The early detection of illnesses hinges on the swift, ongoing, and easy tracking of crucial biomarkers. Researchers at the National University of Singapore (NUS) and the Agency for Science, Technology and Research (A*STAR) have created an innovative sensor that allows for the constant and immediate monitoring of solid-state epidermal biomarkers (SEB), introducing a new form of health indicators.
Led by Assistant Professor Liu Yuxin from the NUS Institute for Health Innovation & Technology and Dr. Yang Le, Principal Scientist at A*STAR’s Institute of Materials Research and Engineering (IMRE), the team has presented a non-invasive technique to assess health by analyzing biomarkers like cholesterol and lactate directly from the skin.
The wearable, flexible hydrogel-based sensor addresses the limitations of existing methods that depend on biofluid samples such as blood, urine, and sweat. As a result, it presents a promising option for wearables that offer continuous and real-time health monitoring, aiding in the early identification of issues like cardiovascular diseases and strokes. Additionally, it effectively tracks athletes’ lactate levels, which can indicate fatigue and tissue oxygen deprivation, essential for performance. This advancement is particularly relevant in areas like chronic disease management, broad population screening, remote health monitoring, and sports physiology.
The research findings were published in Nature Materials on June 12, 2024, with contributions from A*STAR’s Institute of High Performance Computing, Institute of Molecular and Cell Biology, and Nanyang Technological University in Singapore.
Innovating to overcome existing challenges
Monitoring biomarkers—substances found in bodily fluids that reflect cellular activities—has traditionally involved the analysis of blood, urine, or sweat. While effective, these approaches present challenges: blood tests are invasive and inconvenient, urine analysis can be cumbersome and often lacks real-time capabilities, and sweat testing can be ineffective if the individual is not sweating, as well as uncomfortable due to the use of sweat-inducing drugs. These hurdles complicate the early diagnosis and treatment of diseases.
Solid-state epidermal biomarkers, like cholesterol and lactate, located in the skin’s outer layer (the stratum corneum), are promising indicators correlating with conditions like cardiovascular disease and diabetes. However, direct detection of these biomarkers has been tricky, as traditional solid electrodes lack the necessary charge pathways for effective electrochemical sensing of SEBs.
The research team from NUS and A*STAR has tackled this issue with a cutting-edge sensor design. When worn on the skin, SEBs dissolve into a specially designed ionic conductive hydrogel (ICH) layer, diffuse through the hydrogel, and undergo enzyme-catalyzed electrochemical reactions at the junction of the ICH and an electronically conductive hydrogel (ECH) layer. The resulting physiological data is transmitted wirelessly to an external interface using a flexible printed circuit board, enabling continuous monitoring.
“Our innovative hydrogel sensor technology is essential for the non-invasive detection of solid-state biomarkers on the skin. The ICH layer dissolves the biomarkers while the ECH layer promotes electron transport. This dual-layer structure supports the sequential processes of solvation, diffusion, and reaction of the biomarkers. Another key feature is the sensor’s high sensitivity, allowing for precise detection even at low biomarker levels,” stated Assistant Professor Liu.
“This sensor is the first globally to monitor biomarkers on dry, non-sweaty skin. Its unique bi-layer hydrogel electrode interacts with and detects these biomarkers on our skin, establishing them as a new class of health indicators. Moreover, the stretchable design allows it to conform to the skin, improving both comfort and accuracy. This innovation can revolutionize health and lifestyle monitoring, especially for individuals with chronic conditions that require continuous oversight,” added Dr. Yang.
Reliable, sensitive, and user-friendly
Differing from traditional sensors that necessitate biofluid samples, this device can continuously and non-invasively monitor SEBs directly on the skin, making it especially useful for remote patient monitoring and large-scale health screenings.
In clinical studies, the sensor exhibited strong correlations between the biomarker levels detected on the skin and those found in blood samples, confirming its accuracy and reliability as a potential alternative to blood tests for managing chronic issues like diabetes, hyperlipoproteinemia, and cardiovascular diseases.
The sensor’s heightened sensitivity is another significant advantage, as it can identify lactate and cholesterol at remarkably low concentrations, approaching the sensitivity of mass spectrometry, thus ensuring precise monitoring.
Furthermore, the design minimizes motion artifacts—disruptions caused by the user’s movement that can affect sensor placement and pressure—by a factor of three compared to traditional sensors. This improvement was successfully validated through mathematical modeling. The bi-layer hydrogel’s consistency in readings ensures reliable monitoring while its skin-like flexibility enhances user comfort.
“One potential application of this technology could replace the standard pregnancy glucose tolerance test, reducing the need for multiple blood draws. Instead, our sensor could allow pregnant women to conveniently monitor their sugar levels at home with comparable accuracy to conventional tests. This technology could also benefit diabetes patients by eliminating the need for frequent finger-prick tests,” explained Assistant Professor Liu.
“Another possible use is in daily heart health monitoring, given that cardiovascular disease accounts for nearly one-third of deaths in Singapore. Our research team has initiated a program to collaborate with cardiologists to establish clinical correlations between biomarkers like lactate, cholesterol, and glucose and heart health,” noted Dr. Yang.
Rolling out next-gen sensors
The researchers from NUS and A*STAR plan to further enhance the sensor’s performance by improving its duration and sensitivity. They also look to integrate additional solid-state analytes to expand its use for various biomarkers. Collaborating with hospitals, they aim to provide further clinical validation and make this technology accessible to patients, particularly for continuous glucose monitoring and assessing dynamic resilience quantitatively.
