Gerard Cote, a biomedical engineering professor in the Dwight Look College of Engineering, is looking for a replacement to the traditional finger-stick monitoring technique people with diabetes need to use every day. Diabetes is a disease in which the body does not produce or properly use insulin, a hormone necessary to convert sugar, the body’s basic fuel, into energy. Sugar (glucose) builds up in the blood instead of going to the cells. People with diabetes must check their blood sugar levels several times a day to help keep their diabetes under control. Most monitoring methods require a blood sample obtained by sticking a finger with a needle from an automatic device. Over the years, scientists have been trying to find ways for people with diabetes to measure blood glucose without having to puncture the skin for a blood sample. Hundreds of research groups worldwide are racing to develop a noninvasive glucose sensor, Cote said. Cote is director of the Department of Biomedical Engineering’s Optical Bio-Sensing Laboratory, where research focuses on developing optical diagnostics and sensors for medical applications using lasers, fiberoptics and electronics. He and his colleagues are investigating new, noninvasive ways to test blood sugar levels. One of the experimental systems Cote is testing involves fluorescent polymer microbeads that could be implanted just under a patient’s skin. Glucose levels affect how much light the beads emit, which could be measured with a wristwatch-like monitor. The research is funded by grants from the State of Texas Advanced Research Program and the National Science Foundation and is administered through the Texas Engineering Experiment Station. "Obviously, it isn’t totally noninvasive since you need to implant the beads, but once they’re in, the monitoring process does not involve any daily punctures," Cote said. The idea got started at a meeting of SPIE-The International Society for Optical Engineering, where Cote attended a talk by a physician who removes tattoos with lasers. "He said, ’Boy, wouldn’t it be nice if we came up with a way to have a smart tattoo instead of just putting ink particles under the skin.’ That started me thinking," Cote said. "I got together with Michael Pishko in the Look College’s chemical engineering department. We put our heads together and came up with this approach of polymer beads that are implanted just underneath the skin or in the skin layers. The beads would glow, or fluoresce, differently as glucose concentrations changed." The American Diabetes Association estimates that 17 million people in the United States have diabetes, but that one third are unaware they have the disease. About 10 percent have Type 1 diabetes, in which the body fails to produce insulin and which is usually diagnosed in children and young adults. An overwhelming 90 percent have Type 2 diabetes, which develops most often in middle-aged and older adults and results from insulin resistance combined with insulin deficiency. Pain-free glucose monitoring would make it easier for people with diabetes to check glucose levels throughout the day. Although Pishko is now an associate professor of chemical engineering at Penn State University, Cote continues to collaborate with him on the fluorescent glucose sensor project. Both researchers recently completed three years on the scientific review committee of the Juvenile Diabetes Research Foundation and were honored with the foundation’s Mary Ann Kugel Award for their service. The committee’s members review proposals for diabetes research and advise the foundation on their merits. Many of the foundation’s members are parents of children with Type 1 diabetes (previously known as juvenile diabetes). Cote has heard many of their stories. "There’s nothing more frustrating to these parents than to see their child break out in a sweat and not know if it’s because the child’s glucose level is too high or if the glucose level is too low. One parent said it’s like his child is near a cliff and he doesn’t know if she’s walking toward the cliff or away from it." In Cote’s experimental process, two molecular compounds - dextran, a macromolecule composed of glucose subunits, and concanavalin A (conA), a protein that recognizes sugar - are encapsulated in polyethylene glycol (PEG) beads. PEG is a polymer commonly used for orthopedic implants because of its compatibility with human tissue. Dextran is tagged with one fluorescent dye color, or fluorophore, while conA is tagged with another. The experimental microgel beads, injected just under the skin, are too big to enter cells - unlike tattooing, in which cells absorb the pigment. Instead, the beads remain in the spaces between the cells, called the interstitial spaces. Fluid in those spaces contains water and glucose molecules small enough to pass through the PEG and reach the fluorophore-tagged polymers. Cote said the level of glucose in interstitial fluid is related to the blood glucose level that’’s measured by the traditional needle-stick method. The dextran molecules bind to the conA molecules. Together, under light from a laser or light-emitting diode, they emit a certain color under fluorescence. However, when glucose enters the picture, it competes with dextran, displacing the dextran molecules and binding to the conA. The fluorescent color changes according to the amount of glucose present. In preliminary studies, the researchers injected the microbeads under a rat’s skin and found that the rat tolerated the implant. The beads did fluoresce under the rat’s skin and indicated a change in glucose level. "The reason we’re so optimistic about the fluorescent method is because of its specificity," Cote said. "We know that if we implant this, it’s going to respond, and the response is going to be to glucose. With longer-lasting fluorophores, the implants could stay under a person’s skin for up to a year before having to be replaced. "The technology to develop the smart tattoo is here," Cote said. "It’s a matter of doing the work and testing the principles." Human testing could start within five years. This invention is protected under U.S. Patent No. 6,485,703 issued November 26, 2002. The A&M System Technology Licensing Office is currently seeking one or more industrial partners to facilitate commercialization of the procedure. For more information about licensing this technology, please contact Page Heller at p-heller@tamu.edu or 979-847-8682. Please reference TAMUS Project #1240.
