Optical redox ratio and endogenous porphyrins in the detection of urinary bladder cancer:a patient biopsy analysis

Bladder cancer is among the most common cancers in the UK and conventional detection techniques suffer from low sensitivity, low specificity, or both. Recent attempts to address the disparity have led to progress in the field of autofluorescence as a means to diagnose the disease with high efficiency, however there is still a lot not known about autofluorescence profiles in the disease. The multi-functional diagnostic system "LAKK-M" was used to assess autofluorescence profiles of healthy and cancerous bladder tissue to identify novel biomarkers of the disease. Statistically significant differences were observed in the optical redox ratio (a measure of tissue metabolic activity), the amplitude of endogenous porphyrins and the NADH/porphyrin ratio between tissue types. These findings could advance understanding of bladder cancer and aid in the development of new techniques for detection and surveillance.

Optical in-fiber Bragg grating sensor systems for medical applications

Two in-fiber Bragg grating (FBG) temperature sensor systems for medical applications are demonstrated: (1) an FBG flow-directed thermodilution catheter based on interferometric detection of wavelength shift that is used for cardiac monitoring; and (2) an FBG sensor system with a tunable Fabry-Perot filter for in vivo temperature profiling in nuclear magnetic resonance (NMR) machines. Preliminary results show that the FBG sensor is in good agreement with electrical sensors that are widely used in practice. A field test shows that the FBG sensor system is suitable for in situ temperature profiling in NMR machines for medical applications.

Optical fibre sensors with applications in gas and biological sensing

This thesis describes the study of various grating based optical fibre sensors for applications in refractive index sensing. The sensitivity of these sensors has been studied and in some cases enhanced using novel techniques. The major areas of development are as follows. The sensitivity of long period gratings (LPGs) to surrounding medium refractive index (SRI) for various periods was investigated. The most sensitive period of LPG was found to be around 160 µm and this was due to the core mode coupling to a single cladding mode but phase matching at two wavelength locations, creating two attenuation peaks, close to the waveguide dispersion turning point. Large angle tilted fibre gratings (TFGs) have similar behaviour to LPGs, in that they couple to the co-propagating cladding modes. The tilted structure of the index modulation within the core of the fibre gives rise to a polarisation dependency, differing the large angle TFG from a LPG. Since the large angle TFG couple to the cladding mode they are SRI sensitive, the sensitivity to SRI can be further increased through cladding etching using HF acid. The thinning of the cladding layer caused a reordering of the cladding modes and shifted to more SRI sensitive cladding modes as the investigation discovered. In a SRI range of 1.36 to 1.40 a sensitivity of 506.9 nm/URI was achieved for the etched large angle TFG, which is greater than the dual resonance LPG. UV inscribed LPGs were coated with sol-gel materials with high RIs. The high RI of the coating caused an increase in cladding mode effective index which in turn caused an increase in the LPG sensitivity to SRI. LPGs of various periods of LPG were coated with sol-gel TiO2 and the optimal thickness was found to vary for each period. By coating of the already highly SRI sensitive 160µm period LPG (which is a dual resonance) with a sol-gel TiO2, the SRI sensitivity was further increased with a peak value of 1458 nm/URI, which was an almost 3 fold increase compared to the uncoated LPG. LPGs were also inscribed using a femtosecond laser which produced a highly focused index change which was no uniform throughout the core of the optical fibre. The inscription technique gave rise to a large polarisation sensitivity and the ability to couple to multiple azimuthal cladding mode sets, not seen with uniform UV inscribed gratings. Through coupling of the core mode to multiple sets of cladding modes, attenuation peaks with opposite wavelength shifts for increasing SRI was observed. Through combining this opposite wavelength shifts, a SRI sensitivity was achieved greater than any single observed attenuations peak. The maximum SRI achieved was 1680 nm/URI for a femtosecond inscribed LPG of period 400 µm. Three different types of surface plasmon resonance (SPR) sensors with a multilayer metal top coating were investigated in D shape optical fibre. The sensors could be separated into two types, utilized a pre UV inscribed tilted Bragg grating and the other employed a post UV exposure to generate surface relief grating structure. This surface perturbation aided the out coupling of light from the core but also changed the sensing mechanism from SPR to localised surface plasmon resonance (LSPR). This greatly increased the SRI sensitivity, compared to the SPR sensors; with the gold coated top layer surface relief sensor producing the largest SRI sensitivity of 2111.5nm/URI was achieved. While, the platinum and silver coated top layer surface relief sensors also gave high SRI sensitivities but also the ability to produce resonances in air (not previously seen with the SPR sensors). These properties were employed in two applications. The silver and platinum surface relief devices were used as gas sensors and were shown to be capable of detecting the minute RI change of different gases. The calculated maximum sensitivities produced were 1882.1dB/URI and 1493.5nm/URI for silver and platinum, respectively. Using a DFB laser and power meter a cheap alternative approach was investigated which showed the ability of the sensors to distinguish between different gases and flow rates of those gases. The gold surface relief sensor was coated in a with a bio compound called an aptamer and it was able to detect various concentrations of a biological compound called Thrombin, ranging from 1mM to as low as 10fM. A solution of 2M NaCl was found to give the best stripping results for Thrombin from the aptamer and showed the reusability of the sensor. The association and disassociation constants were calculated to be 1.0638×106Ms-1 and 0.2482s-1, respectively, showing the high affinity of the Aptamer to thrombin. This supports existing working stating that aptamers could be alternative to enzymes for chemical detection and also helps to explain the low detection limit of the gold surface relief sensor.

Advanced optical fibre gratings and applications

DUE TO COPYRIGHT RESTRICTIONS ONLY AVAILABLE FOR CONSULTATION AT ASTON UNIVERSITY LIBRARY AND INFORMATION SERVICES WITH PRIOR ARRANGEMENT This thesis describes a detailed study of advanced optical fibre sensors based on fibre Bragg grating (FBG), tilted fibre Bragg grating (TFBG) and long-period grating (LPG) and their applications in optical communications and sensing. The major contributions presented in this thesis are summarised below.The most important contribution from the research work presented in this thesis is the implementation of in-fibre grating based refractive index (RI) sensors, which could be the good candidates for optical biochemical sensing. Several fibre grating based RI sensors have been proposed and demonstrated by exploring novel grating structures and different fibre types, and employing efficient hydrofluoric acid etching technique to enhance the RI sensitivity. All the RI devices discussed in this thesis have been used to measure the concentration of sugar solution to simulate the chemical sensing. Efforts have also been made to overcome the RI-temperature cross-sensitivity for practical application. The demonstrated in-fibre grating based RI sensors could be further implemented as potential optical biosensors by applying bioactive coatings to realise high bio-sensitivity and bio-selectivity.Another major contribution of this thesis is the application of TFBGs. A prototype interrogation system by the use of TFBG with CCD-array was implemented to perform wavelength division multiplexing (WDM) interrogation around 800nm wavelength region with the advantages of compact size, fast detection speed and low-cost. As a high light, a novel in-fibre twist sensors utilising strong polarisation dependant coupling behaviour of an 81°-TFBG was presented to demonstrate the high torsion sensitivity and capability of direction recognition.

Analysis and optimisation of the performance of nonlinear optical communication systems

We investigate the feasibility of simultaneous suppressing of the amplification noise and nonlinearity, representing the most fundamental limiting factors in modern optical communication. To accomplish this task we developed a general design optimisation technique, based on concepts of noise and nonlinearity management. We demonstrate the immense efficiency of the novel approach by applying it to a design optimisation of transmission lines with periodic dispersion compensation using Raman and hybrid Raman-EDFA amplification. Moreover, we showed, using nonlinearity management considerations, that the optimal performance in high bit-rate dispersion managed fibre systems with hybrid amplification is achieved for a certain amplifier spacing – which is different from commonly known optimal noise performance corresponding to fully distributed amplification. Required for an accurate estimation of the bit error rate, the complete knowledge of signal statistics is crucial for modern transmission links with strong inherent nonlinearity. Therefore, we implemented the advanced multicanonical Monte Carlo (MMC) method, acknowledged for its efficiency in estimating distribution tails. We have accurately computed acknowledged for its efficiency in estimating distribution tails. We have accurately computed marginal probability density functions for soliton parameters, by numerical modelling of Fokker-Plank equation applying the MMC simulation technique. Moreover, applying a powerful MMC method we have studied the BER penalty caused by deviations from the optimal decision level in systems employing in-line 2R optical regeneration. We have demonstrated that in such systems the analytical linear approximation that makes a better fit in the central part of the regenerator nonlinear transfer function produces more accurate approximation of the BER and BER penalty. We present a statistical analysis of RZ-DPSK optical signal at direct detection receiver with Mach-Zehnder interferometer demodulation

Real-time detection of DNA interactions with long-period fiber-grating-based biosensor

Using an optical biosensor based on a dual-peak long-period fiber grating, we have demonstrated the detection of interactions between biomolecules in real time. Silanization of the grating surface was successfully realized for the covalent immobilization of probe DNA, which was subsequently hybridized with the complementary target DNA sequence. It is interesting to note that the DNA biosensor was reusable after being stripped off the hybridized target DNA from the grating surface, demonstrating a function of multiple usability.

A simple, sensitive and selective quantum-dot-based western blot method for the simultaneous detection of multiple targets from cell lysates

Quantum dots (Qdots) are fluorescent nanoparticles that have great potential as detection agents in biological applications. Their optical properties, including photostability and narrow, symmetrical emission bands with large Stokes shifts, and the potential for multiplexing of many different colours, give them significant advantages over traditionally used fluorescent dyes. Here, we report the straightforward generation of stable, covalent quantum dot-protein A/G bioconjugates that will be able to bind to almost any IgG antibody, and therefore can be used in many applications. An additional advantage is that the requirement for a secondary antibody is removed, simplifying experimental design. To demonstrate their use, we show their application in multiplexed western blotting. The sensitivity of Qdot conjugates is found to be superior to fluorescent dyes, and comparable to, or potentially better than, enhanced chemiluminescence. We show a true biological validation using a four-colour multiplexed western blot against a complex cell lysate background, and have significantly improved previously reported non-specific binding of the Qdots to cellular proteins.

Analytical first order comparison of amplitude and phase noise in single and dual Mach-Zehnder interferometer detection schemes for DQPSK transmission systems

An analytical first order calculation of the impact of Gaussian white noise on a novel single Mach-Zehnder Interferometer demodulation scheme for DQPSK reveals a constant Q factor ratio to the conventional scheme.

Two-dimensional optical power distribution of side-out-coupled radiation from tilted FBGs in multimode fibre

Two-dimensional optical power distribution of the out-coupled radiation from UV-inscribed tilted fibre Bragg gratings (TFBGs) in multimode fibre (MMF) has been side-detected with high spatial/spectral resolution, showing a near-identical radiation mode profile to that measured from the fibre-end detection method. A comparative investigation of the radiation characteristics of TFBGs fabricated in singlemode fibre (SMF) and MMF clearly indicates that the radiation out-coupling is stronger and spatially more confined in MMF. The unique spatial-to-spectral encoding property of the coupling mechanism offers potential application in low-cost WDM devices.

Long-period fibre grating based biosensor for detection of DNA hybridisation

We implement an optical biosensor using long-period fibre grating immobilised with probe DNA. It has been used to detect hybridisation of target DNA, showing a high sensitivity and reusability function.

Microstructures made in optical fiber with femtosecond laser

Different types of microstructures including microchannels and microslots were made in optical fibers using femtosecond laser inscription and chemical etching. Integrated with UV-inscribed fiber Bragg gratings, these microstructures have miniature, robustness and high sensitivity features and have been used to implement novel devices for various sensing applications. The fiber microchannels were used to detect the refractive index change of liquid presenting sensitivities up to 7.4 nm/refractive index unit (RIU) and 166.7 dB/RIU based on wavelength and power detection, respectively. A microslot-in-fiber based liquid core waveguide as a refractometer has been proposed and the device was used to measure refractive index, and a sensitivity up to 945 nm/RIU (10-6/pm) was obtained. By filling epoxy in the microslot and subsequent UV light curing, a hybrid waveguide grating structure with polymer core and glass cladding was fabricated. The obtained device was highly thermal responsive, demonstrating a linear coefficient of 211 pm/°C.

Spatial contrast sensitivity and external noise: applications to optical and neural modulation transfer functions

The thesis will show how to equalise the effect of quantal noise across spatial frequencies by keeping the retinal flux (If-2) constant. In addition, quantal noise is used to study the effect of grating area and spatial frequency on contrast sensitivity resulting in the extension of the new contrast detection model describing the human contrast detection system as a simple image processor. According to the model the human contrast detection system comprises low-pass filtering due to ocular optics, addition of light dependent noise at the event of quantal absorption, high-pass filtering due to the neural visual pathways, addition of internal neural noise, after which detection takes place by a local matched filter, whose sampling efficiency decreases as grating area is increased. Furthermore, this work will demonstrate how to extract both the optical and neural modulation transfer functions of the human eye. The neural transfer function is found to be proportional to spatial frequency up to the local cut-off frequency at eccentricities of 0 - 37 deg across the visual field. The optical transfer function of the human eye is proposed to be more affected by the Stiles-Crawford -effect than generally assumed in the literature. Similarly, this work questions the prevailing ideas about the factors limiting peripheral vision by showing that peripheral optical acts as a low-pass filter in normal viewing conditions, and therefore the effect of peripheral optics is worse than generally assumed.

Optical fibre sensors and their applications in the industrial weighing and aerospace industries

This thesis presents the design, fabrication and testing of novel grating based Optical Fibre Sensor (OFS) systems being interrogated using “off the shelf” interrogation systems, with the eventual development of marketable commercial systems at the forefront of the research. Both in the industrial weighing and aerospace industries, there has been a drive to investigate the feasibility of using optical fibre sensors being deployed where traditionally their electrical or mechanical counterparts would traditionally have been. Already, in the industrial weighing industry, commercial operators are deploying OFS-based Weigh-In-Motion (WIM) systems. Likewise, in the aerospace industry, OFS have been deployed to monitor such parameters as load history, impact detection, structural damage, overload detection, centre of gravity and the determination of blade shape. Based on the intrinsic properties of fibre Bragg gratings (FBGs) and Long Period Fibre Gratings (LPFGs), a number of novel OFS-based systems have been realised. Experimental work has shown that in the case of static industrial weighing, FBGs can be integrated with current commercial products and used to detect applied loads. The work has also shown that embedding FBGs in e-glass, to form a sensing patch, can result in said patches being bonded to rail track, forming the basis of an FBG-based WIM system. The results obtained have been sufficiently encouraging to the industrial partner that this work will be progressed beyond the scope of the work presented in this thesis. Likewise, and to the best of the author’s knowledge, a novel Bragg grating based systems for aircraft fuel parameter sensing has been presented. FBG-based pressure sensors have been shown to demonstrate good sensitivity, linearity and repeatability, whilst LPFG-based systems have demonstrated a far greater sensitivity when compared to FBGs, as well the advantage of being potentially able to detect causes of fuel adulteration based on their sensitivity to refractive index (RI). In the case of the LPFG-based system, considerable work remains to be done on the mechanical strengthening to improve its survivability in a live aircraft fuel tank environment. The FBG system has already been developed to an aerospace compliant prototype and is due to be tested at the fuel testing facility based at Airbus, Filton, UK. It is envisaged by the author that in both application areas, continued research in this area will lead to the eventual development of marketable commercial products.

High birefringence fibre interrogating interferometer for optical sensing applications

The use of high birefringence fiber interrogating interferometer for optical sensing applications was discussed. The method is of low cost and permits simple adjustment of the optical path difference and has much lower sensitivity to environmental perturbation. The polarization-maintaining (PM) fiber interferometer adopted a heterodyne approach using interferometric wavelength shift detection. The study showed that the inclusion of power amplifier driving a multi-element piezoelectric stack will enable the bandwidth to be pushed up into the kHz regime.

Drusen detection in retro-mode imaging by a scanning laser ophthalmoscope

Purpose: The Nidek F-10 is a scanning laser ophthalmoscope that is capable of a novel fundus imaging technique, so-called ‘retro-mode’ imaging. The standard method of imaging drusen in age-related macular degeneration (AMD) is by fundus photography. The aim of the study was to assess drusen quantification using retro-mode imaging. Methods: Stereoscopic fundus photographs and retro-mode images were captured in 31 eyes of 20 patients with varying stages of AMD. Two experienced masked retinal graders independently assessed images for the number and size of drusen, using purpose-designed software. Drusen were further assessed in a subset of eight patients using optical coherence tomography (OCT) imaging. Results: Drusen observed by fundus photography (mean 33.5) were significantly fewer in number than subretinal deposits seen in retro-mode (mean 81.6; p < 0.001). The predominant deposit diameter was on average 5 µm smaller in retro-mode imaging than in fundus photography (p = 0.004). Agreement between graders for both types of imaging was substantial for number of deposits (weighted ? = 0.69) and moderate for size of deposits (weighted ? = 0.42). Retro-mode deposits corresponded to drusen on OCT imaging in all eight patients. Conclusion: The subretinal deposits detected by retro-mode imaging were consistent with the appearance of drusen on OCT imaging; however, a larger longitudinal study would be required to confirm this finding. Retro-mode imaging detected significantly more deposits than conventional colour fundus photography. Retro-mode imaging provides a rapid non-invasive technique, useful in monitoring subtle changes and progression of AMD, which may be useful in monitoring the response of drusen to future therapeutic interventions.