Stretchy gel sensor detects solid-state skin biomarkers

Researchers from the National University of Singapore (NUS) and the Agency for Science, Technology and Research (A*STAR) have developed a novel sensor that enables the continuous, real-time detection of solid-state epidermal biomarkers (SEB), a new category of health indicators.

Led by Assistant Professor Liu Yuxin from NUS and Dr Yang Le from A*STAR, the research team’s innovation offers a non-invasive method to monitor health by detecting biomarkers such as cholesterol and lactate — directly on the skin.

The wearable, stretchable, hydrogel-based sensor overcomes the limitations of current methods that rely on biofluid samples, such as blood, urine and sweat. This makes it a promising alternative for wearable, continuous and real-time health monitoring that could facilitate early detection of conditions such as cardiovascular diseases and stroke. It can also monitor athletes’ lactate levels, an indication of exhaustion and tissue hypoxia, which affect their performance.

Monitoring biomarkers traditionally involves analysing biofluids such as blood, urine and sweat; while effective, these methods usually come with challenges. Blood tests are invasive and inconvenient, while urine analyses can be cumbersome and lack real-time capability. Probing biomarkers from sweat, though non-invasive, is limited by the difficulty of inducing sweat in inactive individuals and the discomfort of using sweat-inducing drugs. All of these pose barriers to the early diagnosis and treatment of diseases.

SEBs offer an alternative; these biomarkers, which include cholesterol and lactate, are found in the sternum corneum, the outermost layer of the skin, and have shown correlations with diseases such as cardiovascular disease and diabetes. Detecting these biomarkers directly has been difficult. For instance, traditional solid electrodes lack the necessary charge transport pathways to enable electrochemical sensing of SEBs.

The researchers overcame this challenge with their novel sensor design; when the device is worn on the skin, SEBs dissolve into the ionic conductive hydrogel (ICH) layer, diffuse through the hydrogel matrix and undergo electrochemical reactions catalysed by enzymes at the junction between the ICH and electronically conductive hydrogel layer. Relevant physiological data is then transmitted wirelessly to an external user interface via a flexible printed circuit board, providing continuous monitoring capabilities. The sensor is produced using a scalable and cost-effective manufacturing process known as screen printing.

Assistant Professor Liu said the hydrogel sensor technology is key to enabling the non-invasive detection of solid-state biomarkers on skin, adding that the ionic conductive hydrogel layer that solvates the biomarkers and the electronically conductive hydrogel layer facilitates electron transport. This bilayer enables the subsequent solvation, diffusion and electrochemical reaction of the biomarkers. The sensor’s sensitivity with biomarkers can also be detected in low amounts.

“This wearable sensor is the first in the world that can monitor biomarkers on dry or non-sweaty skin. The sensor’s novel bilayer hydrogel electrode interacts with and detects biomarkers on our skin, allowing them to become a new class of health indicators. The stretchable design enhances comfort and accuracy as well, by adapting to our skin’s natural elasticity. This innovation can change the way we approach health and lifestyle monitoring, particularly for those living with chronic conditions requiring constant health monitoring,” Yang said.

In clinical studies, the sensor demonstrated correlations between the biomarkers detected on the skin and those found in blood samples, thereby validating the sensor’s accuracy and its potential as an alternative to blood tests for monitoring chronic diseases such as hyperlipoproteinemia and cardiovascular conditions.

The sensor can also detect solid-state lactate and cholesterol at low levels; its sensitivity approaches that of mass spectrometry, which ensures the precise monitoring of these biomarkers. The sensor’s design also reduces motion artefacts, which occur when the user’s movements affect the placement of the sensor or its contact pressure to the skin, by three times compared to conventional counterparts.

“One of the possible applications of this technology is to replace the pregnancy diabetic test, commonly known as the glucose tolerance test. Rather than subject pregnant women to multiple blood draws, our sensor could be used to track real-time sugar levels conveniently in patients’ homes, with a similar level of accuracy as traditional tests. This also can be applied to diabetes in general, replacing the need for regular finger-prick tests,” Liu said.

“Another potential application is to use the sensor in the daily monitoring of heart health, as cardiovascular disease accounts for almost one-third of deaths in Singapore. The research team has embarked on a research program to work closely with cardiologists in establishing clinical correlation between biomarkers — lactate, cholesterol and glucose — with heart health,” Yang said.

The researchers plan to enhance the sensor’s performance by increasing its working time and sensitivity. They also aim to integrate additional solid-state analytes, broadening the sensor’s applicability to other biomarkers. The team’s research findings have been published in the journal Nature Materials.

Image caption: The sensor comprises an ionic electronic bilayer hydrogel that can detect solid-state biomarkers from the skin. The sensor is connected to a flexible printed circuit board which transmits data wirelessly to a user interface. Image credit: NUS iHealthtech.