Enzymatic glucose sensors. Improved long-term performance in vitro and in vivo.

We studied the long-term in vitro and in vivo performance of enzyme electrode glucose sensors. Single commercially produced enzyme-active membranes remained functional for estimating glucose in vitro for 14-36 months. These membranes were implanted subcutaneously in rats for 1 year and, upon explanation, remained functional for measuring glucose in vitro. Sensors with these membranes plus an additional outer membrane with lower glucose permeability allowed glucose monitoring in the low oxygen tension of subcutaneous tissue. These sensors were surgically implanted in three nondiabetic dogs. Each sensor implant was coupled to a radio transmitter to allow continuous long-term glucose monitoring in these awake unrestrained dogs. In vivo sensor performance was evaluated by intravenous glucose infusion, with reference blood glucose determinations made in the clinical laboratory. These subcutaneously implanted sensors tracked changes in plasma glucose for up to 12 weeks. The in vivo initial response for three sensor implants was approximately 35 sec (n = 8). Sensor peak response to glucose after bolus infusion ranged from 3 to 14 min. Stability of sensor sensitivity within +/- 15% for more than 1 month was demonstrated in two of the dogs. Sensor lifetime was limited not by loss of enzyme activity, but by biodegradation of the outermost polyurethane membrane. The findings suggest that long-term continuous monitoring of blood glucose using a subcutaneously implanted enzyme electrode sensor may be possible.

Development and evaluation of a wearable blood glucose monitor.

Complex operation, prolonged set-up time, reliability problems, high cost, and excessive size limits the use of currently available extracorporeal continuous blood glucose analyzers. A self-calibrating, wearable blood glucose monitor has been developed to overcome these impediments. The wearable blood glucose monitor is a 410 g forearm-mounted instrument with three miniature pumps for blood sampling, calibration, and insulin infusion, and a flow cell containing an enzyme-electrode sensor capable of determining plasma glucose levels accurately and precisely in undiluted whole blood. The unit is connected to a computer controller with graphics display. Venous blood is drawn from a 21 gauge single lumen cannula through the sensor flow cell. A rate determination of glucose is completed in 20 sec and the blood is returned to the arm vein. Heparinized saline wash solution follows. No blood loss or significant systemic heparinization occurs. Cycle time is set from 2 to 5 min. The method is linear to at least 300 mg/dl glucose, independent of hematocrit, and free of interferences from blood constituents at normal venous pO2 with a coefficient of variation of 1-3% between calibrations. The sensor has a service life of at least 3 weeks. This wearable blood glucose monitor, with its high performance sensor, reduced size, and ease of operation, shows promise for evaluating and treating diabetes.