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.

M-line spectroscopy on mid-infrared Si photonic crystals for fluid sensing and chemical imaging.

The presented work demonstrates the design and characterization of Si-based photonic crystal waveguides operating as an evanescent wave absorption sensor in the mid-IR range λ = 5-6 µm. The photonic crystal structure is fabricated in a Si slab upon a thin Si(3)N(4)/TEOS/Si(3)N(4) membrane. M-line spectroscopy is used to verify the presence of guided waves. Different fillings of the photonic crystal holes have been realized to avoid sample residuals in the holes and, at the same time, to obtain spectral tuning of the structures by modification of the refractive index contrast with the photonic background. The chip displays sensitivity to fluid droplets in two-prism experiments. The output signal is quantitatively related to the fluid's absorption coefficient thereby validating the experimental method.

Multi-mode absorption spectroscopy using a quantum cascade laser for simultaneous detection of NO and H2O.

Detection of multiple transitions in NO and H2O using multi-mode absorption spectroscopy, MUMAS, with a quantum cascade laser, QCL, operating at 5.3 µm at scan rates up to 10 kHz is reported. The linewidth of longitudinal modes of the QCL is derived from pressure-dependent fits to experimental MUMAS data. Variations in the spectral structure of the broadband, multi-mode, output of the commercially available QCL employed are analysed to provide accurate fits of modelled MUMAS signatures to the experimental data.

Linear cavity optical-feedback cavity-enhanced absorption spectroscopy with a quantum cascade laser.

A cw distributed feedback quantum cascade laser (DFB-QCL) coupled to a two-mirror linear optical cavity has been used to successfully demonstrate optical-feedback cavity-enhanced absorption spectroscopy (OF-CEAS) at 5.5 µm. The noise-equivalent absorption coefficient, α(min), was 2.4×10(-8) cm(-1) for 1 s averaging, limited by etalon-fringing. The temporal stability of the instrument allows NO detection down to 5 ppb in 2 s.

Atomic orientation following predissociation of the C 3Πg Rydberg state of molecular oxygen.

(2 + 1) resonance enhanced multiphoton ionization in combination with time-of-flight mass spectroscopy (TOF-MS) has been used to detect both the O((3)P) and O((1)D) fragments produced as a result of predissociation of the C (3)Πg (v = 0) and (v = 1) Rydberg states of O2, accessed via two-photon absorption from the ground X (3)Σg(-) state. In particular, TOF profiles have been recorded at various fixed two-photon absorption wavelengths within the two bands, with circular polarized probe laser light used to probe the angular momentum orientation of these photofragments. All photofragments are found to display coherent orientation resulting from interference between two possible two-photon absorption pathways. The measured orientation is affected by rotational depolarization due to the long lifetime of the excited C state; once this effect is accounted for the orientation is found to be nearly constant over all dissociation wavelengths. The origin of the coherent orientation is attributed to two-photon absorption to different spin-orbit components of the C state.

Predissociation dynamics of the C 3Πg Rydberg state of molecular oxygen.

(2+1) resonance enhanced multiphoton ionization time-of-flight mass spectroscopy (TOF-MS) has been used to detect both the O((3)P) and O((1)D) fragments produced as a result of predissociation of the C (3)Πg (v = 0) and (v = 1) Rydberg states of O2. In particular, TOF profiles have been recorded at various fixed wavelengths within the two bands in order to investigate the differences in predissociation dynamics of intermediate levels with different values of |Ω| (=0, 1, 2 in this case). TOF profiles have been recorded in multiple geometries to determine both the translational anisotropy and angular momentum alignment of both photofragments as well as the O((3)P) spin-orbit branching ratios produced following a two-photon dissociation. The translational anisotropy is found to be dependent on the dissociation wavelength with the variations found to be consistent with rotational depolarization due to the long lifetime of the excited C state. All photofragments have been found to be aligned, with the relationship between the measured O((3)P) and O((1)D) alignment being found to be consistent with a diabatic model of the dissociation.

Population transfer and rapid passage effects in a low pressure gas using a continuous wave quantum cascade laser.

A continuous wave quantum cascade laser (cw-QCL) operating at 10 µm has been used to record absorption spectra of low pressure samples of OCS in an astigmatic Herriott cell. As a result of the frequency chirp of the laser, the spectra show clearly the effects of rapid passage on the absorption line shape. At the low chirp rates that can be obtained with the cw-QCL, population transfer between rovibrational quantum states is predicted to be much more efficient than in typical pulsed QCL experiments. This optical pumping is investigated by solving the Maxwell Bloch equations to simulate the propagation of the laser radiation through an inhomogeneously broadened two-level system. The calculated absorption profiles show good quantitative agreement with those measured experimentally over a range of chirp rates and optical thicknesses. It is predicted that at a low chirp rate of 0.13 MHz ns(-1), the population transfer between rovibrational quantum states is 12%, considerably more than that obtained at the higher chirp rates utilised in pulsed QCL experiments.

Electronic polarization effects in the photodissociation of Cl2.

Velocity mapped ion imaging and resonantly enhanced multiphoton ionization time-of-flight methods have been used to investigate the photodissociation dynamics of the diatomic molecule Cl(2) following excitation to the first UV absorption band. The experimental results presented here are compared with high level time dependent wavepacket calculations performed on a set of ab initio potential energy curves [D. B. Kokh, A. B. Alekseyev, and R. J. Buenker, J. Chem. Phys. 120, 11549 (2004)]. The theoretical calculations provide the first determination of all dynamical information regarding the dissociation of a system of this complexity, including angular momentum polarization. Both low rank K = 1, 2 and high rank K = 3 electronic polarization are predicted to be important for dissociation into both asymptotic product channels and, in general, good agreement is found between the recent theory and the measurements made here, which include the first experimental determination of high rank K = 3 orientation.

Rapid passage signals from a vibrationally excited target molecule: a pump and probe experiment with continuous wave quantum cascade lasers.

Two 5 µm continuous wave quantum cascade lasers are used to perform a counterpropagating pump and probe experiment on a low pressure sample of nitric oxide. The strong pump field excites a fundamental rovibrational transition and the weaker probe field is tuned to the corresponding rotationally resolved hot band transition. When both light fields are in resonance, rapid passage is observed in the hot band absorption lineshape arising from a minimally damped and velocity-selected sample of molecules in the v=1 state. The measured rapid passage signals are well described by a two-level model based on the optical Bloch equations.

Conformer specific dissociation dynamics of iodocyclohexane studied by velocity map imaging.

The photodissociation dynamics of iodocyclohexane has been studied using velocity map imaging following excitation at many wavelengths within its A-band (230 ≤ λ ≤ 305 nm). This molecule exists in two conformations (axial and equatorial), and one aim of the present experiment was to explore the extent to which conformer-specific fragmentation dynamics could be distinguished. Ground (I) and spin-orbit excited (I∗) state iodine atom products were monitored by 2 + 1 resonance enhanced multiphoton ionization, and total kinetic energy release (TKER) spectra and angular distributions derived from analysis of images recorded at all wavelengths studied. TKER spectra obtained at the longer excitation wavelengths show two distinct components, which can be attributed to the two conformers and the different ways in which these partition the excess energy upon C-I bond fission. Companion calculations based on a simple impulsive model suggest that dissociation of the equatorial (axial) conformer preferentially yields vibrationally (rotationally) excited cyclohexyl co-fragments. Both I and I∗ products are detected at the longest parent absorption wavelength (λ ∼ 305 nm), and both sets of products show recoil anisotropy parameters, ß > 1, implying prompt dissociation following excitation via a transition whose dipole moment is aligned parallel to the C-I bond. The quantum yield for forming I∗ products, Φ(I∗), has been determined by time resolved infrared diode laser absorption methods to be 0.14 ± 0.02 (at λ = 248 nm) and 0.22 ± 0.05 (at λ = 266 nm). Electronic structure calculations indicate that the bulk of the A-band absorption is associated with transition to the 4A(') state, and that the (majority) I atom products arise via non-adiabatic transfer from the 4A(') potential energy surface (PES) via conical intersection(s) with one or more PESs correlating with ground state products.

Laser spectroscopy on volatile sulfur compounds: possibilities for breath analysis.

There is an emerging interest in the detection of volatile sulfur compounds (VSCs) in the breath environment, given their biological relevance as potential signatures of several pathological conditions. Particularly, laser-based spectroscopic sensors are candidates for conducting accurate breath diagnostics in clinical settings. With these aims in mind, the current status of VSC sensing via laser absorption spectroscopy is reviewed in this paper. Attention has been focused on the most promising exhaled markers of pathological conditions, namely hydrogen sulfide, carbonyl sulfide, methanethiol, carbon disulfide and dimethyl sulfide. Details of the most relevant spectroscopic studies conducted on such molecules are presented, together with suggestions on the future direction of this challenging analytical field.

Trace species detection in the near infrared using Fourier transform broadband cavity enhanced absorption spectroscopy: initial studies on potential breath analytes.

Cavity enhanced absorption measurements have been made of several species that absorb light between 1.5 and 1.7 µm using both a supercontinuum source and superluminescent light emitting diodes. A system based upon an optical enhancement cavity of relatively high finesse, consisting of mirrors of reflectivity ∼99.98%, and a Fourier transform spectrometer, is demonstrated. Spectra are recorded of isoprene, butadiene, acetone and methane, highlighting problems with spectral interference and unambiguous concentration determinations. Initial results are presented of acetone within a breath-like matrix indicating ppm precision at <∼10 ppm acetone levels. Instrument sensitivities are sufficiently enhanced to enable the detection of atmospheric levels of methane. Higher detection sensitivities are achieved using the supercontinuum source, with a minimum detectable absorption coefficient of ∼4 × 10(-9) cm(-1) reported within a 4 min acquisition time. Finally, two superluminescent light emitting diodes are coupled together to increase the wavelength coverage, and measurements are made simultaneously on acetylene, CO(2), and butadiene. The absorption cross-sections for acetone and isoprene have been measured with an instrumental resolution of 4 cm(-1) and are found to be 1.3 ± 0.1 × 10(-21) cm(2) at a wavelength of 1671.9 nm and 3.6 ± 0.2 × 10(-21) cm(2) at 1624.7 nm, respectively.

Rapid passage signals induced by chirped quantum cascade laser radiation: K state dependent-delay effects in the nu2 band of NH3.

In this Letter, a 10 microm quantum cascade laser operating in the intrapulse mode is used observe rapid passage (RP) effects within a 40 cm single-pass gas cell containing low pressures of NH(3). The laser tuning range allows the rotational states J=2 with K=0, 1, and 2 to be probed. We show that the RP structures change as a function of optical density and that the magnitude of the delay in the switch from absorption to emission as a function of increased gas pressure is dependent upon the initial value of K. These measurements are qualitatively well modeled using the Maxwell-Bloch equations.

Near-infrared broad-band cavity enhanced absorption spectroscopy using a superluminescent light emitting diode.

A fibre coupled near-infrared superluminescent light emitting diode that emits approximately 10 mW of radiation between 1.62 and 1.7 microm is employed in combination with a broad-band cavity enhanced spectrometer consisting of a linear optical cavity with mirrors of reflectivity approximately 99.98% and either a dispersive near-infrared spectrometer or a Fourier transform interferometer. Results are presented on the absorption of 1,3-butadiene, and sensitivities are achieved of 6.1 x 10(-8) cm(-1) using the dispersive spectrometer in combination with phase-sensitive detection, and 1.5 x 10(-8) cm(-1) using the Fourier transform interferometer (expressed as a minimum detectable absorption coefficient) over several minutes of acquisition time.

Diode laser based studies of the UV photolysis of molecular iodine.

The photolysis of molecular iodine at 193 and 248 nm has been studied by diode laser based frequency-modulated (FM) absorption spectroscopy with detection of the nascent iodine photofragment via the I((2)P(1/2)-(2)P(3/2)) transition at 1.315 microm. Use of narrow band radiation enables nascent measurements with sufficient speed resolution to allow both the character of the initial electronic transition and speed of the fragments to be determined. The time dependence of the integrated area of the measured Doppler profiles has been used to determine both the I* quantum yield and the collisional electronic quenching rate constant of I* (I* = (2)P(1/2)) by I(2). These values are also determined using the diode laser gain versus absorption technique. In the 248 nm case an I* quantum yield of 0.45 +/- 0.04 and 0.42 +/- 0.04 is found by each method, respectively, and an electronic quenching rate constant of (3.6 +/- 0.5) x 10(-11) cm(3) molecule(-1) s(-1), consistent with literature, is determined. The form of the nascent Doppler profile indicates that excitation to a Omega = 1 state dominates, with subsequent dissociation to I((2)P(1/2)) + I((2)P(3/2)), in keeping with assignment of the upper state as 1441 (3)Sigma(+)(1(u)). The deviation from Phi(I*) = 0.5 can be attributed to a contribution from the 1441 (3)Sigma(+)(0(u)(-)) state which dissociates to two ground state iodine atoms. 193 nm excitation exhibits more complicated dynamics and kinetics, including a pressure dependent I* quantum yield. At the low pressures, <200 mTorr, used in the FM Doppler measurements there are two speed components to the profile suggesting multiple dissociation pathways. Firstly, fast iodine fragments indicate single photon absorption in a parallel transition followed by direct dissociation. Secondly, a slower speed component can be attributed to iodine atoms formed after radiative transfer to unbound levels in the ground state and the a' surface. Investigation of the changes in Doppler profiles with time suggest that some of the a' surface population may transfer to the bound B((3)Pi(0u)(+)) state which then in turn undergoes collision-induced predissociation to produce I atoms on the ground electronic state.

Characterization of an external cavity diode laser based ring cavity NICE-OHMS system.

The performance of an external cavity diode laser based noise immune cavity enhanced optical heterodyne molecular spectrometer is presented. To reduce the noise on the signal a ring cavity and a circuit to remove residual amplitude modulation on the pre-cavity laser radiation was implemented. We demonstrate a sensitivity of 4 x 10(-11) cm(-1) Hz(-1/2) using a cavity with a finesse of 2600 on a Doppler-broadened transition of CH(4) at 6610.063 cm(-1).

A chemometric study on human breath mass spectra for biomarker identification in cystic fibrosis.

Alveolar breath samples from a small case-control study population have been collected and measured via ion-molecule reaction mass spectrometry, and a constructive statistical approach to the identification of volatile biomarkers has been formulated by applying multivariate statistical methods on the mass spectra. The nature of the data is such that the number of variables largely exceeds the observations, representing a typical experimental scenario when breath analysis is conducted using mass spectrometry. Principal components analysis has been performed on the high dimensional dataset of molecular abundances, providing evidence of case separation and reducing the number of functional discriminators by almost 90%. Afterwards, a deductive approach based on a binary regression was conducted on the reduced dataset, providing an entirely reliable case discrimination model exclusively depending on the concentrations in the breath mixture of 3 out of a total of 97 metabolites.

Time-resolved detection of the CF3 photofragment using chirped QCL radiation.

This paper demonstrates how a quantum cascade laser (QCL) in its intrapulse mode can provide a simple method for probing the products of a photolysis event. The system studied is the 266 nm photodissociation of CF3I with the CF3 fragments subsequently detected using radiation at approximately 1253 cm(-1) generated by a pulsed QCL. The tuning range provided by the frequency down-chirp of the QCL operated in its intrapulse mode allows a approximately 1 cm(-1) segment of the CF3 nu3 band to be measured following each photolysis laser pulse. Identification of features within this spectral region allows the CF3 ( v = 0) number density to be calculated as a function of pump-probe delay, and consequently the processes which populate and deplete this quantum state may be examined. Rate constants for the population cascade from higher vibrational levels into the v = 0 state, k 1, and for the recombination of the CF3 radicals to form C2F6, k2, are measured. The returned values of k1 = (2.3 +/- 0.34) x 10(-12) cm(3) molecule(-1) s(-1) and k2 = (3.9 +/- 0.34) x 10(-12) cm(3) molecule(-1) s(-1) are found to be in good agreement with reported literature values.

Methyl iodide photodissociation at 193 nm: The I(2P(1/2)) quantum yield.

Methyl iodide photolysis at 193 nm has been studied through probing the I((2)P(1/2)-(2)P(3/2)) transition in the atomic iodine photofragment using diode laser spectroscopy. The I((2)P(1/2)) quantum yield has been determined through two different diode laser techniques and then compared. Frequency-modulated diode laser based absorption spectroscopy was used to extract nascent Doppler lineshapes from which an I((2)P(1/2)) quantum yield of unity is inferred. However when diode laser gain/absorption measurements were made, an I((2)P(1/2)) quantum yield of 0.68 ± 0.04 was found. The reason for this discrepancy is shown to lie in the diode laser gain/absorption method. Molecular iodine is found to be formed during the experiment via atomic iodine recombination and then in turn dissociates to produce both I((2)P(1/2)) and I((2)P(3/2)), thus distorting the returned quantum yield. This conclusion is supported both by the reduction of the I((2)P(1/2)) quantum yield with number of photolysis laser shots when measured using this technique and by the presence of fluoresence which is shown to have excited-state lifetimes and quenching rates that are consistent with those previously measured for the D and D' states of molecular iodine.

Speed dependent rotational angular momentum polarization of the O2 (a 1Deltag) fragment following ozone photolysis in the wavelength range 248-265 nm.

The translational anisotropy and rotational angular momentum polarization of a selection of rotational states of the O2 (a 1Deltag; v=0) photofragment formed from ozone photolysis at 248, 260, and 265 nm have been determined using the technique of resonance enhanced multiphoton ionization in combination with time of flight mass spectrometry. At 248 nm, the dissociation is well described as impulsive in nature with all rotational states exhibiting similarly large, near-limiting values for the bipolar moments describing their angular momentum alignment and orientation. At 265 nm, however, the angular momentum polarization parameters determined for consecutive odd and even rotational states exhibit clear differences. Studies at the intermediate wavelength of 260 nm strongly suggest that such a difference in the angular momentum polarization is speed dependent and this proposal is consistent with the angular momentum polarization parameters extracted and reported previously for longer photolysis wavelengths [G. Hancock et al., Phys. Chem. Chem. Phys. 5, 5386 (2003); S. J. Horrocks et al., J. Chem. Phys. 126, 044308 (2007)]. The alternation of angular momentum polarization for successive odd and even J states may be a consequence of the different mechanisms leading to the formation of the two O2 (a 1Deltag) Lambda doublets. Specifically, the involvement of out of plane parent rotational motion is proposed as the origin for the observed depolarization for the Delta- relative to the Delta+ state.