A wearable and stretchable sensor enables rapid, continuous and non-invasive detection of skin biomarkers in solid state

Early disease detection requires rapid, continuous and convenient monitoring of vital 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 continuous, real-time detection of solid-state epidermal biomarkers (SEBs), a new class of health indicators.

Jointly led by Assistant Professor Liu Yuxin from the NUS Institute of Health Innovation and Technology and the N.1 Institute for Health and the Department of Biomedical Engineering at the NUS College of Design and Engineering, and Dr Yang Le, Senior Scientist and Head of the Department of Sensors and Flexible Electronics at the A*STAR Institute of Materials Research and Engineering (A*STAR IMRE), 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 team’s developed wearable and stretchable hydrogel-based sensor overcomes the limitations of current methods that rely on biofluid samples, such as blood, urine and sweat. It is therefore a promising alternative for wearable, continuous and real-time health monitoring, facilitating the early detection of diseases such as cardiovascular disease and stroke.

It also enables effective monitoring of athletes’ lactate levels, an indicator of tissue exhaustion and hypoxia that affects their performance. This development is particularly relevant in areas such as chronic disease management, population-wide screening, remote patient monitoring and sports physiology.

The team’s results were published in the journal Natural materials June 12, 2024. The A*STAR Institute for High Performance Computing and Institute of Molecular and Cellular Biology, as well as Nanyang Technological University, Singapore, also contributed to the research.

Innovating to overcome existing challenges

Monitoring biomarkers (chemicals in the blood or other body fluids that capture what is happening in a cell or organism at a given moment) traditionally involves analyzing biofluids such as blood, urine and sweat. While effective, these methods come with challenges.

Blood tests are invasive and inconvenient, while urine tests can be time-consuming and not real-time. Sweat biomarker analysis, although noninvasive, is limited by the difficulty of inducing sweating in inactive individuals and the discomfort of using sweat-inducing medications. All of these present barriers to early diagnosis and treatment of disease.

SEBs offer an attractive alternative. These biomarkers, which include cholesterol and lactate, are found in the stratum corneum, the outermost layer of the skin, and have shown strong correlations with diseases such as cardiovascular disease and diabetes. However, direct detection of these biomarkers has proven challenging. For example, traditional solid electrodes lack the charge transport pathways needed to enable electrochemical detection of SEBs.

The NUS and A*STAR research team overcame this challenge with their novel sensor. When the device is worn on the skin, SEBs dissolve in the ionically conductive hydrogel (ICH) layer, diffuse through the hydrogel matrix, and undergo enzyme-catalyzed electrochemical reactions at the junction between the ICH and the electronically conductive hydrogel (ECH) 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 manufactured using a scalable and cost-effective manufacturing process called screen printing.

“Our novel hydrogel sensor technology is essential to enable non-invasive detection of solid-state biomarkers on the skin. The ionically conductive hydrogel layer that solvates the biomarkers and the electronically conductive hydrogel layer facilitate electron transport.

“This bilayer enables the sequential solvation, diffusion and electrochemical reaction of biomarkers. Another highlight is the sensitivity of the sensor, which can accurately detect biomarkers even in small quantities,” said Assistant Professor Liu.

“This wearable sensor is the first in the world to monitor biomarkers on dry or non-sweating skin. The sensor’s novel bilayer hydrogel electrode interacts with and detects biomarkers in our skin, enabling them to become a new class of health indicators. The stretchable design also improves comfort and accuracy by adapting to the natural elasticity of our skin.

“This innovation can change the way we approach health and lifestyle monitoring, especially for people with chronic conditions who require constant health monitoring,” Dr. Yang said.

Reliable, sensitive and friendly

Unlike traditional sensors that require biofluid samples, this sensor can continuously and non-invasively monitor SEB directly on the skin, making it valuable for remote patient monitoring and population-wide health screening.

In clinical studies, the sensor demonstrated strong correlations between biomarkers detected on the skin and those found in blood samples. This validates the accuracy and reliability of the sensor, suggesting that it could be an alternative to blood tests for monitoring chronic diseases such as diabetes, hyperlipoproteinemia and cardiovascular diseases.

Another advantage is the sensitivity of the sensor, which can detect lactate and cholesterol in the solid state at very low levels. This level of sensitivity is close to that of mass spectrometry, which ensures precise monitoring of these biomarkers.

Additionally, the sensor design reduces motion artifacts, which occur when user movements affect the sensor’s positioning or its contact pressure on the skin, by three times compared to conventional counterparts. This new finding was successfully modeled mathematically. By minimizing disturbances caused by motion, the bilayer hydrogel ensures consistent and reliable measurements, while the stretchable, skin-like nature of the device improves user comfort.

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

“Another potential application is the use of the sensor in daily monitoring of heart health, as cardiovascular diseases account for nearly a third of deaths in Singapore. The research team has initiated a research programme to work closely with cardiologists to establish a clinical correlation between biomarkers (lactate, cholesterol and glucose) and heart health,” said Dr Yang.

Deployment of next-generation sensors

The NUS and A*STAR researchers plan to improve the sensor’s performance by increasing its operating time and sensitivity. They also want to integrate other analytes in the solid state, expanding the sensor’s applicability to other biomarkers.

Researchers are also collaborating with hospitals to provide further clinical validation and bring the technology to patients, including for continuous glucose monitoring, as well as quantitative assessment of dynamic resilience.