A more comfortable and reliable blood-sugar monitoring system is being designed by researchers in Sweden for people with diabetes.
After successfully testing a prototype of a microneedle patch on a human subject, the completion of a system for clinical tests is now underway.
Continuous monitoring is a way to safely and reliably lower blood glucose – giving the user a full picture of their glucose levels throughout the day and helping them avoid severe hypoglycemia.
But the continuous glucose monitoring systems (known as CGMS) in use today have two main drawbacks: they are uncomfortable, since they require a minimum 7mm needle that’s inserted into the skin; and, because of their size, they take measurements in the fat tissue – not the most ideal location.
a Illustration of the typical implementation of a commercial CGM system. The focus of this work is specifically on the development, integration, and intradermal insertion of the sensing part of the CGM system. b Illustration of the cross-section of the developed CGM device inserted into the skin. The sensing probe is assembled inside a hollow microneedle lumen with the sensing electrodes facing the opening that allow diffusion from and to the dermal interstitial fluid. c Enlarged view of the three sensing electrodes facing the lateral opening of the microneedle
Researchers at KTH Royal Institute of Technology in Stockholm have developed a promising alternative: a microneedle patch that is 50 times smaller than the needles used in today’s CGM systems.
The CGM device consists of two components: a miniaturized electrochemical sensing probe (70 × 700 × 50 μm3) and a 700 μm-long silicon microneedle.
These two parts were independently microfabricated using standard MEMS fabrication techniques, and then assembled as a last step.
The microneedle geometry was previously developed to have a sharp tip geometry for easy penetration and a side opening to avoid tissue clogging the lumen during insertion (Roxhed et al. 2007).
The same microneedles were previously successfully used for insulin delivery (Roxhed et al. 2008), as well as intradermal injection of rabies vaccine in humans in a clinical study (Vescovo et al. 2017).
SEM top views of the sensors, before functionalization and assembly. a “T-shaped” sensor, with electrical contact pads on top and the three sensing electrodes on the probe at the bottom. b Closer view of the configuration with three long parallel electrodes, providing equal conditions at each electrode during measurement. c Alternative version with three vertically patterned electrodes, potentially enabling distinct functionalization of the different electrodes
The combination of the patch and an extremely miniaturized three-electrode enzymatic sensor was shown in a recent study to be capable of correctly and dynamically tracking blood glucose levelsover time, with a delay of about 10 minutes, when applied to a human subject’s forearm.
a Assembled CGM device, attached to the 3D printed plastic holder, with the sensor inserted in the microneedle lumen. Inset: SEM picture of the hollow silicon microneedle, with the side opening close to the sharp tip. b Close-up view of the microneedle opening. For visualization purposes, the opening has been enlarged by laser ablation to display the three-electrode sensor inside the microneedle lumen
One of the researchers, doctoral student Federico Ribet, says the next steps are to develop a transferable adhesive patch, along with algorithms and embedded electronics for a fully-realized system to take to clinical trial.
“Our solution is painless to the user,” Ribet says. “We measure directly in the skin, and there are no nerve receptors that detect pain – just a fine mesh of very tiny blood vessels.”
Within the dermis, the hollow microneedles rely on natural capillary action to fill up with interstitial fluid, the liquid surrounding the cells in the skin.
Nutrients like sugar, diffuse out of the blood capillaries in this fluid to reach the cells.
“An important distinction is that unlike commercially available CGMS which measure the subcutaneous fat tissue, ours measures within the skin less than 1mm deep, where the interstitial fluid follows closer and more homogeneously the blood-glucose oscillations,” Ribet says.
This would offer an alternative to pricking one’s fingers several times a day to take a blood test, although a user would still occasionally have to do so – as they do with commercial CGMS – in order to recalibrate the sensor and get the most accurate and immediate readings.
But with this new system, that could one day change. Ribet points out that the most advanced CGM device now on the market is factory calibrated and reduces the frequency of having to conduct a finger blood test.
He says the research team at KTH believes it could ultimately match, or even surpass this level of quality.
More information: Federico Ribet et al. Real-time intradermal continuous glucose monitoring using a minimally invasive microneedle-based system, Biomedical Microdevices (2018). DOI: 10.1007/s10544-018-0349-6
Provided by: KTH Royal Institute of Technology
