Scientists have developed a new biochip sensor that can measure concentrations of glucose in a complex solution similar to human saliva.
The advance is an important step toward a device that would enable people with diabetes to test their glucose levels without drawing blood.
Researchers from Brown University developed the new chip that makes use of a series of specific chemical reactions combined with plasmonic interferometry, a means of detecting chemical signature of compounds using light.
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“We have demonstrated the sensitivity needed to measure glucose concentrations typical in saliva, which are typically 100 times lower than in blood,” said Domenico Pacifici, assistant professor of engineering at Brown, who led the research.
“Now we are able to do this with extremely high specificity, which means that we can differentiate glucose from the background components of saliva,” Pacifici said.
The biochip is made from a one-inch-square piece of quartz coated with a thin layer of silver. Etched in the silver are thousands of nanoscale interferometers – tiny slits with a groove on each side.
When light is shined on the chip, the grooves cause a wave of free electrons in the silver, a surface plasmon polariton, to propagate toward the slit.
When a liquid is deposited on the chip, the light and the surface plasmon waves propagate through that liquid before they interfere with each other.
That alters the interference patterns picked up by the detectors, depending on the chemical makeup of the liquid.
By adjusting the distance between the grooves and the center slit, the interferometers can be calibrated to detect the signature of specific compounds or molecules, with high sensitivity in extremely small sample volumes.
In the study, researchers used dye chemistry to create a trackable marker for glucose. The researchers added microfluidic channels to the chip to introduce two enzymes that react with glucose in a very specific way.
The first enzyme, glucose oxidase, reacts with glucose to form a molecule of hydrogen peroxide. This molecule then reacts with the second enzyme, horseradish peroxidase, to generate a molecule called resorufin, which can absorb and emit red light, thus colouring the solution.
The researchers could then tune the interferometers to look for the red resorufin molecules.
The team tested its combination of dye chemistry and plasmonic interferometry by looking for glucose in artificial saliva, a mixture of water, salts and enzymes that resembles the real human saliva.
They found that they could detect resorufin in real time with great accuracy and specificity.
They were able to detect changes in glucose concentration of 0.1 micromoles per litre – 10 times the sensitivity that can be achieved by interferometers alone.
The research is published in the journal Nanophotonics.