For measuring blood sugar concentration, viscosimetric affinity sensors have, among other things, been developed which can be miniaturized and used in an implanted form (DE 195 01 159) or as transdermal sensors (DE 197 14 087).
Viscosimetric affinity sensors for determining sugar levels are based on a sensitive fluid, a concentrated solution consisting of macromolecular branched dextran and the tetravalent bonding protein concanavalin A (ConA), with the specificity of glucose, being situated in a dialysis chamber coupled to a device for measuring viscosity. The viscosity of the sensitive fluid is high when the dextran molecules are cross-linked via their exposed terminal glucose groups by ConA, and is reduced, dependent on concentration, with the free glucose penetrating the dialysis chamber by diffusion from a glycosuric external solution.
A particularly favorable method of affinity viscosimetry involves measuring the viscosity, once dialysis has been performed in the segment of a microdialysis fiber, by measuring the flow resistor of a downstream capillary (DE 197 14 087). A known problem in affinity viscosimetry is that the viscosity of the sensitive fluid is dependent not only on the concentration of glucose but to a large extent also on the temperature and on the concentration of the active glycopexic protein (Ballerstädt and Ehwald, Biosensors & Bioelectronics 9: 557-567, 1994; Ehwald et al., Analytical Biochemistry 234: 1-8, 1996). In order to release the signals of a viscosimetric affinity sensor for glucose from this significant temperature-dependency, relative values having low temperature-dependency can be formed (Ballerstädt and Ehwald, Biosensors & Bioelectronics 9: 557-567, 1994). Up until now, only methods for discontinuously determining the relative values by consecutively measuring the viscosity changed by glucose and the reference viscosity have been known. A method for continuously determining such relative values in a sensor on-line has not been known up until now.
Developing a viscosimetric affinity sensor which operates on-line requires a method for preparing readings which converts viscosity-dependent measured values provided by the sensor on-line into glucose concentration. In this connection, the aim is that the sensor detects a measured value which is directly dependent, in a linear relationship, on the glucose concentration and is simultaneously independent of the temperature and the concentration of active ConA in the sensitive fluid. The method to this effect has not been known up until now.
USPTO Backgrounds
USPTO Backgrounds