Systematic study of polymer gas sampling bags for offline analysis of exhaled breath.

Polymeric bags are a widely applied, simple, and cost-effective method for the storage and offline analysis of gaseous samples. Various materials have been used as sampling bags, all known to contain impurities and differing in their cost, durability, and storage capabilities. Herein, we present a comparative study of several well-known bag materials, Tedlar (PVF), Kynar (PVDF), Teflon (PTFE), and Nalophan (PET), as well as a new material, ethylene vinyl copolymer (EVOH), commonly used for storing food. We investigated the influences of storage conditions, humidity, bag cleaning, and light exposure on volatile organic compound concentration (acetone, acetic acid, isoprene, benzene, limonene, among others) in samples of exhaled human breath stored in bags for up to 48 h. Specifically, we show high losses of short-chain fatty acids (SCFAs) in bags of all materials (for most SCFAs, less than 50% after 8 h of storage). We found that samples in Tedlar, Nalophan, and EVOH bags undergo changes in composition when exposed to UV radiation over a period of 48 h. We report high initial impurity levels in all the bags and their doubling after a period of 48 h. We compare secondary electrospray ionization and proton transfer reaction mass spectrometry in the context of offline analysis after storage in sampling bags. We provide an analytical perspective on the temporal evolution of bag contents by presenting the intensity changes of all significantm/zfeatures. We also present a simple, automated, and cost-effective offline sample introduction system, which enables controlled delivery of collected gaseous samples from polymeric bags into the mass spectrometer. Overall, our findings suggest that sampling bags exhibit high levels of impurities, are sensitive to several environmental factors (e.g. light exposure), and provide low recoveries for some classes of compounds, e.g. SCFAs.

Handheld methanol detector for beverage analysis: interlaboratory validation.

Methanol is a toxic alcohol contained in alcoholic beverages as a natural byproduct of fermentation or added intentionally to counterfeits to increase profit. To ensure consumer safety, many countries and the EU have established strict legislation limits for methanol content. Methanol concentration is mostly detected by laboratory instrumentation since mobile devices for routine on-site testing of beverages in distilleries, at border stations or even at home are not available. Here, we validated a handheld methanol detector for beverage analysis in an ISO 5725 interlaboratory trial: a total of 119 measurements were performed by 17 independent participants (distilleries, universities, authorities, and competence centers) from six countries on samples with relevant methanol concentrations (0.1, 1.5 vol%). The detector was based on a microporous separation filter and a nanostructured gas sensor allowing on-site measurement of methanol down to 0.01 vol% (in the liquid) within only 2 min by laymen. The detector showed excellent repeatability (<5.4%), reproducibility (<9.5%) and small bias (<0.012 vol%). Additional measurements on various methanol-spiked alcoholic beverages (whisky, rum, gin, vodka, tequila, port, sherry, liqueur) indicated that the detector is not interfered by environmental temperature and spirit composition, featuring excellent linearity (R2 > 0.99) down to methanol concentrations of 0.01 vol%. This device has been recently commercialized (Alivion Spark M-20) with comparable accuracy to the gold-standard gas chromatography and can be readily applied for final product inspection, intake control of raw materials or to identify toxic counterfeit products.

Structure-Function Relationship of Highly Reactive CuOx Clusters on Co3 O4 for Selective Formaldehyde Sensing at Low Temperatures.

Designing reactive surface clusters at the nanoscale on metal-oxide supports enables selective molecular interactions in low-temperature catalysis and chemical sensing. Yet, finding effective material combinations and identifying the reactive site remains challenging and an obstacle for rational catalyst/sensor design. Here, the low-temperature oxidation of formaldehyde with CuOx clusters on Co3 O4 nanoparticles is demonstrated yielding an excellent sensor for this critical air pollutant. When fabricated by flame-aerosol technology, such CuOx clusters are finely dispersed, while some Cu ions are incorporated into the Co3 O4 lattice enhancing thermal stability. Importantly, infrared spectroscopy of adsorbed CO, near edge X-ray absorption fine structure spectroscopy and temperature-programmed reduction in H2 identified Cu+ and Cu2+ species in these clusters as active sites. Remarkably, the Cu+ surface concentration correlated with the apparent activation energy of formaldehyde oxidation (Spearman's coefficient ρ = 0.89) and sensor response (0.96), rendering it a performance descriptor. At optimal composition, such sensors detected even the lowest formaldehyde levels of 3 parts-per-billion (ppb) at 75°C, superior to state-of-the-art sensors. Also, selectivity to other aldehydes, ketones, alcohols, and inorganic compounds, robustness to humidity and stable performance over 4 weeks are achieved, rendering such sensors promising as gas detectors in health monitoring, air and food quality control.

Dynamic Breath Limonene Sensing at High Selectivity.

Liver diseases (e.g., cirrhosis, cancer) cause more than two million deaths per year worldwide. This is partly attributed to late diagnosis and insufficient screening techniques. A promising biomarker for noninvasive and inexpensive liver disease screening is breath limonene that can indicate a deficiency of the cytochrome P450 liver enzymes. Here, we introduce a compact and low-cost detector for dynamic and selective breath limonene sensing. It comprises a chemoresistive sensor based on Si/WO3 nanoparticles pre-screened by a packed bed Tenax separation column at room temperature. We demonstrate selective limonene detection down to 20 parts per billion over up to three orders of magnitude higher concentrated acetone, ethanol, hydrogen, methanol, and 2-propanol in gas mixtures, as well as robustness to 10-90% relative humidity. Most importantly, this detector recognizes the individual breath limonene dynamics of four healthy volunteers following the ingestion (swallowing or chewing) of a limonene capsule. Limonene release and subsequent metabolization are monitored from breath measurements in real time and in excellent agreement (R2 = 0.98) with high-resolution proton transfer reaction mass spectrometry. This study demonstrates the potential of the detector as a simple-to-use and noninvasive device for the routine monitoring of limonene levels in exhaled breath to facilitate early diagnosis of liver dysfunction.

Environmental formaldehyde sensing at room temperature by smartphone-assisted and wearable plasmonic nanohybrids.

Formaldehyde is a toxic and carcinogenic indoor air pollutant. Promising for its routine detection are gas sensors based on localized surface plasmon resonance (LSPR). Such sensors trace analytes by converting tiny changes in the local dielectric environment into easily readable, optical signals. Yet, this mechanism is inherently non-selective to volatile organic compounds (like formaldehyde) and yields rarely detection limits below parts-per-million concentrations. Here, we reveal that chemical reaction-mediated LSPR with nanohybrids of Ag/AgOx core-shell clusters on TiO2 enables highly selective formaldehyde sensing down to 5 parts-per-billion (ppb). Therein, AgOx is reduced by the formaldehyde to metallic Ag resulting in strong plasmonic signal changes, as measured by UV/Vis spectroscopy and confirmed by X-ray diffraction. This interaction is highly selective to formaldehyde over other aldehydes, alcohols, ketones, aromatic compounds (as confirmed by high-resolution mass spectrometry), inorganics, and quite robust to relative humidity changes. Since this sensor works at room temperature, such LSPR nanohybrids are directly deposited onto flexible wristbands to quantify formaldehyde between 40-500 ppb at 50% RH, even with a widely available smartphone camera (Pearson correlation coefficient r = 0.998). Such chemoresponsive coatings open new avenues for wearable devices in environmental, food, health and occupational safety applications, as demonstrated by an early field test in the pathology of a local hospital.

Handheld Device for Selective Benzene Sensing over Toluene and Xylene.

More than 1 million workers are exposed routinely to carcinogenic benzene, contained in various consumer products (e.g., gasoline, rubbers, and dyes) and released from combustion of organics (e.g., tobacco). Despite strict limits (e.g., 50 parts per billion (ppb) in the European Union), routine monitoring of benzene is rarely done since low-cost sensors lack accuracy. This work presents a compact, battery-driven device that detects benzene in gas mixtures with unprecedented selectivity (>200) over inorganics, ketones, aldehydes, alcohols, and even challenging toluene and xylene. This can be attributed to strong Lewis acid sites on a packed bed of catalytic WO3 nanoparticles that prescreen a chemoresistive Pd/SnO2 sensor. That way, benzene is detected down to 13 ppb with superior robustness to relative humidity (RH, 10-80%), fulfilling the strictest legal limits. As proof of concept, benzene is quantified in indoor air in good agreement (R2 ≥ 0.94) with mass spectrometry. This device is readily applicable for personal exposure assessment and can assist the implementation of low-emission zones for sustainable environments.

Highly selective gas sensing enabled by filters.

Portable and inexpensive gas sensors are essential for the next generation of non-invasive medical diagnostics, smart air quality monitoring & control, human search & rescue and food quality assessment to name a few of their immediate applications. Therein, analyte selectivity in complex gas mixtures like breath or indoor air remains the major challenge. Filters are an effective and versatile, though often unrecognized, route to overcome selectivity issues by exploiting additional properties of target analytes (e.g., molecular size and surface affinity) besides reactivity with the sensing material. This review provides a tutorial for the material engineering of sorption, size-selective and catalytic filters. Of specific interest are high surface area sorbents (e.g., activated carbon, silica gels and porous polymers) with tunable properties, microporous materials (e.g., zeolites and metal-organic frameworks) and heterogeneous catalysts, respectively. Emphasis is placed on material design for targeted gas separation, portable device integration and performance. Finally, research frontiers and opportunities for low-cost gas sensing systems in emerging applications are highlighted.

Room-Temperature Catalyst Enables Selective Acetone Sensing.

Catalytic packed bed filters ahead of gas sensors can drastically improve their selectivity, a key challenge in medical, food and environmental applications. Yet, such filters require high operation temperatures (usually some hundreds °C) impeding their integration into low-power (e.g., battery-driven) devices. Here, we reveal room-temperature catalytic filters that facilitate highly selective acetone sensing, a breath marker for body fat burn monitoring. Varying the Pt content between 0-10 mol% during flame spray pyrolysis resulted in Al2O3 nanoparticles decorated with Pt/PtOx clusters with predominantly 5-6 nm size, as revealed by X-ray diffraction and electron microscopy. Most importantly, Pt contents above 3 mol% removed up to 100 ppm methanol, isoprene and ethanol completely already at 40 °C and high relative humidity, while acetone was mostly preserved, as confirmed by mass spectrometry. When combined with an inexpensive, chemo-resistive sensor of flame-made Si/WO3, acetone was detected with high selectivity (≥225) over these interferants next to H2, CO, form-/acetaldehyde and 2-propanol. Such catalytic filters do not require additional heating anymore, and thus are attractive for integration into mobile health care devices to monitor, for instance, lifestyle changes in gyms, hospitals or at home.

The Electrophilicity of Surface Carbon Species in the Redox Reactions of CuO-CeO2 Catalysts.

Electronic metal-support interactions (EMSI) describe the electron flow between metal sites and a metal oxide support. It is generally used to follow the mechanism of redox reactions. In this study of CuO-CeO2 redox, an additional flow of electrons from metallic Cu to surface carbon species is observed via a combination of operando X-ray absorption spectroscopy, synchrotron X-ray powder diffraction, near ambient pressure near edge X-ray absorption fine structure spectroscopy, and diffuse reflectance infrared Fourier transform spectroscopy. An electronic metal-support-carbon interaction (EMSCI) is proposed to explain the reaction pathway of CO oxidation. The EMSCI provides a complete picture of the mass and electron flow, which will help predict and improve the catalytic performance in the selective activation of CO2 , carbonate, or carbonyl species in C1 chemistry.

Detecting methanol in hand sanitizers.

The coronavirus disease 2019 (COVID-19) pandemic has increased dramatically the demand for hand sanitizers. A major concern is methanol adulteration that caused more than 700 fatalities in Iran and U.S.A. (since February 2020). In response, the U.S. Food and Drug Administration has restricted the methanol content in sanitizers to 0.063 vol% and blacklisted 212 products (as of November 20, 2020). Here, we present a low-cost, handheld, and smartphone-assisted device that detects methanol selectively in sanitizers between 0.01 and 100 vol% within two minutes. It features a nanoporous polymer column that separates methanol selectively from confounders by adsorption. A chemoresistive gas sensor detects the methanol. When tested on commercial sanitizers (total 76 samples), methanol was quantified in excellent (R2 = 0.99) agreement to "gold standard" gas chromatography. Importantly, methanol quantification was hardly interfered by sanitizer composition and viscosity. This device meets an urgent need for on-site methanol screening by authorities, health professionals, and even laymen.

Screening Methanol Poisoning with a Portable Breath Detector.

Methanol poisoning outbreaks after consumption of adulterated alcohol frequently overwhelm health care facilities in developing countries. Here, we present how a recently developed low-cost and handheld breath detector can serve as a noninvasive and rapid diagnostic tool for methanol poisoning. The detector combines a separation column and a micromachined chemoresistive gas sensor fully integrated into a device that communicates wirelessly with a smartphone. The performance of the detector is validated with methanol-spiked breath of 20 volunteers (105 breath samples) after consumption of alcoholic beverages. Breath methanol concentrations were quantified accurately within 2 min in the full breath-relevant range (10-1000 ppm) in excellent agreement (R2 = 0.966) with benchtop mass spectrometry. Bland-Altman analysis revealed sufficient limits of agreement (95% confidence intervals), promising to indicate reliably the clinical need for antidote and hemodialysis treatment. This simple-in-use detector features high diagnostic capability for accurate measurement of methanol in spiked breath, promising for rapid screening of methanol poisoning and assessment of severity. It can be applied readily by first responders to distinguish methanol from ethanol poisoning and monitor in real time the subsequent hospital treatment.

Superior Acetone Selectivity in Gas Mixtures by Catalyst-Filtered Chemoresistive Sensors.

Acetone is a toxic air pollutant and a key breath marker for non-invasively monitoring fat metabolism. Its routine detection in realistic gas mixtures (i.e., human breath and indoor air), however, is challenging, as low-cost acetone sensors suffer from insufficient selectivity. Here, a compact detector for acetone sensing is introduced, having unprecedented selectivity (>250) over the most challenging interferants (e.g., alcohols, aldehydes, aromatics, isoprene, ammonia, H2, and CO). That way, acetone is quantified with fast response (<1 min) down to, at least, 50 parts per billion (ppb) in gas mixtures with such interferants having up to two orders of magnitude higher concentration than acetone at realistic relative humidities (RH = 30-90%). The detector consists of a catalytic packed bed (30 mg) of flame-made Al2O3 nanoparticles (120 m2 g-1) decorated with Pt nanoclusters (average size 9 nm) and a highly sensitive chemo-resistive sensor made by flame aerosol deposition and in situ annealing of nanostructured Si-doped ε-WO3 (Si/WO3). Most importantly, the catalytic packed bed converts interferants continuously enabling highly selective acetone sensing even in the exhaled breath of a volunteer. The detector exhibits stable performance over, at least, 145 days at 90% RH, as validated by mass spectrometry.

Selective formaldehyde detection at ppb in indoor air with a portable sensor.

Formaldehyde is a carcinogenic indoor air pollutant emitted from wood-based furniture, building materials, paints and textiles. Yet, no low-cost sensor exists for on-site monitoring to fulfill stringent current and upcoming (e.g., 8 parts-per-billion by volume, ppb, in France by 2023) exposure guidelines. Here, we present an inexpensive and handheld formaldehyde detector with proven performance in real indoor air. Selectivity is achieved by a compact packed bed column of nanoporous polymer sorbent that separates formaldehyde from interferants present in ambient air. Downstream, a highly sensitive nanoparticle-based chemoresistive Pd-doped SnO2 sensor detects formaldehyde in the relevant concentration range down to 5 ppb within 2 min. As a proof-of-concept, we measured formaldehyde in indoor air and from different wood product emissions, in excellent agreement (R2 > 0.98) with high-resolution proton-transfer-reaction time-of-flight mass spectrometry. This detector is simple-in-use and readily applicable for on-site formaldehyde exposure monitoring at home or work. It is promising for internet-of-things (IOT) sensing networks or even wearables for personal exposure assessment.

Breath acetone change during aerobic exercise is moderated by cardiorespiratory fitness.

Exhaled breath acetone (BrAce) was investigated during and after submaximal aerobic exercise as a volatile biomarker for metabolic responsiveness in high and lower-fit individuals in a prospective cohort pilot-study. Twenty healthy adults (19-39 years) with different levels of cardiorespiratory fitness (VO2peak), determined by spiroergometry, were recruited. BrAce was repeatedly measured by proton-transfer-reaction time-of-flight mass spectrometry (PTR-TOF-MS) during 40-55 min submaximal cycling exercise and a post-exercise period of 180 min. Activity of ketone and fat metabolism during and after exercise were assessed by indirect calorimetric calculation of fat oxidation rate and by measurement of venous ß-hydroxybutyrate (ßHB). Maximum BrAce ratios were significantly higher during exercise in the high-fit individuals compared to the lower-fit group (t-test; p= 0.03). Multivariate regression showed 0.4% (95%-CI = -0.2%-0.9%, p= 0.155) higher BrAce change during exercise for every ml kg-1 min-1 higher VO2peak. Differences of BrAce ratios during exercise were similar to fat oxidation rate changes, but without association to respiratory minute volume. Furthermore, the high-fit group showed higher maximum BrAce increase rates (46% h-1) in the late post-exercise phase compared to the lower-fit group (29% h-1). As a result, high-fit young, healthy individuals have a higher increase in BrAce concentrations related to submaximal exercise than lower-fit subjects, indicating a stronger exercise-related activation of fat metabolism.

Thickness Optimization of Highly Porous Flame-Aerosol Deposited WO3 Films for NO2 Sensing at ppb.

Nitrogen dioxide (NO2) is a major air pollutant resulting in respiratory problems, from wheezing, coughing, to even asthma. Low-cost sensors based on WO3 nanoparticles are promising due to their distinct selectivity to detect NO2 at the ppb level. Here, we revealed that controlling the thickness of highly porous (97%) WO3 films between 0.5 and 12.3 µm altered the NO2 sensitivity by more than an order of magnitude. Therefore, films of WO3 nanoparticles (20 nm in diameter by N2 adsorption) with mixed γ- and ε-phase were deposited by single-step flame spray pyrolysis without affecting crystal size, phase composition, and film porosity. That way, sensitivity and selectivity effects were associated unambiguously to thickness, which was not possible yet with other sensor fabrication methods. At the optimum thickness (3.1 µm) and 125 °C, NO2 concentrations were detected down to 3 ppb at 50% relative humidity (RH), and outstanding NO2 selectivity to CO, methanol, ethanol, NH3 (all > 105), H2, CH4, acetone (all > 104), formaldehyde (>103), and H2S (835) was achieved. Such thickness-optimized and porous WO3 films have strong potential for integration into low-power devices for distributed NO2 air quality monitoring.

Rapid and Selective NH3 Sensing by Porous CuBr.

Fast and selective detection of NH3 at parts-per-billion (ppb) concentrations with inexpensive and low-power sensors represents a long-standing challenge. Here, a room temperature, solid-state sensor is presented consisting of nanostructured porous (78%) CuBr films. These are prepared by flame-aerosol deposition of CuO onto sensor substrates followed by dry reduction and bromination. Each step is monitored in situ through the film resistance affording excellent process control. Such porous CuBr films feature an order of magnitude higher NH3 sensitivity and five times faster response times than conventional denser CuBr films. That way, rapid (within 2.2 min) sensing of even the lowest (e.g., 5 ppb) NH3 concentrations at 90% relative humidity is attained with outstanding selectivity (30-260) over typical confounders including ethanol, acetone, H2, CH4, isoprene, acetic acid, formaldehyde, methanol, and CO, superior to state-of-the-art sensors. This sensor is ideal for hand-held and battery-driven devices or integration into wearable electronics as it does not require heating. From a broader perspective, the process opens exciting new avenues to also explore other bromides and classes of semiconductors (e.g., sulfides, nitrides, carbides) currently not accessible by flame-aerosol technology.

Catalytic Filter for Continuous and Selective Ethanol Removal Prior to Gas Sensing.

Ethanol is a major confounder in gas sensing because of its omnipresence in indoor air and breath from disinfectants or alcoholic beverages. In fact, most modern gas sensors (e.g., graphene, carbon nanotubes, or metal oxides) are sensitive to ethanol. This is challenging because ethanol is often present at higher concentrations than target analytes. Here, a simple and modular packed bed filter is presented that selectively and continuously removes ethanol (and other alcohols like 1-butanol, isopropanol, and methanol) over critical acetone, CH4, H2, toluene, and benzene at 30-90% relative humidity. This filter consists of catalytically active ZnO nanoparticles (dBET = 55 nm) made by flame aerosol technology and annealing. Continuous oxidation of ethanol to CO2 and H2 was observed at filter temperatures above 260 °C while below that, unwanted acetaldehyde was formed. Most remarkably, ethanol concentrations up to 185 ppm were removed from exhaled breath in preliminary tests with an alcohol intoxicated volunteer, as confirmed by mass spectrometry. At the same time, almost 4 orders of magnitude lower (e.g., 0.025 ppm) acetone concentrations were preserved. This was superior to previous catalyst filters (e.g., CuO, SnO2, and Fe2O3) with overlapping ethanol and acetone conversions and related to ZnO's surface basicity. The ZnO filter performance was stable (±2.5% conversion variability) for, at least, 21 days. Finally, when combined with a Si-doped WO3 sensor, the filter effectively mitigated ethanol interference when sensing acetone without compromising the sensor's fast response and recovery times. Such catalytic filters can be combined readily with all gas sensors.

Palladium embedded in SnO2 enhances the sensitivity of flame-made chemoresistive gas sensors.

Palladium is used commonly to enhance the performance of chemoresistive metal-oxide gas sensors. Typically, this enhancement is attributed to the presence of Pd clusters on the surface of their metal-oxide support (i.e. SnO2). Possible Pd incorporation or embedding into the support rarely has been considered. Here, SnO2 particles (15 - 21 nm in diameter measured by N2 adsorption) with different Pd contents (0 - 3 mol%) were prepared by flame spray pyrolysis (FSP). Leaching these particles with HNO3 and characterization by inductively coupled plasma - optical emission spectrometry (ICP-OES) indicated that only 36 - 60% of Pd have been removed (e.g., from the SnO2 surface). The rest was embedded within the SnO2 particles. Annealing prior to leaching decreased by ~30% that Pd surface content. Most interestingly, such SnO2 particles (with only embedded Pd) show higher sensor response to acetone, ethanol and CO at 350 °C compared to SnO2 particles containing both surface and embedded Pd (i.e. before leaching). As a result, such sensors can detect acetone with high (> 25) signal-to-noise ratio at levels down to 5 ppb at 50% relative humidity. Graphical abstractFlame-made SnO2 nanoparticles with embedded and surface Pd (triangles) exhibit lower sensor response to acetone, ethanol and CO than SnO2 from which the surface Pd had been removed by leaching (circles).

A pocket-sized device enables detection of methanol adulteration in alcoholic beverages.

Alcoholic drinks contaminated, either accidentally or deliberately, by methanol claimed at least 789 lives in 2019, mostly in Asia. Here, a palm-sized, multi-use sensor-smartphone system is presented for on-demand headspace analysis of beverages. The analyser quantified methanol concentrations in 89 pure and methanol-contaminated alcoholic drinks from 6 continents and performed accurately for 107 consecutive days. This device could help consumers, distillers, law-enforcing authorities and healthcare workers to easily screen methanol in alcoholic beverages.

Breath Sensors for Health Monitoring.

Breath sensors can revolutionize medical diagnostics by on-demand detection and monitoring of health parameters in a noninvasive and personalized fashion. Despite extensive research for more than two decades, however, only a few breath sensors have been translated into clinical practice. Actually, most never even left the scientific laboratories. Here, we describe key challenges that currently impede realization of breath sensors and highlight strategies to overcome them. Specifically, we start with breath marker selection (with emphasis on metabolic and inflammatory markers) and breath sampling. Next, the sensitivity, stability, and selectivity requirements for breath sensors are described. Concepts are elaborated to systematically address these requirements by material design (focusing on chemoresistive metal oxides), orthogonal arrays, and filters. Finally, aspects of portable device integration, user communication, and clinical applicability are discussed.