Abhijit Maity

Halloysite Nanotubes Capturing Isotope Selective Atmospheric CO2

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.

Oxygen-18 stable isotope of exhaled breath CO2 as a non-invasive marker of Helicobacter pylori infection

We report for the first time the time-dependent excretion kinetics of 18O/16O isotope ratios of CO2 in exhaled breath samples using an optical cavity-enhanced integrated cavity output spectroscopy (ICOS) method for the detection of Helicobacter pylori (H. pylori) infection in human stomach. We observed large differences in the oxygen-18 isotopic fractionations of breath CO2 between H. pylori positive and negative individuals in response to orally administered, both unlabelled and labelled 13C-enriched urea, suggesting a potential link between H. pylori infections and the 18O-isotopic exchange in exhaled breath. An optimal diagnostic cut-off point of 18O/16O isotope ratios of breath CO2 for the presence of H. pylori infection was determined to be 1.92‰ using the receiver operating characteristic curve (ROC) analysis, which exhibited both diagnostic sensitivity and specificity of 100% with an accuracy of 100%. Moreover, the methodology of monitoring 18O in breath CO2 manifested both positive and negative predictive values of 100%, demonstrating excellent diagnostic accuracy and suggesting that breath C18O16O could be used as a potential marker for the identification of H. pylori infections. Our findings also suggest that monitoring the 18O/16O isotope ratios of breath CO2 is a valid and sufficiently robust novel non-invasive approach for the accurate and specific detection of H. pylori infection in real-time, which may open new perspectives in the molecular diagnosis of H. pylori infection for large-scale screening purposes, early detection and follow-up of patients.

Residual gas analyzer mass spectrometry for human breath analysis: a new tool for the non-invasive diagnosis of Helicobacter pylori infection

A residual gas analyzer (RGA) coupled with a high vacuum chamber is described for the non-invasive diagnosis of the Helicobacter pylori (H. pylori) infection through ¹³C-urea breath analysis. The present RGA-based mass spectrometry (MS) method is capable of measuring high-precision ¹³CO₂ isotope enrichments in exhaled breath samples from individuals harboring the H. pylori infection. The system exhibited 100% diagnostic sensitivity, and 93% specificity alongside positive and negative predictive values of 95% and 100%, respectively, compared with invasive endoscopy-based biopsy tests. A statistically sound diagnostic cut-off value for the presence of H. pylori was determined to be 3.0‰ using a receiver operating characteristic curve analysis. The diagnostic accuracy and validity of the results are also supported by optical off-axis integrated cavity output spectroscopy measurements. The δ¹³(DOB)C‰ values of both methods correlated well (R² = 0.9973 at 30 min). The RGA-based instrumental setup described here is simple, robust, easy-to-use and more portable and cost-effective compared to all other currently available detection methods, thus making it a new point-of-care medical diagnostic tool for the purpose of large-scale screening of the H. pylori infection in real time. The RGA-MS technique should have broad applicability for ¹³C-breath tests in a wide range of biomedical research and clinical diagnostics for many other diseases and metabolic disorders.

Oxygen-18 isotope of breath CO 2 linking to erythrocytes carbonic anhydrase activity: a biomarker for pre-diabetes and type 2 diabetes

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.

Non-invasive 13C-glucose breath test using residual gas analyzer-mass spectrometry: a novel tool for screening individuals with pre-diabetes and type 2 diabetes

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.

Continuous wave external-cavity quantum cascade laser-based high-resolution cavity ring-down spectrometer for ultrasensitive trace gas detection

A high-resolution cavity ring-down spectroscopic (CRDS) system based on a continuous wave (cw) mode-hop-free (MHF) external-cavity quantum cascade laser (EC-QCL) operating at λ∼5.2  μm has been developed for ultrasensitive detection of nitric oxide (NO). We report the performance of the high-resolution EC-QCL based cw-CRDS instrument by measuring the rotationally resolved Λ-doublet e and f components of the P(7.5) line in the fundamental band of NO at 1850.169  cm-1 and 1850.179  cm-1. A noise-equivalent absorption coefficient of 1.01×10-9  cm-1  Hz-1/2 was achieved based on an empty cavity ring-down time of τ0=5.6  μs and standard deviation of 0.11% with averaging of six ring-down time determinations. The CRDS sensor demonstrates the advantages of measuring parts per billion NO concentrations in N2, as well as in human breath samples with ultrahigh sensitivity and specificity. The CRDS system could also be generalized to measure simultaneously many other trace molecular species within the broad tuning range of cw EC-QCL, as well as for studying the rotationally resolved hyperfine structures.

An EC-QCL based N2O sensor at 5.2 μm using cavity ring-down spectroscopy for environmental applications

Nitrous oxide (N2O) is an important anthropogenic greenhouse gas emitted into the atmosphere that can contribute to ozone destruction. Considering its environmental importance, the real-time monitoring and molecule-specific detection of atmospheric N2O with high sensitivity have received much attention in the 21st century. In this study, a widely tunable continuous wave (cw) external-cavity quantum cascade laser (EC-QCL)-based cavity ring-down spectroscopy (CRDS) in the mid-infrared region has been used to measure the mixing ratios of N2O in ambient air. The detection of atmospheric N2O was made using a rotationally resolved R(8e) absorption line of N2O centred at 1887.666 cm−1. Several atmospheric air samples were collected at various locations in Kolkata on seven consecutive days in different periods of the day. In situ measurements were carried out by the EC-QCL-based high-resolution cw-CRDS method. The laser-based CRDS sensor allowed us to perform direct, quantitative and selective measurements of atmospheric N2O mixing ratios at the levels of parts per billion by volume (ppbv). A significant change in N2O levels was observed in different sub-areas depending on the source of local pollution. We also observed a marked difference in N2O levels between morning and afternoon sessions of the day in a particular sub-area. The CRDS sensor for the detection of N2O allows a minimum detectable absorption coefficient of αmin = 4.8 × 10−9 cm−1 and an estimated detection limit of 4.5 ppbv at atmospheric pressure is also reported.

Assessing Atmospheric CO2 Entrapped in Clay Nanotubes using Residual Gas Analyzer

A residual gas analyzer (RGA) coupled with a high-vacuum chamber has been explored to measure atmospheric CO2 entrapped in aminosilane-modified clay nanotubes. Ambient CO2 uptake efficacy together with stability of these novel adsorbents composed of both primary and/or secondary amine sites has been demonstrated at standard ambient temperature and pressure. The unprecedented sensitivity and accuracy of the RGA-based mass spectrometry technique toward atmospheric CO2 measurement has been substantiated with a laser-based optical cavity-enhanced integrated cavity output spectroscopy. The adsorption kinetics of atmospheric CO2 on amine-functionalized clay nanotubes followed the fractional-order kinetic model compared to that of the pseudo-first-order or pseudo-second-order rate equations. The efficiency along with stability of these novel adsorbents has also been demonstrated by their repetitive use for CO2 capture in the oxidative environment. Our findings thus point to a fundamental study on the atmospheric CO2 adsorption by amine-loaded adsorbents using an easy handling and low-cost benchtop RGA-based mass spectrometer, opening a new strategy for CO2 capture and sequestering study.

Diagnosis of small intestinal bacterial overgrowth in irritable bowel syndrome patients using high-precision stable 13CO2/12CO2 isotope ratios in exhaled breath

Hydrogen breath tests (HBT) are widely used for the diagnosis of small intestinal bacterial overgrowth (SIBO) in patients with irritable bowel syndrome (IBS). However, the conclusions drawn from these studies are highly controversial, and several discrepancies exist in the results. The aim of our study is to develop an alternative 13C-glucose breath test (13C-GBT) methodology by measuring high-precision 13CO2/12CO2 isotope ratios in exhaled breath to accurately diagnose SIBO using an optical cavity-enhanced CO2 isotope analyzer. In all, 118 diarrhea-predominant (IBS-D) patients diagnosed according to ROME III criteria underwent 13C-GBT and HBT following the ingestion of a test meal containing 50 mg 13C-enriched glucose with 50 g glucose. The excretion of 13CO2 enrichments and a cumulative percentage dose of 13C-recovered (c-PDR) significantly depleted (p < 0.001) for the positive SIBO patients (n = 25) compared to the patients with negative SIBO (n = 53) as diagnosed by HBT. A cut-off value of 5.47‰ at 45 min was indicative of a positive SIBO syndrome. Subsequently, a portion of IBS-D individuals (n = 20) whose HBTs were negative but 13C-GBTs were positive, suggesting HBT often fails to diagnose SIBO when the patients may have “non-hydrogen-producing” bacteria. 13C-GBT also correctly diagnosed SIBO in patients (n = 20) within the “grey-zone” and during the preclinical phase of SIBO as opposed to HBT. The prevalence of SIBO with IBS-D in Indian population was estimated to be 45.7%. Our study demonstrates 13C-GBT, for the first time, as a clinically valid and sufficiently robust alternative diagnostic methodology for an accurate evaluation of SIBO in IBS-D patients and superior to HBT.

Mechanisms linking metabolism of Helicobacter pylori to 18O and 13C-isotopes of human breath CO2

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.