Embedded biosensors increase major longevity with coating technology that inhibits biofusion

Wearable, implantable biosensors that can accurately detect biological molecules in non-invasive or invasive ways have great potential to monitor patients’ physiology and response to treatment. For example, wearable glucose monitors that measure blood glucose levels and convert these measurements into easily readable, continuous, recorded electrical signals, have become essential for managing diabetic patients. Similar biosensors have been developed to report on electrolyte monitoring in sweat, biomarkers in interstitial fluids near the skin surface, and internal tissue function.

However, these embedded biosensor devices are only useful for a limited time, as they are thought to be interacting with target molecules, as they are thought to be accumulating on the sensor surface and blocking interactions with target molecules (analysis). Furthermore, implanted biosensors can cause so-called “foreign body responses” through undesirable stimulation of nearby proinflammatory immune cells that can cause a fibrous tissue response.

Overcoming this challenge opens the doors for many clinical diagnostic and research applications, such as long-term steady-state monitoring of patients with chronic or autoimmune diseases. Evaluation of a patient’s response to existing or new treatments tested in clinical trials. Measurement of physiological and pathological signals in many organs, including the brain.

Now, a multidisciplinary research team at Harvard University’s WYSS Institute, committed to significantly increasing the lifespan of embedded and wearable biosensors while retaining electrical signaling activity, has developed a new coating technique that allows for continuous measurement of analytes of various biofluids in our bodies for weeks.

As the team demonstrated, coatings, when overlaid with electrochemical sensor devices, inhibited the growth of P. aeruginosa, a bacterial species involved in the formation of antibiotic-resistant biofilms in biosensors and other implanted devices. The coating also prevented primary human fibroblast adhesion and unwanted activation of nearby immune cells, designed to bind two fully functional inflammatory proteins for at least three weeks, and maintained the detection capabilities of the proof-of-concept sensor. Their findings are published in the journal Biosensors.

“This new coating technology, which can provide durable protection for implantable biosensor devices, has removed the central bottleneck in the next generation electrochemical development of in vivo sensors. In the age of personalized medicine and digital health, it introduced the Donald Institute, the editor of letter executive supervision.

“This is also a testament to the laser-sharp focus of WYSS’s electrochemical sensor team on solving problems that significantly slow clinical care advances.” He is also a Judas Folklore Professor of Vascular Biology at Harvard University School of Medicine and Boston Children’s Hospital, and Hanjorg is a Biologically Inspired Engineering Professor at Harvard John A. Paulson Engineering Applied Science.

The new coating technology is based on the tradition of highly innovative electrochemical biosensor development at the WYSS Institute. Some of the platform’s innovations are now commercialized by WYSS-enabled startup StatAdx, which uses drops of blood obtained from patients to develop assays that detect diverse molecular changes in the human brain.

However, the first author, Sofia Wareham-Mathiasen, Ph.D., to allow continuous electrochemical biomarker measurements in vivo over a period of several weeks. And colleagues on Ingber’s team created a new coating consisting of cross-linked lattices of bovine serum albumin (BSA) and functionalized graphene. While graphene components ensure efficient electrical signaling, BSA lattices form a natural barrier to potential lifetimes and the non-specific binding of most molecular contaminants. It can also include stable inclusion of analyte detection antibodies in coatings as well as antibiotics that actively fight biofooling.

In their proof-of-concept study, the team demonstrated that two important inflammation biomarkers could be detected continuously and accurately over three weeks using specially designed sensors exposed to complex human plasma. At the same time interval, the coating resisted the attachment of human fibroblasts and the formation of biofilms normally produced by P. aeruginosa, making them less noticeable in proinflammatory immune cells.

Furthermore, coatings can be manufactured from low-cost components in a simple, scalable process to facilitate the production of large quantities of in vivo biosensors. The WYSS Institute patents this new coating technology and is looking for partners to drive advances into real-world applications to directly impact patient lives and scientific discoveries.

Another author on this study is Pawan Jolly, a former senior WYSS scientist who was committed to advancement in WYSS’s electrochemical biosensor platform. Novo Nordisk industry collaborator Henrik Bengtsson and Thomas Bjarnsholt of the Costarton Biofilm Centre at the University of Copenhagen, Denmark. WYSS researchers Nandhinee Radha Shanmugam, Badrinath Jagannath, Pranav Prabhala, Yunhao Zhai, Alican Ozkan, Arash Naziripour and Rohini Singh.