Micro interstitial fluid extraction and detection device integrated with the optimal extraction conditions for noninvasive glucose monitoring

Interstitial fluid glucose sensors have promising prospects in noninvasive glucose monitoring. However, the commonly used method of extracting interstitial fluid, reverse iontophoresis (RI), still remains to be optimized to solve problems such as insufficient extraction flux and skin irritation. To find the optimal RI conditions, in this study we explored the effects of multiple factors such as current frequency, duration, duty cycle and their interactions on extraction with the design of experiments (DOE) method. A multifunctional extraction and detection device was designed to control extraction conditions and measure the surface water content of the extraction electrode in situ and real time. A micro glucose monitoring device (MicroTED) combined with a cheap and flexible paper-based electrode was developed under the determined optimal extraction conditions. In on-body continuous glucose monitoring tests carried out to verify the performance of the device, the optimized conditions can facilitate stable extraction of up to 1.0 mg without any skin discomfort. The mean Pearson correlation coefficient between the measurement results of MicroTED and commercial glucometer is above 0.9. In the Clarke error grid analysis, all data points fell within Clarke error grid areas A and B, demonstrating the feasibility of further clinical application of the device.