Design, development, and evaluation of a novel microneedle array-based continuous glucose monitor

Abstract

The development of accurate, minimally invasive continuous glucose monitoring (CGM) devices has been the subject of much work by several groups, as it is believed that a less invasive and more user-friendly device will result in greater adoption of CGM by persons with insulin-dependent diabetes. This article presents the results of preliminary clinical studies in subjects with diabetes of a novel prototype microneedle-based continuous glucose monitor. In this device, an array of tiny hollow microneedles is applied into the epidermis from where glucose in interstitial fluid (ISF) is transported via passive diffusion to an amperometric glucose sensor external to the body. Comparison of 1396 paired device glucose measurements and fingerstick blood glucose readings for up to 72-hour wear in 10 diabetic subjects shows the device to be accurate and well tolerated by the subjects. Overall mean absolute relative difference (MARD) is 15% with 98.4% of paired points in the A+B region of the Clarke error grid. The prototype device has demonstrated clinically accurate glucose readings over 72 hours, the first time a microneedle-based device has achieved such performance.

Keywords: continuous glucose; interstitial fluid; microneedle; minimally invasive.

Figure 1.

Schematic of the sensor pod portion of the prototype device.

Figure 2.

(A) Photograph of the microneedle array. (B) SEM photograph of several microneedles.

Figure 3.

Sample plots of the device performance over 72 hours. Device signal is shown as a solid line, and the comparative blood glucose measurements are shown as discrete points. Comparative points used as calibrations are designated with a square symbol.

Figure 4.

Clarke error grid analysis (EGA) for the 1396 paired points from 37 devices over up to 72 hours in this trial.

Figure 5.

Example plots of 2 devices worn simultaneously by a subject to demonstrate interdevice precision.