Breath Acetone Concentration Research Articles

Zinc Oxide-Based Acetone Gas Sensors for Breath Analysis: A Review.

Acetone is one of the toxic, explosive, and harmful gases. It may cause several health hazard issues such as narcosis and headache. Acetone is also regarded as a key biomarker to diagnose several diseases as well as monitor the disorders in human health. Based on clinical findings, acetone concentration in human breath is correlated with many diseases such as asthma, halitosis, lung cancer, and diabetes. Thus, its investigation can become a new approach for health monitoring. Better management at the early stages of such diseases has the potential not only to reduce deaths associated with the disease but also to reduce medical costs. ZnO-based sensors show great potential for acetone gas due to their high chemical stability, simple synthesis process, and low cost. The findings suggested that the acetone sensing performance of such sensors can be significantly improved by manipulating the microstructure (surface area, porosity, etc.), composition, and morphology of ZnO nanomaterials. This article provides a comprehensive review of the state-of-the-art research activities, published during the last five years (2016 to 2020), related to acetone gas sensing using nanostructured ZnO (nanowires, nanoparticles, nanorods, thin films, etc). It focuses on different types of nanostructured ZnO-based acetone gas sensors. Furthermore, several factors such as relative humidity, acetone concentrations, and operating temperature that affects the acetone gas sensing properties- sensitivity, long-term stability, selectivity as well as response and recovery time are discussed in this review. We hope that this work will inspire the development of high-performance acetone gas sensors using nanostructured materials.

The Most Common Methods for Breath Acetone Concentration Detection: A Review

The number of diabetic patients in the world continue to increase. Therefore, new methods need to be developed to help the lives of affected people by improving the ability of diabetic monitoring in more efficient and faster ways. These methods should focus on making the devices more affordable, easier to use, less painful, in addition to the accuracy of readings compared with the commercially available ones. Various studies have shown a good correlation between volatile acetone concentration in the breath and ketone bodies in the blood. The breath analysis for diagnosis of diabetes mellitus is an attractive method since it does not need finger pricking. Research was done for measuring breath acetone concentration as a non-invasive method to monitor diabetes. In this paper, I will review the most common techniques that are used for breath acetone detection. A comparison between these techniques and the possibility of using them for the diagnosis of diabetes mellitus are presented and discussed in detail. Finally, this review emphasizes the need for cheap, highly sensitive, easy to use and portable devices to help individuals living with diabetes mellitus to monitor their disease.

Pt-decorated foam-like Ga-In bimetal oxide nanofibers for trace acetone detection in exhaled breath

The concentration of acetone in exhaled breath is an efficient indicator for the diagnosis of diabetes. However, it is difficult to detect acetone in exhaled breath due to the extremely low acetone concentration, rather complex composition and very high humidity. Herein, we report Pt-decorated foam-like Ga-In bimetal oxide nanofibers (Pt-GIO) for trace concentration acetone detection. We found that the Pt-GIO based sensor exhibits enhanced sensing response towards acetone compared with that of Ga-In bimetal oxide (GIO), due to the formation of Schottky contact between Pt and n-type GIO, leading to the increased chemisorbed oxygen. As a result, the Pt-GIO based sensors gives a high response (3.2), short response time (13 s) to 1.8 ppm acetone and very low detection limit (300 ppb). The Pt-GIO sensor also gives good stability and is nearly insensitive to moisture in the range of 40% RH to 95%. These advantages including high response, low detection limit, short response time and high moisture resistance endow Pt-GIO a promising sensing material for acetone detection in exhaled breath.

Vacuum Ultraviolet Absorption Spectroscopy Analysis of Breath Acetone Using a Hollow Optical Fiber Gas Cell.

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.

Investigation of Acetone Vapour Sensing Properties of a Ternary Composite of Doped Polyaniline, Reduced Graphene Oxide and Chitosan Using Surface Plasmon Resonance Biosensor.

This work reports the use of a ternary composite that integrates p-Toluene sulfonic acid doped polyaniline (PANI), chitosan, and reduced graphene oxide (RGO) as the active sensing layer of a surface plasmon resonance (SPR) sensor. The SPR sensor is intended for application in the non-invasive monitoring and screening of diabetes through the detection of low concentrations of acetone vapour of less than or equal to 5 ppm, which falls within the range of breath acetone concentration in diabetic patients. The ternary composite film was spin-coated on a 50-nm-thick gold layer at 6000 rpm for 30 s. The structure, morphology and chemical composition of the ternary composite samples were characterized by FTIR, UV-VIS, FESEM, EDX, AFM, XPS, and TGA and the response to acetone vapour at different concentrations in the range of 0.5 ppm to 5 ppm was measured at room temperature using SPR technique. The ternary composite-based SPR sensor showed good sensitivity and linearity towards acetone vapour in the range considered. It was determined that the sensor could detect acetone vapour down to 0.88 ppb with a sensitivity of 0.69 degree/ppm with a linearity correlation coefficient of 0.997 in the average SPR angular shift as a function of the acetone vapour concentration in air. The selectivity, repeatability, reversibility, and stability of the sensor were also studied. The acetone response was 87%, 94%, and 99% higher compared to common interfering volatile organic compounds such as propanol, methanol, and ethanol, respectively. The attained lowest detection limit (LOD) of 0.88 ppb confirms the potential for the utilisation of the sensor in the non-invasive monitoring and screening of diabetes.

CO2 laser photoacoustic spectrometer for measuring ethylene, acetone, and ammonia in the breath of patients with renal disease

We applied our lab-built CO2 laser photoacoustic spectrometer, which has a multi-component measurement capability, for measuring the ammonia, acetone, and ethylene trace gases in the breath of 10 renal disease patients and 30 healthy volunteers. We argue that not only ammonia but also acetone and ethylene can become potential biomarkers for renal disease. We found that the breath ammonia and acetone concentrations from the renal disease patients are significantly higher than that of the healthy volunteers. While for ethylene, we found that the breath ethylene concentration from renal disease patients is not significantly higher than in the healthy volunteer. Besides a reconfirmation of the breath ammonia concentration as a biomarker for renal disease, our results open up a possibility for the breath acetone to be a possible biomarker for renal disease.

Colorimetric detection of gaseous acetone based on a reaction between acetone and 4-nitrophenylhydrazine in porous glass

Higher concentrations of acetone are typically detected in the air exhaled by patients suffering from diabetes; therefore, the breath acetone concentration could be expected to act as a non-invasive biomarker for diabetes. Here, an analytical chip was developed for the detection of gaseous acetone. This chip was composed of porous glass impregnated with 4-nitrophenylhydrazine (4-NPH). After exposure to an acetone atmosphere, the chip exhibited specific absorption peaks at 256 and 390 nm that were attributed to the 4-NPH acetone derivative (Acetone-4-NPH). Additionally, it was found that the absorbances at 256 and 390 nm increased upon increasing both the acetone concentration and the exposure time. The chip worked cumulatively and could detect gaseous acetone using the absorbance at either 256 or 390 nm, in addition to the exposure time. It was also found that the chip turned yellow after exposure to an acetone atmosphere. Colorimetric analysis using the RGB values obtained from photographic images of the chip showed a negative correlation between the absorbance at 390 nm and the B/G value. This allowed us to estimate gaseous acetone concentrations using color variations in the analytical chip.

Acetone sensors for non-invasive diagnosis of diabetes based on metal–oxide–semiconductor materials

In recent years, clinical studies have found that acetone concentration in exhaled breath can be taken as a characteristic marker of diabetes. Metal–oxide–semiconductor (MOS) materials are widely used in acetone gas sensors due to their low cost, high sensitivity, fast response/recovery time, and easy integration. This paper reviews recent progress in acetone sensors based on MOS materials for diabetes diagnosis. The methods of improving the performance of acetone sensor have been explored for comparison, especially in high humidity conditions. We summarize the current excellent methods of preparations of sensors based on MOSs and hope to provide some help for the progress of acetone sensors in the diagnosis of diabetes.

Enhancement Acetone Sensing Performances of SnO2 Nanorod Arrays By Decorating Noble Metal Catalysts

Introduction Breath analysis using gas chromatography (GC) to identify more than 200 compounds in the human breath came into practice in the 1970s [1]. Endogenous compounds such as inorganic gases (NO, CO) and VOCs (acetone, ethanol, ammonia, ethane and pentane) in the human breath serve as a biomarker for several diseases [2]. Breath acetone is related to diabetes [3], fasting [4], fat metabolism [5], and other numerous diseases [6].The breath acetone concentration is measured by gas chromatography-mass spectrometry (GC-MS), selected ion flow tube mass spectrometry (SIFT-MS), ion mobility spectrometry (IMS), and proton transfer reaction mass spectrometry (PTR-MS), which are commonly used in the laboratory. As the conventional tools for breath analysis are disadvantageous in terms of cost, portability, and the complexity, so we developed a cheap, and portable breath analyzer.Method The breath acetone analyzer comprised a sampling loop, a packed column, three solenoid valves, a mini-sized pump, and a sensor based on SnO2 nanorod (NR) arrays. SnO2 is one of the metal oxide materials that shows high sensitivity to small amount of gases and has strong durability. The mixed gas was passed through the column for the separation of acetone by the difference of interaction with stationary phase. Acetone is separated from the exhaled breath by the packed column within 100 seconds. The operation temperature of the column is maintained at 30 oC. The separated acetone gas was detected by the SnO2-based sensors.The SnO2 NR arrays were synthesized by using glancing angle deposition method on SiO2 wafers. And various kinds of catalyst such as Au, Pd, Pt were deposit on the surface of SnO2 NR arrays. The tests performed at various temperatures (154 - 434 oC) optimized the operation temperature of the breath acetone analyzer system within the boundary. The breath acetone analyzer was used to detect air balanced acetone gas (50 ppm). At optimized operation temperature, the air balanced acetone gas was used to confirm the detection limits of SnO2 NR arrays-based sensors. The resistance of the SnO2 NR arrays –based sensor was converted to a sensor signal (log(R)) by the breath acetone analyzer. The response of the SnO2 NR arrays sensor was defined as:Sensor Signal: ∆(log(R)) = log(R)max – log(R)min , where log(R)max is the maximum resistance before exposure of the acetone and log(R)min is the minimum resistance at acetone exposure. Results and Conclusions The response of the sensor increased with the operating temperature and decreased after an optimal point. Optimal temperature for bare SnO2 NR, Pd-coated SnO2, Pt-coated SnO2 NR, and Au-coated SnO2 NR were 315 oC, 275 oC, 315 oC and 434 oC, respectively. The Figure 1 shows response of bare and catalysts decorated SnO2 NR arrays for various concentrations of acetone. It exhibits the effect of various metal catalysts on sensing properties. The Au-coated SnO2 NR arrays had superior acetone sensing properties than other sensors. The response of the SnO2 NR array based sensors increased with increasing acetone concentration. Au-coated SnO2 NR array sensors could detect acetone as low as 0.1 ppm at 434 oC, which is sufficient to analyze breath acetone (~ 0.5 ppm for normal cases). Depending on the type of gases, there should be a difference in time due to the difference of interaction between the stationary phase and gas. Therefore, we will conduct experiments with mixed gas samples and confirm selectivity of the device. In conclusion, we demonstrated that Au metal catalyst exhibited the largest enhancement among metal decorated SnO2 NR sensors for the detection of acetone.

A Novel Portable Breath Acetone Analyzer Using a MEMS Gas Sensor Array for Fat Loss Monitoring

IntroductionThe development of portable breath acetone analyzer has become an emerging research field in human healthcare and medical instrumentation, because the breath acetone is an important gaseous biomarker for monitoring fat burning [1, 2]. The exhaled acetone increase is a substantial indicator of the total ketone bodies produced by the liver in case of fasting, diets, exercise, and diabetes mellitus [3, 4].The general gas analyzers based on spectrometry measurements are proven to be highly sensitive and accurate [5, 6]. But they currently have some drawbacks like complexity, expense, and bulky size, and require more studies. In this study, we fabricated a novel portable breath acetone analyzer based on the MEMS metal oxide gas sensor arrays. And the developed portable breath acetone analyzer using the sensor arrays offered simple but powerful classification ability for a group of polar volatile organic compounds (VOCs), such as ethanol, formaldehyde, and acetone respectively, by using a principal component analysis (PCA) and good responses to the exhaled breath. Method Figure 1 shows the schematic design and photograph of a fabricated breath acetone analyzer. It comprised breath sampler and gas detection module. The breath sampler that consisted of orifice plate, heater, CO2 sensor and pressure sensor was designed to collect the end-tidal breath. The gas detection chamber that consisted of humidity sensor, temperature sensor and four-kinds of MEMS gas sensors was designed to measure accurately the acetone concentration. And the gas flow line was controlled to minimize the influence of the external environment by one micro vacuum pump and three solenoid valves. The analyzer was mm in size and 1.3 kg in weight.To confirm the sensing-characteristics of the fabricated breath acetone analyzer, first we did measure the responses of MEMS gas sensor array to the simply simulated breath gas, containing 2% CO2, 45% humidity and air, and those with three different 2 ppm VOCs of ethanol, formaldehyde, and acetone respectively. We confirmed the linear response to the concentration ranges of 0~ 1 ppm and investigated the classification properties of the analyzer using the PCA. We measured the exhaled-breath changes of a volunteer who was ordered to do the running exercise. The volunteer did a programmed running exercise for activating the body fat burning process. The program consists of a 20 minutes-long exercise including two running steps with a speed of 8 km/h for 5 minutes and a speed of 9 km/h for 10 minutes. 4-times breath measurements were performed using the analyzer: just before the exercise, right after the running, and thereafter 1 hour, and 2 hours during the post-running rest. Results and Conclusions Figure 2 shows classification results for test VOCs using PCA analysis, and the confirmed the classification possibility for each tested VOCs. We confirmed the acetone increase as time pass after exercise with GC-MS analysis and applied the analyzer to the human exhaled breath to monitor fat loss in exercise. Figure 3 shows the exhaled human breath measurement results of volunteers using the breath acetone analyzer according to the passage of the time. The measurement time (the red-colored region of graphs) and the washing time of the fabricated breath analyzer were set to 200 seconds and 150 seconds, respectively. The response values of the sensors changed linearly as a function of time passed after the exercise. The normalized responses of the p-type gas sensor (Fig.3 a, b, and c) decrease, while that of the n-type sensor (Fig.3 d) increased as time passes after exercise. It indicates that the breath acetone concentration of the volunteer increase with exercise which enhances the body fat metabolism. We are carrying out clinical tests of the analyzer with a permission of IRB in Seoul National University Hospital at Bundang and the details will discuss in the conference.

Effect of inhaled acetone concentrations on exhaled breath acetone concentrations at rest and during exercise

Real-time measurements of the differences in inhaled and exhaled, unlabeled and fully deuterated acetone concentration levels, at rest and during exercise, have been conducted using proton transfer reaction mass spectrometry. A novel approach to continuously differentiate between the inhaled and exhaled breath acetone concentration signals is used. This leads to unprecedented fine grained data of inhaled and exhaled concentrations. The experimental results obtained are compared with those predicted using a simple three compartment model that theoretically describes the influence of inhaled concentrations on exhaled breath concentrations for volatile organic compounds with high blood:air partition coefficients, and hence is appropriate for acetone. An agreement between the predicted and observed concentrations is obtained. Our results highlight that the influence of the upper airways cannot be neglected for volatiles with high blood:air partition coefficients, i.e. highly water soluble volatiles.

Flow Compensated Gas Sensing Array for Improved Performances in Breath-Analysis Applications

Metal-oxide gas sensors have great potential for emerging applications, including breath analysis due to their small form factor, low cost, and low power, which enables integration in consumer electronics, such as smartphone accessories, wearables, and, in the future, smartwatches and phones. Acetone concentration in breath is an important biomarker for well-being and biomedical applications, such as weight loss and ketoacidosis monitoring. In this article, we present a monolithically integrated array of gas sensors combined with a flow sensor in order to provide better quantification of acetone. In particular, this work demonstrates improvement in the acetone selectivity thanks to the combination of three different metal oxides and the ability to compensate with the flow variation.

Characterization of DNPH-coated microreactor chip for analysis of trace carbonyls with application for breath analysis

The analysis of trace carbonyls including aldehydes and ketones is important for monitoring environmental air quality, determining toxicity of aerosol of electronic cigarette, and detecting diseases by breath analysis. This work reports investigation of a single microreactor chip with HClO4-acidified DNPH coating for capture and analysis of carbonyls in air and exhaled breath. Three aldehydes and three ketones were spiked into one liter synthetic air in Tedlar bags serving as gaseous carbonyl standard for characterization of capture efficiency (CE). The HClO4-acidified DNPH showed higher CE of carbonyls than conventionally-used acid including H3PO4 and H2SO4 acidified DNPH under the microreactor conditions. The microreactor conditions including HClO4 to DNPH molar ratio, DNPH to carbonyls molar ratio, and gaseous sample flow rate through the microreactor were studied in detail and thereby optimized. Under the optimized conditions, 100% of CEs for aldehydes and above 80% for ketones were obtained. The microreactor chips were applied to determine acetone concentration in exhaled breath.

On-line monitoring human breath acetone during exercise and diet by proton transfer reaction mass spectrometry.

This study aims to develop a method for monitoring fat loss by detection of breath acetone. A new method combining direct breath sampling system and proton transfer reaction MS (PTR-MS) was developed for on-line detection of breath acetone. The breath acetone of 272 volunteers was detected respectively when exercise or diet. Exercises perennially can make the breath acetone increase by 40-130%. Dinner fasting for 1 week can make it increase by 140%. Exercise and diet are two useful methods to lose fat. Determination of breath acetone concentration using the direct breath sampling system-proton transfer reaction MS can help design scheme of exercise and diet for losing weight.

Gas sniffer (YSZ-based electrochemical gas phase sensor) toward acetone detection

Acetone sniffer, because of its ability of continuous non-invasive monitoring, is recognized as a potential method for the diagnosis of diabetes. In this study, mixed potential electrochemical sensors based on YSZ and K2NiF4 -type oxides Sm2-xSrxNiO4 (x = 0.4, 0.6 and 0.8) sensing electrode were fabricated as bio-sniffer for diagnosis of diabetics by detecting acetone concentration in exhaled breath. The results showed that when Sm1.4Sr0.6NiO4 was used as sensing material, the fabricated sensor exhibited the best performance in comparison with other sensors, the present device also exhibited prominent reliability, excellent humidity resistance and good stability over 30 days. What’s more, the low detection limit of sensor to acetone was 300 ppb, indicating that the sensor had ability for acetone detection in exhaled breath. The exhaled breathes of the diabetics with ketosis were used for detection and results showed that the sensor had a manifest and stable signal. Besides, the response and recovery time were also acceptable to real-time detection. In addition, the relationship of the blood ketone level and the acetone concentration in exhaled breath was given in the paper. Above all, the fabricated sensor has enormous potentiality for the diabetes monitoring through breath analysis.

Highly selective real-time detection of breath acetone by using ZnO quantum dots with a miniaturized gas chromatographic column

In this study, we developed a breath acetone analyzer based on a miniaturized gas chromatography (GC) column integrated with ZnO quantum dots (QDs); this analyzer is capable of analyzing a wide range of breath acetone concentrations within 2 min using a small volume (1 ml) of human breath without pre-concentration. The average size of the ZnO QDs, which were synthesized by a wet chemical method, was approximately 6 nm. The developed analyzer could detect acetone concentrations as low as 0.1 ppm. The response of the ZnO QDs increased with increasing acetone concentration and was strongly correlated with the concentration (R2 = 0.9915). The miniaturized GC column effectively separated acetone from the breath. In addition, a preliminary testing of the breath acetone analyzer was performed through the breath analysis of volunteers who were on ketogenic and normal diets. The results showed that the acetone content in the breath of the volunteer who was on a ketogenic diet for three days was 1.2 ppm.

In-Situ Measurement of Exhaled Formaldehyde and Acetone Kinetics As Early-Stage Non-Invasive Markers of Lung Disease Using Nanostructured Polymeric Membranes

Early stage discovery of lung cancer can significantly improve patient prognosis. Unfortunately, the impact of a well-known technique such as computed tomography screening on mortality rates is uncertain. It has been postulated that tumor growth may lead to peroxidation of cell membranes and is responsible for the observed emission of volatile organic compounds (VOC’s) such as acetone and formaldehyde. This observation has stimulated significant recent effort in the measurement of these compounds in exhaled breath. While promising approaches have been developed for analyzing average VOC concentrations in exhaled breath, an unrecognized drawback to current efforts is the presumption that gas partitioning between the blood and gas phases occurs so rapidly that the time averaged concentration of collected VOCs is representative of their saturation concentration in the lungs. In fact, when one considers the mass transport resistances encountered, VOC lung concentration is likely to be time-dependent and any sensing approach must have sufficient time resolution to capture the dynamic evolution of this concentration during a typical breath exhalation period of not more than 40 seconds in a high humidity environment. In this presentation, we describe development of an optical exhaled gas sensing approach utilizing a nanostructured polymeric membrane that meets these requirements and demonstrates the dynamic evolution of exhaled breath biomarker concentration. We show that the activity of a solid acid catalyst toward the heterogeneous condensation reactions of immobilized resorcinol reagent with gas-phase acetone and formaldehyde can be preserved even at 100% ambient relative humidity through the incorporation of organic acids such as vanillic or tiglic. The reaction produces a colored flavan and poly-condensation products that permits highly selective and sensitive correlation to acetone and formaldehyde concentrations in exhaled breath. Such behavior relies on the complex heterophase morphology of the membrane as will be described. Figure 1

Measurement of breath acetone in patients referred for an oral glucose tolerance test

Breath acetone concentrations were measured in 141 subjects (aged 19–91 years, mean = 59.11 years, standard deviation = 12.99 years), male and female, undergoing an oral glucose tolerance test (OGTT), having been referred to clinic on suspicion of type 2 diabetes. Breath samples were measured using an ion-molecule-reaction mass spectrometer, at the commencement of the OGTT, and after 1 and 2 h. Subjects were asked to observe the normal routine before and during the OGTT, which includes an overnight fast and ingestion of 75 g glucose at the beginning of the routine. Several groups of diagnosis were identified: type 2 diabetes mellitus positive (T2DM), n = 22; impaired glucose intolerance (IGT), n = 33; impaired fasting glucose, n = 14; and reactive hypoglycaemia, n = 5. The subjects with no diagnosis (i.e. normoglycaemia) were used as a control group, n = 67. Distributions of breath acetone are presented for the different groups. There was no evidence of a direct relationship between blood glucose (BG) and acetone measurements at any time during the study (0 h: p = 0.4482; 1 h: p = 0.6854; and 2 h: p = 0.1858). Nor were there significant differences between the measurements of breath acetone for the control group and the T2DM group (0 h: p = 0.1759; 1 h: p = 0.4521; and 2 h: p = 0.7343). However, the ratio of breath acetone at 1 h to the initial breath acetone was found to be significantly different for the T2DM group compared to both the control and IGT groups (p = 0.0189 and 0.011, respectively). The T2DM group was also found to be different in terms of ratio of breath acetone after 1 h to that at 2 h during the OGTT. And was distinctive in that it showed a significant dependence upon the level of BG at 2 h (p = 0.0146). We conclude that single measurements of the concentrations of breath acetone cannot be used as a potential screening diagnostic for T2DM diabetes in this cohort, but monitoring the evolution of breath acetone could open a non-invasive window to aid in the diagnosis of metabolic conditions.

Water-Resistant Polymeric Acid Membrane Catalyst for Acetone Detection in the Exhaled Breath of Diabetics.

Endogenous volatile organic compounds (VOCs) such as acetone in exhaled human breath are associated with metabolic conditions in the bloodstream. Development of compact, rapid detectors of exhaled breath chemical composition in clinical settings is challenging due to the small sample size that can be collected during a single exhalation as well as spectroscopic interference by the abundance of water. In this paper, we show that the activity of a catalytic polymer membrane (Nafion 117) toward the heterogeneous condensation reaction of immobilized resorcinol reagent with gas-phase acetone can be preserved even at 100% ambient relative humidity through the incorporation of organic acids such as vanillic or tiglic. The reaction produces a colored flavan product that permits highly selective and sensitive correlation to acetone concentration in exhaled breath. Such behavior suggests solvent displacement, analogous to homogeneous liquid-phase systems. However, unlike classic acid-base equilibria, the extent of optode water resistance is shown to increase with the pKa of the imbibed organic acid while peak signal intensity of the imbibed acid undergoes a bathochromic shift to longer wavelengths. These observations are consistent with competition between organic acid deprotonation by water in a mixed solvent system on the one hand and immobilization on the other. Finally, we demonstrate how when applied to the direct chemical analysis of acetone in exhaled human breath, the approach yields excellent correlation to blood glucose in diabetics.

On the Metabolism of Exogenous Ketones in Humans.

Background and aims: Currently there is considerable interest in ketone metabolism owing to recently reported benefits of ketosis for human health. Traditionally, ketosis has been achieved by following a high-fat, low-carbohydrate “ketogenic” diet, but adherence to such diets can be difficult. An alternative way to increase blood D-β-hydroxybutyrate (D-βHB) concentrations is ketone drinks, but the metabolic effects of exogenous ketones are relatively unknown. Here, healthy human volunteers took part in three randomized metabolic studies of drinks containing a ketone ester (KE); (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, or ketone salts (KS); sodium plus potassium βHB.Methods and Results: In the first study, 15 participants consumed KE or KS drinks that delivered ~12 or ~24 g of βHB. Both drinks elevated blood D-βHB concentrations (D-βHB Cmax: KE 2.8 mM, KS 1.0 mM, P < 0.001), which returned to baseline within 3–4 h. KS drinks were found to contain 50% of the L-βHB isoform, which remained elevated in blood for over 8 h, but was not detectable after 24 h. Urinary excretion of both D-βHB and L-βHB was <1.5% of the total βHB ingested and was in proportion to the blood AUC. D-βHB, but not L-βHB, was slowly converted to breath acetone. The KE drink decreased blood pH by 0.10 and the KS drink increased urinary pH from 5.7 to 8.5. In the second study, the effect of a meal before a KE drink on blood D-βHB concentrations was determined in 16 participants. Food lowered blood D-βHB Cmax by 33% (Fed 2.2 mM, Fasted 3.3 mM, P < 0.001), but did not alter acetoacetate or breath acetone concentrations. All ketone drinks lowered blood glucose, free fatty acid and triglyceride concentrations, and had similar effects on blood electrolytes, which remained normal. In the final study, participants were given KE over 9 h as three drinks (n = 12) or a continuous nasogastric infusion (n = 4) to maintain blood D-βHB concentrations greater than 1 mM. Both drinks and infusions gave identical D-βHB AUC of 1.3–1.4 moles.min.Conclusion: We conclude that exogenous ketone drinks are a practical, efficacious way to achieve ketosis.