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With the aim to capture and subsequent selective trapping of CO2, a nanocomposite has been developed through selective modification of the outer surface of the halloysite nanotubes (HNTs) with an organosilane to make the nanocomposite a novel solid-phase adsorbent to adsorb CO2 from the atmosphere at standard ambient temperature and pressure. The preferential adsorption of three major abundant isotopes of CO2 (12C16O2, 13C16O2, and 12C16O18O) from the ambient air by amine functionalized HNTs has been explored using an optical cavity-enhanced integrated cavity output spectroscopy. CO2 adsorption/desorption cycling measurements demonstrate that the adsorbent can be regenerated at relatively low temperature and thus, recycled repeatedly to capture atmospheric CO2. The amine grafted halloysite shows excellent stability even in oxidative environments and has high efficacy of CO2 capture, introducing a new route to the adsorption of isotope selective atmospheric CO2.

Carbonic anhydrase (CA), a well-characterized metalloenzyme, is associated with oxygen-18 ( 18O)-isotopic fractionations of CO2. To investigate how CA activity links the 18O of breath CO2 to pre-diabetes (PD) and type 2 diabetes (T2D) during metabolism, we studied pre- and post-dose CA activities in erythrocytes with simultaneous monitoring of 18O/ 16O-isotope ratios of breath CO2 and thereafter elucidated potential metabolic pathways underlying CA alteration in the pathogenesis of T2D. Here we show that the post-dose CA activity in both T2D and PD was markedly enhanced, whereas the non-diabetic controls (NDC) exhibited a considerable reduction in post-dose CA activity when compared with their basal CA activities. However, T2D and PD exhibited isotopic enrichments of 18O in breath CO2, while a marked depletion of 18O in CO2 was manifested in NDC. Thus, the isotopic enrichments and depletions of 18O in breath CO2 were well correlated with the changes in CA activities for controls, PD and T2D. Our findings suggest the changes in CA activities in erythrocytes may contribute to the pathogenesis of T2D and the breath C 18O 16O regulated by the CA activity as a potential biomarker for non-invasive assessment of T2D, and thus may open a new method for treating T2D.

Detection of biomarkers in exhaled breath has been gaining increasing attention as a tool for diagnosis of specific diseases. However, rapid and accurate quantification of biomarkers associated with specific diseases requires the use of analytical methods capable of fast sampling and preconcentration from breath matrix. In this regard, solid phase microextraction and needle trap technology are becoming increasingly popular in the field of breath analysis due to the unique benefits imparted by such methods, such as the integration of sampling, extraction, and preconcentration in a single step. This review discusses recent advances in breath analysis using these sample preparation techniques, providing a summary of recent developments of analytical methods based on breath volatile organic compounds analysis, including the successful identification of various biomarkers related to human diseases.

The gastric pathogen Helicobacter pylori utilize glucose during metabolism, but the underlying mechanisms linking to oxygen-18 (18O) and carbon-13 (13C)-isotopic fractionations of breath CO2 during glucose metabolism are poorly understood. Using the excretion dynamics of 18O/16O and 13C/12C-isotope ratios of breath CO2, we found that individuals with Helicobacter pylori infections exhibited significantly higher isotopic enrichments of 18O in breath CO2 during the 2h-glucose metabolism regardless of the isotopic nature of the substrate, while no significant enrichments of 18O in breath CO2 were manifested in individuals without the infections. In contrast, the 13C-isotopic enrichments of breath CO2 were significantly higher in individuals with Helicobacter pylori compared to individuals without infections in response to 13C-enriched glucose uptake, whereas a distinguishable change of breath 13C/12C-isotope ratios was also evident when Helicobacter pylori utilize natural glucose. Moreover, monitoring the 18O and 13C-isotopic exchange in breath CO2 successfully diagnosed the eradications of Helicobacter pylori infections following a standard therapy. Our findings suggest that breath 12C18O16O and 13C16O16O can be used as potential molecular biomarkers to distinctively track the pathogenesis of Helicobacter pylori and also for eradication purposes and thus may open new perspectives into the pathogen’s physiology along with isotope-specific non-invasive diagnosis of the infection.

We report, for the first time, the clinical feasibility of a novel residual gas analyzer mass spectrometry (RGA-MS) method for accurate evaluation of the (13)C-glucose breath test ((13)C-GBT) in the diagnosis of pre-diabetes (PD) and type 2 diabetes mellitus (T2D). In T2D or PD, glucose uptake is impaired and results in blunted isotope enriched (13)CO2 production in exhaled breath samples. Using the Receiver operating characteristics (ROC) curve analysis, an optimal diagnostic cut-off point of the (13)CO2/(12)CO2 isotope ratios expressed as the delta-over-baseline (DOB) value, was determined to be δDOB(13)C‰ = 28.81‰ for screening individuals with non-diabetes controls (NDC) and pre-diabetes (PD), corresponding to a sensitivity of 100% and specificity of 94.4%. We also determined another optimal diagnostic cut-off point of δDOB(13)C‰ = 19.88‰ between individuals with PD and T2D, which exhibited 100% sensitivity and 95.5% specificity. Our RGA-MS methodology for the (13)C-GBT also manifested a typical diagnostic positive and negative predictive value of 96% and 100%, respectively. The diagnostic accuracy, precision and validity of the results were also confirmed by high-resolution optical cavity enhanced integrated cavity output spectroscopy (ICOS) measurements. The δDOB(13)C‰ values measured with RGA-MS method, correlated favourably (R(2) = 0.979) with those determined by the laser based ICOS method. Moreover, we observed that the effects of endogenous CO2 production related to basal metabolic rates in individuals were statistically insignificant (p = 0.37 and 0.73) on the diagnostic accuracy. Our findings suggest that the RGA-MS is a valid and sufficiently robust method for the (13)C-GBT which may serve as an alternative non-invasive point-of-care diagnostic tool for routine clinical practices as well as for large-scale diabetes screening purposes in real-time.

New strategies for an accurate and early detection of insulin resistance are important to delay or prevent the acute onset of type 2 diabetes (T2D). Currently, insulin sensitivity index (ISI0,120) is considered to be a viable invasive method of whole-body insulin resistance for use in clinical settings in comparison with other invasive sensitivity indexes like homeostasis model assessment (HOMA), and quantitative insulin sensitivity check index (QUICKI). To investigate how these sensitivity indexes link the 13C/12C-carbon isotopes of exhaled breath CO2 to pre-diabetes (PD) and type 2 diabetes in response to glucose ingestion, we studied excretion dynamics of 13C/12C-isotopic fractionations of breath CO2. Here, we show that 13C/12C-isotope ratios of breath CO2 were well correlated with blood glucose, insulin, glycosylated-hemoglobin as well as with HOMA-IR and 1/QUICKI. Conversely, the strongest correlation was observed between 1/ISI0,120 and breath CO2 isotopes. Consequently, we determined several optimal diagnostic cut-off points of 1/ISI0,120 and 13CO2/12CO2-isotope ratios to distinctively track the evolution of PD prior to the onset of T2D. Our findings suggest that isotopic breath CO2 is a novel method for accurate estimation of ISI0,120 and thus may open new perspectives into the isotope-specific non-invasive evaluation of insulin resistance for large-scale real-time diabetes screening purposes.