Genes linked to cancer and other diseases may now be easier to detect with a new method that uses liquid lasers to distinguish mutated DNA from healthy DNA by a single base. Researchers at the University of Michigan say their technique works 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 the mutated genes, it emits a fluorescent beacon. Although it sounds effective, 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. Using this liquid laser, University of Michigan professor Xudong Fan and his team have developed a highly sensitive technique to identify mutated DNA that differs from healthy DNA by a single base. The fine white horizontal line is the capillary cavity that enables the laser to amplify the intrinsic difference in the light signals from healthy and mutated DNA. (Image: Nicole Casal Moore) “Sometimes, we can fail to see the difference,” said Xudong Fan, an associate professor 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 fluorescence method, the mutated DNA signal may be only a few tenths of a percent higher than the background noise. With Fan’s approach, the signal is hundreds of times brighter. “We found a clever way to amplify the intrinsic difference in the signals,” Fan said. To amplify the difference, he did a bit of backtracking. Researchers have developed a highly sensitive technique based on laser emission for differentiating a target DNA strand from strands that contain single base mismatches. Laser emission is used to amplify the small difference in signals that are generated by the different strands after they bind with a molecular beacon. The conversion is similar to analog-to-digital. (Image: Christopher Burke) Liquid lasers, discovered in the late 1960s, amplify light by passing it through a dye, rather than a crystal, as solid-state lasers do. Fan has worked to develop these for the past five years. In his unique setup, the signal is amplified in a glass capillary called a “ring resonator cavity.” Last year, Fan and his team discovered that they could employ DNA to turn a liquid laser on and off. His group is one of just a few in the world to accomplish this, Fan said. At the time, they had no practical applications in mind. That is, until now. Fan and his group began to investigate what was causing the different laser outputs, using their findings to detect differences in the DNA. “I had an intuition, and it turns out the output difference was huge,” Fan said The discovery could advance the understanding of the genetic basis of diseases and also prove useful for applications in personalized medicine, which aims to target drugs and other therapies to individual patients based on a thorough knowledge of their genetic information. The group’s findings are reported in Angewandte Chemie. The university is in pursuit of patent protection for the intellectual property and is seeking commercialization partners to help bring the technology to market. For more information, visit: www.engin.umich.edu