Highly integrated watch for noninvasive continual glucose monitoring

Abstract

This article reports a highly integrated watch for noninvasive continual blood glucose monitoring. The watch employs a Nafion-coated flexible electrochemical sensor patch fixed on the watchband to obtain interstitial fluid (ISF) transdermally at the wrist. This reverse iontophoresis-based extraction method eliminates the pain and inconvenience that traditional fingerstick blood tests pose in diabetic patients' lives, making continual blood glucose monitoring practical and easy. All electronic modules, including a rechargeable power source and other modules for signal processing and wireless transmission, are integrated onto a watch face-sized printed circuit board (PCB), enabling comfortable wearing of this continual glucose monitor. Real-time blood glucose levels are displayed on the LED screen of the watch and can also be checked with the smartphone user interface. With 23 volunteers, the watch demonstrated 84.34% clinical accuracy in the Clarke error grid analysis (zones A + B). In the near future, commercial products could be developed based on this lab-made prototype to provide the public with noninvasive continual glucose monitoring.

Keywords: Biosensors; Electrical and electronic engineering.

Fig. 1. Overall design of the watch for noninvasive continual glucose monitoring.

a Exploded view of the watch. b Diagram of the printed circuit board (PCB) in the watch showing each functional module. (1) Constant current source, (2) A/D differential module, (3) microcontroller, (4) bluetooth module, and (5) power supply. c Structure of the flexible glucose sensor patch for interstitial fluid (ISF) extraction and glucose detection. d Working mechanism of reverse iontophoresis for noninvasive ISF extraction achieved with the glucose sensor patch. e System-level block diagram of the watch and user interface on a smartphone, showing the synergy among the functional units

Fig. 2. Working principle of the glucose sensor patch and characterization in a semi-infinite diffusion environment.

a Layer-by-layer diagram of sensor patch components. b The two-step mechanism of glucose detection: glucose oxidase (GOx)-catalyzed glucose oxidation, yielding H₂O₂, and Prussian blue (PB)-catalyzed H₂O₂ reduction. The electrocatalyst PB consumes an electron during the reaction, causing an amperometric response. c Amperometric responses of glucose sensor patches with (SP#2, 3 replicates) and without (SP#1, 3 replicates) Nafion film in the two-week test, demonstrating the long-term stability of the sensors, especially with Nafion modification. Data represent the mean ± s.d. of three replicates. d Comparison of the percentage decrease in sensor sensitivity between SP#1 and SP#2. Data represent the mean ± s.d. of three replicates. ***p < 0.001 by Student’s t-test. e Amperometric responses of SP#2 to glucose in contrast to interference components lactic acid (LA) and hyaluronic acid (HA)

Fig. 3. Performance test of glucose sensors in a small volume of solution.

a Schematic diagram of glucose monitoring in the thin-layer electrochemical model. b Current–time behavior of the sensors with 4 μL of glucose solution at different concentrations. c Linear fit of b and 1/b against glucose concentration C. d Comparison of the correlation coefficients corresponding to the linear fits in (c). Data represent the mean ± s.d. of three replicates. ***p < 0.01 by Student’s t-test

Fig. 4. On-body test of the watch.

a Photograph of a volunteer wearing the watch with blood glucose levels displayed in real time. b Workflow of the glucose-monitoring watch. c The blood glucose variation curve of a volunteer measured by the watch during the daytime compared to true blood glucose values (reference) obtained from finger blood. d Glucose concentrations before and after a meal measured by the watch from five volunteers. Data represent the mean ± s.d. of five replicates. ***p < 0.001 by Student’s t-test. e Plot of glucose concentrations measured from 23 volunteers by the watch and by a commercial glucose meter