Researchers at
Texas A&M University have engineered a wearable, tissue-adhesive biosensor
that detects inflammation biomarkers in the mouth with molecular precision.
Credit: Rachel Barton/Texas A&M Engineering
Detecting gum disease currently requires a dentist chair and a 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 research is published in the journal Science Advances.
Sensitivity and accuracy
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 1 followed by 15 zeros—equals just 1 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.
"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."
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."
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 health care
from reactive responses to anticipatory action.
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.
Provided by Texas A&M University
Source: A patch that sticks inside your mouth could spot inflammation early

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