Precision detection of select human lung cancer biomarkers and cell lines using honeybee olfactory neural circuitry as a novel gas sensor.

Human breath contains biomarkers (odorants) that can be targeted for early disease detection. It is well known that honeybees have a keen sense of smell and can detect a wide variety of odors at low concentrations. Here, we employ honeybee olfactory neuronal circuitry to classify human lung cancer volatile biomarkers at different concentrations and their mixtures at concentration ranges relevant to biomarkers in human breath from parts-per-billion to parts-per-trillion. We also validated this brain-based sensing technology by detecting human non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) cell lines using the 'smell' of the cell cultures. Different lung cancer biomarkers evoked distinct spiking response dynamics in the honeybee antennal lobe neurons indicating that those neurons encoded biomarker-specific information. By investigating lung cancer biomarker-evoked population neuronal responses from the honeybee antennal lobe, we classified individual human lung cancer biomarkers successfully (88% success rate). When we mixed six lung cancer biomarkers at different concentrations to create 'synthetic lung cancer' vs. 'synthetic healthy' human breath, honeybee population neuronal responses were able to classify those complex breath mixtures reliably with exceedingly high accuracy (93-100% success rate with a leave-one-trial-out classification method). Finally, we employed this sensor to detect human NSCLC and SCLC cell lines and we demonstrated that honeybee brain olfactory neurons could distinguish between lung cancer vs. healthy cell lines and could differentiate between different NSCLC and SCLC cell lines successfully (82% classification success rate). These results indicate that the honeybee olfactory system can be used as a sensitive biological gas sensor to detect human lung cancer.

Electronic nose based analysis of exhaled volatile organic compounds spectrum reveals asthmatic shifts and consistency in controls post-exercise and spirometry.

Analyzing exhaled volatile organic compounds (VOCs) with an electronic nose (e-nose) is emerging in medical diagnostics as a non-invasive, quick, and sensitive method for disease detection and monitoring. This study investigates if activities like spirometry or physical exercise affect exhaled VOCs measurements in asthmatics and healthy individuals, a crucial step for e-nose technology's validation for clinical use. The study analyzed exhaled VOCs using an e-nose in 27 healthy individuals and 27 patients with stable asthma, before and after performing spirometry and climbing five flights of stairs. Breath samples were collected using a validated technique and analyzed with a Cyranose 320 e-nose. In healthy controls, the exhaled VOCs spectrum remained unchanged after both lung function test and exercise. In asthmatics, principal component analysis and subsequent discriminant analysis revealed significant differences post-spirometry (vs. baseline 66.7% cross validated accuracy [CVA],p< 0.05) and exercise (vs. baseline 70.4% CVA,p< 0.05). E-nose measurements in healthy individuals are consistent, unaffected by spirometry or physical exercise. However, in asthma patients, significant changes in exhaled VOCs were detected post-activities, indicating airway responses likely due to constriction or inflammation, underscoring the e-nose's potential for respiratory condition diagnosis and monitoring.

P-N Heterojunction formation: Metal Sulfide@Metal Oxide Chemiresistor for ppb H2S Detection from Exhaled Breath and Food Spoilage at Flexible Room Temperature.

The development of a portable, low-cost sensor capable of accurately detecting H2S gas in exhaled human breath at room temperature is highly anticipated in the fields of human health assessment and food spoilage evaluation. However, achieving outstanding gas sensing performance and applicability for flexible room-temperature operation with parts per billion H2S gas sensors still poses technical challenges. To address this issue, this study involves the in situ growth of MoS2 nanosheets on the surface of In2O3 fibers to construct a p-n heterojunction. The In2O3@MoS2-2 sensor exhibits a high response of 460.61 to 50 ppm of H2S gas at room temperature, which is 19.5 times higher than that of the pure In2O3 sensor and 322.1 times higher than that of pure MoS2. The In2O3@MoS2-2 also demonstrates a minimum detection limit of 3 ppb and maintains a stable response to H2S gas even after being bent 50 times at a 60° angle. These exceptional gas sensing properties are attributed to the increase in oxygen vacancies and chemisorbed oxygen on In2O3@MoS2-2 nanofibers as well as the formation of the p-n heterojunction, which modulates the heterojunction barrier. Furthermore, in this study, we successfully applied the In2O3@MoS2-2 sensor for oral disease and detection of food spoilage conditions, thereby providing new design insights for the development of portable exhaled gas sensors and gas sensors for evaluating food spoilage conditions at room temperature.

Benchmarking breath analysis using peppermint approach with gas chromatography ion mobility spectrometer coupled to micro thermal desorber.

The Peppermint Initiative, established within the International Association of Breath Research, introduced the peppermint protocol, a breath analysis benchmarking effort designed to address the lack of inter-comparability of outcomes across different breath sampling techniques and analytical platforms. Benchmarking with gas chromatography-ion mobility spectrometry (GC-IMS) using peppermint has been previously reported however, coupling micro-thermal desorption (µTD) to GC-IMS has not yet, been benchmarked for breath analysis. To benchmarkµTD-GC-IMS for breath analysis using the peppermint protocol. Ten healthy participants (4 males and 6 females, aged 20-73 years), were enrolled to give six breath samples into Nalophan bags via a modified peppermint protocol. Breath sampling after peppermint ingestion occurred over 6 h att= 60, 120, 200, 280, and 360 min. The breath samples (120 cm3) were pre-concentrated in theµTD before being transferred into the GC-IMS for detection. Data was processed using VOCal, including background subtractions, peak volume measurements, and room air assessment. During peppermint washout, eucalyptol showed the highest change in concentration levels, followed byα-pinene andß-pinene. The reproducibility of the technique for breath analysis was demonstrated by constructing logarithmic washout curves, with the average linearity coefficient ofR2= 0.99. The time to baseline (benchmark) value for the eucalyptol washout was 1111 min (95% CI: 529-1693 min), obtained by extrapolating the average logarithmic washout curve. The study demonstrated thatµTD-GC-IMS is reproducible and suitable technique for breath analysis, with benchmark values for eucalyptol comparable to the gold standard GC-MS.

Assessment of Maximum Oxygen Uptake in Elite Youth Soccer Players: A Comparative Analysis of Smartwatch Technology, Yoyo Intermittent Recovery Test 2, and Respiratory Gas Analysis.

The maximum oxygen uptake (VO2max) is a critical factor for endurance performance in soccer. Novel wearable technology may allow frequent assessment of V̇O2max during non-fatiguing warm-up runs of soccer players with minimal interference to soccer practice. The aim of this study was to assess the validity of VO2max provided by a consumer grade smartwatch (Garmin Forerunner 245, Garmin, Olathe, USA, Software:13.00) and the YoYo Intermittent Recovery Run 2 (YYIR2) by comparing it with respiratory gas analysis. 24 trained male youth soccer players performed different tests to assess VO2max: i) a treadmill test employing respiratory gas analysis, ii) YYIR2 and iii) during a non-fatiguing warm-up run of 10 min wearing a smartwatch as recommended by the device-manufacturer on 3 different days within 2 weeks. As the device-manufacturer indicates that validity of smartwatch-derived VO2max may differ with an increase in runs, 16 players performed a second run with the smartwatch to test this claim. The main evidence revealed that the smartwatch showed an ICC of 0.37 [95% CI: -0.25; 0.71] a mean absolute percentage error (MAPE) of 5.58% after one run, as well as an ICC of 0.54 [95% CI: -0.3; 8.4] and a MAPE of 1.06% after the second run with the smartwatch. The YYIR2 showed an ICC of 0.17 [95% CI: -5.7; 0.6]; and MAPE of 4.2%. When using the smartwatch for VO2max assessment in a non-fatiguing run as a warm-up, as suggested by the device manufacturer before soccer practice, the MAPE diminishes after two runs. Therefore, for more accurate VO2max assessment with the smartwatch, we recommend to perform at least two runs to reduce the MAPE and enhance the validity of the findings.

Impact of breath sample collection method and length of storage of breath samples in Tedlar bags on the level of selected volatiles assessed using gas chromatography-ion mobility spectrometry (GC-IMS).

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.

A noval transparent triboelectric nanogenerator as electronic skin for real-time breath monitoring.

Against the backdrop of advancements in modern multifunctional wearable electronics, there is a growing demand for simple, sustainable, and portable electronic skin (e-skin), posing significant challenges. This study aims to delineate the development of a straightforward, transparent, highly sensitive, and high power-density electronic skin based on a triboelectric nanogenerator(S-TENG), designed for harvesting human body energy and real-time monitoring of the physiological motion status. Our e-skin incorporates thermally treated polyvinylidene fluoride (PVDF) fiber membranes as the contact layer and a film of silver nanowires as the conductive electrodes. The resulting contact-separation type e-skin exhibits an impressive transparency of 80 %, along with a nice sensitivity value, capable of detecting a light touch from a 0.13 g sponge and demonstrating good working stability and breathability. Leveraging the triboelectric effect, our e-skin generates an open-circuit voltage of 301 V and a short-circuit current of 2.7 µA under an extrinsic force of 8 N over an interaction area of 4 × 4 cm2, achieving a power density up to 306 mW/m2. With its signal processing circuitry, the integrated S-TENG showcases nice energy harvesting and signal transmission capabilities. Accordingly, we contend that S-TENG has potential applications in energy capture and real-time human motion state monitoring. This research is anticipated to blaze a novel and practical trail for self-powered wearable devices and personalized health rehabilitation training regimens.

Periodic open and closed resonators as a biosensor using two computational methods.

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.

Highly Sensitive and Fast Responding Flexible Force Sensors Using ZnO/ZnMgO Coaxial Nanotubes on Graphene Layers for Breath Sensing.

The authors report the fabrication of highly sensitive, rapidly responding flexible force sensors using ZnO/ZnMgO coaxial nanotubes grown on graphene layers and their applications in sleep apnea monitoring. Flexible force sensors are fabricated by forming Schottky contacts to the nanotube array, followed by the mechanical release of the entire structure from the host substrate. The electrical characteristics of ZnO and ZnO/ZnMgO nanotube-based sensors are thoroughly investigated and compared. Importantly, in force sensor applications, the ZnO/ZnMgO coaxial structure results in significantly higher sensitivity and a faster response time when compared to the bare ZnO nanotube. The origin of the improved performance is thoroughly discussed. Furthermore, wireless breath sensing is demonstrated using the ZnO/ZnMgO pressure sensors with custom electronics, demonstrating the feasibility of the sensor technology for health monitoring and the potential diagnosis of sleep apnea.

Nanowire Array Breath Acetone Sensor for Diabetes Monitoring.

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.

Advances in proteomics methods for the analysis of exhaled breath condensate.

The analysis of exhaled breath condensate (EBC) demonstrates a promising avenue of minimally invasive biopsies for diagnostics. EBC is obtained by cooling exhaled air and collecting the condensation to be utilized for downstream analysis using various analytical methods. The aqueous phase of breath contains a large variety of miscible small compounds including polar electrolytes, amino acids, cytokines, chemokines, peptides, small proteins, metabolites, nucleic acids, and lipids/eicosanoids-however, these analytes are typically present at minuscule levels in EBC, posing a considerable technical challenge. Along with recent improvements in devices for breath collection, the sensitivity and resolution of liquid chromatography coupled to online mass spectrometry-based proteomics has attained subfemtomole sensitivity, vastly enhancing the quality of EBC sample analysis. As a result, proteomics analysis of EBC has been expanding the field of breath biomarker research. We present an au courant overview of the achievements in proteomics of EBC, the advancement of EBC collection devices, and the current and future applications for EBC biomarker analysis.

Detection of trace volatile organic compounds in spiked breath samples: a leap towards breathomics.

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.

Simultaneous Biomechanical and Biochemical Monitoring for Self-Powered Breath Analysis.

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.

Highly Sensitive Surface Plasmon Resonance Humidity Sensor Based on a Polyvinyl-Alcohol-Coated Polymer Optical Fiber.

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.

Tunable diode laser-based two-line thermometry: a noncontact thermometer for active body temperature measurement.

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.

Accuracy of a breath ketone analyzer to detect ketosis in adults and children with type 1 diabetes.

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.

3D-printed smartphone-based device for fluorimetric diagnosis of ketosis by acetone-responsive dye marker and red emissive carbon dots.

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.

Wearable Collector for Noninvasive Sampling of SARS-CoV-2 from Exhaled Breath for Rapid Detection.

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.

Nose in malignant mesothelioma-Prediction of response to immune checkpoint inhibitor treatment.

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.