Clinical evaluation of a transcutaneous interrogated fluorescence lifetime-based microsensor for continuous glucose reading

Abstract

Background: Continuous glucose monitoring is presently used worldwide. Accuracy, precision, durability, invasiveness, and lack of drift of sensors and lag time are key parameters essential to these systems. This article describes a new online minimally invasive biodegradable microsensor for optical, transcutaneous interrogation, which has at least 14 days of functionality.

Method: Studies were performed in vitro and in vivo on pigs, as well as on type 1 diabetic humans. Functionality has been ensured in laboratory settings, and precision and durability have been tested in vivo. During in vivo studies, venous blood samples were used as reference. Results were based on one single point calibration per experiment.

Results: Excellent stability was found in 14-day in vitro trials as well as in vivo in up to 70-hour trials. The overall median relative absolute difference of type 1 diabetic patients was 11.4%. Error grid analysis showed 97.7% of all values in the A+B zone. Comparable results were found in animal studies. No sensor drift was observed in any trial.

Conclusion: Results point toward the possibility of developing a stable and precise minimally invasive glucose reader for at least 2 weeks of continuous use.

Keywords: accuracy; continuous glucose monitoring; fluorescence; lifetime; variability.

Figure 1.

Microsensor capsule placed in the dermis just below the basal membrane. The microsensor is interrogated by the reader unit (not shown) aligned with the microsensor on top of the skin.

Figure 2.

Dose–response characteristics of an AF594-MBL/HMCV1-Dex assay in a microsensor container. Phase readings are performed in vitro and have a precision of ±0.02°. The curve parameters for this particular set of data are ϕ₀ = 37.86 °; Δϕ_max = 7.0°, and K_D = 41.5 mmol/liter.

Figure 3.

Data for male patient type 1, diabetes duration 11 years. The line shows the glucose estimate obtained by the every 5-minute interrogation of the PreciSense microsensor, and the points show the venous blood glucose from the patient.

Figure 4.

Point EGA plot for the lowest gradient interval during the trial, i.e., 85% of the data sets acquired is shown here. Data points are from the last six patients participating in the 3-day trials.