Modified hydrogel matrices in fibre optic sensors

Common problems encountered in clinical sensing are those of non-biocompatibility, and slow response time of the device. The latter, also applying to chemical sensors, is possibly due to a lack of understanding of polymer support or membrane properties and hence failure to optimise membranes chosen for specific sensor applications. Hydrogels can be described as polymers which swell in water. In addition to this, the presence of water in the polymer matrix offers some control of biocompatibility. They thus provide a medium through which rapid transport of a sensed species to an incorporated reagent could occur. This work considers the feasibility of such a system, leading to the design and construction of an optical sensor test bed. The development of suitable membrane systems and of suitable coating techniques in order to apply them to the fibre optics is described. Initial results obtained from hydrogel coatings implied that the refractive index change in the polymer matrix, due to a change in water content with pH is the major factor contributing to the sensor response. However the presence of the colourimetric reagent was also altering the output signal obtained. An analysis of factors contributing to the overall response, such as colour change and membrane composition were made on both the test bed, via optical response, and on whole membranes via measurement of water content change. The investigation of coatings with low equilibrium water contents, of less than 10% was carried out and in fact a clearer signal response from the test bed was noted. Again these membranes were suprisingly responding via refractive index change, with the reagent playing a primary role in obtaining a sensible or non-random response, although not in a colourimetric fashion. A photographic study of these coatings revealed some clues as to the physical nature of these coatings and hence partially explained this phenomenon. A study of the transport properties of the most successful membrane, on a coated wire electrode and also on the fibre optic test bed, in a series of test environments, indicated that the reagent was possibly acting as an ion exchanger and hence having a major influence on transport and therefore sensor characteristics.

The temperature dependence of the electro-optic kerr effect in solutions

A novel Kerr cell of greater optical path length and temperature stability has been designed and built. The Kerr effect experimental has been substantially automated using an Apple IIe computer. Software has been written allowing the computer to partially control the Kerr effect equipment and to acquire and analyse the relevant data.The temperature dependent electro-optic Kerr effect of 2-methyl-4-nitroaniline, p-nitroaniline, nitrobenzene, aniline, and toluene as solutions in 1, 4-dioxane has been studied. The Kerr effect measurements combined with dipole moment, depolarisation ratio, dielectric, and electronic polarisation measurements have been used to calculate the first hyperpolarisability of the solute.Although first hyperpolarisabilities for the compounds studied have been measured in various physical states using a variety of experimental techniques, it is gratifying to find that the values presented in this thesis have a linear relationship with values reported by other workers.

Effect of dopamine on synchronous neuronal oscillations in the globus pallidus-subthalamic nucleus network

Changes in the pattern of activity of neurones within the basal ganglia are relevant in the pathophysiology and symptoms of Parkinson’s disease. The globus pallidus (GP) – subthalamic nucleus (STN) network has been proposed to form a pacemaker driving regenerative synchronous bursting activity. In order to test whether this activity can be sustained in vitro a 20o parasagittal slice of mouse midbrain was developed which preserved functional connectivity between the STN and GP. Mouse STN and GP cells were characterised electrophysiologically by the presence or absence of a voltage sag in response to hyperpolarising current steps indicative of Ih and the presence of rebound depolarisations. The presence of evoked and spontaneous post-synaptic GABA and glutamatergic currents indicated functional connectivity between the STN and GP. In control slices, STN cells fired action potentials at a regular rate, activity which was unaffected by bath application of the GABAA receptor antagonist picrotoxin (50 μM) or the glutamate receptor antagonist CNQX (10 μM). Paired extracellular recordings of STN cells showed uncorrelated firing. Oscillatory burst activity was induced pharmacologically using the glutamate receptor agonist, NMDA (20 μM), in combination with the potassium channel blocker apamin (50 -100 nM). The burst activity was unaffected by bath application of picrotoxin or CNQX while paired STN recordings showed uncorrelated activity indicating that the activity is not produced by the neuronal network. Thus, no regenerative activity is evident in this mouse brain preparation, either in control slices or when bursting is pharmacologically induced, suggesting the requirement of other afferent inputs that are not present in the slice. Using single-unit extracellular recording, dopamine (30 μM) produced an excitation of STN cells. This excitation was independent of synaptic transmission and was mimicked by both the Dl-like receptor agonist SKF38393 (10 μM) and the D2-like receptor agonist quinpirole (10 μM). However, the excitation was partially reduced by the D1-like antagonist SCH23390 (2 μM) but not by the D2-like antagonists sulpiride (10 μM) and eticlopride (10 μM). Using whole-recordings, dopamine was shown to induce membrane depolarisation. This depolarisation was caused either by a D1-like receptor mediated increase in a conductance which reversed at -34 mV, consistent with a non-specific cation conductance, or a D2-like receptor mediated decrease in conductance which reversed around -100 mV, consistent with a potassium conductance. Bath application of dopamine altered the pattern of the burst-firing produced by NMDA an apamin towards a more regular pattern. This effect was associated with a decrease in amplitude and ll1crease in frequency of TTX-resistant plateau potentials which underlie the burst activity.

The combination of smart hydrogels and fibre optic sensor technology for analyte detection

The subject of investigation of the present research is the use of smart hydrogels with fibre optic sensor technology. The aim was to develop a costeffective sensor platform for the detection of water in hydrocarbon media, and of dissolved inorganic analytes, namely potassium, calcium and aluminium. The fibre optic sensors in this work depend upon the use of hydrogels to either entrap chemotropic agents or to respond to external environmental changes, by changing their inherent properties, such as refractive index (RI). A review of current fibre optic technology for sensing outlined that the main principles utilised are either the measurement of signal loss or a change in wavelength of the light transmitted through the system. The signal loss principle relies on changing the conditions required for total internal reflection to occur. Hydrogels are cross-linked polymer networks that swell but do not dissolve in aqueous environments. Smart hydrogels are synthetic materials that exhibit additional properties to those inherent in their structure. In order to control the non-inherent properties, the hydrogels were fabricated with the addition of chemotropic agents. For the detection of water, hydrogels of low refractive index were synthesized using fluorinated monomers. Sulfonated monomers were used for their extreme hydrophilicity as a means of water sensing through an RI change. To enhance the sensing capability of the hydrogel, chemotropic agents, such as pH indicators and cobalt salts, were used. The system comprises of the smart hydrogel coated onto an exposed section of the fibre optic core, connected to the interrogation system measuring the difference in the signal. Information obtained was analysed using a purpose designed software. The developed sensor platform showed that an increase in the target species caused an increase in the signal lost from the sensor system, allowing for a detection of the target species. The system has potential applications in areas such as clinical point of care, water detection in fuels and the detection of dissolved ions in the water industry.

Fibre Bragg grating sensor interrogation using an acousto-optic tunable filter and low-coherence interferometry

We describe how an acousto-optic tunable filter can be used to both demultiplex the signals from multiple fibre Bragg grating sensors and simultaneously provide wide bandwidth signal demodulation in a system using interferometric wavelength shift detection. In an experimental demonstration, the approach provided a noise limited strain resolution of 24.9 n epsilon Hz(-1/ 2) at 15 Hz.

Autonomic dysfunction and systemic oxidative stress associated with glaucomatous optic neuropathy

There were four principal sections to the work: 1. Investigation of ocular and systemic vascular risk factors in POAG. The principal findings of this work were: a). Glaucoma patients exhibit an anticipatory reaction to the physical stress, similar to subjects at risk for cardiovascular diseases; a blunted BP response and a reduction in ONH blood flow in response to cold provocation was also recorded. b). Silent myocardial ischaemic episodes occurred during peaks in systemic BP and HR. c). Independent of a positive history for cardiovascular diseases, patients suffering from POAG demonstrate a blunt circadian rhythm of the ANS. 2. Assessment of the relationship between vascular and systemic vascular risk factors in GON. The principal findings of this work were: a). POAG patients demonstrate a high sympathetic tonus over a 24-h period. b). POAG patients with lower OBF demonstrate both 24-h systemic BP and HRV abnormalities. c). OBF alterations observed in some glaucoma patients could be either primary or secondary to systemic haemodynamic disturbances and not a consequence of ONH damage. 3. Assessment of the level of systemic anti-oxidant defence in POAG patients. The principal finding of this work was: Patients suffering from POAG demonstrated significantly lower GSH and t-GSH levels than normal controls. 4. Investigation of the effect of treatment with latanoprost 0.005% on visual function and OBF. The findings of this work were: a). Treatment with latanoprost 0.005% resulted in a significant decrease in IOP and increase in OPP. VF damage progression has also been stopped. b). Treatment with latanoprost 0.005% resulted in a significant increase in the OBF parameters measured at the ONH and peripapillary retina levels. Finally, the importance of a clear protocol for managing new POAG cases is highlighted and a clinical conduit is proposed.

Topographic, haemodynamic and psychophysical investigation of glaucomatous optic neuropathy

Loss of optic nerve head (ONH) axons in primary open angle glaucoma (POAG) has been attributed to both mechanical and vascular factors. Confocal scanning laser ophthalmoscopy (cSLO) provides a promising tool for the topographic follow-up of the ONH in glaucoma, while scanning laser Doppler flowmetry (SLDF) facilitates the rapid non-invasive assessment of retinal capillary blood flow. The purposes of these investigations were to optimise the techniques and explore their potential to classify and monitor disease. Preliminary investigations explored the reproducibility and validity of cSLO and SLDF and showed that: For cSLO: In a model eye, measurements are accurate over a range of axial lengths. For best reproducibility, seven images per visit are required, with a contour line located on Elschnig's scleral ring and transferred automatically between images. For SLDF: Three perfusion images are required for optimum reproducibility. Physiological changes induced by gas perturbation can be measured. Cross-sectional comparison of groups of normal subjects and early POAG patients showed that: cSLO parameters differentiate the early POAG group. Blood volume measured by SLDF showed group differences in superior nasal retina only. Longitudinal investigation of ONH topography, haemodynamic and visual field indices in normal subjects and POAG patients showed that: cSLO detects topographical change over time more frequently in the POAG group. Important parameters include: C:D area ratio, cup and rim area, mean depth in contour, volumes above and below reference and surface. Factor analysis identified "cup" and "rim" factors that can be used to detect change over time in individual patients. Blood flow changes were most apparent in the inferior nasal peripapillary retina of the POAG group. Perimetry is of clinical value for the identification of glaucoma but is less sensitive than cSLO for monitoring glaucomatous change.

Optic sensors of high refractive-index responsivity and low thermal cross sensitivity that use fiber Bragg gratings of >80° tilted structures

For the first time to the authors' knowledge, fiber Bragg gratings (FBGs) with >80° tilted structures have been fabricated and characterized. Their performance in sensing temperature, strain, and the surrounding medium's refractive index was investigated. In comparison with normal FBGs and long-period gratings (LPGs), >80° tilted FBGs exhibit significantly higher refractive-index responsivity and lower thermal cross sensitivity. When the grating sensor was used to detect changes in refractive index, a responsivity as high as 340nm/refractive-index unit near an index of 1.33 was demonstrated, which is three times higher than that of conventional LPGs.

Fibre optic sensors for high speed hypervelocity impact studies and low velocity drop tests

The initial aim of this project was to develop a non-contact fibre optic based displacement sensor to operate in the harsh environment of a 'Light Gas Gun' (LGG), which can 'fire' small particles at velocities ranging from 1-8.4 km/s. The LGG is used extensively for research in aerospace to analyze the effects of high speed impacts on materials. Ideally the measurement should be made close to the centre of the impact to minimise corruption of the data from edge effects and survive the impact. A further requirement is that it should operate at a stand-off distance of ~ 8cm. For these reasons we chose to develop a pseudo con-focal intensity sensor, which demonstrated resolution comparable with conventional PVDF sensors combined with high survivability and low cost. A second sensor was developed based on 'Fibre Bragg Gratings' (FBG) which although requiring contact with the target the low weight and very small contact area had minimal effect on the dynamics of the target. The FBG was mounted either on the surface of the target or tangentially between a fixed location. The output signals from the FBG were interrogated in time by a new method. Measurements were made on composite and aluminium plates in the LGG and on low speed drop tests. The particle momentum for the drop tests was chosen to be similar to that of the particles used in the LGG.

Optic disc haemorrhage audit

Poster section INTRODUCTION. Retrospective Analysis PURPOSE. To evaluate the morphology and location of optic disc haemorrhages (ODH) identified at diabetic retinopathy (DR) screening to establish whether particular ODH are predictive of ocular disease (e.g. glaucoma). METHODS. Retrospective analysis of 77 patients who presented with ODH at DR screening in the Birmingham and Black Country screening programme between June 2009-March 2010. Mean age was 71 years (range 39-89). Cup/disc ratio (CDR), location and morphology of the haemorrhage were recorded. The outcome of the referral and the status of the ODH were followed up a year later. RESULTS. Of the 77 referred, 34 patients were unassessed for possible glaucoma. Of the 43 patients that were assessed in the hospital eye service for glaucoma, 11 (26%) were diagnosed with glaucoma. These glaucoma patients mostly presented with flame haemorrhages (64%) and blot haemorrhages (36%). Haemorrhages tended to adjoin the margin of the OD (64%), and were more commonly flame shaped (64%). They less commonly occurred in the optic disc itself (36%), and were all blot shaped. The OD Cup/disc ratio (CDR) of the patients with glaucoma (n=11) ranged from 0.33-0.57. It is interesting to note the highest CDR was 0.68 in the 77 patients referred. 32 patients were confirmed as not having glaucoma. 24 (75%) of these patients presented with an ODH adjoining the margin, of which 20 (83%) were flame, and 4 blot (17%) shaped. Only 8 (25%) presented with an ODH in the OD, of which 6 (75%) were blot shaped. One year follow up of the 77 referred cases revealed that the ODH resolved in 45 (57%) patients while 10 (13%) still had an ODH present. 15 (21%) were still under ophthalmology hence digital retinal photos were not available for assessment. Six patients (8%) (age range 71-91 years) died within the year, and one lost to follow up. CONCLUSIONS. The results suggest that a significant number of patients with ODH have glaucoma and that the differing morphology of the haemorrhage is not a major predictor i.e. blot versus flame shaped, adjoining or in the optic disc. The cup/disc ratio did not predict glaucoma either.

The significance of microaneurysms and haemorrhages within one optic disc diameter of the fovea

Free paper session INTRODUCTION. Microaneurysms and haemorrhages within the macula area are a poor predictor of macular oedema as shown by optical coherence tomography (OCT). Our research suggests that it is safe and cost effective to screen patients who present with these surrogate markers annually. PURPOSE. To determine whether microaneurysms (ma) and haemorrhages (hm) within one optic disc diameter of the fovea (ma/hm<1DD) are significant predictors of macular oedema. METHODS. Data were collected over a one-year period from patients attending digital diabetic retinopathy screening. Patients who presented with ma/hm<1DD also had an OCT scan. The fast macula scan on the Stratus OCT was used and an ophthalmologist reviewed the scans to determine whether macular oedema was present. Macular oedema was identified by thickening on the OCT cross-sections. Patients were split into two groups. Group one (325 eyes) included those with best VA?6/9 and group two (30 eyes) with best VA =6/12. Only patients who had no other referable features of diabetic retinopathy were selected. RESULTS. In group one, 6 (1.8%) out of 325 eyes showed thickening on the OCT and were referred to hospital eye service (HES) for further investigation. In group two, 6 (20%) out of 30 eyes showed thickening and were referred to HES. CONCLUSIONS. Ma/hm<1DD become more significant predictors of macular oedema when VA is reduced. Results confirm the grading criteria concerning microaneurysms predicting macular oedema for referable maculopathy in the English national screening programme. OCT is a useful method to accurately identify patients requiring referral to HES.

A sulphonate based hydrogel for nucleus pulposus repair

Introduction: Lower back pain treatment and compensation costs >$80 billion overall in the US. 75% of back pain is due to disc degeneration in the lumbar region of the spine. Current treatment comprises of painkillers and bed rest or as a more radical solution – interbody cage fusion. In the early stages of disc degeneration the patient would benefit from addition of an injectable gel which polymerises in situ to support the degenerated nucleus pulposus. This involves a material which is an analogue of the natural tissue capable of restoring the biomechanical properties of the natural disc. The nucleus pulposus of the intervertebral disc is an example of a natural proteoglycan consisting of a protein core with negatively charged keratin and chondroitin sulphate attached. As a result of the high fixed charge density of the proteoglycan, the matrix exerts an osmotic swelling pressure drawing sufficient water into support the spinal system. Materials and Methods: NaAMPs (sodium 2- acrylamido 2-methyl propane sulphonic acid) and KSPA (potassium 3- sulphopropyl acrylate) were selected as monomers, the sulphonate group being used to mimic the natural sulphate group. These are used in dermal applications involving chronic wounds and have acceptably low cytotoxicity. Other hydrophilic carboxyl, amide and hydroxyl monomers such as 2-hydroxyethyl acrylamide, ß-carboxyethyl acrylate, acryloyl morpholine, and polyethylene glycol (meth)acrylate were used as diluents together with polyethyleneglycol di(meth)acrylate and hydrophilic multifunctional macromers as cross-linker. Redox was the chosen method of polymerisation and a range of initiators were investigated. Components were packaged in two solutions each containing a redox pair. A dual syringe method of injection into the cavity was used, the required time for polymerisation is circa 3-7 minutes. The final materials were tested using a Bohlin CVO Rheometer cycling from 0.5-25Hz at 37oC to measure the modulus. An in-house compression testing method was developed, using dialysis tubing to mimic the cavity, the gels were swelled in solutions of various osmolarity and compressed to ~ 20%. The pre-gel has also been injected into sheep spinal segments for mechanical compression testing to demonstrate the restoration of properties upon use of the gel. Results and Discussion: Two systems resulted using similar monomer compositions but different initiation and crosslinking agents. NaAMPs and KSPA were used together at a ratio of ~1:1 in both systems with 0.25-2% crosslinking agent, diacrylate or methacrylate. The two initiation systems were ascorbic acid/oxone, and N,N,N,N - tetramethylethylenediamine (TEMED)/ potassium persulphate. These systems produced gelation within 3-7 and 3-5 minutes respectively. Storage of the two component systems was shown to be stable for approximately one month after mixing, in the dark, refrigerated at 1-4oC. The gelation was carried out at 37oC. Literature values for the natural disc give elastic constants ranging from 3-8kPa. The properties of the polymer can be tailored by altering crosslink density and monomer composition and are able to match those of the natural disc. It is possible to incorporate a radio-opaque (histodenz) to enable x-ray luminescence during and after injection. At an inclusion level of 5% the gel is clearly visible and polymerisation and mechanical properties are not altered. Conclusion: A two-pac injection system which will polymerise in situ, that can incorporate a radio-opaque, has been developed. This will reinforce the damaged nucleus pulposus in degenerative disc disease restoring adequate hydration and thus biomechanical properties. Tests on sheep spine segments are currently being carried out to demonstrate that a disc containing the gel has similar properties to an intact disc in comparison to one with a damaged nucleus.

A quantitative analysis of optic nerve axons in elderly control subjects and patients with Alzheimer's disease

Objective: To study the density and cross-sectional area of axons in the optic nerve in elderly control subjects and in cases of Alzheimer's disease (AD) using an image analysis system. Methods: Sections of optic nerves from control and AD patients were stained with toluidine blue to reveal axon profiles. Results: The density of axons was reduced in both the center and peripheral portions of the optic nerve in AD compared with control patients. Analysis of axons with different cross-sectional areas suggested a specific loss of the smaller sized axons in AD, i.e., those with areas less that 1.99 μm2. An analysis of axons >11 μm2 in cross-sectional area suggested no specific loss of the larger axons in this group of patients. Conclusions: The data suggest that image analysis provides an accurate and reproducible method of quantifying axons in the optic nerve. In addition, the data suggest that axons are lost throughout the optic nerve with a specific loss of the smaller-sized axons. Loss of the smaller axons may explain the deficits in color vision observed in a significant proportion of patients with AD.

Respiratory function monitoring using a real-time three-dimensional fiber-optic shaping sensing scheme based upon fiber Bragg gratings

An array of in-line curvature sensors on a garment is used to monitor the thoracic and abdominal movements of a human during respiration. The results are used to obtain volumetric changes of the human torso in agreement with a spirometer used simultaneously at the mouth. The array of 40 in-line fiber Bragg gratings is used to produce 20 curvature sensors at different locations, each sensor consisting of two fiber Bragg gratings. The 20 curvature sensors and adjoining fiber are encapsulated into a low-temperature-cured synthetic silicone. The sensors are wavelength interrogated by a commercially available system from Moog Insensys, and the wavelength changes are calibrated to recover curvature. A three-dimensional algorithm is used to generate shape changes during respiration that allow the measurement of absolute volume changes at various sections of the torso. It is shown that the sensing scheme yields a volumetric error of 6%. Comparing the volume data obtained from the spirometer with the volume estimated with the synchronous data from the shape-sensing array yielded a correlation value 0.86 with a Pearson's correlation coefficient p <0.01.