)2021 04 16.
Article En | MEDLINE | ID: mdl-33752195

COVID-19 is a highly transmissible respiratory illness that has rapidly spread all over the world causing more than 115 million cases and 2.5 million deaths. Most epidemiological projections estimate that the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus causing the infection will circulate in the next few years and raise enormous economic and social issues. COVID-19 has a dramatic impact on health care systems and patient management, and is delaying or stopping breath research activities due to the risk of infection to the operators following contact with patients, potentially infected samples or contaminated equipment. In this scenario, we investigated whether virus inactivation procedures, based on a thermal treatment (60 °C for 1 h) or storage of tubes at room temperature for 72 h, could be used to allow the routine breath analysis workflow to carry on with an optimal level of safety during the pandemic. Tests were carried out using dry and humid gaseous samples containing about 100 representative chemicals found in exhaled breath and ambient air. Samples were collected in commercially available sorbent tubes, i.e. Tenax GR and a combination of Tenax TA, Carbograph 1TD and Carboxen 1003. Our results showed that all compounds were stable at room temperature up to 72 h and that sample humidity was the key factor affecting the stability of the compounds upon thermal treatment. Tenax GR-based sorbent tubes were less impacted by the thermal treatment, showing variations in the range 20%-30% for most target analytes. A significant loss of aldehydes and sulphur compounds was observed using carbon molecular sieve-based tubes. In this case, a dry purge step before inactivation at 60 °C significantly reduced the loss of the target analytes, whose variations were comparable to the method variability. Finally, a breath analysis workflow including a SARS-CoV-2 inactivation treatment is proposed.


Breath Tests/instrumentation , COVID-19/virology , SARS-CoV-2/physiology , Virus Inactivation , Volatile Organic Compounds/chemistry , Breath Tests/methods , Humans , Pandemics , Specimen Handling/methods , Temperature , Volatile Organic Compounds/analysis
18.
Cancer ; 127(8): 1286-1292, 2021 04 15.
Article En | MEDLINE | ID: mdl-33739456

BACKGROUND: Detection of disease by means of volatile organic compounds from breath samples using sensors is an attractive approach to fast, noninvasive and inexpensive diagnostics. However, these techniques are still limited to applications within the laboratory settings. Here, we report on the development and use of a fast, portable, and IoT-connected point-of-care device (so-called, SniffPhone) to detect and classify gastric cancer to potentially provide new qualitative solutions for cancer screening. METHODS: A validation study of patients with gastric cancer, patients with high-risk precancerous gastric lesions, and controls was conducted with 2 SniffPhone devices. Linear discriminant analysis (LDA) was used as a classifying model of the sensing signals obatined from the examined groups. For the testing step, an additional device was added. The study group included 274 patients: 94 with gastric cancer, 67 who were in the high-risk group, and 113 controls. RESULTS: The results of the test set showed a clear discrimination between patients with gastric cancer and controls using the 2-device LDA model (area under the curve, 93.8%; sensitivity, 100%; specificity, 87.5%; overall accuracy, 91.1%), and acceptable results were also achieved for patients with high-risk lesions (the corresponding values for dysplasia were 84.9%, 45.2%, 87.5%, and 65.9%, respectively). The test-phase analysis showed lower accuracies, though still clinically useful. CONCLUSION: Our results demonstrate that a portable breath sensor device could be useful in point-of-care settings. It shows a promise for detection of gastric cancer as well as for other types of disease. LAY SUMMARY: A portable sensor-based breath analyzer for detection of gastric cancer can be used in point-of-care settings. The results are transferrable between devices via advanced IoT technology. Both the hardware and software of the reported breath analyzer could be easily modified to enable detection and monitirng of other disease states.


Biosensing Techniques/instrumentation , Breath Tests/instrumentation , Point-of-Care Systems , Precancerous Conditions/diagnosis , Stomach Neoplasms/diagnosis , Adult , Aged , Aged, 80 and over , Area Under Curve , Biosensing Techniques/methods , Breath Tests/methods , Case-Control Studies , Discriminant Analysis , Female , Humans , Male , Middle Aged , Nanotechnology , Sensitivity and Specificity
19.
Sci Rep ; 11(1): 7185, 2021 03 30.
Article En | MEDLINE | ID: mdl-33785837

The presence of ammonia within the body has long been linked to complications stemming from the liver, kidneys, and stomach. These complications can be the result of serious conditions such as chronic kidney disease (CKD), peptic ulcers, and recently COVID-19. Limited liver and kidney function leads to increased blood urea nitrogen (BUN) within the body resulting in elevated levels of ammonia in the mouth, nose, and skin. Similarly, peptic ulcers, commonly from H. pylori, result in ammonia production from urea within the stomach. The presence of these biomarkers enables a potential screening protocol to be considered for frequent, non-invasive monitoring of these conditions. Unfortunately, detection of ammonia in these mediums is rather challenging due to relatively small concentrations and an abundance of interferents. Currently, there are no options available for non-invasive screening of these conditions continuously and in real-time. Here we demonstrate the selective detection of ammonia using a vapor phase thermodynamic sensing platform capable of being employed as part of a health screening protocol. The results show that our detection system has the remarkable ability to selectively detect trace levels of ammonia in the vapor phase using a single catalyst. Additionally, detection was demonstrated in the presence of interferents such as carbon dioxide (CO2) and acetone common in human breath. These results show that our thermodynamic sensors are well suited to selectively detect ammonia at levels that could potentially be useful for health screening applications.


Ammonia/analysis , Biomarkers/analysis , Breath Tests/instrumentation , Breath Tests/methods , COVID-19 , Carbon Dioxide , Equipment Design , Humans , Humidity , Renal Insufficiency, Chronic , Temperature , Thermodynamics
20.
Sensors (Basel) ; 21(2)2021 Jan 12.
Article En | MEDLINE | ID: mdl-33445436

Human breath is a biomarker of body fat metabolism and can be used to diagnose various diseases, such as diabetes. As such, in this paper, a vacuum ultraviolet (VUV) spectroscopy system is proposed to measure the acetone in exhaled human breath. A strong absorption acetone peak at 195 nm is detected using a simple system consisting of a deuterium lamp source, a hollow-core fiber gas cell, and a fiber-coupled compact spectrometer corresponding to the VUV region. The hollow-core fiber functions both as a long-path and an extremely small-volume gas cell; it enables us to sensitively measure the trace components of exhaled breath. For breath analysis, we apply multiple regression analysis using the absorption spectra of oxygen, water, and acetone standard gas as explanatory variables to quantitate the concentration of acetone in breath. Based on human breath, we apply the standard addition method to obtain the measurement accuracy. The results suggest that the standard deviation is 0.074 ppm for healthy human breath with an acetone concentration of around 0.8 ppm and a precision of 0.026 ppm. We also monitor body fat burn based on breath acetone and confirm that breath acetone increases after exercise because it is a volatile byproduct of lipolysis.


Acetone/analysis , Breath Tests/methods , Spectrophotometry, Ultraviolet/methods , Adipose Tissue/metabolism , Breath Tests/instrumentation , Equipment Design , Exercise , Healthy Volunteers , Humans , Monitoring, Physiologic/instrumentation , Monitoring, Physiologic/methods , Optical Fibers , Regression Analysis , Sensitivity and Specificity , Spectrophotometry, Ultraviolet/instrumentation , Vacuum , Volatile Organic Compounds/analysis , Young Adult
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