ICL-Based OF-CEAS: A Sensitive Tool for Analytical Chemistry.

Optical-feedback cavity-enhanced absorption spectroscopy (OF-CEAS) using mid-infrared interband cascade lasers (ICLs) is a sensitive technique for trace gas sensing. The setup of a V-shaped optical cavity operating with a 3.29 µm cw ICL is detailed, and a quantitative characterization of the injection efficiency, locking stability, mode matching, and detection sensitivity is presented. The experimental data are supported by a model to show how optical feedback affects the laser frequency as it is scanned across several longitudinal modes of the optical cavity. The model predicts that feedback enhancement effects under strongly absorbing conditions can cause underestimations in the measured absorption, and these predictions are verified experimentally. The technique is then used in application to the detection of nitrous oxide as an exemplar of the utility of this technique for analytical gas phase spectroscopy. The analytical performance of the spectrometer, expressed as noise equivalent absorption coefficient, was estimated as 4.9 × 10-9 cm -1 Hz-1/2, which compares well with recently reported values.

The Molecular Bronchoscope: A Tool for Measurement of Spatially Dependent CO2 Concentrations in the Lungs.

Respiratory physicians use bronchoscopy for visual assessment of the lungs' topography and collecting tissue samples for external analysis. We propose a novel bronchoscope tool that would enable spatially dependent measurements of the functioning of the lungs by determining local concentrations of carbon dioxide, which will be produced by healthy parts of the lung at rates that are higher than from portions where gas exchange is impaired. The gas analyzer is based on a compact laser absorption spectrometer making use of fiber optics for delivery and return of low intensity diode laser radiation to and from the measurement chamber at the distal end of a flexible conduit. The appropriate optical wavelength was chosen such that light is selectively absorbed only by gaseous CO2. The optical absorption takes place over a short path (8.8 mm) within a rigid, 12 mm long, perforated probe tip. Wavelength modulation spectroscopy was adopted as the analytical technique to reduce the noise on the optical signal and yield measurements of relative CO2 concentration every 180 ms with a precision as low as 600 part-per-million by volume. The primary objective of such a device is to see if additional spatial information about the lungs functionality can be gathered, which will complement visual observation.

RF noise induced laser perturbation for improving the performance of non-resonant cavity enhanced absorption spectroscopy.

We present a novel strategy for suppressing mode structure which often degrades off-axis cavity enhanced absorption spectra. This strategy relies on promoting small, random fluctuations in the optical frequency by perturbing the injection current of the diode laser source with radio frequency (RF) bandwidth-limited white noise. A fast and compact oxygen sensor, constructed from a 764 nm vertical-cavity surface-emitting laser (VCSEL) and an optical cavity with re-entrant configuration, is employed to demonstrate the potential of this scheme for improving the sensitivity and robustness of a field-deployable cavity spectrometer. The RF spectral density of the current noise injected into the VCSEL has been measured, and correlated to the effects on the optical spectral signal-to-noise ratio (SNR) and laser linewidth for a range of re-entrant geometries. A fourfold gain in the SNR has been achieved using the RF noise perturbation for the optimal off-axis alignment, which led to a minimum detectable absorption (MDA) predicted from an Allan variance study as low as 4.3 × 10(-5) at 1 s averaging. For the optically forbidden oxygen transition under investigation, a limit of detection (SNR = 1) of 810 ppm was achieved for a 10 ms acquisition time. This performance level paves the way for a fast, sensitive, in-line oxygen spectrometer that lends itself to a range of applications in respiratory medicine.

Enhancing the sensitivity of mid-IR quantum cascade laser-based cavity-enhanced absorption spectroscopy using RF current perturbation.

The sensitivity of mid-IR quantum cascade laser (QCL) off-axis cavity-enhanced absorption spectroscopy (CEAS), often limited by cavity mode structure and diffraction losses, was enhanced by applying a broadband RF noise to the laser current. A pump-probe measurement demonstrated that the addition of bandwidth-limited white noise effectively increased the laser linewidth, thereby reducing mode structure associated with CEAS. The broadband noise source offers a more sensitive, more robust alternative to applying single-frequency noise to the laser. Analysis of CEAS measurements of a CO(2) absorption feature at 1890 cm(-1) averaged over 100 ms yielded a minimum detectable absorption of 5.5×10(-3) Hz(-1/2) in the presence of broadband RF perturbation, nearly a tenfold improvement over the unperturbed regime. The short acquisition time makes this technique suitable for breath applications requiring breath-by-breath gas concentration information.

Demonstration of a mid-infrared cavity enhanced absorption spectrometer for breath acetone detection.

A high-resolution absorption spectrum of gaseous acetone near 8.2 µm has been taken using both Fourier transform and quantum cascade laser (QCL)-based infrared spectrometers. Absolute absorption cross sections within the 1215-1222 cm(-1) range have been determined, and the spectral window around 1216.5 cm(-1) (σ = 3.4 × 10(-19) cm(2) molecule(-1)) has been chosen for monitoring trace acetone in exhaled breath. Acetone at sub parts-per-million (ppm) levels has been measured in a breath sample with a precision of 0.17 ppm (1σ) by utilizing a cavity enhanced absorption spectrometer constructed from the QCL source and a linear, low-volume, optical cavity. The use of a water vapor trap ensured the accuracy of the results, which have been corroborated by mass spectrometric measurements.

Demonstration of a novel laser-driven light source for broadband spectroscopy between 170 nm and 2.1 µm.

Combining broadband light sources with optical cavities is a well established approach to sensitive monitoring of trace species in both gas and liquid phases. Here we investigate for the first time the potential of a novel source based on laser-driven xenon plasma technology for spectroscopic studies of gaseous species over the 170-2100 nm spectral range.

Evaluation of stakeholder opinion about Long Term Care Facilities for People with Dementia perceived quality: a web-based survey in the Italian context.

BACKGROUND AND AIM: Italy is a country where the percentage of elderly population is very high (23% over 65). The aim of the investigation is to bring out which aspects of the spaces intended to accommodate elderly People with Dementia pathologies should be most present and potentially interested in becoming cornerstones of a new model of Long-Term Care facilities (LTC). METHODS: This research uses a case studies analysis followed by a web based survey as methodological tools. The questions were identified following an analysis of recent European case studies. The survey has been submitted to a panel of stakeholders (users, pratictioner, designer and manager in the healthcare sector). It is articulated in eight items touching on functional, configurational, and perceptual aspects of the LTC. RESULTS: The 210 responses received provided a basis for comparison with the trend lines detected by the case study analysis, establishing continuity on some configurational aspects and providing divergent views for others. The research found a strong need to introduce new service activities and technologies aimed at the care and assistance of guests with dementia. These specific needs often involve the introduction of new spaces and environments or the redefinition of the same, where already present. CONCLUSIONS: The results highlights that a new model of residence must incorporate new technological applications, outdoor spaces, that are perceived significantly by both patients and practitioners, and improve well-being of all users.

Optical detection of the anesthetic agent propofol in the gas phase.

The anesthetic agent propofol (2,6-diisopropylphenol) is the most widely used intravenously administered drug in general anesthesia. However, a viable online capability to monitor metabolized levels of propofol in patients does not currently exist. Here we show for the first time that optical spectroscopy has good potential to detect metabolized propofol from patients' exhaled breath. We present quantitative absorption measurements of gas phase propofol both in the ultraviolet and middle-infrared spectral regions. We demonstrate that a detection limit in the subparts-per-billion concentration range can be reached with photoacoustic spectroscopy in the UV spectral region, paving the way for the development of future optical monitors.

Grating Spectrometry and Spatial Heterodyne Fourier Transform Spectrometry: Comparative Noise Analysis for Raman Measurements.

The desire for portable Raman spectrometers is continuously driving the development of novel spectrometer architectures where miniaturisation can be achieved without the penalty of a poorer detection performance. Spatial heterodyne spectrometers are emerging as potential candidates for challenging the dominance of traditional grating spectrometers, thanks to their larger etendue and greater potential for miniaturisation. This paper provides a generic analytical model for estimating and comparing the detection performance of Raman spectrometers based on grating spectrometer and spatial heterodyne spectrometer designs by deriving the analytical expressions for the performance estimator (signal-to-noise ratio, SNR) for both types of spectrometers. The analysis shows that, depending on the spectral characteristics of the Raman light and on the values of some instrument-specific parameters, the ratio of the SNR estimates for the two spectrometers (RSNR) can vary as much as by two orders of magnitude. Limit cases of these equations are presented for a subset of spectral regimes which are of practical importance in real-life applications of Raman spectroscopy. In particular, under the experimental conditions where the background signal is comparable or larger than the target Raman line and shot noise is the dominant noise contribution, the value of RSNR is, to a first order of approximation, dependent solely on the relative values of each spectrometer's etendue and on the number of row pixels in the detector array. For typical values of the key instrument-specific parameters (e.g., etendue, number of pixels, spectral bandwidth), the analysis shows that spatial heterodyne spectrometer-based Raman spectrometers have the potential to compete with compact grating spectrometer designs for delivering in a much smaller footprint (10-30 times) levels of detection performance that are approximately only five to ten times poorer.

Phase-shift cavity ring-down spectroscopy using mid-IR light from a difference frequency generation PPLN waveguide.

Approximately 200 microW of mid-infrared (mid-IR) light around 3081 cm(-1), produced by difference frequency generation (DFG) in a periodically poled lithium niobate crystal waveguide, has been used for phase-shift cavity ring-down spectroscopy measurements. The overlapping (12)C(2)H(4) (R)P(0)(14) and (P)R(6)(10) and (12)CH(2) (13)CH(2) (P)Q(3)(10) rotational lines of the nu(9) fundamental ethene vibrational band at 3081.0016 cm(-1) were probed in proof-of-principle experiments, and ethene detection was demonstrated with a minimum absorption coefficient of 1.4 x 10(-7) cm(-1) (approximately 4 min acquisition time). The compact DFG system, with a >35 cm(-1) tuning range, has a considerable potential for use in trace gas detection and in molecular spectroscopy.

Mid-infrared ethene detection using difference frequency generation in a quasi-phase-matched LiNbO3 waveguide.

A periodically poled LiNbO3 (PPLN) crystal waveguide has been used to produce up to 200 microW of mid-infrared light around 3081 cm(-1) with a wide tunability range of approximately 35 cm(-1). Two commercial near-infrared diode lasers at 1.064 microm (pump) and 1.583 microm (signal) are mixed in a nonlinear optical crystal to achieve difference frequency generation. The 48 mm long directly-bonded quasi-phase-matched (QPM) PPLN waveguide shows a conversion efficiency of 12.3% W(-1). Applications in trace gas detection have been demonstrated for ethene, using multipass absorption coupled with wavelength modulation spectroscopy, and cavity enhanced absorption spectroscopy with a lock-in detection scheme: bandwidth reduced sensitivities of alpha(min)=8 x 10(-9) and 1.6 x 10(-8) cm(-1) Hz(-1/2)(2sigma), respectively, have been achieved.

Assessment of water-soluble pi-extended squaraines as one- and two-photon singlet oxygen photosensitizers: design, synthesis, and characterization.

Singlet oxygen sensitization by organic molecules is a topic of major interest in the development of both efficient photodynamic therapy (PDT) and aerobic oxidations under complete green chemistry conditions. We report on the design, synthesis, biology, and complete spectroscopic characterization (vis-NIR linear and two-photon absorption spectroscopy, singlet oxygen generation efficiencies for both one- and two-photon excitation, electrochemistry, intrinsic dark toxicity, cellular uptake, and subcellular localization) of three classes of innovative singlet oxygen sensitizers pertaining to the family of symmetric squaraine derivatives originating from pi-excessive heterocycles. The main advantage of pi-extended squaraine photosensitizers over the large number of other known photosensitizers is their exceedingly strong two-photon absorption enabling, together with sizable singlet oxygen sensitization capabilities, for their use at the clinical application relevant wavelength of 806 nm. We finally show encouraging results about the dark toxicity and cellular uptake capabilities of water-soluble squaraine photosensitizers, opening the way for clinical small animal PDT trials.

Potential for noninvasive assessment of lung inhomogeneity using highly precise, highly time-resolved measurements of gas exchange.

Inhomogeneity in the lung impairs gas exchange and can be an early marker of lung disease. We hypothesized that highly precise measurements of gas exchange contain sufficient information to quantify many aspects of the inhomogeneity noninvasively. Our aim was to explore whether one parameterization of lung inhomogeneity could both fit such data and provide reliable parameter estimates. A mathematical model of gas exchange in an inhomogeneous lung was developed, containing inhomogeneity parameters for compliance, vascular conductance, and dead space, all relative to lung volume. Inputs were respiratory flow, cardiac output, and the inspiratory and pulmonary arterial gas compositions. Outputs were expiratory and pulmonary venous gas compositions. All values were specified every 10 ms. Some parameters were set to physiologically plausible values. To estimate the remaining unknown parameters and inputs, the model was embedded within a nonlinear estimation routine to minimize the deviations between model and data for CO2, O2, and N2 flows during expiration. Three groups, each of six individuals, were studied: young (20-30 yr); old (70-80 yr); and patients with mild to moderate chronic obstructive pulmonary disease (COPD). Each participant undertook a 15-min measurement protocol six times. For all parameters reflecting inhomogeneity, highly significant differences were found between the three participant groups ( P < 0.001, ANOVA). Intraclass correlation coefficients were 0.96, 0.99, and 0.94 for the parameters reflecting inhomogeneity in deadspace, compliance, and vascular conductance, respectively. We conclude that, for the particular participants selected, highly repeatable estimates for parameters reflecting inhomogeneity could be obtained from noninvasive measurements of respiratory gas exchange. NEW & NOTEWORTHY This study describes a new method, based on highly precise measures of gas exchange, that quantifies three distributions that are intrinsic to the lung. These distributions represent three fundamentally different types of inhomogeneity that together give rise to ventilation-perfusion mismatch and result in impaired gas exchange. The measurement technique has potentially broad clinical applicability because it is simple for both patient and operator, it does not involve ionizing radiation, and it is completely noninvasive.

In-airway molecular flow sensing: A new technology for continuous, noninvasive monitoring of oxygen consumption in critical care.

There are no satisfactory methods for monitoring oxygen consumption in critical care. To address this, we adapted laser absorption spectroscopy to provide measurements of O2, CO2, and water vapor within the airway every 10 ms. The analyzer is integrated within a novel respiratory flow meter that is an order of magnitude more precise than other flow meters. Such precision, coupled with the accurate alignment of gas concentrations with respiratory flow, makes possible the determination of O2 consumption by direct integration over time of the product of O2 concentration and flow. The precision is illustrated by integrating the balance gas (N2 plus Ar) flow and showing that this exchange was near zero. Measured O2 consumption changed by <5% between air and O2 breathing. Clinical capability was illustrated by recording O2 consumption during an aortic aneurysm repair. This device now makes easy, accurate, and noninvasive measurement of O2 consumption for intubated patients in critical care possible.

Laser-based absorption spectroscopy as a technique for rapid in-line analysis of respired gas concentrations of O2 and CO2.

The use of sidestream analyzers for respired gas analysis is almost universal. However, they are not ideal for measurements of respiratory gas exchange because the analyses are both temporally dissociated from measurements of respiratory flow and also not generally conducted under the same physical conditions. This study explores the possibility of constructing an all optical, fast response, in-line breath analyzer for oxygen and carbon dioxide. Using direct absorption spectroscopy with a diode laser operating at a wavelength near 2 µm, measurements of expired carbon dioxide concentrations were obtained with an absolute limit of detection of 0.04% at a time resolution of 10 ms. Simultaneously, cavity enhanced absorption spectroscopy at a wavelength near 760 nm was employed to obtain measurements of expired oxygen concentrations with an absolute limit of detection of 0.26% at a time resolution of 10 ms. We conclude that laser-based absorption spectroscopy is a promising technology for in-line analysis of respired carbon dioxide and oxygen concentrations.