Novel approaches to engineer glucose biosensors

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.Designing a biosensor capable of continuously monitoring blood glucose concentration in people with diabetes has been a major challenge for over three decades. In this work we attempt to develop a novel microspike based minimally invasive biosensor for this purpose. Also, as a part of an ongoing study, we attempt to improve the current design of coil-type implantable biosensors. Microspikes, which are able to painlessly penetrate the skin layer, were fabricated using lithographic techniques and sputtered with gold to serve as an electrode. The biosensor design is based on thiomalic acid self-assembled monolayer (SAM) on which glucose oxidase was immobilised by a simple coupling technique together with a tetrathiafulvalene mediator entrapped in an epoxy-polyurethane permselective membrane. Functional testing revealed that such modified sensors are capable of detecting glucose concentration within the clinically relevant range. This was followed by studying the microspike based biosensors incorporated into the microfluidics platform mimicking the sensor behaviour in interstitial fluid. Data from these experiments revealed that the sensor response is mainly dependent on enzyme kinetics rather than membrane permeability to glucose. In contrast, an attempt to address the reproducibility issues of coil-type biosensors is presented. The hypothesis for this study was that a crosslinked hydrogel would have a sufficiently uniform porosity and hydrophilicity to address the variability in sensor sensitivity. The hydrogel was prepared by crosslinking di-hydroxyethyl methacrylate, hydroxyethyl methacrylate and N-vinyl pyrrolidone with 2.5 mol% ethylene glycol dimethacrylate using the water soluble initiators – ammonium persulphate and sodium metabisulfite under a nitrogen atmosphere. The hydrogel was applied to the sensor by dip coating during polymerisation. Electrochemical measurements revealed that the response characteristics of sensors coated with this membrane are highly consistent. Scanning Electrochemical Microscopy (SECM) was used to spatially resolve glucose diffusion through the membrane by measuring the consequent hydrogen peroxide release and compared with an epoxy- polyurethane membrane

Novel approaches to engineer glucose biosensors

Designing a biosensor capable of continuously monitoring blood glucose concentration in people with diabetes has been a major challenge for over three decades. In this work we attempt to develop a novel microspike based minimally invasive biosensor for this purpose. Also, as a part of an ongoing study, we attempt to improve the current design of coil-type implantable biosensors. Microspikes, which are able to painlessly penetrate the skin layer, were fabricated using lithographic techniques and sputtered with gold to serve as an electrode. The biosensor design is based on thiomalic acid self-assembled monolayer (SAM) on which glucose oxidase was immobilised by a simple coupling technique together with a tetrathiafulvalene mediator entrapped in an epoxy-polyurethane permselective membrane. Functional testing revealed that such modified sensors are capable of detecting glucose concentration within the clinically relevant range. This was followed by studying the microspike based biosensors incorporated into the microfluidics platform mimicking the sensor behaviour in interstitial fluid. Data from these experiments revealed that the sensor response is mainly dependent on enzyme kinetics rather than membrane permeability to glucose. In contrast, an attempt to address the reproducibility issues of coil-type biosensors is presented. The hypothesis for this study was that a crosslinked hydrogel would have a sufficiently uniform porosity and hydrophilicity to address the variability in sensor sensitivity. The hydrogel was prepared by crosslinking di-hydroxyethyl methacrylate, hydroxyethyl methacrylate and N-vinyl pyrrolidone with 2.5 mol% ethylene glycol dimethacrylate using the water soluble initiators – ammonium persulphate and sodium metabisulfite under a nitrogen atmosphere. The hydrogel was applied to the sensor by dip coating during polymerisation. Electrochemical measurements revealed that the response characteristics of sensors coated with this membrane are highly consistent. Scanning Electrochemical Microscopy (SECM) was used to spatially resolve glucose diffusion through the membrane by measuring the consequent hydrogen peroxide release and compared with an epoxy- polyurethane membrane.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

An integrated silicon sensor with microfluidic chip for monitoring potassium and pH

We present ion-sensitive field effect transistor-based sensors, integrated with a microfluidic chip, for monitoring pH and potassium cations. The sensor is strategically located at the base of a well so that the response time of the device depends both on the mean flow through the device and the diffusion coefficient of the analyte being monitored. This would enable monitoring of ions in the presence of larger molecules. The dependence of the device response time on diffusive transport of analytes was examined through a numerical study of the flow field and the passive diffusion of a chemical species. The predicted device response time was compared with the experimental measurements and reasonable agreement found. The general dependence of device response time on geometry, flow rate, and analyte diffusion coefficient was derived. These devices can be used with biological fluids where monitoring of pH and cations provide vital information about the well-being of patients. © 2010 Springer-Verlag

Reconstruction of primary vertices at the ATLAS experiment in Run 1 proton–proton collisions at the LHC

This paper presents the method and performance of primary vertex reconstruction in proton–proton collision data recorded by the ATLAS experiment during Run 1 of the LHC. The studies presented focus on data taken during 2012 at a centre-of-mass energy of √s=8 TeV. The performance has been measured as a function of the number of interactions per bunch crossing over a wide range, from one to seventy. The measurement of the position and size of the luminous region and its use as a constraint to improve the primary vertex resolution are discussed. A longitudinal vertex position resolution of about 30μm is achieved for events with high multiplicity of reconstructed tracks. The transverse position resolution is better than 20μm and is dominated by the precision on the size of the luminous region. An analytical model is proposed to describe the primary vertex reconstruction efficiency as a function of the number of interactions per bunch crossing and of the longitudinal size of the luminous region. Agreement between the data and the predictions of this model is better than 3% up to seventy interactions per bunch crossing

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements