Wearable and implantable biosensors capable of accurately detecting biological molecules in a non-invasive or minimally invasive way offer enormous potential for monitoring patients’ health and their responses to treatments. A notable example is wearable glucose monitors, which track blood glucose levels and convert the data into easily interpretable and continuously recorded electrical signals, playing a crucial role in managing diabetes. Similar biosensors have been designed to monitor electrolytes in sweat, biomarkers in interstitial fluid near the skin's surface, and to track the function of internal tissues. However, these implantable biosensors are limited in their utility due to a challenge known as "biofouling." Biofouling occurs when bacteria, human cells, or molecules from the body's biofluids accumulate on the sensor surface, interfering with the sensor’s ability to bind to its target molecule (analyte), disrupting its electrical signal generation. Additionally, implanted biosensors can trigger "foreign body responses," which activate pro-inflammatory immune cells and may lead to fibrotic tissue formation.

Overcoming these challenges would significantly enhance the potential of clinical diagnostics and research, enabling long-term monitoring for chronic or autoimmune diseases, assessing responses to existing and experimental therapies in clinical trials, and tracking physiological and pathological signals from organs such as the brain. To address this, a multidisciplinary team of researchers at the Wyss Institute for Biologically Inspired Engineering, Harvard University (Boston, MA, USA), has developed a novel coating technology that promises to greatly extend the lifespan of wearable and implanted biosensors while maintaining their electrical signal functionality. This new approach enables the continuous monitoring of analytes in various biofluids within the body, potentially for weeks at a time.

The new coating builds on the Wyss Institute's history of groundbreaking electrochemical biosensor technologies. The team demonstrated that when applied to electrochemical sensors, this coating prevented the growth of Pseudomonas aeruginosa, a bacterial species responsible for the formation of antibiotic-resistant biofilms on biosensors and other implants. Additionally, the coating stopped the adhesion of primary human fibroblasts and inhibited unwanted immune cell activation, all while preserving the sensor’s ability to detect key inflammatory proteins for over three weeks.

This coating consists of a cross-linked structure made from bovine serum albumin (BSA) and functionalized graphene. The graphene ensures efficient electrical signaling, while the BSA lattice forms a natural barrier that prevents the binding of various biological and molecular contaminants. This structure also allows for the stable incorporation of antibodies that detect specific analytes, as well as antibiotic drugs to combat biofouling. In a proof-of-concept study, the team successfully demonstrated the continuous and accurate detection of two key biomarkers of inflammation over more than three weeks using specially designed sensors exposed to complex human plasma.

During this period, the coating effectively resisted fibroblast cell attachment and the formation of biofilms typically created by P. aeruginosa, while also remaining undetected by pro-inflammatory immune cells. Furthermore, the coating can be produced from cost-effective components using a simple, scalable process, enabling large-scale production of in vivo biosensors. The Wyss Institute has patented this innovative coating technology and is actively seeking partners to help advance it toward real-world applications that can make a direct impact on patient care and scientific research.

“With this novel coating technology, which can offer durable protection of implantable biosensor devices, we have removed a central bottleneck in the development of next-generation electrochemical in vivo sensors. In the age of personalized medicine and digital health, it brings a plethora of diagnostic and research applications within reach,” said Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who led the study. 

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