Detection of Asthma Inhaler Use via Terahertz Spectroscopy.

Inhaled medications are commonplace for administering bronchodilators, anticholinergics, and corticosteroids. While they have a defined legitimate use, they are also used in sporting events as performance-enhancing drugs. These performance enhancers can be acquired via both legal (i.e., at a pharmacy through over-the-counter medications or through a prescription) and illicit (i.e., black market and foreign pharmacies) means, thus making monitoring procurement impossible. While urine tests can detect these pharmacological agents hours after they have been inhaled, there is a significant lag time before they are observed in urine. Direct detection of these inhaled agents is complicated and requires a multiplexed approach due to the sheer number of inhaled pharmacological agents. Therefore, detection of propellants, which carry the drug into the lungs, provides a simpler path forward toward detection of broad pharmacological agents. In this paper, we demonstrate the first use of terahertz spectroscopy (THz) to detect inhaled medications in human subjects. Notably, we were able to detect and quantitate the propellant, HFA-134a, in breath up to 30 min after using an asthma inhaler, enabling the use of a point-of-care device to monitor exhaled breath for the presence of propellants. We also demonstrate via simulations that the same approach can be leveraged to detect and identify next-generation propellants, specifically HFA-152a. As a result, we provide evidence that a single point-of-care THz sensor can detect when individuals have used pressure-mediated dose inhalers (pMDIs) without further modification of the hardware.

Terahertz Spectroscopic Molecular Sensor for Rapid and Highly Specific Quantitative Analytical Gas Sensing.

Quantitative analytical gas sampling is of great importance in a range of environmental, safety, and scientific applications. In this article, we present the design, operation, and performance of a recently developed tabletop terahertz (THz) spectroscopic molecular sensor capable of rapid (minutes) and sensitive detection of polar gaseous analytes with near "absolute" specificity. A novel double-coil absorption cell design and an array of room-temperature sorbent-based preconcentration modules facilitate quantitative THz detection of light polar volatile compounds, which often challenge the capabilities of established gas sensing techniques. Acetone, ethanol, methanol, acetaldehyde, formaldehyde, and isoprene are detected at low parts-per-billion to high parts-per-trillion levels. This work evaluates performance-limiting factors for THz spectroscopy-based chemical identification: (1) spectral signal to noise and (2) preconcentrator efficiency.

Improved Sensitivity MEMS Cantilever Sensor for Terahertz Photoacoustic Spectroscopy.

In this paper, a microelectromechanical system (MEMS) cantilever sensor was designed, modeled and fabricated to measure the terahertz (THz) radiation induced photoacoustic (PA) response of gases under low vacuum conditions. This work vastly improves cantilever sensitivity over previous efforts, by reducing internal beam stresses, minimizing out of plane beam curvature and optimizing beam damping. In addition, fabrication yield was improved by approximately 50% by filleting the cantilever's anchor and free end to help reduce high stress areas that occurred during device fabrication and processing. All of the cantilever sensors were fabricated using silicon-on-insulator (SOI) wafers and tested in a custom built, low-volume, vacuum chamber. The resulting cantilever sensors exhibited improved signal to noise ratios, sensitivities and normalized noise equivalent absorption (NNEA) coefficients of approximately 4.28 × 10(-10) cm(-1)·WHz(-1/2). This reported NNEA represents approximately a 70% improvement over previously fabricated and tested SOI cantilever sensors for THz PA spectroscopy.

Impact of atmospheric clutter on Doppler-limited gas sensors in the submillimeter/terahertz.

It is well known that clutter (spectral interference) from atmospheric constituents can be a severe limit for spectroscopic point sensors, especially where high sensitivity and specificity are required. In this paper, we will show for submillimeter/terahertz (SMM/THz) sensors that use cw electronic techniques the clutter limit for the detection of common target gases with absolute specificity (probability of false alarm ≪ 10⁻¹°) is in the ppt (1 part in 10¹²) range or lower. This is because the most abundant atmospheric gases are either transparent to SMM/THz radiation (e.g., CO2) or have spectra that are very sparse relative to the 105 Doppler-limited resolution elements available (e.g., H2O). Moreover, the low clutter limit demonstrated for cw electronic systems in the SMM/THz is independent of system size and complexity.

Determination of precise relative energies of conformers of n-propanol by rotational spectroscopy.

The rotational spectrum of n-propanol (n-CH(3)CH(2)CH(2)OH) was studied with several techniques of contemporary broadband rotational spectroscopy at frequencies from 8 to 550 GHz. Rotational transitions in all five conformers of the molecule, Gt, Gg, Gg', Tt, and Tg, have been unambiguously assigned. Over 6700 lines of the Gt, Gg, and Gg' species, for quantum number values reaching K(a) = 33 and J = 67, were fitted in a joint analysis leading to the determination of DeltaE(Gg-Gt) = 47.82425(25) cm(-1) and DeltaE (Gg'-Gg) = 3.035047(11) cm(-1). Stark effect measurements in supersonic expansion were used to further confirm the assignment. The results are compared with those for the ethanol molecule and with ab initio calculations, allowing several inferences to be drawn concerning the differences in the large amplitude torsional potential of the hydroxyl group in the two molecules.

Submillimeter spectroscopy for chemical analysis with absolute specificity.

A sensor based on rotational signatures in the submillimeter (SMM) region is described. This sensor uses frequency synthesis techniques in the region around 10 GHz, with nonlinear diode frequency multiplication to 210-270 GHz. This provides not only a nearly ideal instrument function, but also frequency control and agility that significantly enhance the performance of the spectrometer as a sensor. The SMM frequencies provide significantly stronger absorptions and broader spectroscopic coverage than lower-frequency microwave systems. Among the characteristics of the sensor are absolute specificity, low atmospheric clutter, good sensitivity, and near-term paths to systems that are both compact and very inexpensive.

Analysis of the FASSST rotational spectrum of NCNCS in view of quantum monodromy.

Quantum monodromy has a strong impact on the ro-vibrational energy levels of chain molecules whose bending potential energy function has the form of the bottom of a champagne bottle (i.e. with a hump or punt) around the linear configuration. NCNCS, cyanogen iso-thiocyanate, is a particularly good example of such a molecule and clearly exhibits a distinctive monodromy-induced dislocation of the energy level pattern at the bending-rotation energy at the top of the potential energy hump. Indeed, NCNCS [B. P. Winnewisser et al., Phys. Rev. Lett. 2005, 95, 243002] and the water molecule [N. F. Zobov et al., Chem. Phys. Lett. 2005, 414, 193-197] were the first two molecules for which experimental confirmation of quantum monodromy was obtained. We used the fast scan sub-millimetre spectroscopic technique (FASSST) to extend the measurements and spectral analysis to pure rotational transitions (end-over-end) in bending vibrational states lying well above the monodromy point. The analysis of 9204 lines assigned to 7 vibrational states, presented here, shows that the topological properties of the bending potential function are mapped onto every aspect of the ro-vibrational energy levels involving excitation of the quasi-linear bending vibration. In order to model the large amplitude dynamics of such a molecular system, and also to achieve some insight beyond satisfactory parameters for reproducing the spectrum, we used the generalized semi-rigid bender (GSRB) Hamiltonian, which is described in some detail. This Hamiltonian provides a good description of the energy levels over the seven bending states observed, coming close to experimental accuracy. Due to high J values of the measured rotational transitions (J

Chemical analysis in the submillimetre spectral region with a compact solid state system.

A new analytical system that uses the rotational signatures of gas phase molecules is described and demonstrated. It uses a solid state source to probe molecular systems in the millimetre and submillimetre wave range, the only region of the electromagnetic spectrum not yet used extensively for analytical purposes. It employs the FAst Scan Submillimetre Spectroscopy Technique (FASSST), which leads to an especially simple system architecture. Among the attributes of the system are generality, sensitivity, 'absolute' specificity, small size, simplicity, and the potential for very low cost. Applications to problems of analytical interest are also discussed.

Experimental confirmation of quantum monodromy: the millimeter wave spectrum of cyanogen isothiocyanate NCNCS.

We have made energy-momentum maps for the experimental end-over-end rotational energy and the two-dimensional bending vibrational energy, both of which confirm the dominating effects of nontrivial quantum monodromy in cyanogen isothiocyanate. Accidental resonances in the rotational spectra yield accurate intervals between bending states.