Automatic in situ calibration of in vivo glucose sensors - by comparing measured value with reference signal from independent model, calculating quality control values and correcting sensor signal if these exceed specified limits

摘要

Automatic in situ calibration of intracorporeal glucose measuring devices (esp. enzymatic glucose electrodes) comprises amperometric measurement of glucose concn. with an in vivo sensor and simultaneous generation of an independent glucose reference signal (Xs) according to a model of the biological system in which the naturally continuous changes in individual biological systems are accounted for. A mean glucose concn. (Xm) is generated in time intervals from a number of glucose determinations and stored in a sequence of glucose concn. values in relation to the actual time of day, and values compared with Xs. In the event that the physiologically relevant tolerance range (I2SD of Xm) violated, two quality control values are determined, i.e. the actual predictive value (PWA) = Xm(tn)/Xs(tn) (tn = time and the actual normalised drift (NRDA) = Xs(tn)-Xm(tn)/Xs(tn) and from the successive values of these, by means of continuous linear regression, dynamic predictive value (PWD) and dynamic normalised drift (NRDD) are determined, over first and second time windows. If these 4 values exceed predetermined limit values, the long term drift (NDRL) is estimated over a third time window by continuous non-linear regresion; it represents the predictive goodness of the measuring device. If NDRL exceeds a predetermined limit value then either (1) automatic correction to the measuring sensor signal or (2) interruption of the measuring process is signalled. This includes, in parallel to the glucose measuring system (which includes an amplifier) a model reference module which is influenced (in the same way as a biological system) by values of nutrient uptake, insulin supply and physical load. Between this module and the measurement amplifier is an initialisation module which (a) makes the individual-specific adjustments of the simulation model to the actual biological system and (b) does the initial in situ calibration. A comparison module compares X and Xs while the 4 quality control quantities are calculated in a subsequent signal processing unit. A summation module detects any over stepping of the limits and, if necessary, activates an adaptation module, connected to the measurment amplifier, which corrects the measurement signal or halts the measurement process. The time windows are 360 min. for PWD; 720 min. for NRDD and 1440 min. for NRDL. The fig. shows measured (points) and simulated (line values of subcutaneous glucose concn. over a 24 hr. period. Food was consumed at about 0800 and 1900 and insulin admin. at about 0.700, 1100, 1700 and 2200. USE/ADVANTAGE - The glucose measuring devices are used in diagnosis and insulin therapy. This method provides automatic calibration under normal living conditions.