Nanofluidics sorts DNA one molecule at a time to study cancer-causing changes

Cornell nanotechnology researchers have devised a new tool to study epigenetic changes in DNA that can cause cancer and other diseases: a nanoscale fluidic device that sorts and collects DNA, one molecule at a time.

Epigenetics refers to chemical changes in DNA that do not alter the actual genetic code, but can influence the expression of genes and can be passed on when cells reproduce. One of the most important is DNA methylation, where methyl groups -- small structures of carbon and hydrogen -- are appended to DNA. Biologists study this by chemically precipitating out the methylated molecules, but these methods require large samples and often damage or throw away molecules they are supposed to find. Nanofluidics offers a way to select individual molecules out of tiny samples and collect them for further study.

The new device, developed in the lab of Harold Craighead, the Charles W. Lake Jr. Professor of Engineering, is described in the May 21 early online edition of the Proceedings of the National Academy of Sciences.

The process begins with a biochemical reaction that attaches a fluorescent tag to methylated DNA molecules. Then the sample is driven through a nanofluidic channel about 250 nanometers across -- so small that DNA molecules go through one at a time. Lasers illuminate the stream and cause fluorescence. When a fluorescing molecule goes by, a detector triggers a pulsed electric field that pushes the molecule to one side just before the channel splits into a Y. Methylated molecules go down one branch, everything else down the other.

"The color identity becomes a barcode for how the molecules are treated," explained Ben Cipriany, Ph.D. ’12, lead researcher on the project, drawing an analogy to the methods used by the post office to sort packages on a conveyor belt. "Eventually we could use multiple colors, each representing a different epigenetic characteristic," he added.