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Tiny sensors may reduce diabetics' skin pricks

Sunday, October 01, 2000

By Byron Spice, Post-Gazette Science Editor

For diabetics who take insulin to control their blood sugar levels, sticking themselves with a needle to test their blood glucose is a way of life. A diabetic might stick herself four, six or even 10 times a day to adjust insulin doses so that glucose levels remain as close to normal as possible.

But bioengineer Jerome Schultz thinks he might be able to eliminate most of those needle sticks with a tiny implantable sensor no bigger than a bit of thread. Inserted just underneath the upper layer of the skin, it could continuously monitor glucose levels. Glucose levels could be read by shining a light through the skin.

The sensor is a dream Schultz has been pursuing for years and, though not yet ready for human trials, he reported significant progress in the Sept. 15 issue of the journal Analytical Chemistry.

"We finally got the chemistry down," he said, noting the sensor responds to changes in glucose levels within two or three minutes and that it accurately measures glucose both at higher than normal levels and, perhaps more critically, at low levels that can result in a person slipping into a diabetic coma.

Schultz, director of the University of Pittsburgh Center for Biotechnology and Bioengineering, is not alone in his attempts to develop a glucose sensor.

Diabetes is both an increasingly common disease and one that can have devastating consequences, such as heart disease, blindness and nerve disorders, if glucose levels aren't carefully controlled.

Many schemes for monitoring glucose levels have been tried and a few recently have gone on the market, or soon will.

As yet, none is quite as good as clinicians might hope, said Dr. Dorothy Becker, chief of pediatric endocrinology at Children's Hospital. "But the technology's getting there," she added, and every patient who depends on insulin may well come to depend on such a device.

Though eliminating the pain and bother of needle sticks is something that sounds good to nondiabetics, Becker said the real value of continuous monitoring has less to do with relieving pain than with relieving fear.

Attaching a glucose monitor to an alarm system could alert users that a diabetic's glucose level had dipped dangerously low, she explained. This could be particularly important at night, when glucose levels naturally drop and when family members aren't likely to notice that a sleeping diabetic has become comatose.

In the longer term, continuous glucose monitors might be used to control insulin pumps, which would deliver insulin automatically, mimicking the function of the pancreas.

Schultz, whose work is supported by the Juvenile Diabetes Foundation, "is considered one of the foremost people in the field," Becker said.

Rather than measuring blood glucose levels, Schultz's sensor would measure the amount of glucose coursing through the skin itself.

The sensor is made of a hollow, porous fiber -- the same type used in the filters that remove waste products from the blood during kidney dialysis. The fiber is filled with porous, carbohydrate beads which have been coated with a dye to block out light.

The third component of the sensor is a protein from the jack bean called concanavalin A, or con A. No one is quite sure what con A does in the bean, Schultz said, but its propensity to bind with carbohydrates has long made it a tool used by biochemists. Con A was once used for blood typing, for instance.

Schultz has tagged con A with a chemical that fluoresces green when it is illuminated.

In his sensor, the con A tends to hide inside the coated beads, bound to the carbohydrate there and shielded from outside light. But when glucose flows through the sensor's porous membrane and into the beads, the glucose binds to con A, freeing the con A particles from the beads. When the con A particles flow out of the beads, they can be illuminated with outside light, causing their fluorescent tags to produce green light.

Thus, by shining a light through the skin to the sensor, Schultz can measure the amount of glucose by noting the strength of the green fluorescent signal.

He envisions someday implanting the thread-like sensors near a diabetic's wrist. Devices for illuminating and reading the sensor might be packaged into something the size of a wristwatch that could be worn directly over the sensor, he said.

The implanted sensors would have to be replaced periodically -- perhaps as frequently as every few months. Needle sticks wouldn't be totally eliminated -- users would have to test their glucose levels by the conventional method every few days to calibrate the sensor system.

Schultz's research team has tested the sensor by placing it in mice and injecting the mice with glucose. Further studies will be necessary in animals with diabetes. At least two additional years of animal testing will be necessary before any human trials could be contemplated, Schultz said.

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