ABSTRACT
Affinity sensors for glucose are based on a different measuring principle than the commercially available amperometric needle type sensors: reversible affinity interaction of glucose with specific receptors is the primary recognition mechanism instead of an enzymatic glucose oxidation. A novel pulsed-flow micro-fluidic system was used to characterize first the viscosity of a sensitive liquid containing the glucose receptor Concanavalin A and dextran and in a second approach to characterize the geometry of a fluidic resistance. In the viscometric sensor, glucose of the sensitive liquid is equilibrated, while passing through a dialysis chamber, with the surrounding medium. With the membrane flow sensor, the viscosity of the liquid remains constant but the pores of the flow-resisting membrane contain a swellable hydrogel affecting the width of the pores. Two types of hydrogel were tested with the membrane flow sensor; one is highly sensitive to pH and salt concentration, the other contains receptors of phenyl boronic acids to obtain sensitivity to glucose. The viscometric affinity sensor (first approach) showed a linear response over 0 to 30 mmol/L glucose concentration range. The disturbing effect of air bubbles could be compensated for. The sensing proof of principle of the second approach could be demonstrated by its linear response to different saline concentrations; however, the glucose-sensitive membrane developed showed only a small response to glucose. Glucose monitoring based on this pulsed flow measuring principle offers interesting alternatives for the development of CGM systems with different options for the glucose sensing part.
ABSTRACT
OBJECTIVE: A viscometric affinity sensor has been developed to measure the interstitial glucose concentration continuously. In a pilot clinical study its performance was assessed under conditions close to everyday life. Additionally, different insertion sites were tested for their suitability to apply subcutaneous glucose sensors. METHODS: Twelve subjects, 10 of whom with type 1 diabetes, were examined for 8 h. Sensors were applied subcutaneously at the forearm and the abdomen of each subject. Capillary blood glucose references were obtained from the finger tip every 30 min. Retrospective calibration was carried out individually with Deming regression. RESULTS: After retrospective calibration the 95% limits of agreement in the plot of the differences between sensor signals and references versus their means were +/-60 mg/dL. The sensitivity of the sensors remained stable over the entire measuring period, without any significant differences between the sensors at forearm and abdomen. Correcting for the observed time delay of 15 min between references and sensor values the limits of agreements were reduced to +/-38 mg/dL. Furthermore, error grid analysis showed 89.3% of the paired values in zone A and 9.6% in zone B. Only 1.1% were clinically unacceptable (zone D). CONCLUSIONS: The performance of the viscometric affinity sensor shows the potential of the measuring principle under in vivo conditions. Forearm and abdomen seem to be similarly well suited for the application of subcutaneous sensors. The signal stability over time and the absence of enzymatic, chemical, or electrode reactions are advantages of the viscometric affinity principle.
