Image: D. DEAMER / UCSC
From diagnostic testing to molecular computing, scientists would like to have the means to distinguish between nearly identical strands of DNA. And in a report in this month's issue of Nature Biotechnology, researchers from the University of California at Santa Cruz describe a prototype device that might just offer a solution. David Deamer and his colleagues have developed a membrane containing a tiny pore that sucks in hundreds of single strands of DNA a second, analyzes them and then spits them back out¿as if "tasting the solution," Deamer says.
The nanopore is in fact an alpha-hemolysin ion channel, a kind of toxin that Staphylococcus bacteria use to punch holes in cell membranes. At its mouth, the pore is about 2.5 nanometers wide¿just wide enough for a double-stranded DNA molecule to enter (top image). Farther in, however, the channel narrows to less than 2 nanometers so that only single strands pulled from the double strand can continue on through (bottom image).
The negatively charged DNA molecules are sucked into the pore in the first place by an ionic current, generated by applying voltage across the membrane. In the experiment, the scientists used synthetic DNA molecules, folded in two like hairpins. They further used machine learning methods to train a program to recognize signals from these different but similar DNA molecules. Deamer notes that with a few modifications, the detector might help in rapid DNA sequencing or in detecting so-called single nucleotide polymorphisms (SNPs). "But the best application," his colleague Mark Akeson adds, "may be entirely unforeseen by any of us."