Towards continuous glucose monitoring: in vivo evaluation of a miniaturized glucose sensor implanted for several days in rat subcutaneous tissue

Abstract

A miniaturized amperometric, enzymatic, glucose sensor (outer diameter 0.45 mm) was evaluated after implantation in the subcutaneous tissue of normal rats. A simple experimental procedure was designed for the long-term assessment of the sensor's function which was performed by recording the current during an intraperitoneal glucose load. The sensor was calibrated by accounting for the increase in the current during the concomitant increase in plasma glucose concentration, determined in blood sampled at the tail vein. This made it possible to estimate the glucose concentration in subcutaneous tissue. During the glucose load, the change in subcutaneous glucose concentration followed that in blood with a lag time consistently shorter than 5 min. The estimations of subcutaneous glucose concentration during these tests were compared to the concomitant plasma glucose concentrations by using a grid analysis. Three days after implantation (n = 6 experiments), 79 estimations were considered accurate, except for five which were in the acceptable zone. Ten days after implantation (n = 5 experiments), 101 estimations were accurate, except for one value, which was still acceptable. The sensitivity was around 0.5 nA.mmol-1.l-1 on day 3 and day 10. A longitudinal study on seven sensors tested on different days demonstrated a relative stability of the sensor's sensitivity. Finally, histological examination of the zone around the implantation site revealed a fibrotic reaction containing neocapillaries, which could explain the fast response of the sensor to glucose observed in vivo, even on day 10. We conclude that this miniaturized glucose sensor, whose size makes it easily implanted, works for at least ten days after implantation into rat subcutaneous tissue.

On line continuous monitoring of subcutaneous tissue glucose in men by combining portable glucosensor with microdialysis

“…This was the case in our fasted healthy volunteers as well as in the Type 2 diabetic patients, whose fasting blood glucose did not change substantially over the period of calibration. In an animal study [20], a two-point in vivo calibration was performed: one calibration point was the fasting blood glucose, and the second calibration point was the peak after an intraperitoneal glucose load. As this procedure would be difficult to perform under the circum-stances of daily life, for which a device for continuous glucose monitoring in a diabetic patient must function, we used the easier one-point calibration.…”

Recent Advances in Continuous Glucose Monitoring: Biocompatibility of Glucose Sensors for Implantation in Subcutis

“…The infiltration of neutrophils and macrophages in the tissue surrounding the implanted sensor is a common observation. The study of Mang and colleagures 55 contributed 12,26 uncontrolled sensor production, i.e., ill-defined material selection 57 or nonsterile sensors, 58 size of sensors, 58 and duration of implantation. 26,55,57 Moreover, evaluation of the inflammation has in general been restricted to a histomorphological examination performed on hematoxylin and eosin (HE)-stained sections.…”

Advances and prospects in glucose assay technology

“…One possible approach is the hydrogen peroxidebased enzyme electrode sensor [7][8][9][10][11][12][13][14]. This design has a membrane containing immobilized glucose oxidase coupled to a peroxide-sensitive catalytic anode.…”