Brown University biochip may lead to saliva glucose detector

Brown University researchers have created an experimental biochip that may one day test for miniscule levels of glucose in saliva rather than requiring diabetics to suffer repeated and painful finger pricks, lead scientist Domenico Pacifici told Mass High Tech in an interview.

The researchers used a technique called plasmonic interferometry — a convergence of nanotechnology and surface plasmonics, which explores the interaction of electrons and photons (light). Pacifici, an assistant professor in Brown’s School of Engineering in Providence, R.I., said the experimental device holds promise for other types of tests. He said surgeons already have expressed interest in the technology to check levels of cytokines, which are small cell-signaling molecules released when someone suffers an injury. By monitoring cytokine levels on a battlefield, for example, surgeons can determine the best time to operate on a patient with multiple injuries, he said.

“It could be possible to use these biochips to carry out the screening of multiple biomarkers for individual patients, all at once and in parallel, with unprecedented sensitivity,” Pacifici said. The results of the research, which resulted in a proof-of-concept biochip, were published in a recent issue of Nano Letters.

Each plasmonic interferometer — there are thousands of them per square millimeter — consists of a slit flanked by two grooves etched in a silver metal film. Changes in light intensity transmitted through the slit of each plasmonic interferometer provide information about the glucose concentration.

Some 26 million Americans have diabetes and typically check their glucose level by drawing blood, often with a pin prick to the finger tip, he said. “Finger pricks are not convenient, and compliance is a problem, especially in little kids,” Pacifici said. “Our test would be something that you put in your mouth for a few seconds, and then insert into a test machine to read it.”

A challenge for Pacifici and his fellow researchers is that glucose in human saliva is typically about 100 times less concentrated than in the blood. That is why they turned to plasmonic interferometers, which can pick up on such small concentrations.

“This is a proof of concept that plasmonic interferometers can be used to detect molecules in low concentrations, using a footprint that is 10 times smaller than a human hair,” he said. The technique could be used to detect other chemicals or substances, from anthrax to biological compounds at the same time on the same chip, he added.

To create the sensor, the researchers carved a slit about 100 nanometers wide and etched two 200 nanometer-wide grooves on either side of it. The slit captures incoming photons and confines them. The grooves scatter the incoming photons, which interact with the free electrons on the sensor’s metal surface. Those free electron-photon interactions create surface plasmon polaritons, special waves that move along the sensor’s surface until they meet the photons in the slit, like two ocean waves coming from different directions and colliding with each other. This wave interference determines the light intensity transmitted through the slit. The presence of the chemical measured on the sensor’s surface generates a change in the relative phase difference between the two surface plasmon waves, which in turn causes a change in light intensity.

The National Science Foundation and Brown funded the research. Pacifici said he is looking for more funding externally to move the project along more quickly. That could include a spinout company. Brown has filed a provisional patent on the technology.

Pacifici said he expects to develop a prototype in the next two years, and within five years to start testing the device. He and his co-workers are now building a database of the different components of saliva that will help them hone the current biochip for detecting glucose. Saliva contains about 99 percent water, but the remaining 1 percent includes various cells and glucose, so the biochip needs to be made more specific.

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