Millions of diabetics prick their finger for a drop of blood a few times a day to check glucose levels. Besides being uncomfortable, these tests can miss sudden dips or bursts in blood sugar. Frequent readings are easier with sensors that can be implanted in a patient’s skin. But the glucose sensors available today can cause infections after a few days, and they are bulky and expensive.
Researchers led by Gerald Loeb, a biomedical-engineering professor at the University of Southern California, are now working on a glucose-sensor design based on optical technology. The design shows promise for making sensitive, affordable, and less invasive sensors.
The technique involves measuring the change in fluorescent emissions that occurs when glucose binds to certain molecules. The sensor is a tiny optical fiber that could be implanted in a patient’s skin. To read glucose concentrations, a portable analyzer will shine ultraviolet light into the free end of the fiber and measure the fluorescence, says Loeb.
Attached to the end of the fiber inside the skin is a polyethylene-glycol polymer matrix interspersed with pairs of tightly bound chemicals, each tagged with a different fluorescent molecule. Under ultraviolet light, the bound molecules shine at one wavelength. When the researchers place the matrix in a glucose solution, glucose molecules knock out and replace one of the chemicals, dextran. As a result, the chemical complex starts emitting at two different wavelengths. The ratio of the fluorescence intensities at the two wavelengths is in proportion to the glucose concentration.
According to Loeb, the sensor should be cheap and disposable. “Essentially, it’s a dot of polymerized goop on the end of an optical fiber,” he says. “A few-centimeters-long optical fiber is going to be pennies, and the dot of goop would be even less.”
It might also be more reliable than existing devices, because the chemistry doesn’t consume glucose. Commercially available implantable sensors measure the voltage caused by a chemical reaction that consumes glucose. If the concentration around the sensor goes down, and glucose from the surrounding tissue doesn’t flow in quickly enough, one could be measuring a value that is lower than the actual concentration in the body, Loeb says.
Meanwhile, Gerard Cote, a biomedical-engineering professor at Texas A&M University who first developed the chemical mechanism that Loeb’s optical-fiber sensor employs, is attempting to make a similar glucose sensor using a slightly different design. Cote and Michael Pishko, a chemical engineer at Penn State, are developing 20-micrometer-wide polyethylene-glycol beads that could be implanted just under a person’s skin, like a tattoo. A light-emitting diode on a wristwatch-type analyzer would shine light on the beads and measure the fluorescence. “The beads would be totally implantable, and the skin would heal over it,” Cote says, so there is nothing “that penetrates the skin and opens the body to infection.”
Current implanted glucose sensors require inserting an electrode under the skin; a metal wire connects the electrode to a monitoring device. The electrode has to be held in place with an adhesive tape. However, such devices can quickly cause infection and must be replaced every three days, which can get expensive. “They are looked upon as a foreign body, a splinter, and the body tries to reject them,” says George Wilson, a chemistry professor involved in biosensor research at the University of Kansas.
Loeb says that it should be possible to leave his glucose-sensing fiber inside human skin for a few months. He has implanted his fiber in pigs for up to three months without causing an inflammation.
So far, Loeb has tested his fiber-optic system in glucose solutions and has found that it is sensitive to the range of glucose concentrations that are found in the human body. But the system’s response inside living animals will be crucial to letting researchers know if it works. “There is an enormous difference between a sensor that operates in solution and a sensor that operates in animals,” Wilson says.
Once the optical glucose sensor is tested in animals, it would need to go through clinical trials, which can take four to five years. If everything goes as planned, both Loeb and Cote believe that their sensors could be available as products in five to ten years.