A near-infrared laser dispersion spectrometer with phase modulation for open-path methane sensing.

A laser-based open-path dispersion spectrometer for measuring atmospheric methane has been developed with the goal of achieving a very simple architecture, yet enabling molecular dispersion measurements immune to optical power variation. Well-mature, near-infrared photonics components were retained to demonstrate a compact, cost-effective, and low-power consumption dispersion spectrometer. In particular, measurements immune to received optical power variations are demonstrated despite the use of only phase modulation and are supported by the development of the corresponding physical model. The instrument has been validated under laboratory conditions, finding a precision of 2.6 ppb 100 m for a 2 s measurement, and demonstrated through atmospheric measurements performed continuously over six days with an 86 m path length.

Broadband gas phase absorber detection and quantification by chirped laser dispersion spectroscopy at 1.55†µm.

The demonstration and first evaluation of chirped laser dispersion spectroscopy (CLaDS) for quantitative measurements of gas molecules with broad spectral features is reported. The demonstration is conducted on propyne (methyl acetylene) gas, using a widely tunable external cavity near infrared laser, λ ≈ 1.55 µm, whose frequency can be swept at 2.6 MHz/µs. A direct baseband downconversion scheme is implemented to recover molecular dispersion, with a cost-effective 32 GHz radio frequency architecture. Laboratory tests demonstrate in particular the value of laser dispersion spectroscopy for the sensing of turbid media with a large range of variations, owing to a significant immunity of the detection scheme to variations in received optical power. Normalized minimum concentration measurable in the 1.5 ms scan is ∼0.7 ppm.m.√Hz.

Hollow waveguide-miniaturized quantum cascade laser heterodyne spectro-radiometer.

A miniature thermal infrared laser heterodyne spectro-radiometer based on hybrid optical integration is demonstrated. A quantum cascade laser emitting at 953 cm-1 (10.5 µm) is used as the local oscillator. Integration is achieved using hollow waveguides inscribed in a copper substrate, with slot-encapsulated optical components positioned to maintain fundamental hybrid mode coupling. The demonstrator performances are studied in the laboratory and show a noise level within 1.6 times of the ideal case. Atmospheric high-resolution transmittance spectroscopy of carbon dioxide and water vapor in solar occultation is demonstrated. The total column concentrations are derived as well as measurement uncertainties, 399.5 ± 2.2 ppm for CO2 and 1066 ± 62 ppm for H2O. The miniature laser heterodyne spectro-radiometer demonstration opens the prospect for nanosatellite-based high spectral resolution thermal infrared atmospheric sounding.

Hollow waveguide integrated laser spectrometer for 13CO2/12CO2 analysis.

Using hollow waveguide hybrid optical integration, a miniaturized mid-infrared laser absorption spectrometer for 13CO2/12CO2 isotopologue ratio analysis is presented. The laser analyzer described focuses on applications where samples contain a few percent of CO2, such as breath analysis and characterization of geo-carbon fluxes, where miniaturization facilitates deployment. As part of the spectrometer design, hollow waveguide mode coupling and propagation is analyzed to inform the arrangement of the integrated optical system. The encapsulated optical system of the spectrometer occupies a volume of 158 × 60 × 30 mm3 and requires a low sample volume (56 µL) for analysis, while integrating a quantum cascade laser, coupling lens, hollow waveguide cell and optical detector into a single copper alloy substrate. The isotopic analyzer performance is characterized through robust error propagation analysis, from spectral inversion to calibration errors. The analyzer achieves a precision of 0.2‰ in 500 s integration. A stability time greater than 500 s was established to allow two-point calibration. The accuracy achieved is 1.5‰, including a contribution of 0.7‰ from calibrant gases that can be addressed with improved calibration mixtures.

Broadband standoff detection of large molecules by mid-infrared active coherent laser spectrometry.

A widely tunable active coherent laser spectrometer (ACLaS) has been demonstrated for standoff detection of broadband absorbers in the 1280 to 1318 cm-1 spectral region using an external cavity quantum cascade laser as a mid-infrared source. The broad tuning range allows detection and quantification of vapor phase molecules, such as dichloroethane, ethylene glycol dinitrate, and tetrafluoroethane. The level of confidence in molecular mixing ratios retrieved from interfering spectral measurements is assessed in a quantitative manner. A first qualitative demonstration of condensed phase chemical detection on nitroacetanilide has also been conducted. Detection performances of the broadband ACLaS have been placed in the context of explosive detection and compared to that obtained using distributed feedback quantum cascade lasers.

Middle infrared active coherent laser spectrometer for standoff detection of chemicals.

Using a quantum cascade laser emitting at 7.85 µm, a middle infrared active coherent laser spectrometer has been developed for the standoff detection of vapor phase chemicals. The first prototype has been tested using diffuse target backscattering at ranges up to ~30 m. Exploiting the continuous frequency tuning of the laser source, spectra of water vapor, methane, nitrous oxide, and hydrogen peroxide were recorded. A forward model of the instrument was used to perform spectral unmixing and retrieve line-of-sight integrated concentrations and their one-sigma uncertainties. Performance was found to be limited by speckle noise originating from topographic targets. For absorbers with large absorption cross sections such as nitrous oxide (>10(-19) cm(2)·molecule(-1)), normalized detection sensitivities range between 14 and 0.3 ppm·m·Hz(-1/2), depending on the efficiency of the speckle reduction scheme implemented.

Hollow waveguide photomixing for quantum cascade laser heterodyne spectro-radiometry.

An integrated optic approach, using hollow waveguides, has been evaluated for a compact, rugged, high efficiency heterodyne optical mixing circuit in the middle infrared. The approach has involved the creation of hollow waveguides and alignment features for a beam combiner component in a glass-ceramic substrate. The performance of the integrated beam combiner was tested as part of a full laser heterodyne spectro-radiometer in which a quantum cascade laser local oscillator emitting at 9.7 µm was mixed with incoherent radiation. The performance has been evaluated with both cryogenically-cooled and peltier-cooled photomixers demonstrating consistent detection limits of two and five times the shot noise limit, respectively. The hollow waveguide mixer has also shown advantages in temporal stability, laser spatial mode cleansing, and reduced sensitivity to optical feedback.

Atmospheric observations of multiple molecular species using ultra-high-resolution external cavity quantum cascade laser heterodyne radiometry.

We demonstrate a widely tunable laser heterodyne radiometer operating in the thermal IR during an atmospheric observation campaign in the solar occultation viewing mode. An external cavity quantum cascade laser tunable within a range of 1120 to 1238 cm(-1) is used as the local oscillator (LO) of the instrument. Ultra-high-resolution (60 MHz or 0.002 cm(-1) transmission spectroscopy of several atmospheric species (water vapor, ozone, nitrous oxide, methane, and dichlorodifluoromethane) has been demonstrated within four precisely selected molecule-specific narrow spectral windows (∼1 cm(-1). Atmospheric transmission lines within each selected window were fully resolved through mode-hop-free continuous tuning of the LO frequency. Comparison measurements were made simultaneously with a high-resolution Fourier transform spectrometer to demonstrate the advantages of the laser heterodyne system for atmospheric sounding at high spectral and spatial resolutions.

Characterisation of transmission Raman spectroscopy for rapid quantitative analysis of intact multi-component pharmaceutical capsules.

A detailed characterisation of the performance of transmission Raman spectroscopy was performed from the standpoint of rapid quantitative analysis of pharmaceutical capsules using production relevant formulations comprising of active pharmaceutical ingredient (API) and 3 common pharmaceutical excipients. This research builds on our earlier studies that identified the unique benefits of transmission Raman spectroscopy compared to conventional Raman spectroscopy. These include the ability to provide bulk information of the content of capsules, thus avoiding the sub-sampling problem, and the suppression of interference from the capsule shell. This study demonstrates, for the first time, the technique's insensitivity to the amount of material held within the capsules. Different capsules sizes with different overall fill weights (100-400 mg) and capsule shell colours were assayed with a single calibration model developed using only one weight and size sample set (100 mg) to a relative error of typically <3%. The relative root mean square error of prediction of the concentration of API for the main sample set (nominal content 75%, w/w) was 1.5% with a 5s acquisition time. Models built using the same calibration set also predicted the 3 low level excipients with relative errors of 5-15%. The quantity of API was also predicted (with a relative error within ∼3%) using the same model for capsules prepared with different generations of API (i.e. API manufactured via different processes). The study provides further foundation blocks for the establishment of this emerging technique as a routine pharmaceutical analysis tool, capitalising on the inherently high chemical specificity of Raman spectroscopy and the non-invasive nature of the measurement. Ultimately, this technique has significant promise as a Process Analytical Technology (PAT) tool for online production application.

Technique for enhancing signal in conventional backscattering fluorescence and Raman spectroscopy of turbid media.

We demonstrate experimentally, for the first time, the feasibility of passively enhancing fluorescence and Raman signals from diffusely scattering media in a conventional backscattering collection geometry. The method employs transmission of the collimated excitation laser beam through a "unidirectional" dielectric mirror placed directly in front of the sample. This permits laser light that escapes from the sample surface to be reflected back into the sample where it can be more usefully employed in generating Raman and fluorescence signals. This leads to improved Raman signal, higher signal-to-noise ratio, and shorter acquisition times. Feasibility studies performed on standard pharmaceutical tablets and on sheets of Teflon, using a single enhancing element, demonstrate signal enhancement factors of 6 (fluorescence) and 3 (Raman). Potential applications of this simple device include improving quality control of pharmaceutical products, disease diagnosis of biological tissue, forensics, and security screening.

Emerging non-invasive Raman methods in process control and forensic applications.

This article reviews emerging Raman techniques (Spatially Offset and Transmission Raman Spectroscopy) for non-invasive, sub-surface probing in process control and forensic applications. New capabilities offered by these methods are discussed and several application examples are given including the non-invasive detection of counterfeit drugs through blister packs and opaque plastic bottles and the rapid quantitative analysis of the bulk content of pharmaceutical tablets and capsules without sub-sampling.

Non-invasive quantitative assessment of the content of pharmaceutical capsules using transmission Raman spectroscopy.

This study demonstrates how transmission Raman spectroscopy can be used in the quantitative, non-invasive probing of the bulk content of production line relevant pharmaceutical products contained within capsules with a strong interfering Raman signal (principally TiO(2)). This approach is particularly beneficial in situations where the conventional Raman backscattering method is hampered or fails due to excessive Raman or fluorescence signals emanating from surface layers (capsule or coating) that pollute the much weaker subsurface Raman signals. In these feasibility experiments the interfering surface Raman signal was effectively suppressed, relative to the Raman signal of the internal content, by a factor of 33, in the transmission geometry in comparison with the conventional backscattering Raman approach. In conjunction with the superior bulk probing ability of the transmission Raman geometry, which effectively removes the sub-sampling problem inherent to conventional Raman spectroscopy, and multivariate analysis (principal component analysis (PCA), partial least squares (PLS) and classical least squares (CLS) regression), this provides an analytical tool well suited for rapid control monitoring applications in the pharmaceutical industry. The measured relative root mean square error of prediction (RMSEP) of the concentration of the active pharmaceutical ingredient (API) was 1.2 and 1.8% with 5 and 1s acquisition times, respectively.

Characterization of genuine and fake artesunate anti-malarial tablets using Fourier transform infrared imaging and spatially offset Raman spectroscopy through blister packs.

In support of the efforts to combat the illegal sale and distribution of counterfeit anti-malarial drugs, we evaluated a new analytical approach for the characterization and fast screening of fake and genuine artesunate tablets using a combination of Raman spectroscopy, Spatially Offset Raman Spectroscopy (SORS) and Attenuated Total Reflection-Fourier Transform Infrared (ATR-FTIR) imaging. Vibrational spectroscopy provided chemically specific information on the composition of the tablets; the complementary nature of Raman scattering and FTIR imaging allowed the characterization of both the overall and surface composition of the tablets. The depth-resolving power of the SORS approach provided chemically specific information on the overall composition of the tablets, non-invasively, through a variety of packaging types. Spatial imaging of the tablet surface (using ATR-FTIR) identified the location of domains of excipients and active ingredients with high sensitivity and enhanced spatial resolution. The advantages provided by a combination of SORS and ATR-FTIR imaging in this context confirm its potential for inclusion in the analytical protocol for forensic investigation of counterfeit medicines.

Infrared spectroscopy and structure of photochemically protonated biomolecules in the gas phase: a noradrenaline analogue, lysine and alanyl alanine.

A novel photochemical technique combined with mass spectrometry and resonant infrared multiphoton dissociation spectroscopy (R-IRMPD) has been used to record infrared vibrational spectra of the free protonated noradrenaline analogue, 2-amino-1-phenylethanol (APE-H(+)), the amino acid, lysine (Lys-H(+)), and the dipeptide, alanyl alanine (Ala-Ala-H(+)) in the gas phase. Coupling their spectra, obtained in the OH, NH and CH stretch regions, with ab initio calculations has allowed assignment of their preferred protonation sites and conformations. This simple technique will have wide applicability in future investigations of protonated biomolecular structure and conformation.

Structure, electronic circular dichroism and Raman optical activity in the gas phase and in solution: a computational and experimental investigation.

A computational (ab initio and molecular dynamics) and experimental exploration of the relative importance of molecular conformation and explicit solvent effects on the electronic circular dichroism (ECD) of chiral molecules, is presented. The exploration includes an assessment of the validity of angular correlation (sector) rules linking ECD to molecular conformation. It is based upon studies of 1-(R) phenylethanol (including its Raman optical activity spectrum), the corresponding 'benchmark' base, 1-(R)-phenylethylamine and its protonated cation; their hydrated clusters in the gas phase; and their non-polar and aqueous solutions. Emphasis is placed on the influence of specific, hydrogen bonded interactions with the aqueous solvent. The theoretical validity of the (otherwise empirical) sector rule in the neutral molecules and in their specifically hydrated clusters has been established--but with a reversal of the 'historical' sign convention. Protonation of the amine leads to a breakdown of the conventional sector rule but the change in its ECD intensity can still be related to the side chain dihedral angular dependence of its rotatory strength, computed ab initio for its explicitly hydrated clusters. Comparisons between ECD spectra measured in aqueous and in hydrocarbon solutions and the results of molecular dynamics calculations for aqueous solutions at 300 K, identify solvent induced structural change as the principal determinant of their relative ECD spectral intensities. Further links connecting the structures and conformations of chiral molecules and their explicitly solvated clusters in the gas phase, to their structures and conformational populations in solution can be expected through measurement, ab initio computation and analysis of their vibrational, ROA spectra.