Subcutaneous-type glucose sensors

Development of Subcutaneous-Type Glucose Sensors for Implantable or Portable Artificial Pancreas... 

Figure 3. Structure of a subcutaneous type glucose sensor...

Glucose sensor IH and W have more desirable properties than that of the sensor I, so that they are promising as a subcutaneous type glucose sensor for an implantable artificial pancreas. Now, life time test and in vivo testing of these sensors are going to be performed, and the results of these tests will be reported in the future. 

D. Bindra, Y. Zhang, G. Wilson, R. Sternberg, D.Trevenot, G. Reach, and D. Moatti, Design and in vitro studies of a needle-type glucose sensor for subcutaneous monitoring. Anal. Chem. 63, 1692-1696 (1991). 

Moussy F, Harrison DJ, O Brien DW, Rajette RV. Performance of subcutaneously implanted needle-type glucose sensors employing a novel trilayer coating. Analytical Chemistry 1993, 65, 2072-2077. 

Fig. 9 shows the time dependence of the relative sensor output and the relative response time of the ferrocene-mediated needle-type glucose sensor covered with a poly(MPC-c -BMA) membrane or a PVA membrane when the sensor was inserted continuously into the subcutaneous tissue of rats. By using the mediator, sensor... 

Figure 10. Continuous monitoring of subcutaneous tissue glucose concentrations and blood glucose regulation in an insulin requiring NIDDM patient with a ferrocene-mediated needle-type glucose sensor covered with poly(MPC-co-BMA) membrane.

Shichiri M, Yamasaki Y, Nao K, Sekiya M, Ueda N (1988) In vivo characteristics of needle-type glucose sensor-measurements of subcutaneous glucose concentrations in human volunteers. Horm Metab Res Suppl Ser 20 17-20... 

Their biosensor consisted in a Pt wire on which GOD was immobilized by the electropolymerization of m-phenylenediamine. The advantage of this type of immobilization consists in creating an effective barrier against electrochemical interference due to the polymer formed onto the electrode. Moreover, an extended linearity for the glucose sensor was also obtained, and this was a requisite for the direct measurement of the subcutaneous glucose at diabetic levels, since in practice an extremely low dilution of the subcutaneous fluid was realized. 

Figure 4-17 Schematics of various implantable electrochemical/optical sensors useful for continuous in vivo monitoring (A) catheter style amperometric oxygen sensor (B) design of Paratrend intravascular combined PO2, PCO2, and pH sensor (hybrid electrochemical/optical design) (C) needle type electrochemical glucose sensor useful for monitoring glucose subcutaneously to track blood glucose levels continuously.

Several implanted biosensors have been developed and evaluated in both animals and humans (see Chapter 4). Detection systems are based on enzymes, electrodes, or fluorescence. The most widely studied method is an electrochemical sensor that uses glucose oxidase. This sensor can be implanted intravenously or subcutaneously. Intravenous implantation in dogs for up to 3 months has demonstrated the feasibility of this approach. Alternatives to enzymes are being developed, including artificial glucose receptors. Less success has been achieved with subcutaneous implants. Implantation of a needle type of sensor into the subcutaneous tissue induces a host of inflammatory responses that alters the sensitivity of the device. Microdialysis with hoUow fibers or ultrafiltration with biologically inert material can decrease this problem. 

Figure 9. Time course of relative output currents and response times of needle-type standard glucose sensor covered with PVA membrane and these of needle-type ferrocene-mediated glucose sensors covered with PVA membrane or poly(MPC-co-BMA) membrane when these sensors were inserted into subcutaneous tissue of normal rat.

Therefore, another type of planar glucose biosensor with Pt electrodes on a sihcon substrate has therefore been developed for in vivo measurements [61]. The enzyme glucose oxidase was immobilized by the well known GDA-BSA method and the whole sensor was covered subsequently by a polyurethane membrane. This sihcon chip has to be sawed and assembled on a flexible carrier for in vivo application, the assembled catheter was successfully evaluated in rats [79]. This sensor gives encouraging results in aqueous solutions and subcutaneous apphcations. Drawbacks of this include the complicated mounting and assembling procedures which are difficult and cumbersome. 

---