This review highlights recent advances towards non-invasive and continuous glucose monitoring devices, with a particular focus placed on monitoring glucose concentrations in alternative physiological fluids to blood.

Glucose Sensing for Diabetes Monitoring: Recent Developments.

There is great need for stand-alone luminescence-based chemosensors that exemplify selectivity, sensitivity, and applicability and that overcome the challenges that arise from complex, real-world media. Discussed herein are recent developments toward these goals in the field of supramolecular luminescent chemosensors, including macrocycles, polymers, and nanomaterials. Specific focus is placed on the development of new macrocycle hosts since 2010, coupled with considerations of the underlying principles of supramolecular chemistry as well as analytes of interest and common luminophores. State-of-the-art developments in the fields of polymer and nanomaterial sensors are also examined, and some remaining unsolved challenges in the area of chemosensors are discussed.

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Supramolecular Luminescent Sensors

In this paper, we demonstrated a room-temperature acetone gas sensor based on a tin dioxide (SnO2)-reduced graphene oxide (RGO) hybrid composite film. The SnO2–RGO composite film sensor was fabricated on a PCB substrate with rectangular-ambulatory-plane interdigitated microelectrodes by using a facile hydrothermal method. The presence of small SnO2 nanoparticles on RGO sheets was characterized by SEM, XRD and BET measurements, demonstrating good structures without irreversible restacking of sheets and agglomeration. The sensing properties of the SnO2–RGO hybrid film sensor were investigated by exposing it to various concentrations of acetone gas at room temperature. It was found that the presented sensor exhibited not only an excellent response to acetone gas, but also a fast response–recovery time and good repeatability, exhibiting the unique advantages of the SnO2–RGO hybrid composite as a building block for sensor fabrication. The gas response of the SnO2–RGO hybrid composite was about 2-fold higher than that of the pure RGO film, and the possible sensing mechanism was mainly attributed to the high surface area, three-dimensional porous nanostructure and special interactions between the RGO sheets and SnO2 nanoparticles.

Room-temperature high-performance acetone gas sensor based on hydrothermal synthesized SnO2-reduced graphene oxide hybrid composite

https://iopscience.iop.org/article/10.1149/1945-7111/ab67a6/pdf

Review—Non-Invasive Monitoring of Human Health by Exhaled Breath Analysis: A Comprehensive Review

The development of gas sensor that is capable of detecting ppb-level detection of acetone and possesses high response toward low-concentration acetone remains a great challenge. Herein, we present the construction of the W18O49/Ti3C2Tx composites based on the in situ grown of the 1D W18O49 nanorods (NRs) on the surfaces of the 2D Ti3C2Tx Mxene sheets via a facile solvothermal process. The W18O49/Ti3C2Tx composites exhibit high response to low concentration acetone (11.6 to 20 ppm acetone), ideal selectivity, long-term stability, very low limit of detection of 170 ppb acetone, and fast response and recover rates (5.6/6 s to 170 ppb acetone). Compared to the W18O49 NRs and Ti3C2Tx sheets, the W18O49/Ti3C2Tx composites show significant improvement on the acetone-sensing performance, which can be ascribed to the homogeneous distribution of the W18O49 NRs on the Ti3C2Tx surface, the removal of the fluorine-containing groups from the Ti3C2Tx after the solvothermal process, and the synergistic interfacial interactions between the W18O49 NRs and the Ti3C2Tx sheets. The synthesis of the 1D/2D W18O49/Ti3C2Tx Mxene composites provides a new avenue to develop other promising hybrids for acetone sensing.

W18O49/Ti3C2Tx Mxene nanocomposites for highly sensitive acetone gas sensor with low detection limit

Since the ancient discovery of the 'sweet odor' in human breath gas, pursuits of the breath analysis-based disease diagnostics have never stopped. Actually, the 'smell' of the breath, as one of three key disease diagnostic techniques, has been used in Eastern-Medicine for more than three thousand years. With advancement of measuring technologies in sensitivity and selectivity, more specific breath gas species have been identified and established as a biomarker of a particular disease. Acetone is one of the breath gases and its concentration in exhaled breath can now be determined with high accuracy using various techniques and methods. With the worldwide prevalence of diabetes that is typically diagnosed through blood testing, human desire to achieve non-blood based diabetic diagnostics and monitoring has never been quenched. Questions, such as is breath acetone a biomarker of diabetes and how is the breath acetone related to the blood glucose (BG) level (the golden criterion currently used in clinic for diabetes diagnostic, monitoring, and management), remain to be answered. A majority of current research efforts in breath acetone measurements and its technology developments focus on addressing the first question. The effort to tackle the second question has begun recently. The earliest breath acetone measurement in clearly defined diabetic patients was reported more than 60 years ago. For more than a half-century, as reviewed in this paper, there have been more than 41 independent studies of breath acetone using various techniques and methods, and more than 3211 human subjects, including 1581 healthy people, 242 Type 1 diabetic patients, 384 Type 2 diabetic patients, 174 unspecified diabetic patients, and 830 non-diabetic patients or healthy subjects who are under various physiological conditions, have been used in the studies. The results of the breath acetone measurements collected in this review support that many conditions might cause changes to breath acetone concentrations; however, the results from the six independent studies using clearly-defined Type 1 and Type 2 diabetic patients unanimously support that an elevated mean breath acetone concentration exists in Type 1 diabetes. Note that there is some overlap between the ranges of breath acetone concentration in individual T1D patients and healthy subjects; this reminds one to be careful when using an acetone breath test on T1D diagnostics. Comparatively, it is too early to draw a general conclusion on the relationship between a breath acetone level and a BG level from the very limited data in the literature.

http://iopscience.iop.org/article/10.1088/1752-7155/7/3/037109/pdf

Is breath acetone a biomarker of diabetes? A historical review on breath acetone measurements.

Kennard-Stone combined with least square support vector machine method for noncontact discriminating human blood species

Breath analysis has been considered a suitable tool to evaluate diseases of the respiratory system and those that involve metabolic changes, such as diabetes. Breath acetone has long been known as a biomarker for diabetes. However, the results from published data by far have been inconclusive regarding whether breath acetone is a reliable index of diabetic screening. Large variations exist among the results of different studies because there has been no “best-practice method” for breath-acetone measurements as a result of technical problems of sampling and analysis. In this mini-review, we update the current status of our development of a laser-based breath acetone analyzer toward real-time, one-line diabetic screening and a point-of-care instrument for diabetic management. An integrated standalone breath acetone analyzer based on the cavity ringdown spectroscopy technique has been developed. The instrument was validated by using the certificated gas chromatography-mass spectrometry. The linear fittings suggest that the obtained acetone concentrations via both methods are consistent. Breath samples from each individual subject under various conditions in total, 1257 breath samples were taken from 22 Type 1 diabetic (T1D) patients, 312 Type 2 diabetic (T2D) patients, which is one of the largest numbers of T2D subjects ever used in a single study, and 52 non-diabetic healthy subjects. Simultaneous blood glucose (BG) levels were also tested using a standard diabetic management BG meter. The mean breath acetone concentrations were determined to be 4.9 ± 16 ppm (22 T1D), and 1.5 ± 1.3 ppm (312 T2D), which are about 4.5 and 1.4 times of the one in the 42 non-diabetic healthy subjects, 1.1 ± 0.5 ppm, respectively. A preliminary quantitative correlation (R = 0.56, p < 0.05) between the mean individual breath acetone concentration and the mean individual BG levels does exist in 20 T1D subjects with no ketoacidosis. No direct correlation is observed in T1D subjects, T2D subjects, and healthy subjects. The results from a relatively large number of subjects tested indicate that an elevated mean breath acetone concentration exists in diabetic patients in general. Although many physiological parameters affect breath acetone, under a specifically controlled condition fast (<1 min) and portable breath acetone measurement can be used for screening abnormal metabolic status including diabetes, for point-of-care monitoring status of ketone bodies which have the signature smell of breath acetone, and for breath acetone related clinical studies requiring a large number of tests.

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A Portable Real-Time Ringdown Breath Acetone Analyzer: Toward Potential Diabetic Screening and Management

Blood species identification using Near-Infrared diffuse transmitted spectra and PLS-DA method ☆

Breath analysis is a promising new technique for nonintrusive disease diagnosis and metabolic status monitoring. One challenging issue in using a breath biomarker for potential particular disease screening is to find a quantitative relationship between the concentration of the breath biomarker and clinical diagnostic parameters of the specific disease. In order to address this issue, we need a new instrument that is capable of conducting real-time, online breath analysis with high data throughput, so that a large scale of clinical test (more subjects) can be achieved in a short period of time. In this work, we report a fully integrated, standalone, portable analyzer based on the cavity ringdown spectroscopy technique for near-real time, online breath acetone measurements. The performance of the portable analyzer in measurements of breath acetone was interrogated and validated by using the certificated gas chromatography-mass spectrometry. The results show that this new analyzer is useful for reliable online (online introduction of a breath sample without pre-treatment) breath acetone analysis with high sensitivity (57 ppb) and high data throughput (one data per second). Subsequently, the validated breath analyzer was employed for acetone measurements in 119 human subjects under various situations. The instrument design, packaging, specifications, and future improvements were also described. From an optical ringdown cavity operated by the lab-set electronics reported previously to this fully integrated standalone new instrument, we have enabled a new scientific tool suited for large scales of breath acetone analysis and created an instrument platform that can even be adopted for study of other breath biomarkers by using different lasers and ringdown mirrors covering corresponding spectral fingerprints.

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Zhennan Wang

Papers

Is breath acetone a biomarker of diabetes? A historical review on breath acetone measurements.

Kennard-Stone combined with least square support vector machine method for noncontact discriminating human blood species

A Portable Real-Time Ringdown Breath Acetone Analyzer: Toward Potential Diabetic Screening and Management

Blood species identification using Near-Infrared diffuse transmitted spectra and PLS-DA method ☆

A fully integrated standalone portable cavity ringdown breath acetone analyzer