Computational Fluorescence Suppression in Shifted Excitation Raman Spectroscopy.

Fiber-based Raman spectroscopy in the context of in vivo biomedical application suffers from the presence of background fluorescence from the surrounding tissue that might mask the crucial but inherently weak Raman signatures. One method that has shown potential for suppressing the background to reveal the Raman spectra is shifted excitation Raman spectroscopy (SER). SER collects multiple emission spectra by shifting the excitation by small amounts and uses these spectra to computationally suppress the fluorescence background based on the principle that Raman spectrum shifts with excitation while fluorescence spectrum does not. We introduce a method that utilizes the spectral characteristics of the Raman and fluorescence spectra to estimate them more effectively, and compare this approach against existing methods on real world datasets.

Tri-mode optical biopsy probe with fluorescence endomicroscopy, Raman spectroscopy, and time-resolved fluorescence spectroscopy.

We present an endoscopic probe that combines three distinct optical fibre technologies including: A high-resolution imaging fibre for optical endomicroscopy, a multimode fibre for time-resolved fluorescence spectroscopy, and a hollow-core fibre with multimode signal collection cores for Raman spectroscopy. The three fibers are all enclosed within a 1.2 mm diameter clinical grade catheter with a 1.4 mm end cap. To demonstrate the probe's flexibility we provide data acquired with it in loops of radii down to 2 cm. We then use the probe in an anatomically accurate model of adult human airways, showing that it can be navigated to any part of the distal lung using a commercial bronchoscope. Finally, we present data acquired from fresh ex vivo human lung tissue. Our experiments show that this minimally invasive probe can deliver real-time optical biopsies from within the distal lung - simultaneously acquiring co-located high-resolution endomicroscopy and biochemical spectra.

Containing a sustainable urbanized environment through SuDS devices in management trains.

Generating an effective and efficient sustainable drainage philosophy is imperative in alleviating the risk of flooding in a complex UK climate that is categorised by excessive rainfall. The Sustainable Drainage Systems (SuDS) approach offers a revolutionary change in using heightened flow rates and large capacities of water to our advantage, while also disguising the attenuated water into the urbanized environment. This research explores the result of integrating several SuDS devices in management trains with the sole purpose of significantly reducing overall water quantity. It will compare and contrast and prove how SuDS is more dependable than the conventional pipe-based drainage system that is characterized by its ability to remove water to the outflow quickly. Furthermore, in order to determine how a SuDS device is implemented into the natural environment, a case study was conducted at a residential area in Gibside View, Winlaton in Gateshead. The research exhibits how the newly implemented Detention basin had to be retrofitted into the already inadequate drainage system that once lived there; all in thought of alleviating the significant flooding events that were once reported to have occurred prior. As a verification method in terms of effectiveness, a questionnaire was conducted through convenient and purposive sampling at the Case Study location; data was accumulated door-to-door inside a 300 m radius of the detention basin and received about 180 valid responses. The results showed persistence of respondents who detailed flooding events prior to installing the Detention basin, who then recognised a fundamental change in the minimization of water quantity and flooding issues. The results of this research showed why Detention Basins continue to be identified as one of the most successful water reduction-based SuDS devices available for development nationwide implementation.

Sub millimetre flexible fibre probe for background and fluorescence free Raman spectroscopy.

Using the shifted-excitation Raman difference spectroscopy technique and an optical fibre featuring a negative curvature excitation core and a coaxial ring of high numerical aperture collection cores, we have developed a portable, background and fluorescence free, endoscopic Raman probe. The probe consists of a single fibre with a diameter of less than 0.25 mm packaged in a sub-millimetre tubing, making it compatible with standard bronchoscopes. The Raman excitation light in the fibre is guided in air and therefore interacts little with silica, enabling an almost background free transmission of the excitation light. In addition, we used the shifted-excitation Raman difference spectroscopy technique and a tunable 785 nm laser to separate the fluorescence and the Raman spectrum from highly fluorescent samples, demonstrating the suitability of the probe for biomedical applications. Using this probe we also acquired fluorescence free human lung tissue data.

Molecular detection of Gram-positive bacteria in the human lung through an optical fiber-based endoscope.

PURPOSE: The relentless rise in antimicrobial resistance is a major societal challenge and requires, as part of its solution, a better understanding of bacterial colonization and infection. To facilitate this, we developed a highly efficient no-wash red optical molecular imaging agent that enables the rapid, selective, and specific visualization of Gram-positive bacteria through a bespoke optical fiber-based delivery/imaging endoscopic device. METHODS: We rationally designed a no-wash, red, Gram-positive-specific molecular imaging agent (Merocy-Van) based on vancomycin and an environmental merocyanine dye. We demonstrated the specificity and utility of the imaging agent in escalating in vitro and ex vivo whole human lung models (n = 3), utilizing a bespoke fiber-based delivery and imaging device, coupled to a wide-field, two-color endomicroscopy system. RESULTS: The imaging agent (Merocy-Van) was specific to Gram-positive bacteria and enabled no-wash imaging of S. aureus within the alveolar space of whole ex vivo human lungs within 60 s of delivery into the field-of-view, using the novel imaging/delivery endomicroscopy device. CONCLUSION: This platform enables the rapid and specific detection of Gram-positive bacteria in the human lung.

Time-Resolved Spectroscopy of Fluorescence Quenching in Optical Fibre-Based pH Sensors.

Numerous optodes, with fluorophores as the chemical sensing element and optical fibres for light delivery and collection, have been fabricated for minimally invasive endoscopic measurements of key physiological parameters such as pH. These flexible miniaturised optodes have typically attempted to maximize signal-to-noise through the application of high concentrations of fluorophores. We show that high-density attachment of carboxyfluorescein onto silica microspheres, the sensing elements, results in fluorescence energy transfer, manifesting as reduced fluorescence intensity and lifetime in addition to spectral changes. We demonstrate that the change in fluorescence intensity of carboxyfluorescein with pH in this "high-density" regime is opposite to that normally observed, with complex variations in fluorescent lifetime across the emission spectra of coupled fluorophores. Improved understanding of such highly loaded sensor beads is important because it leads to large increases in photostability and will aid the development of compact fibre probes, suitable for clinical applications. The time-resolved spectral measurement techniques presented here can be further applied to similar studies of other optodes.

Ultrafast-laser-ablation-assisted spatially selective attachment of fluorescent sensors onto optical fibers.

A robust method to selectively attach specific fluorophores onto the individual cores of a multicore fiber is reported in this Letter. The method is based on the use of ultrafast laser pulses to nanostructure the facet of the fiber core, followed by amine functionalization and sensor conjugation. This surface-machining protocol not only enables precise spatial selectivity, but it also facilitates high deposition densities of the sensor moieties. As a proof of concept, the successful deposition of three different fluorophores onto selected cores of a multicore fiber is demonstrated. The protocol was developed to include attachment of a fluorescence-based pH sensor using the ratiometric carboxynapthofluorescein.

High fidelity fibre-based physiological sensing deep in tissue.

Physiological sensing deep in tissue remains a clinical challenge. Here a flexible miniaturised sensing optrode providing a platform to perform minimally invasive in vivo in situ measurements is reported. Silica microspheres covalently coupled with a high density of ratiometrically configured fluorophores were deposited into etched pits on the distal end of a 150 µm diameter multicore optical fibre. With this platform, photonic measurements of pH and oxygen concentration with high precision in the distal alveolar space of the lung are reported. We demonstrated the phenomenon that high-density deposition of carboxyfluorescein covalently coupled to silica microspheres shows an inverse shift in fluorescence in response to varying pH. This platform delivered fast and accurate measurements (±0.02 pH units and ±0.6 mg/L of oxygen), near instantaneous response time and a flexible architecture for addition of multiple sensors.

Controlled core-to-core photo-polymerisation - fabrication of an optical fibre-based pH sensor.

The fabrication of fluorescence-based pH sensors, embedded into etched pits of an optical fibre via highly controllable and spatially selective photo-polymerisation is described and the sensors validated.

Quantitative characterization of endoscopic imaging fibers.

We describe a technique for the quantitative characterization of endoscopic imaging fibers using an interference pattern as the standard object to be imaged. The visibility of the pattern at the other end of the fiber is then analyzed as wavelength and fringe period are varied. We demonstrate the use of the technique by comparing three fibers: two fabricated in-house from the same preform, designed to minimize inter-core coupling at visible wavelengths less than 650 nm, and a commercial imaging fiber. The techniques discussed are currently being used to optimize fibers for fluorescence bronchoscopy to be used in intensive care clinics.

Long-term psychiatric morbidity in the aftermath of CS spray trauma.

The physical effects of CS spray are well documented. However, less is known about the impact of its use by the police on the psychological health of those exposed. In this study we explored the psychiatric morbidity of a group of 30 individuals who experienced the same trauma, a significant part of which was exposure to CS spray. Just over a quarter suffered post-traumatic stress disorder. It is proposed that more attention needs to be paid to the psychological effects of the use of CS spray by the police. Consistent with other studies, a past psychiatric history and a more external locus of control was associated with post-traumatic morbidity. The latter finding may have implications for psychological interventions after exposure to trauma.