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Instead of unpleasantly pricking their fingers, diabetics may one day simply spit onto a sensor in order to keep their glucose levels in check, thanks to technology being developed by Brown researchers.

The team of faculty, graduate students and undergraduates reported its findings in a paper published online Dec. 26 in the journal Nano Letters.

Though they have not yet made a prototype, the team has a provisional patent and is seeking a way to develop their idea into an actual product, said Domenico Pacifici, assistant professor of engineering and an author of the paper. "The technology is there, it's just a question of design," he said.

"We were dreaming, what if you could do it on an iPhone?" Pacifici said. In theory, the team's experimental setup could be scaled down into a single chip that could then be implanted onto a smartphone. A user could put a small saliva sample on the chip and immediately know his or her glucose levels. "That would be a cool app," he said.


Fingerprints instead of pricks

The underlying concept behind the team's idea is the interaction of electromagnetic waves on the surface of a silver film. Devices that measure these wave interference patterns are called interferometers, and the team built thousands of them into sensors. Each interferometer, only micrometers long, consists of a slit and two shallow grooves etched onto the silver surface.

When light strikes the film, the wave patterns on the surface create a specific "fingerprint" depending on how the grooves and slits are arranged, said Tayhas Palmore, professor of engineering and an author of the paper. A liquid on top of the film changes how the waves interfere, and thus shifts the fingerprint. The size of the shift can be directly correlated to the glucose concentration of the liquid. 

This technique is "really trying to push the boundaries of what we know," said Pacifici. When he introduced the idea to the graduate students in his lab, they were skeptical. "I think they thought I was kind of crazy," he said. But to see his idea become a reality, he said, is "the best thing ever."

Alec Roelke '12 and Vihang Mehta '12 have been working with Pacifici for over a year and are the two undergraduate authors of the paper. Roelke carried out the computer simulations that predicted the wave patterns, while Mehta collected experimental data from the interferometers the team manufactured themselves. When the researchers looked at the predicted and observed fingerprints side by side, the patterns matched up surprisingly well, Mehta said. "It was a point of big success."

Jing Feng GS and Vince Siu GS, the first authors of the paper, designed and built micro-channels to carry glucose solution through a chip containing thousands of interferometers. The chip can measure extremely small changes in glucose concentrations and requires only 20 femtoliters of fluid­. To put that in perspective, one milliliter contains 1 trillion femtoliters.


A sweet possibility

But there are foreseeable challenges in developing this technology into a functional device. The team's tests were carried out using solutions containing only glucose, "but there's a lot of other stuff in saliva," Pacifici said. There are several ways to get around that, he said, such as incorporating a filter into the device.

Alternatively, "you could find a glucose signature" in the fingerprint and isolate that signal to determine the glucose concentration, Palmore said.

The project did not start out with the goal of creating a device for diabetes. Originally, the team was focused on ways to monitor cytokines, which are indicators released in the blood after an injury, said Mehta

Palmore was the one who suggested trying to monitor glucose, which she said presents a bigger and simpler target than cytokines. In scientific research, diabetes "is one of the holy grails," Pacifici said. "We got a lot of emails from parents, asking us, ‘Please keep working on this.'" Especially for young children, finger pricks can be a painful and unpleasant way of checking glucose, so diabetes patients are eager for a better option. 

Ava Runge '15 was diagnosed with Type 1 diabetes in high school and still tests her blood five or six times a day. Though Runge said she is used to the sensation of pricking the same spot on her hand all the time, she said that she does not always check her blood when she should, because "it's an extra inconvenience and a lot of setup." Runge said she would use a device if it required her to check her glucose less frequently.

One question that remains is whether saliva glucose concentrations are accurate indicators of blood glucose concentrations ­— and this correlation is essential for the usefulness of the potential device. The team could not find any systematic studies definitively linking the two, said Pacifici, but their device could end up being a tool in such a study. 

Even if the device is not applicable to diabetes, Palmore said, the potential for this technology is immense, since it can measure the amount of a substance with incredible sensitivity. 

For example, doctors could eventually do full blood screening tests on the same chip, Pacifici said. For engineers, "this is dreaming," he said.


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