Molecular beacons would be ideal diagnostics for detecting point
mutations in disease genes if they weren’t so hard to
distinguish. These noose-shaped DNA segments are engineered to
light up when they bind to target DNA, such as a mutated cancer
gene. However, it has been difficult to detect the difference
between complete complementarity and binding that is mismatched
by one or two nucleotides, because an imperfect match still has
a chance—though a smaller one—of binding and fluorescing. Xudong
Fan and Yuze Sun of the University of Michigan bypassed the
problem by creating an amplification step based on physics
rather than biochemistry. They inserted the molecular beacons
and target sequences that differed by one nucleotide into the
head of a liquid laser, thereby replacing the laser’s light-
generating crystal or usual liquid dye with the sample medium.
When mismatched, the probes lit up in the laser chamber, but the
fluorescence was not strong enough to create the feedback needed
to initiate an emitted lase