The wearable sweat monitoring patch on the skin. Image Credit: Hyunjae Lee and Changyeong Song

 
People with diabetes need to closely monitor their blood glucose levels multiple times every day, usually using a device that pricks their finger for a blood test to assess whether they need insulin shots or other drugs. Since blood collection and shots can be painful, not all patients do it as regularly as they need to—which can lead to dangerous fluctuations in their blood glucose levels.

Researchers have worked for years on methods to improve and even automate blood glucose monitoring and insulin/drug delivery. For example, insulin pumps make drug delivery easier, and recently designed artificial pancreas systems offer closed-loop monitoring and drug delivery. Now, researchers in Korea have just developed a wearable, and potentially disposable, glucose monitoring and drug-delivery system that uses sweat, not blood, to determine glucose levels.

The results, published today in Science Advances, suggest it’s a major upgrade. There are several differences between the artificial pancreas and the sweat-based monitoring system, according to lead author Hyunjae Lee, of Seoul National University in the Republic of Korea. While both devices can check blood glucose in real time and deliver necessary drugs, the artificial pancreas’s drug-delivery needles are permanently embedded subcutaneously, and the device itself is made of rigid plastic, which "might cause discomfort," Lee tells mental_floss.

The sweat-based system, on the other hand, is transfer-printed onto a thin silicone skin patch. It’s made of flexible and stretchable electronics, a series of stretchable graphene sensors—humidity, glucose, pH, and temperature—packed as closely as possible. The sensors’ electrodes are made from porous gold nanoparticles, whose structure helps create an electrochemically active surface area in order to analyze what’s in your sweat. Above a heating strip, which helps create humidity and generate sweat more quickly, is a film strip of drug-loaded microneedles, 0.6 inches by 0.8 inches. These are loaded with metformin, a drug used to control glucose in Type 2 diabetes. (At present, the sweat-based patch has not been tested on insulin, whose molecules are too big for delivery through the microneedles, though Lee hopes to work on designing one that can work with insulin in the future.)

Detail of the wearable sweat-analysis sensors. Image Credit: Hyunjae Lee and Changyeong Song

 
Sweat accumulates in the porous sweat-uptake layer of the patch, which also helps screen out negatively charged molecules, including drugs that may interfere with the glucose sensing. A waterproof band helps prevent the patch from peeling away from the skin. When the sweat covers the glucose and pH sensors, the measurements begin. "When blood glucose is high, [the] therapeutic part activates microneedle-based drug delivery," automatically, Lee explains.

Researchers adhered the patch to five healthy human subjects, ages 20 to 60. It takes 10–15 minutes for the device to generate enough sweat to measure glucose levels, though exercise could speed that process up. However, Lee says they took into account that for some people with diabetes, "sweat generation through exercise could be a burden." He adds, "Considering [that] point, we miniaturized sensor design that allows for reliable sweat analysis even with an infinitesimal amount of sweat."

The participants’ blood glucose levels were tested using a commercial glucose meter one hour before and after a meal as a comparison. The researchers found that the sweat-glucose sensor measurements were comparable to those of a commercial blood glucose assay kit.

Human clinical trials are not yet scheduled for the drug-delivery process, so to test this part of the system, Lee’s team turned to mice. They took 16 diabetic mice, 8 to 12 weeks old, and fasted them overnight before the experiment. They attached drug-loaded microneedles to their shaved abdomens, which had been stained with a special blue dye. Then, they used an embedded heating element to activate the microneedles, since the mice can’t produce enough sweat to do so. The microneedles' successful penetration of the skin was made visible by the blue dye.

The experimental groups of mice that received the drug delivery of metformin showed a significant decrease in blood glucose levels compared to the control groups that did not receive the drug. "In the animal experiment, we could confirm that blood glucose was continuously decreased and continued for six hours after microneedle therapy," Lee says.

While the system shows great success, Lee acknowledges there are adjustments to be made. "The sensor should be more sensitive and reliable to enhance accuracy of sweat-based glucose monitoring system," he says. In order to control the amount of drug delivered, they will also need to study "the correlation between sweat and blood glucose levels more thoroughly."

Despite the need for further research, Lee feels their device "can surely contribute to improve the quality of life of diabetic patients."