The Blood Glucose Sensor

The blood glucose sensor is the most successful commercial biosensor developed so far. It is used for home testing by individuals suffering from diabetes. About 5% of the population in western countries suffer from this condition and most of them are required to control their blood glucose level several times a day. Thus, a 

Typically, ferrocenium/ferrocene are used as oxidised/reduced mediator couple. In the absence of the mediator, oxygen, O2, and GOx (red.) react to form hydrogen peroxide, H2O2, and GOx (ox). The mediator ferrocene can be re-oxidised at the electrode at much less extreme potentials than H2O2 and thus background current from other blood components can be minimised. 

GOx has proven to be an almost ideal bioreceptor. It can be produced cheaply by soil fungi and it withstands greater extremes of pH, ionic strength and temperature than many other enzymes. Also it reacts readily over the concentration range of glucose encountered in human blood samples. Furthermore, the oxidation current is directly proportional to the amount of glucose in the sample. 

Opperating a sensor of the type shown in Fig. 5.19 is straightforward. A drop of blood is applied to a disposable electrode strip, which can be inserted into the device. The electrical current is read after 20 s and this is converted to a glucose concentration, which is then displayed on the instrument. 

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Biosensors with their oft-quoted (ideal) properties would seem to be ready partners for industrial analysts who want information at point-of-need, but as has been pointed out many times, few examples have had the same success as the blood glucose sensors for use in the home (albeit this is an example from medicine rather than industry). The reasons for this have also been pointed out many times, the principal one being that the development and manufacture of the blood glucose sensors is supported by the sadly huge market for diabetic testing and the large amount of investment capital which accrues to that market [6,7]. Further, blood is a sample of reasonably constant composition (in this context), the information is truly useful to the client and the desire for information at home means there is less competition from laboratory-based instruments. This is in contrast to the diverse requirements for analysis in the food industry (for example) which make up a series of... 

The advancement in our understanding of mediated enzyme electrochemistry since the pioneering work of Hill and colleagues can be easily appreciated when it is realised that a commercial blood glucose sensor, the size of a pen, became commercially available only about a decade later. 

The closed-loop system (often termed the artificial pancreas ) is essentially a more sophisticated version of the system described above. It consists not only of a pump and infusion device, but also of an integral glucose sensor and computer that analyses the blood glucose data obtained and adjusts the flow rate accordingly. The true potential of such systems remains to be assessed. 

Before dealing with the central topic, I would like to raise some further issues pertinent to it, and indeed to the development of thick-film sensors in general. Thick-film sensors are an important part of biosensor research because some blood glucose sensors for use in the home are made this way—if these are successful surely others can be Further, thick-film technology is not expensive and allows research laboratories to produce quickly, reasonably uniform devices in sufficient numbers for well replicated experiments. At the same time, some insight can be gained into the nature and demands of an industrial production process. 

The system does not display a glucose result for the first 10 h of operation to allow the equilibration of the sensor inside the body. The user is instructed to calibrate the sensor at hours 10, 12, 24, and 72, after insertion, by a blood glucose measurement. The blood glucose meter is built into the receiver, so the calibration is done automatically when a blood glucose measurement is made. After 5 days the user is instmcted to remove and dispose of the sensor support mount. The transmitter is reusable and contains replaceable batteries. The transmitter and mount are water resistant and can be worn during showers. The receiver is not water resistant because the receiver contains the open port for insertion of a blood glucose test strip. 

The first glucose sensors to be discovered were the pancreatic -cells in the islets of Langerhans these manufacture the hormone insulin and release it into the blood when glucose concentration rises. Islet tissue also contains a-cells, which manufacture the antagonistic hormone glucagon. Insulin secretion is a complex process, and the islet cells receive additional signals from the gut and the autonomic nervous system, which modulate the insulin release to match the food that has been eaten. 

The possibility of miniaturization and the use of optical beams for detection make nanophotonic structures suitable for medical analyte sensors for example to monitor the blood glucose level noninvasively. Another attractive configuration is to attach the nanophotonic structure to the distal end of an optical fiber for remote sensing such as in monitoring water quality. 

The physiological oxygen concentrations in arterial blood, 0.15 mmol/1, and venous blood, 0.01 mmol/1, are much lower than that of glucose (5-15 mmol/1). Continuous flow-through blood glucose sensors based on oxygen probes therefore exhibit a nonlinear current-concentration dependence (Layne et al., 1976). 

INSULIN PRODUCTION The islet of Langerhans contains four major ceU types, each of which synthesizes and secretes a distinct polypeptide hormone insulin in the j3 (B) cell, glucagon in the a (A) cell, somatostatin in the S (D) cell, and pancreatic polypeptide in the PP or F cell. The P cells make up 60-80% of the islet and form its central core with the a, 6 and F cells in a discontinuous mantle around this core. The geographical organization of islet cells facilitates coordinated control of groups of cells. Blood in the islet flows from the j3 cells to a and S cells. Thus, the j3 cell is the primary glucose sensor for the islet, and the other cell types presumably are exposed to particularly high concentrations of insulin. 

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