Pulmonary Surfactant in Adult ARDS: Current Perspectives and Future Directions.

Acute respiratory distress syndrome (ARDS) is a major cause of hypoxemic respiratory failure in adults, leading to the requirement for mechanical ventilation and poorer outcomes. Dysregulated surfactant metabolism and function are characteristic of ARDS. A combination of alveolar epithelial damage leading to altered surfactant synthesis, secretion, and breakdown with increased functional inhibition from overt alveolar inflammation contributes to the clinical features of poor alveolar compliance and alveolar collapse. Quantitative and qualitative alterations in the bronchoalveolar lavage and tracheal aspirate surfactant composition contribute to ARDS pathogenesis. Compared to neonatal respiratory distress syndrome (nRDS), replacement studies of exogenous surfactants in adult ARDS suggest no survival benefit. However, these studies are limited by disease heterogeneity, variations in surfactant preparations, doses, and delivery methods. More importantly, the lack of mechanistic understanding of the exact reasons for dysregulated surfactant remains a significant issue. Moreover, studies suggest an extremely short half-life of replaced surfactant, implying increased catabolism. Refining surfactant preparations and delivery methods with additional co-interventions to counteract surfactant inhibition and degradation has the potential to enhance the biophysical characteristics of surfactant in vivo.

Prediction of Neonatal Respiratory Distress Biomarker Concentration by Application of Machine Learning to Mid-Infrared Spectra.

The authors of this study developed the use of attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) combined with machine learning as a point-of-care (POC) diagnostic platform, considering neonatal respiratory distress syndrome (nRDS), for which no POC currently exists, as an example. nRDS can be diagnosed by a ratio of less than 2.2 of two nRDS biomarkers, lecithin and sphingomyelin (L/S ratio), and in this study, ATR-FTIR spectra were recorded from L/S ratios of between 1.0 and 3.4, which were generated using purified reagents. The calibration of principal component (PCR) and partial least squares (PLSR) regression models was performed using 155 raw baselined and second derivative spectra prior to predicting the concentration of a further 104 spectra. A three-factor PLSR model of second derivative spectra best predicted L/S ratios across the full range (R2: 0.967; MSE: 0.014). The L/S ratios from 1.0 to 3.4 were predicted with a prediction interval of +0.29, -0.37 when using a second derivative spectra PLSR model and had a mean prediction interval of +0.26, -0.34 around the L/S 2.2 region. These results support the validity of combining ATR-FTIR with machine learning to develop a point-of-care device for detecting and quantifying any biomarker with an interpretable mid-infrared spectrum.

Study of waveguide background at visible wavelengths for on-chip nanoscopy.

On-chip super-resolution optical microscopy is an emerging field relying on waveguide excitation with visible light. Here, we investigate two commonly used high-refractive index waveguide platforms, tantalum pentoxide (Ta2O5) and silicon nitride (Si3N4), with respect to their background with excitation in the range 488-640 nm. The background strength from these waveguides were estimated by imaging fluorescent beads. The spectral dependence of the background from these waveguide platforms was also measured. For 640 nm wavelength excitation both the materials had a weak background, but the background increases progressively for shorter wavelengths for Si3N4. We further explored the effect of the waveguide background on localization precision of single molecule localization for direct stochastic optical reconstruction microscopy (dSTORM). An increase in background for Si3N4 at 488 nm is shown to reduce the localization precision and thus the resolution of the reconstructed images. The localization precision at 640nm was very similar for both the materials. Thus, for shorter wavelength applications Ta2O5 is preferable. Reducing the background from Si3N4 at shorter wavelengths via improved fabrication will be worth pursuing.

Extraordinary evanescent field confinement waveguide sensor for mid-infrared trace gas spectroscopy.

Nanophotonic waveguides are at the core of a great variety of optical sensors. These structures confine light along defined paths on photonic chips and provide light-matter interaction via an evanescent field. However, waveguides still lag behind free-space optics for sensitivity-critical applications such as trace gas detection. Short optical pathlengths, low interaction strengths, and spurious etalon fringes in spectral transmission are among the main reasons why on-chip gas sensing is still in its infancy. In this work, we report on a mid-infrared integrated waveguide sensor that successfully addresses these drawbacks. This sensor operates with a 107% evanescent field confinement factor in air, which not only matches but also outperforms free-space beams in terms of the per-length optical interaction. Furthermore, negligible facet reflections result in a flat spectral background and record-low absorbance noise that can finally compete with free-space spectroscopy. The sensor performance was validated at 2.566 µm, which showed a 7 ppm detection limit for acetylene with only a 2 cm long waveguide.

A general model for taper coupling of multiple modes of whispering gallery resonators and application to analysis of coupling-induced Fano interference in a single cavity.

In this paper, we give a general model for analysis of multimode Whispering Gallery Mode (WGM) resonators coupled to multimode tapered fibers based on the coupled-mode theory. Such formulation takes into account the asymmetry of the taper-resonator coupling. Simulations for a microsphere show that the tapered fiber coupling mechanism induces cross-coupling between coherent orthonormal WGMs. We show that the degree of such cross-coupling depends basically on the fiber diameter, air-gap between the taper and resonator, intrinsic losses and eccentricity. The WGM cross-coupling affects the total transmission and spectral line-shape of the internal powers resulting in a controllable transformation of the line-shape to non-Lorentzian spectra. This analysis can be utilized to precisely determine the output and intra-cavity intensity of multimode microresonators, which is important in lasers, nonlinear optical signal generation and realization of optical delays.

Design of rare-earth-doped microbottle lasers.

Coupling strength in taper-coupled microbottle resonators can be tuned by offsetting the taper along the resonator profile, similar to controlling the air-gap in microsphere excitation, and hence, achieve desired coupling characteristics for a specific mode. Such flexibility makes microbottles attractive and adaptable laser cavities. In this paper, lasing characteristics of Yb3+-doped microbottle laser (MBL) coupled to tapered fiber are theoretically investigated. It is demonstrated that desired lasing characteristics for a particular mode are achievable by controlling the taper-resonator coupling, intrinsic quality factor (Q) and dopant concentration. Although, high Q whispering gallery cavities provide high internal powers, which is favorable especially for low gain materials, they lack high output powers. Hence, care should be taken in designing MBLs to attain the highest possible output power. Here, we address such issues, and optimized the required resonator parameters (for both pump and signal) for a low threshold pump power, high efficiency and desired lasing wavelength.

Chalcogenide glass waveguides with paper-based fluidics for mid-infrared absorption spectroscopy.

We demonstrate the integration of paper fluidics with mid-infrared (MIR) chalcogenide waveguides to introduce liquid samples to the waveguide evanescent field for analysis. Spectroscopy of model analytes (water and isopropyl alcohol) having well-defined mid-IR absorptions, on a ZnSe rib waveguide fabricated on silicon, is demonstrated in the wavelength range of 2.6-3.7 µm, showing their O-H and C-H stretching absorptions. The results are compared with a theoretical waveguide model, achieving good agreement. It is concluded that the presence of paper in the evanescent field does not interfere with the waveguide measurements, opening up opportunities to combine low-cost paper-based fluidics and integrated photonic technologies.

Germanium-on-silicon waveguides operating at mid-infrared wavelengths up to 8.5 µm.

We report transmission measurements of germanium on silicon waveguides in the 7.5-8.5 µm wavelength range, with a minimum propagation loss of 2.5 dB/cm at 7.575 µm. However, we find an unexpected strongly increasing loss at higher wavelengths, potential causes of which we discuss in detail. We also demonstrate the first germanium on silicon multimode interferometers operating in this range, as well as grating couplers optimized for measurement using a long wavelength infrared camera. Finally, we use an implementation of the "cut-back" method for loss measurements that allows simultaneous transmission measurement through multiple waveguides of different lengths, and we use dicing in the ductile regime for fast and reproducible high quality optical waveguide end-facet preparation.

Fabrication and characterization of high-contrast mid-infrared GeTe4 channel waveguides.

We report the fabrication and characterization of high index contrast (Δn≈0.9) GeTe4 channel waveguides on ZnSe substrate for evanescent-field-based biosensing applications in the mid-IR spectral region. GeTe4 films were deposited by RF sputtering and characterized for their structure, composition, transparency, and dispersion. The lift-off technique was used to pattern the waveguide channels. Waveguiding from 2.5-3.7 and 6.4-7.5 µm was demonstrated, and mode intensity profile and estimated propagation losses are given for the 3.5 µm wavelength.

Packaged, high-Q, microsphere-resonator-based add-drop filter.

In this Letter a packaged add-drop filter composed of a silica microsphere resonator and two fiber tapers is demonstrated theoretically and experimentally. A two-step fabrication process using an UV curable polymer is shown to stabilize the microsphere resonator with a diameter of 153 µm coupled to two tapered microfibers with diameters of 1.5 µm which are used as add and drop ports. A high loaded quality factor (Q-factor) of 0.9×10(5) and a free spectral range (FSR) of about 104 pm are obtained at around 1550 nm from the microsphere for the parallel coupling tapered fibers in the add-drop configuration. This device has a range of advantages, such as ease of fabrication, low-cost, and compatibility with traditional and commercial fiber systems.

Integrated Nd-doped borosilicate glass microsphere laser.

A neodymium-doped BK7 glass microsphere laser integrated with a planar ion-exchanged waveguide pumped at 0.8 µm has been demonstrated. The pump radiation was launched by evanescent coupling from the waveguide, and the signal radiation was coupled out through the same waveguide, offering the potential for robustly assembled fully integrated active optical circuits. The dependence of the lasing spectra on pump power and wavelength were studied in detail to clarify the whispering-gallery-mode behavior at the pump and lasing wavelengths.

Optical excitation and probing of whispering gallery modes in bottle microresonators: potential for all-fiber add-drop filters.

We have investigated the optical excitation and probing of bottle microresonators experimentally, using fiber tapers. The channel-dropping characteristics of such devices are shown to depend on the excitation configuration. In addition, the axial leakage behavior of these microresonators is characterized.

Mirrorless buried waveguide laser in monoclinic double tungstates fabricated by a novel combination of ion milling and liquid phase epitaxy.

Buried channel waveguides were fabricated by liquid phase epitaxial growth of a lattice-matched KY(0.58)Gd(0.22)Lu(0.17)Tm(0.03)(WO4)2 film on a microstructured KY(WO4)2 substrate. Channels were transferred to the substrates by standard photolithography and Ar-ion milling. The bottom and sidewalls of the milled channels were smooth enough (rms roughness = 70 nm and 20 nm, respectively) to favour the epitaxial growth of the active layer without defects at the boundary of substrate/epitaxial layer. The refractive index contrast was sufficient to enable light confinement and guided modes with low scattering losses were observed at wavelengths between 1440 nm and 1640 nm. CW laser operation at 1840 nm at room temperature was observed with feedback provided only by Fresnel reflection at the end faces, with slope efficiencies of 4% and 9% for TE and TM polarizations, respectively.