March 14th 2017

System provides a novel closed-loop solution for noninvasive sweat-based diabetes management.

Investigators have developed a simple and accurate sweat-based glucose monitoring and maintenance device, according to astudypublished inScience Advances.

Although the electrochemical analysis of sweat using soft bioelectronics on human skin provides a novel route for noninvasive glucose monitoring with patients who must undergo painful blood collection.

However, sweat-based glucose sensing still faces several challenges such as difficulty in sweat collection, activity variation of glucose oxidase due to lactic acid secretion and ambient temperature changes, and delamination of the enzyme when exposed to mechanical friction and skin deformation, according to the authors.

In a new study, investigators present a wearable and disposable sweat-based glucose monitoring device integrated with a feedback transdermal drug delivery module.

The system only requires a small amount of sweat, and the investigators used electrochemically active, porous metal electrodes to enhance the systems’ sensitivity.

The porous structure allows for the formation of strong linkage among enzymes, which results in the increased reliability of the sensors under mechanical friction and deformation. In addition to being smaller in size, the device features more sensors compared with other designs.

“It was quite a challenge to find the optimal size of the sensors,” said first author Dr Hyunjae Lee. “If the size is too small, the signal becomes too small or the surface functionalization becomes difficult to handle.”

In the glucose and pH sensors, the reference and counter electrodes are designed to be packed as closely as possible to minimize the required amount of sweat, according to the authors.

To produce a more accurate reading and feedback therapy, the patch system incorporates an additional sweat uptake layer and a waterproof band. The sweat uptake layer consists of water-soluble and porous carbohydrate network, which allows it to efficiently absorb the sweat. Additionally, the waterproof band facilitates the sweat collection and keeps the patch intact even under physical deformation of the skin.

The system also enables precise and timely drug delivery. Drugs for the feedback therapy are put on 2 different temperature-responsive phase change nanoparticles (PCNs), which are embedded in microneedles. The microneedles are also coated with phase change materials (PCMs).

When the system detects a high glucose level, the integrated heater modulates thermal actuation to activate PCN1 alone or both PCNs. Once the temperature reaches 40°C, only the drugs inside PCN1 are released. Whereas at 45°C, the drugs in both PCN1 and PCN2 are released.

The authors noted that the additional PCM spray coating prevents dissolution before the controlled melting of the PCM.

“The previous systems cannot prevent natural diffusion of drugs from drug reservoir, and rely heavily upon elevation of temperature to enhance the rate of drug diffusion,” Dr Lee said. “Our system uses PCMs to prevent drug release by using the melting properties of phase change materials above critical temperature, enabling stepwise drug delivery. Furthermore, different drugs can also be loaded in phase change nanoparticles for stepwise and multiple drug delivery.”

The thermoresponsive microneedles that are controlled by 3 multichannel heaters can deliver the drug up to 6 steps of drug dosages as a response to the sweat glucose level, according to the study.

The study also used a disposable, sweat-based strip sensor, which is more convenient for the sweat analysis compared with the patch system. This is because it is small enough in size to be used easily, and it can be operated to absorb generated sweat on the skin. Furthermore, the stripe-like sensor can analyze the sweat glucose levels once connected to the ZIF connector.

“This convenient and accurate system is also compatible for mass production as it uses the metal electrode that can be easily fabricated via a conventional semiconductor fabrication process,” Dr Lee said. “Although there is still room for improvement before applying our system into the clinical application, this approach can surely contribute to improve the quality of life of diabetic patients by managing blood glucose more easily.”

In addition to being used in diabetes management, the device may be able to be applied to other diseases.

“The fundamental mechanism underlying this system can be applied in the diagnosis and clinical treatments of various diseases not to mention diabetes,” said corresponding author Dae-Hyeong Kim.

Related Content