Graphene-based wearable electronic patch for diabetes control

Enzyme-based glucose sensors can be affected by environmental factors. For example, the mechanical deformation of wearable sensors during daily activities may lead to fractures in the sensor electronics that cause them to malfunction. The lactic acid present in sweat reduces the pH to 4–5, which affects the accuracy of enzyme-based sensors, as do variations in the ambient temperature. Therefore, a glucose monitoring system needs to be mechanically deformable, with correction of the results in real time based on simultaneous measurements of the pH and temperature. It would also be advantageous if the device were transparent, to make it discreet in use, and if microneedles were used for drug delivery, which would make the process painless.

Our recently developed graphene-based diabetes patch provides a potential solution to meet these needs (see Figure 1). The patch consists of multiple sensors, actuators, and sweat-control layers for the systematic collection of sweat, sensing of glucose, and feedback-controlled transdermal drug delivery. First, a layer for the uptake of sweat absorbs secreted sweat, of which the amount is monitored by an integrated humidity sensor. When the relative humidity exceeds 80%, other sensors (for example, glucose, pH, and temperature sensors) begin their measurements. The pH and temperature sensors measure the pH of sweat and the ambient temperature, respectively. These environmental parameters are used to correct the glucose concentration in sweat, which is measured by an integrated glucose sensor, in real time.

Under normal conditions, microneedles in the patch are coated by the biocompatible phase-change material (PCM) tridecanoic acid and are separated from the interstitial fluid in the skin. These microneedles are made from the water-soluble polymer polyvinylpyrrolidone (PVP) and contain drugs active against type II diabetes, such as metformin. However, under hyperglycemic conditions, thermal actuation by embedded microheaters causes the PCM coating layer to melt at ∼41°C, which activates the microneedles. Consequently, the microneedles are dissolved by biological fluids, which enables transdermal drug delivery. We have demonstrated sensing using the diabetes patch on human skin, and successfully tested feedback-controlled drug delivery on genetically modified diabetic mice. In the case of hypoglycemia, an integrated strain gauge measures tremors and, when necessary, drug delivery is stopped accordingly.

To ensure that the electrochemical sensors are highly sensitive and mechanically soft, we use functionalized graphene synthesized by chemical vapor deposition (CVD). The graphene hybrid electrode, which consists of gold-doped graphene on a gold mesh, is not only highly transparent but also exhibits good electrical and electrochemical properties, for example, high conductivity. As it is mechanically soft, the graphene-based electrode can be used in wearable devices. Although graphene grown by CVD has good electrical, optical, and mechanical properties, its intrinsic electrochemical activity is low because of its low defect density. However, graphene hybrid structures functionalized with electrochemically active organic or inorganic materials display high sensitivity to biomarkers for use in electrochemical sensors.

These improvements to wearable diabetes patches provide non-invasive control of blood glucose levels via pain-free monitoring of blood glucose without blood sampling and feedback-controlled drug delivery without injections. These have both been important goals in the long-term treatment of diabetes. To improve the functioning of our devices, we now need to ensure the long-term reliability and stability of the glucose monitoring system and develop a more efficient method of sweat collection. Even while we are working on resolving these issues, our wearable electronic patches will still lead to a better future for diabetes patients.

This work was supported by IBS-R006-D1.