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Pitt researchers working on blood-sugar sensors that won't require finger prick
Tuesday, July 15, 2003

Diabetics may eventually be able to test their blood sugar levels by wearing a contact lens or a skin implant, instead of having to prick their fingers several times a day.

Two teams of researchers at the University of Pittsburgh are working on new sensors to test glucose levels, one of which is described in a paper that will be published today in the journal Analytical Chemistry.

More than 1 million Americans have Type 1 diabetes and can't make their own insulin, a hormone that converts blood sugar to energy. Diabetics must test their blood sugar levels frequently, sometimes up to six times a day, and must supplement the hormone through injections or pumps.

Bioengineering professors Jerome Schultz and Kaiming Ye, authors of the paper, have developed a sensor that is based on a glucose-sensing protein from bacteria and a fluorescent protein from jellyfish.

Their genetically engineered protein is shaped like a thumb and forefinger with the fluorescent protein at the tip of each. Without glucose, the finger and thumb are pinched together, and the protein glows. In the presence of glucose, the finger and thumb move apart. The more glucose, the less the protein glows.

Ye came from his job as a professor in Japan to join Schultz's lab and provide his expertise in molecular biology.

"I may have some ideas, but he can actually figure out the genetics of how to do it," Schultz said.

The sensor could be implanted under the skin of the wrist or placed in a contact lens.

Schultz, director of Pitt's Center for Biotechnology and Bioengineering, imagines that the wrist implant could be read by a wristwatch-like device that would shine a light on the implant, measure the resulting glow and display the glucose level.

Schultz and Ye's protein is so sensitive that the levels of glucose found in the blood are too high for it to measure accurately. "What we're trying to do now is genetically engineer the protein to be less sensitive," Schultz said.

However, putting their sensor in a contact lens is an option. "It's estimated that the glucose concentration in tears is anywhere from 1/20 to 1/100 of that in blood," said Schultz.

The pair also plan to genetically engineer an array of such proteins, calibrated to sense different levels of glucose, depending on what part of the body they are to be used for. The technology is still years away from human trials.

Approaching the glucose-sensing problem from a different perspective, chemistry professor Sanford "Sandy" Asher is working on a gel that changes from red to violet as glucose levels fluctuate from too low to too high. Normal levels would appear green.

To develop the sensors for clinical use, Asher turned to Dr. David Finegold, professor of pediatrics at the Pitt medical school.

The researchers felt that the eye would be a convenient location for the sensor.

"We had always hoped that we could sense glucose in tear fluid," said Asher. They are currently studying the relationship between glucose in the blood and glucose in tears.

The sensor could be worn either in a contact lens or in a plastic insert that would fit under the lower eyelid.

In the contact lens, the sensor would be visible, but "small enough that you would have to be attentive to notice it," Asher said.

The insert under the lower eyelid would not be visible unless the lid was pulled down. This version would be easier to wear than a contact, said Asher.

"People who don't wear contacts wouldn't mind using this," he said.

These sensors are photonic crystals -- small polystyrene spheres suspended in gels. The crystals diffract light, much like opals, which contain spheres of silica.

When exposed to glucose, the gel expands, causing the spheres to spread apart and the gel to change color.

One tricky part of the process is that because the light is diffracted, the sensor could appear different colors from different angles.

However, if the placement of the light source and the eye remained the same each time, results would be accurate. Asher envisions providing a compact mirror with a small light inside, similar to those used for applying makeup, to standardize the angle of view.

Users would match the color of the sensor to a color wheel within the compact, which would have gradations comparable to those of existing test strips.

In April, Pitt licensed the technology to startup company Glucose Sensing Technologies Ltd. of Murrysville. Asher estimated that it would be another three years before the product reaches the market.

Atlanta-based company Ciba Vision also is testing glucose-sensing contact lenses.

Wearing a contact lens or having a skin implant would not only be more convenient than finger-pricking; it would likely also be safer, because people would be more likely to test their levels regularly.

"Compliance to the diabetes regimen is demanding and very stressful, especially for children," said Finegold.

"I got into this business to make the lives of people -- especially kids who have this horrible disease -- better," he said. "This is probably one of the most exciting projects I've had the chance to participate in."

First published on July 15, 2003 at 12:00 am
Karen Hoffmann can be reached at khoffmann@post-gazette.com or 412-263-1994.
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