Towards quantifying biomarkers for respiratory distress in preterm infants: Machine learning on mid infrared spectroscopy of lipid mixtures.

Neonatal respiratory distress syndrome (nRDS) is a challenging condition to diagnose which can lead to delays in receiving appropriate treatment. Mid infrared (IR) spectroscopy is capable of measuring the concentrations of two diagnostic nRDS biomarkers, lecithin (L) and sphingomyelin (S) with the potential for point of care (POC) diagnosis and monitoring. The effects of varying other lipid species present in lung surfactant on the mid IR spectra used to train machine learning models are explored.

Multiframe-based non-local means denoising for Raman spectra.

A method for denoising Raman spectra is presented in this paper. The approach is based on the principle that the original signal can be restored by averaging pixels based on structure similarity. Similarity searching and averaging are not limited to the neighbouring pixels but extended throughout the entire signal range across different frames.

Grating-incoupled waveguide-enhanced Raman sensor.

We report a waveguide-enhanced Raman spectroscopy (WERS) platform with alignment-tolerant under-chip grating input coupling. The demonstration is based on a 100-nm thick planar (slab) tantalum pentoxide (Ta2O5) waveguide and the use of benzyl alcohol (BnOH) and its deuterated form (d7- BnOH) as reference analytes. The use of grating couplers simplifies the WERS system by providing improved translational alignment tolerance, important for disposable chips, as well as contributing to improved Raman conversion efficiency.

Bi-frequency operation in a membrane external-cavity surface-emitting laser.

We report on the achievement of continuous wave bi-frequency operation in a membrane external-cavity surface-emitting laser (MECSEL), which is optically pumped with up to 4 W of 808 nm pump light. The presence of spatially specific loss of the intra-cavity high reflectivity mirror allows loss to be controlled on certain transverse cavity modes. The regions of spatially specific loss are defined through the removal of Bragg layers from the surface of the cavity high reflectivity mirror in the form of crosshair patterns with undamaged central regions, which are created using a laser ablation system incorporating a digital micromirror device (DMD).

Coherent waveguide laser arrays in semiconductor quantum well membranes.

Coherent laser arrays compatible with silicon photonics are demonstrated in a waveguide geometry in epitaxially grown semiconductor membrane quantum well lasers transferred on substrates of silicon carbide and oxidised silicon; we record lasing thresholds as low as 60 mW of pump power. We study the emission of single lasers and arrays of lasers in the sub-mm range. We are able to create waveguide laser arrays with modal widths of approximately 5 - 10 µm separated by 10 - 20 µm, using real and reciprocal space imaging we study their emission characteristics and find that they maintain their mutual coherence while operating on either single or multiple longitudinal modes per lasing cavity.

Artificial neural networks for material parameter extraction in terahertz time-domain spectroscopy.

Terahertz time-domain spectroscopy (THz-TDS) is a proven technique whereby the complex refractive indices of materials can be obtained without requiring the use of the Kramers-Kronig relations, as phase and amplitude information can be extracted from the measurement. However, manual pre-processing of the data is still required and the material parameters require iterative fitting, resulting in complexity, loss of accuracy and inconsistencies between measurements. Alternatively approximations can be used to enable analytical extraction but with a considerable sacrifice of accuracy.

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.

The Effect of Haematocrit on Measurement of the Mid-Infrared Refractive Index of Plasma in Whole Blood.

Recent advances suggest that miniaturised mid-infrared (MIR) devices could replace more time-consuming, laboratory-based techniques for clinical diagnostics. This work uses Fourier transform infrared spectroscopy to show that the MIR complex refractive index of whole blood varies across a range of haematocrit. This indicates that the use of an evanescent measurement is not sufficient to optically exclude the cellular content of blood in the MIR, as previously assumed.

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 (TaO) and silicon nitride (SiN), 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.

Waveguide Enhanced Raman Spectroscopy for Biosensing: A Review.

Waveguide enhanced Raman spectroscopy (WERS) utilizes simple, robust, high-index contrast dielectric waveguides to generate a strong evanescent field, through which laser light interacts with analytes residing on the surface of the waveguide. It offers a powerful tool for the direct identification and reproducible quantification of biochemical species and an alternative to surface enhanced Raman spectroscopy (SERS) without reliance on fragile noble metal nanostructures. The advent of low-cost laser diodes, compact spectrometers, and recent progress in material engineering, nanofabrication techniques, and software modeling tools have made realizing portable and cheap WERS Raman systems with high sensitivity a realistic possibility.

Optimized design for grating-coupled waveguide-enhanced Raman spectroscopy.

We report a new design optimization process for planar photonic waveguides applied to waveguide-enhanced Raman spectroscopy (WERS) that combines the optimization of both the surface intensity performance and the grating coupling efficiency. We consider the impact of film thickness on the grating coupling efficiency of two materials with different refractive indices, namely tantalum pentoxide (TaO) and silicon (Si). We propose a new figure-of-merit (FOM) that takes into account both the coupling efficiency and surface intensity dependence for Raman excitation on the film thickness.

Supercontinuum generation in tantalum pentoxide waveguides for pump wavelengths in the 900 nm to 1500 nm spectral region.

We characterize the spectral broadening performance in silica clad and unclad Tantalum pentoxide (TaO) waveguides as a function of the input pulse central wavelength and polarization, sweeping over a wavelength range from 900 nm to 1500 nm, with an average incident power of 110 mW. The waveguides are 0.7 µm high and between 2.

Ge on Si waveguide mid-infrared absorption spectroscopy of proteins and their aggregates.

Specific proteins and their aggregates form toxic amyloid plaques and neurofibrillary tangles in the brains of people suffering from neurodegenerative diseases such as Alzheimer's and Parkinson's. It is important to study these conformational changes to identify and differentiate these diseases at an early stage so that timely medication is provided to patients. Mid-infrared spectroscopy can be used to monitor these changes by studying the line-shapes and the relative absorbances of amide bands present in proteins.

Perspective on Thin Film Waveguides for on-Chip Mid-Infrared Spectroscopy of Liquid Biochemical Analytes.

Miniaturized spectrometers offering low cost, low reagent consumption, high throughput, sensitivity and automation are the future of sensing and have significant applications in environmental monitoring, food safety, biotechnology, pharmaceuticals, and healthcare. Midinfrared (MIR) spectroscopy employing complementary metal oxide semiconductor (CMOS) compatible thin film waveguides and microfluidics shows great promise toward highly integrated and robust detection tools and liquid handling. This perspective provides an overview of the emergence of thin film optical waveguides used for evanescent field sensing of liquid chemical and biological samples for MIR absorption spectroscopy.

Monolithically-integrated cytometer for measuring particle diameter in the extracellular vesicle size range using multi-angle scattering.

Size measurement of extracellular vesicles is hampered by the high cost and measurement uncertainty of conventional flow cytometers which is mainly due to the use of non-specialised free space optics. Integrated cytometry, where the optics and fluidics are embedded in a monolithic chip shows promise for the production of low cost, micro-flow cytometers dedicated for extracellular vesicle (EV) analysis with improved size measurement accuracy and precision. This research demonstrates a unique integrated cytometer for sub-micron particle size measurement using multi-angle scattering analysis.

Optical biosensors based on refractometric sensing schemes: A review.

Biosensor technology is an active field of research and development presenting rapid progress in recent decades, and the subfield of optical biosensors based on refractometric sensing schemes has developed dramatically during this time. This review focuses on advances in the refractometric sensing-based guided-wave optical biosensors particularly in the last two decades. It starts with a concise discussion on the underlying principles of label-free refractometric biosensor.

High index contrast photonic platforms for on-chip Raman spectroscopy.

Nanophotonic waveguide enhanced Raman spectroscopy (NWERS) is a sensing technique that uses a highly confined waveguide mode to excite and collect the Raman scattered signal from molecules in close vicinity of the waveguide. The most important parameters defining the figure of merit of an NWERS sensor include its ability to collect the Raman signal from an analyte, i.e.

Waveguide Absorption Spectroscopy of Bovine Serum Albumin in the Mid-Infrared Fingerprint Region.

Protein sensing in biological fluids provides important information to diagnose many clinically relevant diseases. Mid-infrared (MIR) absorption spectroscopy of bovine serum albumin (BSA) is experimentally demonstrated on a germanium on silicon (GOS) waveguide in the 1900-1000 cm (5.3-10.

FCM Software Aids Extracellular Vesicle Light Scatter Standardization.

The study of extracellular vesicles (EVs) is a rapidly growing field due to their great potential in many areas of clinical medicine including diagnostics, prognostics, theranostics, and therapeutics. Flow cytometry is currently one of the most popular methods of analyzing EVs due to it being a high-throughput, multiparametric technique, that is readily available in the majority of research labs. Despite its wide use, few commercial flow cytometers are designed specifically for the detection of EVs.

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.

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.

Extracellular Vesicle Flow Cytometry Analysis and Standardization.

The term extracellular vesicles (EVs) describes membranous vesicles derived from cells, ranging in diameter from 30 to 1,000 nm with the majority thought to be in the region of 100-150 nm. Due to their small diameter and complex and variable composition, conventional techniques have struggled to accurately count and phenotype EVs. Currently, EV characterization using high-resolution flow cytometry is the most promising method when compared to other currently available techniques, due to it being a high-throughput, single particle, multi-parameter analysis technique capable of analyzing a large range of particle diameters.

Complex refractive index spectra of whole blood and aqueous solutions of anticoagulants, analgesics and buffers in the mid-infrared.

Mid-infrared (MIR) spectroscopy is a powerful tool for characterising the vibrations of molecular bonds and is therefore ideal for label-free detection of chemical species. Recent research into thin-film deposition and etching techniques for mid-infrared materials shows potential for realising miniaturised bedside biosensors for clinical diagnostics exploiting MIR spectroscopy, to replace laboratory based-techniques. However, lack of refractive index information for commonly encountered biological media and analytes hampers optimisation of biosensor performance for maximum sensitivity, especially for devices exploiting evanescent spectroscopy.

Integrated optical waveguide-based fluorescent immunosensor for fast and sensitive detection of microcystin-LR in lakes: Optimization and Analysis.

Nowadays, biosensor technologies which can detect various contaminants in water quickly and cost-effectively are in great demand. Herein, we report an integrated channel waveguide-based fluorescent immunosensor with the ability to detect a maximum of 32 contaminants rapidly and simultaneously. In particular, we use waveguide tapers to improve the efficiency of excitation and collection of fluorescent signals in the presence of fluorophore photobleaching in a solid surface bioassay.

Surface and waveguide collection of Raman emission in waveguide-enhanced Raman spectroscopy.

We demonstrate Raman spectroscopy on a high index thin film tantalum pentoxide waveguide and compare collection of Raman emission from the waveguide end with that from the waveguide surface. Toluene was used as a convenient model analyte, and a 40-fold greater signal was collected from the waveguide end. Simulations of angular and spatial Raman emission distributions showed good agreement with experiments, with the enhancement resulting from efficient collection of power from dipoles near the surface into the high-index waveguide film and substrate, combined with long interaction length.