Daniel Halmer

Whole Body UVA Irradiation Lowers Systemic Blood Pressure by Release of Nitric Oxide From Intracutaneous Photolabile Nitric Oxide Derivates

Rationale: Human skin contains photolabile nitric oxide derivates like nitrite and S-nitroso thiols, which after UVA irradiation, decompose and lead to the formation of vasoactive NO. Objective: Here, we investigated whether whole body UVA irradiation influences the blood pressure of healthy volunteers because of cutaneous nonenzymatic NO formation. Methods and Results: As detected by chemoluminescence detection or by electron paramagnetic resonance spectroscopy in vitro with human skin specimens, UVA illumination (25 J/cm2) significantly increased the intradermal levels of free NO. In addition, UVA enhanced dermal S-nitrosothiols 2.3-fold, and the subfraction of dermal S-nitrosoalbumin 2.9-fold. In vivo, in healthy volunteers creamed with a skin cream containing isotopically labeled 15N-nitrite, whole body UVA irradiation (20 J/cm2) induced significant levels of 15N-labeled S-nitrosothiols in the blood plasma of light exposed subjects, as detected by cavity leak out spectroscopy. Furthermore, whole body UVA irradiation caused a rapid, significant decrease, lasting up to 60 minutes, in systolic and diastolic blood pressure of healthy volunteers by 11±2% at 30 minutes after UVA exposure. The decrease in blood pressure strongly correlated (R2=0.74) with enhanced plasma concentration of nitrosated species, as detected by a chemiluminescence assay, with increased forearm blood flow (+26±7%), with increased flow mediated vasodilation of the brachial artery (+68±22%), and with decreased forearm vascular resistance (−28±7%). Conclusions: UVA irradiation of human skin caused a significant drop in blood pressure even at moderate UVA doses. The effects were attributed to UVA induced release of NO from cutaneous photolabile NO derivates.

Fast exponential fitting algorithm for real-time instrumental use

We report on a very fast fitting algorithm for single exponential functions which is based on the method of successive integration. The algorithm corrects the systematic error of trapezoidal integration. The new algorithm needs only 150 μs for a dataset of 1536 points and is around 700 times faster than the nonlinear Levenberg–Marquardt fit provided by LABVIEW. This makes it suitable for real-time instrumental use. Beside the better time resolution, the acceleration allows more averaging, which leads to higher precision. In our experiment instrumental sensitivity was improved by a factor of 3.7.

Parts per trillion sensitivity for ethane in air with an optical parametric oscillator cavity leak-out spectrometer

Spectroscopic detection of ethane in the 3-microm wavelength region was performed by means of a cw optical parametric oscillator and cavity leak-out. We achieved a minimum detectable absorption coefficient of 1.6 x 10(-10) cm 1/square root of Hz, corresponding to an ethane detection limit of 6 parts per trillion/square root of Hz. For 3-min integration time the detection limit was 0.5 parts per trillion. The levels are to our knowledge the best demonstrated so far. These frequency-tuning capabilities facilitated multigas analysis with simultaneous monitoring of ethane, methane, and water vapor in human breath.

Mid-infrared cavity leak-out spectroscopy for ultrasensitive detection of carbonyl sulfide

We present a ringdown absorption spectrometer based on a continuous-wave CO laser in the mid-infrared spectral region near lambda = 5 microm. Using a linear ringdown cavity (length, 0.5 m) with R > = 99.99% mirrors, we observed a noise-equivalent absorption coefficient of 7 x 10(-11) cm(-1) Hz(-1/2). This is 2 orders of magnitude improved compared with previous values. With this setup we studied the spectroscopic detection of carbonyl sulfide (here abbreviated OCS) traces in ambient air and in exhaled breath. We achieved a detection limit of 7 parts in 10(12) (parts per trillion) OCS in ambient air, which is unprecedented and shows great promise for environmental and biomedical applications.

Time resolved simultaneous detection of 14NO and 15NO via mid-infrared cavity leak-out spectroscopy

We present a ring-down absorption spectrometer based on a continuous-wave CO laser in the mid-infrared spectral region near λ = 5 μm. Using a linear ring-down cavity (length: 0.5 m) with high reflective mirrors (R = 99.988 %), we observed a noise-equivalent absorption coefficient of 3 × 10−10 cm−1Hz−1/2. This corresponds to a noise-equivalent concentration of 800 parts per trillion (ppt) for 14NO and 40 ppt for 15NO in 1 s averaging time. We achieve a time resolution of 1 s which allows time resolved simultaneous detection of the two N isotopes. The δ15N value was obtained with a precision of ±1.2‰ in a sample with a NO fraction of 11 ppm. The simultaneous detection enables the use of 15NO as a tracer molecule for endogenous biomedical processes.

Intercomparison of Infrared Cavity Leak-Out Spectroscopy and Gas Chromatography-Flame Ionization for Trace Analysis of Ethane

Comparison of two different methods for the measurement of ethane at the parts-per-billion (ppb) level is reported. We used cavity leak-out spectroscopy (CALOS) in the 3 microm wavelength region and gas chromatography-flame ionization detection (GC-FID) for the analysis of various gas samples containing ethane fractions in synthetic air. Intraday and interday reproducibilities were studied. Intercomparing the results of two series involving seven samples with ethane mixing ratios ranging from 0.5 to 100 ppb, we found a reasonable agreement between both methods. The scatter plot of GC-FID data versus CALOS data yields a linear regression slope of 1.07 +/- 0.03. Furthermore, some of the ethane mixtures were checked over the course of 1 year, which proved the long-term stability of the ethane mixing ratio. We conclude that CALOS shows equivalent ethane analysis precision compared to GC-FID, with the significant advantage of a much higher time resolution (<1 s) since there is no requirement for sample preconcentration. This opens new analytical possibilities, e.g., for real-time monitoring of ethane traces in exhaled human breath.

CW-OPO-based cavity-leak-out spectrometer for ultrasensitive and selective mid infrared trace gas analysis

An all-solid-state infrared trace gas sensor is presented combining a continuous-wave optical parametric oscillator (OPO) with Cavity Leak-Out spectroscopy (CALOS), a cw version of Cavity Ring Down spectroscopy. The PPLN based pump resonant, singly resonant OPO is pumped at 1064 nm (2 W). Dual cavity design allows to select any desired wavelength within the emission range of the OPO (3.1 - 3.8 μm) and to use different tuning schemes in order to scan absorption features. To detect the CALOS signals the OPO frequency is scanned over the cavity resonance at kHz rates. The high power of the OPO (up to 100 mW at each end of the cavity) allows a strong excitation of the TEM00 mode of the cavity, yielding large detector signals. A noise-equivalent absorption coefficient of 1.6*10-10cm-1/√Hz is reached for integration times up to 180 sec. This corresponds to a detection limit for ethane at sub-ppt level. Measurements at reduced pressure (100 mbar) combined with a scanning of the OPO over cm-1 wide regions allows a multi-gas analysis of ambient air and human breath samples without a cooling-trap.

Compact tunable diode laser with diffraction limited 1000 mW in Littman/Metcalf configuration for cavity ring down spectroscopy

High resolution spectroscopy of environmental and medical gases requires reliable, fast tunable laser light sources in the mid-infrared (MIR) wavelength regime between 3 and 5 μm. Since this wavelength cannot be reached via direct emitting room temperature semiconductor lasers, additional techniques like difference frequency generation (DFG) are essential. Tunable difference frequency generation relies on high power, small linewidth, fast tunable, robust laser diode sources. We report a new, very compact, alignment insensitive, robust, external cavity diode laser system in Littman/Metcalf configuration with an output power of 1000 mW and an almost Gaussian shaped beam quality (M2<1.2). The coupling efficiency for optical waveguides as well as single mode fibers exceeds 70%. The center wavelength is widely tunable within the tuning range of 20 nm via remote control. This laser system operates longitudinally single mode with a mode-hop free tuning range of up to 150 GHz without current compensation and a side-mode-suppression better than 50 dB. This concept can be realized within the wavelength regime between 750 and 1060 nm. We investigated this light source for high resolution spectroscopy in the field of Cavity Ring-Down Spectroscopy (CRDS). Our high powered Littman/Metcalf laser system was part of a MIR-light source which utilizes difference-frequency generation in Periodically Poled Lithium Niobate (PPLN) crystals. At the wavelength of 3.3 μm we were able to achieve a high-resolution absorption spectrum of water with four resolved isotopic H2O components. This application clearly demonstrates the suitability of this laser for high-precision measurements.