The Glucose Sensor Measuring Hydrogen Peroxide by Polarographic Electrode with Immobilized Glucose Oxidase:Application to the Artificial Endocrine Pancreas

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We have developed a bedside type artificial endocrine pancreas, a closed loop control system, which consisted of a continuous blood glucose monitoring device, a microcomputer system, infusion pumps and a printer. In the microcomputer system, 4 major programs are compiled, the first is a glucose forecasting program which compensates the time delay of glucose measuring, the second is an insulin infusion program, the third is a glucose infusion program and the last is a self-adaptive control algorithm for adaptive blood glucose control. The validity of the system has been widely proven in clinical applications. In the conventional artificial endocrine pancreas system, continuous blood glucose measurement was conducted with a Technicon AutoAnalyzer II system using modified glucose-oxidase method, but its total blood sampling volume is rather large (72 ml/day). So in this study, in order to make the size of total artificial endocrine pancreas system smaller and to minimize blood sampling volume, we developed glucose sensor system for continuous glucose monitoring in whole blood glucose, by combining the immobilized glucose oxidase membrane with electrode which measures hydrogen peroxide, one of the reaction products, polarographically. Because the key components in making a low noise glucose sensor with long term stability is its membrane, Cuprophan 100PM ®,(hydrophilic, mean suspected pore size 30Å, membrane breadth 10±0.5 μm) was applied to cover the immobilized glucose oxidase and the hydrogen peroxide electrode was composed of platinum cathode and argent anode, and its diameter is as small as 4 mm. The efficacy of this glucose sensor system was studied with glucose or insulin challenges in anesthetized dogs. The characteristics of this glucose sensor were summerized as follows, 1) high specificity for glucose and a quick response to change of glucose concentration, 2) long term stability, low drift and low noise, 3) linearity and accuracy of measurement over full range of interest, 4) easy to operate and maintain, 5) high bioadaptability indicated by no adhesion of reticulocytes or platelets on membrane surface after long-term use. Although in this glucose sensor system, blood transmission tubing time inside the device was 3 minutes and 40 seconds, and response time in electrode was no less than 20 seconds, this 4 minutes time lag is short enough to detect the change in blood glucose level in order to infuse insulin or glucose timely. By using our glucose sensor system, the whole size of new bedside type artificial endocrine pancreas could be made as small as 50×51×151 cm, and also be minimized the sampling blood volume as small as 30 ml/day. The animal experiments and clinical applications also proved the efficacy of the new bedside type artificial endocrine pancreas.
Japan Society of Clinical Chemistryの論文

The Glucose Sensor Measuring Hydrogen Peroxide by Polarographic Electrode with Immobilized Glucose Oxidase:Application to the Artificial Endocrine Pancreas

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