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It’s a modern medical twist on an ancient art. Scientists at Draper Laboratory, in Cambridge, MA, are developing a nanosensor that could be injected into the skin, much like tattoo dye, to monitor an individual’s blood-sugar level. As the glucose level increases, the “tattoo” would fluoresce under an infrared light, telling a diabetic whether or not she needs an insulin shot following a meal. The researchers have already tested a sodium-sensing version of the device in mice, and will soon begin animal tests of the glucose-specific sensor.

The most reliable way to measure blood sugar is by pricking the finger for a tiny blood sample and using enzyme-laden test strips to detect glucose. In an attempt to free diabetics from this time-consuming and expensive regime, a number of novel glucose-sensing technologies are under development, from implanted devices that continually monitor blood sugar and dispense insulin, to noninvasive sensors that detect glucose through the skin via infrared light.

Heather Clark and her colleagues are developing something designed to operate in between these two extremes. The material consists of 120-nanometer polymer beads coated with a biocompatible material. Within each bead is a fluorescent dye and specialized sensor molecules, designed to detect specific chemicals, such as sodium or glucose.

When injected into the skin, the sensor molecule pulls the target chemical–say, sodium–into the polymer from the interstitial fluid, which surrounds cells. To compensate for the newly acquired positive charge of a sodium ion, a dye molecule releases a positive ion, making the molecule fluoresce. The level of fluorescence increases with the concentration of the chemical target. Scientists can swap in different recognition molecules to measure different targets, including chloride, calcium, and glucose. The range of concentrations that the sensor can detect can be varied by altering the ratio of the components, depending on whether it is important to measure precise concentrations or more broad variability.

The sodium sensor, which could one day be used to monitor dehydration, has shown early success in animals. When injected into rodents’ skin, the beads stay put and fluoresce in response to saline injections. The researchers have developed a glucose sensor that works via a similar mechanism. It has been shown to work in a solution but has not yet been tested in animals.

In the long term, Clark envisions a sensor that would be injected into the surface layers of the skin, shallower than tattoo inks “so that it sloughs off over time,” she says. A fluorescence monitor, resembling an optical mouse, would then be used to measure the light emitted by the tattoo, and the sensor would be reinjected periodically.

“It’s unique because it doesn’t have any components to be used up,” says Clark. Glucose strips, for example, use an enzyme to detect glucose, which needs to be continually replaced. “Other monitors, even nanosensors, have a limited lifetime, which makes implanting them difficult,” she says.

Still, the researchers have a long way to go before the sensor is ready for human testing. While the beads didn’t appear to trigger an immune reaction in initial animal tests, more studies need to be done, says Clark. Assessing the immune response is especially important because that can alter local glucose concentrations, says George Wilson, a chemist at the University of Kansas, in Lawrence. For example, “macrophages [a type of immune cell] eat glucose,” he says. Wilson also cautions that numerous factors can influence the inherent fluorescence of the skin, including skin color and age.

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Credit: Heather Clark, Draper
Video by Heather Clark, Draper

Tagged: Biomedicine, Diabetes, glucose, nanosensor

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