New biosensor offers early warning system for disease

Detecting gum disease currently requires a dentist chair and visual exam, often catching problems only after tissue damage has started. To shift care from reactive to proactive, researchers at Texas A&M University have engineered a wearable, tissue-adhesive biosensor that detects inflammation biomarkers in the mouth with molecular precision.

Dr. Chenglin Wu, associate professor of civil and environmental engineering, developed and tested a multi-layer sensor that can function in the wet oral environment and remain attached while talking and eating. The specialized sensing layer of the patch targets the tumor necrosis factor-alpha (TNF-⍺) protein, a key biomarker for inflammation.

The graphene-MXene sensing layer can bind specific probes that attach only to the target protein. The layer has an inherent conductivity, and when molecules such as the targeted protein bind, the change in charge can be measured. This enables highly sensitive detection at the femtogram-per-milliliter (fg/mL) level.

“For context, a patient with a viral infection might show symptoms at 10 million or 1 billion virus copies per milliliter,” Wu said. “Our sensor could detect 100 to 150 per milliliter.”

The study indicates detection at just 18.2 fg/mL. To put it in perspective, one quadrillion femtograms — that’s a one followed by 15 zeros — equals just one gram. Achieving this sensitivity can be challenging, especially if unwanted biomarkers are also detected. However, the outer layers help improve the patch’s selectivity.

Dynamic tissue adhesion

The tissue-adhesive hydrogel also features a selective-permeable hydrogel layer that helps filter out unwanted molecules.

“My collaborator at Michigan State University engineered a very small opening that will only allow the smaller biomarkers through,” Wu said. “Combining that with the highly selective probe attached to the sensing layer makes for accurate selectivity.”

Dr. Shaoting Lin, an assistant professor of mechanical engineering at Michigan State, helped develop the tissue-adhesive hydrogel and the selective-permeable hydrogel. The robust tissue adhesion also helps the accuracy of the sensing layer.

For context, a patient with a viral infection might show symptoms at 10 million or 1 billion virus copies per milliliter. Our sensor could detect 100 to 150 per milliliter.

“Sensing measurements can be significantly influenced by the dynamic movement of tissues,” Lin said. “A more robust tissue bond allows for a more reliable sensing performance independent of the strain.”

Mesh lattice

The selective permeable layer acts like a mesh lattice, allowing only certain-sized molecules to pass. Chemical interactions between the layer and biomarkers may also contribute to selectivity.

“We systematically tested a few biomolecules of similar size,” Lin said. “Due to the interaction between the biomolecule and the surrounding polymer network, there is an enhanced selectivity that distinguishes the transport of different biomolecules.”

The future of Lin’s work involves studying these different interactions to possibly engineer specific hydrogels that interact with certain biomolecules to target a variety of different biomarkers.

Testing the concept

The researchers tested the non-invasive patch with the help of Dr. Jeffrey Cirillo, a Regents’ Professor in the Department of Microbial Pathogenesis and Immunology at Texas A&M’s College of Medicine. While Lin and Wu engineered the patch materials, Cirillo’s contribution centered on the biological side and evaluating clinical applications.

“My laboratory has a lot of experience working with patients and various models and animal systems,” Cirillo said. “In this instance, we decided to go with guinea pigs because they’re relatively easy to work with and share a number of similar characteristics with humans, particularly with oral inflammation.”

“The TNF-⍺ protein is a cytokine that is almost always involved in inflammation associated with infections of soft tissues,” Cirillo said. “The goal was to see if this type of system would allow rapid, point-of-care detection.”

Biomarker insights

Dr. Hajime Sasaki, an associate professor of dentistry at the University of Michigan, recognized the importance of detecting TNF-α in the oral cavity and offered valuable insights into biomarkers and dental diseases.

Oral infections can cause serious health problems, like gum disease and tooth loss, and can become more severe if left untreated. The ability to quickly diagnose infections before symptoms appear could shift oral healthcare from reactive responses to anticipatory action.

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READ MORE: Oral cancer and microbiome: new insights into tumor growth mechanisms

The animals in this study were used solely to demonstrate that the concept works. Future clinical trials in animals — and eventually humans — will be the next steps for this system.

Future studies could also adapt this type of biosensor for other parts of the body and for different biomarkers, given the versatility of the materials used.