In vitro and Short-term in vivo Characteristics of a Kel-F Thin Film Modified Glucose Sensor

Abstract

The enzyme-based biosensors for continuous glucose monitoring have long been investigated as a promising method of improving glycemic control in persons with diabetes. However, in vitro and in vivo functions of sensors still remain to be further improved to allow wide-spread use of an implantable real-time sensor.First of all, as for a GOx-based sensor, which requires oxygen as a co-substrate to carry out glucose oxidation, it is important to examine the so-called "oxygen effect", which means the dependence of the sensor performance on the oxygen supply. Zhang et al. 1 demonstrated that the demand for oxygen by the sensor is primarily determined by its sensitivity, because the absolute current output is a direct measure of the rate of oxygen consumption. Non-linear sensors exhibit a strong oxygen dependence because the overall process depends on oxygen and glucose fluxes. Many efforts to minimize the oxygen effect have included the use of proper membrane coverage that improves the surface availability of oxygen relative to glucose. Gough et al. 2 reported a novel sensor configuration in which oxygen diffuses into the membrane from two directions while glucose diffuses from only one. Wang and Lu 3 used Kel-F oil, which has very high oxygen solubility, as an internal supply of oxygen for a carbon paste electrode. However, this type of sensor has not yet been successfully implanted in a body to monitor glucose concentration in diabetes. Zhang et al. constructed a practically useful implantable glucose sensor, which was essentially free of oxygen fluctuation, by controlling the sensor's sensitivity and linearity. Sensitivity was controlled by the thickness of an outer polyurethane membrane. The outer layer served to increase the relative oxygen supply because it functioned only as a diffusion barrier to glucose, while it imposed little or no effect on oxygen diffusion.The second issue is to develop a reproducible and predictable method for sensor fabrication. When an enzyme layer is prepared on a miniaturized/microfabricated needle or a microfabricated electrode, electropolymerization has valuable advantages over solvent casting because it is not limited in terms of the geometry and area of the electrode. The method also offers a site-selectivity that makes it suitable for the development of a multianalyte-sensing system, and the uniformity of the polymer film on the electrode surface can cope with more complex geometries. 4,5 Yang et al. fabricated a miniaturized glucose sensor using microfabrication and electropolymerization techniques.6 Glucose oxidase (GOx) was entrapped during the electropolymerization of a 1,3-diaminobenzene (1,3-DAB) on a recessed rectangular microfabricated platinum electrode. On the other hand, many GOx-based sensors prepared by electropolymerization have suffered from problems due to a restricted linear response range, though they have shown high sensitivities and fast responses. As was demonstrated in the study reported by Zhang et al., the restricted linear response range results from ...

Continuous Measurement of Lactate Concentration in Human Subjects through Direct Electron Transfer from Enzymes to Microneedle Electrodes

“…The layer also acts to protect the active surface from mechanical stressors or in some cases biofouling. 30,31 A cellulose acetate diffusion-limiting layer was applied to the working electrode of the lactate-sensing device. The thickness of the layer was modified by using different concentrations of cellulose acetate in an organic solvent and dropcasting onto the working electrode.…”

“…This layer slows diffusion to and from the active surface of the sensor and so extends the linear range to higher concentrations at the cost of lower observed currents and longer response times. The layer also acts to protect the active surface from mechanical stressors or in some cases biofouling. , …”

“…The layer also acts to protect the active surface from mechanical stressors or in some cases biofouling. 30 , 31 …”