Quartz-Enhanced Photoacoustic Spectroscopy Assisted by Partial Least-Squares Regression for Multi-Gas Measurements.

We report on the use of quartz-enhanced photoacoustic spectroscopy (QEPAS) for multi-gas detection. Photoacoustic (PA) spectra of mixtures of water (H2O), ammonia (NH3), and methane (CH4) were measured in the mid-infrared (MIR) wavelength range using a mid-infrared (MIR) optical parametric oscillator (OPO) light source. Highly overlapping absorption spectra are a common challenge for gas spectroscopy. To mitigate this, we used a partial least-squares regression (PLS) method to estimate the mixing ratio and concentrations of the individual gasses. The concentration range explored in the analysis varies from a few parts per million (ppm) to thousands of ppm. Spectra obtained from HITRAN and experimental single-molecule reference spectra of each of the molecular species were acquired and used as training data sets. These spectra were used to generate simulated spectra of the gas mixtures (linear combinations of the reference spectra). Here, in this proof-of-concept experiment, we demonstrate that after an absolute calibration of the QEPAS cell, the PLS analyses could be used to determine concentrations of single molecular species with a relative accuracy within a few % for mixtures of H2O, NH3, and CH4 and with an absolute sensitivity of approximately 300 (±50) ppm/V, 50 (±5) ppm/V, and 5 (±2) ppm/V for water, ammonia, and methane, respectively. This demonstrates that QEPAS assisted by PLS is a powerful approach to estimate concentrations of individual gas components with considerable spectral overlap, which is a typical scenario for real-life adoptions and applications.

Accurate and fast identification of minimally prepared bacteria phenotypes using Raman spectroscopy assisted by machine learning.

The worldwide increase of antimicrobial resistance (AMR) is a serious threat to human health. To avert the spread of AMR, fast reliable diagnostics tools that facilitate optimal antibiotic stewardship are an unmet need. In this regard, Raman spectroscopy promises rapid label- and culture-free identification and antimicrobial susceptibility testing (AST) in a single step. However, even though many Raman-based bacteria-identification and AST studies have demonstrated impressive results, some shortcomings must be addressed. To bridge the gap between proof-of-concept studies and clinical application, we have developed machine learning techniques in combination with a novel data-augmentation algorithm, for fast identification of minimally prepared bacteria phenotypes and the distinctions of methicillin-resistant (MR) from methicillin-susceptible (MS) bacteria. For this we have implemented a spectral transformer model for hyper-spectral Raman images of bacteria. We show that our model outperforms the standard convolutional neural network models on a multitude of classification problems, both in terms of accuracy and in terms of training time. We attain more than 96% classification accuracy on a dataset consisting of 15 different classes and 95.6% classification accuracy for six MR-MS bacteria species. More importantly, our results are obtained using only fast and easy-to-produce training and test data.

Quantum frequency conversion of vacuum squeezed light to bright tunable blue squeezed light and higher-order spatial modes.

Quantum frequency conversion, the process of shifting the frequency of an optical quantum state while preserving quantum coherence, can be used to produce non-classical light at otherwise unapproachable wavelengths. We present experimental results based on highly efficient sum-frequency generation (SFG) between a vacuum squeezed state at 1064 nm and a tunable pump source at 850 nm ± 50 nm for the generation of bright squeezed light at 472 nm ± 4 nm, currently limited by the phase-matching of the used nonlinear crystal. We demonstrate that the SFG process conserves part of the quantum coherence as a 4.2(±0.2) dB 1064 nm vacuum squeezed state is converted to a 1.6(±0.2) dB tunable bright blue squeezed state. We furthermore demonstrate simultaneous frequency- and spatial-mode conversion of the 1064-nm vacuum squeezed state, and measure 1.1(±0.2) dB and 0.4(±0.2) dB of squeezing in the TEM01 and TEM02 modes, respectively. With further development, we foresee that the source may find use within fields such as sensing, metrology, spectroscopy, and imaging.

Isotopic gas analysis by means of mid-infrared photoacoustic spectroscopy targeting human exhaled air.

There is a great need for cost-efficient non-invasive medical diagnostic tools for analyzing humanly exhaled air. Compared to present day methods, photoacoustic spectroscopy (PAS) can provide a compact and portable (bedside), sensitive and inexpensive solution. We demonstrate a novel portable photoacoustic spectroscopic platform for isotopic measurements of methane (CH4). We identify and discriminate the 12CH4- and 13CH4 isotopologues and determine their mixing ratio. An Allan deviation analysis shows that the noise equivalent concentration for CH4 is 200 ppt (pmol/mol) at 100 s of integration time, corresponding to a normalized noise equivalent absorption coefficient of 5.1×10-9Wcm-1Hz-1/2, potentially making the PAS sensor a truly disruptive instrument for bedside monitoring using isotope tracers by providing real-time metabolism data to clinical personnel.

Calibration of Quartz-Enhanced Photoacoustic Sensors for Real-Life Adaptation.

We report on the use of quartz-enhanced photoacoustic spectroscopy for continuous carbon-dioxide measurements in humid air over a period of six days. The presence of water molecules alters the relaxation rate of the target molecules and thus the amplitude of the photoacoustic signal. Prior to the measurements, the photoacoustic sensor system was pre-calibrated using CO2 mole fractions in the range of 0-10-3 (0-1000 ppm) and at different relative humidities between 0% and 45%, while assuming a model hypothesis that allowed the photoacoustic signal to be perturbed linearly by H2O content. This calibration technique was compared against an alternative learning-based method, where sensor data from the first two days of the six-day period were used for self-calibration. A commercial non-dispersive infrared sensor was used as a CO2 reference sensor and provided the benchmark for the two calibration procedures. In our case, the self-calibrated method proved to be both more accurate and precise.

Intrinsic Spectral Resolution Limitations of QEPAS Sensors for Fast and Broad Wavelength Tuning.

Quartz-enhanced photoacoustic sensing is a promising method for low-concentration trace-gas monitoring due to the resonant signal enhancement provided by a high-Q quartz tuning fork. However, quartz-enhanced photoacoustic spectroscopy (QEPAS) is associated with a relatively slow acoustic decay, which results in a reduced spectral resolution and signal-to-noise ratio as the wavelength tuning rate is increased. In this work, we investigate the influence of wavelength scan rate on the spectral resolution and signal-to-noise ratio of QEPAS sensors. We demonstrate the acquisition of photoacoustic spectra from 3.1 µm to 3.6 µm using a tunable mid-infrared optical parametric oscillator. The spectra are attained using wavelength scan rates differing by more than two orders of magnitude (from 0.3 nm s-1 to 96 nm s-1). With this variation in scan rate, the spectral resolution is found to change from 2.5 cm-1 to 9 cm-1. The investigated gas samples are methane (in nitrogen) and a gas mixture consisting of methane, water, and ethanol. For the gas mixture, the reduced spectral resolution at fast scan rates significantly complicates the quantification of constituent gas concentrations.

Cavity-enhanced sum-frequency generation of blue light with near-unity conversion efficiency.

We report on double-resonant highly efficient sum-frequency generation in the blue range. The system consists of a 10-mm-long periodically poled KTP crystal placed in a double-resonant bow-tie cavity and pumped by a fiber laser at 1064.5 nm and a Ti:sapphire laser at 849.2 nm. An optical power of 375 mW at 472.4 nm in a TEM00 mode was generated with pump powers of 250 mW at 849.2 nm and 200 mW at 1064.5 nm coupled into the double-resonant ring resonator with 88% mode-matching. The resulting internal conversion efficiency of 95(±3)% of the photons mode-matched to the cavity constitutes, to the best of our knowledge, the highest overall achieved quantum conversion efficiency using continuous-wave pumping. Very high conversion efficiency is rendered possible due to very low intracavity loss on the level of 0.3% and high nonlinear conversion coefficient up to 0.045(0.015) W-1. Power stability measurements performed over one hour show a stability of 0.8%. The generated blue light can be tuned within 5 nm around the center wavelength of 472.4 nm, limited by the phase-matching of our nonlinear crystal. This can however be expanded to cover the entire blue spectrum (420 nm to 510 nm) by proper choice of nonlinear crystals and pump lasers. Our experimental results agree very well with analytical and numerical simulations taking into account cavity impedance matching and depletion of the pump fields.

Spectrally pure heralded single photons by spontaneous four-wave mixing in a fiber: reducing impact of dispersion fluctuations.

We model the spectral quantum-mechanical purity of heralded single photons from a photon-pair source based on nondegenerate spontaneous four-wave mixing taking the impact of distributed dispersion fluctuations into account. The considered photon-pair-generation scheme utilizes pump-pulse walk-off to produce pure heralded photons and phase matching is achieved through the dispersion properties of distinct spatial modes in a few-mode silica step-index fiber. We show that fiber-core-radius fluctuations in general severely impact the single-photon purity. Furthermore, by optimizing the fiber design we show that generation of single photons with very high spectral purity is feasible even in the presence of large core-radius fluctuations. At the same time, contamination from spontaneous Raman scattering is greatly mitigated by separating the single-photon frequency by more than 32 THz from the pump frequency.

Full-vectorial propagation model and modified effective mode area of four-wave mixing in straight waveguides.

We derive from Maxwell's equations full-vectorial nonlinear propagation equations of four-wave mixing valid in straight semiconductor-on-insulator waveguides. Special attention is given to the resulting effective mode area, which takes a convenient form known from studies in photonic crystal fibers, but has not been introduced in the context of integrated waveguides. We show that the difference between our full-vectorial effective mode area and the scalar equivalent often referred to in the literature may lead to mistakes when evaluating the nonlinear refractive index and optimizing designs of new waveguides. We verify the results of our derivation by comparing it to experimental measurements in a silicon-on-insulator waveguide, taking tolerances on fabrication parameters into account.

Temporal mode sorting using dual-stage quantum frequency conversion by asymmetric Bragg scattering.

The temporal shape of single photons provides a high-dimensional basis of temporal modes, and can therefore support quantum computing schemes that go beyond the qubit. However, the lack of linear optical components to act as quantum gates has made it challenging to efficiently address specific temporal-mode components from an arbitrary superposition. Recent progress towards realizing such a "quantum pulse gate," has been proposed using nonlinear optical signal processing to add coherently the effect of multiple stages of quantum frequency conversion. This scheme, called temporal-mode interferometry [D. V. Reddy, Phys. Rev. A 91, 012323 (2015)], has been shown in the case of three-wave mixing to promise near-unity mode-sorting efficiency. Here we demonstrate that it is also possible to achieve high mode-sorting efficiency using four-wave mixing, if one pump pulse is long and the other short - a configuration we call asymmetrically-pumped Bragg scattering.

Structural basis for inhibition of complement C5 by the SSL7 protein from Staphylococcus aureus.

Staphylococcus aureus secretes the SSL7 protein as part of its immune evasion strategy. The protein binds both complement C5 and IgA, yet it is unclear whether SSL7 cross-links these two proteins and, if so, what purpose this serves the pathogen. We have isolated a stable IgA-SSL7-C5 complex, and our crystal structure of the C5-SSL7 complex confirms that binding to C5 occurs exclusively through the C-terminal beta-grasp domain of SSL7 leaving the OB domain free to interact with IgA. SSL7 interacts with C5 >70 A from the C5a cleavage site without inducing significant conformational changes in C5, and efficient inhibition of convertase cleavage of C5 is shown to be IgA dependent. Inhibition of C5a production and bacteriolysis are all shown to require C5 and IgA binding while inhibition of hemolysis is achieved by the C5 binding SSL7 beta-grasp domain alone. These results provide a conceptual and structural basis for the development of a highly specific complement inhibitor preventing only the formation of the lytic membrane attack complex without affecting the important signaling functions of C5a.