Development and in-vitro evaluation of a potentially implantable fibre-optic glucose sensor probe
This source preferred by Glyn Hadley
Authors: Hadley, G.J.M.
Type I diabetics need regular injections of insulin to survive. Insulin allows the cells of the body to extract glucose from the blood supply to use as fuel. Without insulin the cells turn to other backup fuel sources,this can cause side effects that are quickly fatal or gradual wasting of the bodies tissues. The use of insulin, however, is not danger free, as an incorrect dosage can quickly lead to the reduction of glucose circulating in the blood to drop to a dangerously low level. Without glucose circulating in the blood supply the brain quickly runs out of fuel causing coma and death. Because of this, a means to constantly monitor blood glucose levels has been sought for the last two decades. With such a device, diabetics could judge the correct amount of insulin to inject and be warned of low blood glucose levels. However, to date no reliable portable system has been produced. Recent developments in fibre optic biosensor technology, suggested a possible route to achieves this goal. The work in this thesis presents the development and testing of such a sensor. The sensor presented in this thesis is based around a commercial fibre optic blood gas sensor, the Paratrend 7. The oxygen-sensing element of this device was modified into a glucose sensor using polymer membranes incorporating the enzymes glucose oxidase and catalase. The research was aimed at building a glucose sensor that could be developed into a working blood glucose sensor in the minimum amount of time if the research proved successful. For this reason the Paratrend 7 sensor system was chosen to provide a clinically tested sensor core around which the glucose sensor could be built. The initial experiment, which used a Paratrend7 sensor coated in polyHEMA and glucose oxidase, produced a sensor of diameter of 700µm with a range of 0 to 4mM/1 of glucose and a 90% response time of <100 seconds in a solution with a 15% oxygen tension. The sensor design was then developed to incorporate the enzyme catalase to protect the glucose oxidase and an outer diffusion limiting polyHEMA membrane. This produced a sensor with a range of 0 to 6 mM/l and a response time of <100 seconds. The method of coating the sensors was'then improved, through a series of stages, until an optomised dip coating technique was developed. This technique produced sensors with ranges (in 7.5KPa oxygen tension solutions) between 0 to 3mM/l and 0 to lOmM/1, responsetimes of <100 seconds in some cases and with diameters of 300µm. By using a partial polyurethane outer coat the range of the sensors was increased form 0 to 4mM/l up to 0 to 24mM/1, in one case, with 90% response times in the 100to 500 second range. The sensors were then sterilised using gamma radiation and their performance before and after sterilisation examined. The gamma sterilisation was found to cause a reduction in the range of the sensors,for example 0 to 24 m /I down to 0 to 14mM/l in one case. The affect of 24 hour operation in a 5mM/1 solution of glucose and storage, for up to three months, was then investigated. Both processes were found to reduce the operational range of the sensors,0 to 20 reduced to 0 to 15 mM/i, in one case,for 24 hour operation and form 0 to 15mM/1 reduced to 0 to 11mM/1in one case for a storage time of three months. The use of the enzymes glucose oxidase and catalase together in a fibre optic as can sensor has not been previously reported in the literature as far be ascertained. The comparison of sensor performance before and after gamma sterilisation also appears to be unique as does the gamma sterilisation of a fibre optic glucose sensor.