A new, non-invasive method may do away with the need to draw blood for testing blood glucose and cholesterol levels.

Researchers from the National University of Singapore (NUS) and the Agency for Science, Technology and Research (A*Star) have developed a stretchable, hydrogel-based sensor that can detect such biomarkers in a solid state on the skin.

The technology could be used in wearables for purposes such as chronic disease management and remote patient monitoring, reports Zhaki Abdullah in The Strait Times.‍

Monitoring biomarkers — chemicals found in blood or other body fluids that capture what is happening in a cell or an 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 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 these pose barriers to the early diagnosis and treatment of diseases.

SEBs offer a compelling 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, detecting these biomarkers directly has been difficult. For instance, traditional solid electrodes lack the necessary charge transport pathways to enable electrochemical sensing of SEBs.

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The NUS and A*STAR research team has overcome 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 catalyzed by enzymes at the junction between the ICH and 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 produced using a scalable and cost-effective manufacturing process called screen printing.

“Our novel hydrogel sensor technology is key to enabling the non-invasive detection of solid-state biomarkers on skin. The ionic conductive hydrogel layer that solvates the biomarkers and the electronically conductive hydrogel layer facilitates electron transport. This bilayer enables the sequential solvation, diffusion and electrochemical reaction of the biomarkers. Another highlight is the sensor’s sensitivity with biomarkers being detected precisely even in low amounts,” said Asst Prof Liu.

“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,” said Dr Yang.

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.

Unlike traditional sensors that require biofluid samples, this sensor can continuously and non-invasively monitor SEBs 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 the biomarkers detected on the skin and those found in blood samples. This validates the sensor’s accuracy and reliability, suggesting it could be an alternative to blood tests for monitoring chronic diseases such as diabetes, hyperlipoproteinemia and cardiovascular conditions.

The research team is now working to enhance the sensor's working time and sensitivity and broaden its applicability by adding more solid-state analytes. They have also tapped hospitals for further clinical validation of the device, particularly for continuous glucose monitoring.