Genes linked to cancer could be easier to detect with liquid lasers
This work could advance understanding of the genetic basis of disease. It also has applications in personalized medicine, which aims to target drugs and other therapies to individual patients based on a thorough knowledge of their genes.
The researchers say their technique works much better than the current approach, which uses fluorescent dye and other biological molecules to find and bind to mutated DNA strands. When a patrol molecule catches one of these rogues, it emits a fluorescent beacon. This might sound like a solid system, but it’s not perfect. The patrol molecules tend to bind to healthy DNA as well, giving off a background glow that is only slightly dimmer than a positive signal.
“Sometimes, we can fail to see the difference,” said Xudong Fan, an associate professor of in the Department of Biomedical Engineering and principal investigator on the project. “If you cannot see the difference in signals, you could misdiagnose. The patient may have the mutated gene, but you wouldn’t detect it.”
In the conventional fluorescent technique, the mutated DNA signal might be only a few tens of percent higher than the background noise. With Fan’s new approach it’s hundreds of times brighter.
“We found a clever way to amplify the intrinsic difference in the signals,” Fan said.
He did it with a bit of backtracking. Liquid lasers, discovered in the late ‘60s, amplifies light by passing it through a dye, rather than a crystal, as solid-state lasers do. Fan, who works at the intersection of biomedical engineering and photonics, has been developing them for the past five years. In his unique set-up, a glass capillary called a “ring resonator cavity” amplifies the laser signal.
Last year, Fan and his research group found that they could employ DNA to modulate a liquid laser, or turn it on and off. His group is one of just a few in the world to accomplish this, Fan said. At the time, they didn’t have a practical application in mind. Then they had an epiphany.
“We thought, ‘Let’s look at the laser output. Can we see what’s causing the different outputs and use it to detect differences in the DNA?’” Fan said. “I had an intuition, and it turns out the output difference was huge!”
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