Andreas Wilk

Breath analysis with broadly tunable quantum cascade lasers.

With the availability of broadly tunable external cavity quantum cascade lasers (EC-QCLs), particularly bright mid-infrared (MIR; 3-20 μm) light sources are available offering high spectral brightness along with an analytically relevant spectral tuning range of >2 μm. Accurate isotope ratio determination of (12)CO2 and (13)CO2 in exhaled breath is of critical importance in the field of breath analysis, which may be addressed via measurements in the MIR spectral regime. Here, we combine for the first time an EC-QCL tunable across the (12)CO2/(13)CO2 spectral band with a miniaturized hollow waveguide gas cell for quantitatively determining the (12)CO2/(13)CO2 ratio within the exhaled breath of mice. Due to partially overlapping spectral features, these studies are augmented by appropriate multivariate data evaluation and calibration techniques based on partial least-squares regression along with optimized data preprocessing. Highly accurate determinations of the isotope ratio within breath samples collected from a mouse intensive care unit validated via hyphenated gas chromatography-mass spectrometry confirm the viability of IR-HWG-EC-QCL sensing techniques for isotope-selective exhaled breath analysis.

Substrate-Integrated Hollow Waveguides: A New Level of Integration in Mid-Infrared Gas Sensing

A new generation of hollow waveguide (HWG) gas cells of unprecedented compact dimensions facilitating low sample volumes suitable for broad- and narrow-band mid-infrared (MIR; 2.5-20 μm) sensing applications is reported: the substrate-integrated hollow waveguide (iHWG). iHWGs are layered structures providing light guiding channels integrated into a solid-state substrate material, which are competitive if not superior in performance to conventional leaky-mode fiber optic silica HWGs having similar optical pathlengths. In particular, the provided flexibility in device and optical design and the wide variety of manufacturing strategies, substrate materials, access to the optical channel, and optical coating options highlight the advantages of iHWGs in terms of robustness, compactness, and cost-effectiveness. Finally, the unmatched modularity of this novel waveguide approach facilitates tailoring iHWGs to almost any kind of gas sensor technology providing adaptability to the specific demands of a wide range of sensing scenarios. Device fabrication is demonstrated for the example of a yin-yang-shaped gold-coated iHWG fabricated within an aluminum substrate with a footprint of only 75 mm × 50 mm × 12 mm (L × W × H), yet providing a nominal optical absorption path length of more than 22 cm. The analytical utility of this device for advanced MIR gas sensing applications is demonstrated for the gaseous constituents butane, carbon dioxide, cyclopropane, isobutylene, and methane.

Real-time monitoring of ozone in air using substrate-integrated hollow waveguide mid-infrared sensors

Ozone is a strong oxidant that is globally used as disinfection agent for many purposes including indoor building air cleaning, during food preparation procedures, and for control and killing of bacteria such as E. coli and S. aureus. However, it has been shown that effective ozone concentrations for controlling e.g., microbial growth need to be higher than 5 ppm, thereby exceeding the recommended U.S. EPA threshold more than 10 times. Consequently, real-time monitoring of such ozone concentration levels is essential. Here, we describe the first online gas sensing system combining a compact Fourier transform infrared (FTIR) spectrometer with a new generation of gas cells, a so-called substrate-integrated hollow waveguide (iHWG). The sensor was calibrated using an UV lamp for the controlled generation of ozone in synthetic air. A calibration function was established in the concentration range of 0.3–5.4 mmol m−3 enabling a calculated limit of detection (LOD) at 0.14 mmol m−3 (3.5 ppm) of ozone. Given the adaptability of the developed IR sensing device toward a series of relevant air pollutants, and considering the potential for miniaturization e.g., in combination with tunable quantum cascade lasers in lieu of the FTIR spectrometer, a wide range of sensing and monitoring applications of beyond ozone analysis are anticipated.

Online Analysis of H2S and SO2 via Advanced Mid-Infrared Gas Sensors

Volatile sulfur compounds (VSCs) are among the most prevalent emitted pollutants in urban and rural atmospheres. Mainly because of the versatility of sulfur regarding its oxidation state (2- to 6+), VSCs are present in a wide variety of redox-environments, concentration levels, and molar ratios. Among the VSCs, hydrogen sulfide and sulfur dioxide are considered most relevant and have simultaneously been detected within naturally and anthropogenically caused emission events (e.g., volcano emissions, food production and industries, coal pyrolysis, and various biological activities). Next to their presence as pollutants, changes within their molar ratio may also indicate natural anomalies. Prior to analysis, H2S- and SO2-containing samples are usually preconcentrated via solid sorbents and are then detected by gas chromatographic techniques. However, such analytical strategies may be of limited selectivity, and the dimensions and operation modalities of the involved instruments prevent routine field usage. In this contribution, we therefore describe an innovative portable mid-infrared chemical sensor for simultaneously determining and quantifying gaseous H2S and SO2 via coupling a substrate-integrated hollow waveguides (iHWG) serving as a highly miniaturized mid-infrared photon conduit and gas cell with a custom-made preconcentration tube and an in-line UV-converter device. Both species were collected onto a solid sorbent within the preconcentrator and then released by thermal desorption into the UV-device. Hydrogen sulfide is detected by UV-assisted quantitative conversion of the rather weak IR-absorber H2S into SO2, which provides a significantly more pronounced and distinctively detectable rovibrational signature. Modulation of the UV-device system (i.e., UV-lamp on/off) enables discriminating between SO2 generated from H2S conversion and abundant SO2 signals. After optimization of the operational parameters, calibrations in the range of 0.75-10 ppmv with a limit of detection (LOD) at 77 ppbv for SO2 and 207 ppbv for H2S were established after 20 min of sampling time at 200 mL min(-1). Taking advantage of the device flexibility in terms of sampling time, flow-rate, and iHWG design facilitates tailoring the developed Preconcentrator-UV-device-iHWG device toward a wide variety of application scenarios ranging from environmental/atmospheric monitoring to industrial process monitoring and clinical diagnostics.

Multivariate determination of 13CO2/12CO2 ratios in exhaled mouse breath with mid-infrared hollow waveguide gas sensors.

The 12CO2/13CO2 isotope ratio is a well-known marker in breath for a variety of biochemical processes and enables monitoring, e.g., of the glucose metabolism during sepsis. Using animal models—here, at a mouse intensive care unit—the simultaneous determination of 12CO2 and 13CO2 within small volumes of mouse breath was enabled by coupling a novel low-volume hollow waveguide gas cell to a compact Fourier transform infrared spectrometer combined with multivariate data evaluation based on partial least squares regression along with optimized data preprocessing routines.

iCONVERT: An Integrated Device for the UV-Assisted Determination of H2S via Mid-Infrared Gas Sensors

In this technical note, we describe an integrated device platform for performing in-flow gaseous conversion reactions based on ultraviolet (UV) irradiation. The system combines, using the same footprint, an integrated UV-conversion device (iCONVERT), a preconcentrator unit (iPRECON), and a new generation of mid-infrared (MIR) gas cell simultaneously serving as a photon conduit, i.e., so-called substrate-integrated hollow waveguide (iHWG) optically coupled to a compact Fourier transform-infrared (FT-IR) spectrometer. The iCONVERT is assembled from two blocks of aluminum (dimensions, 75 mm × 50 mm × 40 mm; L × W × D) containing 4 miniaturized UV-lamps (47mm × 6 mm × 47 mm each). For the present study, the iPRECON-iCONVERT-iHWG sensing platform has specifically been tailored to the determination of H2S in gaseous samples. Thereby, the quantitative UV-assisted conversion of the rather weak IR-absorber H2S into the more pronouncedly responding SO2 is used for hydrogen sulfide detection. A linear calibration model was established in the range of 7.5 to 100 ppmv achieving a limit of detection at 1.5 ppmv using 10 min of sample preconcentration (onto Molecular Sieve 5A) at a flow rate of 200 mL min(-1). When compared to a conventional UV-conversion system, the iCONVERT revealed similar performance. Considering the potential for system miniaturization using, e.g., dedicated quantum cascade lasers (QCL) in lieu of the FT-IR spectrometer, the developed sensing platform may be further evolved into a hand-held device.

iPRECON: an integrated preconcentrator for the enrichment of volatile organics in exhaled breath

In this study, a new generation of integrated preconcentrators particularly suited for exhaled breath gas analysis is described. The developed analyzer system comprises a compact preconcentrator (iPRECON) exemplarily tested for sampling isoprene, which readily couples to substrate-integrated hollow waveguides (iHWGs) of the same footprint serving simultaneously as highly miniaturized gas cell and photon conduit in combination with a compact infrared spectrometer.

Optimized design of substrate-integrated hollow waveguides for mid-infrared gas analyzers

Design and analytical performance studies are presented for optimizing a new generation of hollow waveguides suitable for quantitative gas sensing—the so-called substrate-integrated hollow waveguide (iHWG). Taking advantage of a particularly compact Fourier transform infrared spectrometer optimized iHWG geometries are investigated toward the development of a multi-constituent breath analysis tool compatible for usage, e.g., in exhaled mouse breath analysis. Three different iHWG geometries were compared, i.e., straight, meandering one-turn and meandering two-turn waveguide channels aiming at maximizing the related analytical figures-of-merit including the achievable limits of detection for selected exemplary analytes. In addition, efficient coupling of infrared (IR) radiation into straight iHWGs was investigated using integrated optical funnel structures. Calibration functions of butane in nitrogen serving as IR-transparent matrix gas were established and compared for the various iHWG geometries. Given the tidal volume of exhaled breath (EB) samples ranging from a few hundreds of milliliters (human, swine) to a few hundreds of microliters (mouse), it is essential for any given analysis to select an appropriate waveguide geometry and volume yet maintaining (i) a compact footprint ensuring hand-held instrumentation, (ii) modular exchange of the iHWG according to the analysis requirement yet with constant device format, and (iii) enabling inline/online measurement capabilities toward continuous EB diagnostics.

Combined sensing platform for advanced diagnostics in exhaled mouse breath

Breath analysis is an attractive non-invasive strategy for early disease recognition or diagnosis, and for therapeutic progression monitoring, as quantitative compositional analysis of breath can be related to biomarker panels provided by a specific physiological condition invoked by e.g., pulmonary diseases, lung cancer, breast cancer, and others. As exhaled breath contains comprehensive information on e.g., the metabolic state, and since in particular volatile organic constituents (VOCs) in exhaled breath may be indicative of certain disease states, analytical techniques for advanced breath diagnostics should be capable of sufficient molecular discrimination and quantification of constituents at ppm-ppb - or even lower - concentration levels. While individual analytical techniques such as e.g., mid-infrared spectroscopy may provide access to a range of relevant molecules, some IR-inactive constituents require the combination of IR sensing schemes with orthogonal analytical tools for extended molecular coverage. Combining mid-infrared hollow waveguides (HWGs) with luminescence sensors (LS) appears particularly attractive, as these complementary analytical techniques allow to simultaneously analyze total CO2 (via luminescence), the 12CO2/13CO2 tracer-to-tracee (TTR) ratio (via IR), selected VOCs (via IR) and O2 (via luminescence) in exhaled breath, yet, establishing a single diagnostic platform as both sensors simultaneously interact with the same breath sample volume. In the present study, we take advantage of a particularly compact (shoebox-size) FTIR spectrometer combined with novel substrate-integrated hollow waveguide (iHWG) recently developed by our research team, and miniaturized fiberoptic luminescence sensors for establishing a multi-constituent breath analysis tool that is ideally compatible with mouse intensive care stations (MICU). Given the low tidal volume and flow of exhaled mouse breath, the TTR is usually determined after sample collection via gas chromatography coupled to mass spectrometric detection. Here, we aim at potentially continuously analyzing the TTR via iHWGs and LS flow-through sensors requiring only minute (< 1 mL) sample volumes. Furthermore, this study explores non-linearities observed for the calibration functions of 12CO2 and 13CO2 potentially resulting from effects related to optical collision diameters e.g., in presence of molecular oxygen. It is anticipated that the simultaneous continuous analysis of oxygen via LS will facilitate the correction of these effects after inclusion within appropriate multivariate calibration models, thus providing more reliable and robust calibration schemes for continuously monitoring relevant breath constituents.

An approach to the spectral simulation of infrared hollow waveguide gas sensors.

Optical simulations enable to model an entire chemical gas sensing platform based on hollow waveguides (HWGs) operating in the mid-infrared spectral regime using a three-dimensional representation of the sensor components and taking the spectral response to virtual analytes into account. Furthermore, a strategy for including the spectral response of dielectrically coated HWGs is demonstrated. Utilizing experimentally obtained spectroscopic data recorded at well-defined conditions, the complex refractive indices of selected target analytes (i.e., methane, butane, and isobutylene) have been derived based on a refined harmonic oscillator model. In turn, these parameters have enabled to directly assign the dielectric functions of these analytes to virtual objects representing the analyte within the modeled sensor setup. In a next step, spectroscopic sensor response functions have been simulated as absorbance spectra across selected wavelength regimes utilizing spectrally resolved ray-tracing techniques and have been compared to experimental data.