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MEETING NEWS Kim Krieger reports from the American
Physical Society Meeting—Baltimore, Md.
Nanopore arrays for DNA sequencing
XINSHENG SEAN LING
the background current. Ling and colsible combinations! Running each sepaSequencing an entire genome can take leagues got around that problem by years. Xinsheng Sean Ling and colleagues rately through a single nanopore would applying a steady voltage to cancel out take too long. at Brown University hope to reduce the the electrochemical potential difference “Five years ago, there was only one time to mere days by using arrays of across the silicon chip. Jumps from openway to make solid-state nanopores. At nanopores. The investigators have develing pores were obvious spikes against a that time, no one knew how to make oped a new technique to etch hundreds quiet background. of nanopores on a single silicon When the silicon chip was chip. They hope to automate withdrawn from the solution, it the DNA sequencing process had a line of pores along each by mapping small sections of canal. The team outfitted each a DNA sample with each of the pore with a PDMS microfluidic nanopores in the array. channel and wired the entrance The original idea of sequencand exit openings with AgCl ing DNA with nanopores, conelectrodes. When the sample ceived by John Kasianowicz and DNA was added to a pore and co-workers in 1996, proposed an electric field switched on, that a strand of DNA threading the DNA, which is negatively through a nanopore in a memcharged, zipped through the brane would block the flow of pore. The section that latched charged ions through the pore. onto a probe showed up in the The bases differ slightly in size: signal when it clogged the ionic For example, hefty adenine flow. would block the flow of ions However, unencumbered more effectively than smaller One nanopore can test one probe, revealing where that probe’s DNA zipped through the pore guanine. By measuring the sequence appears on the DNA strand passing through the too speedily for the researchers amount of current passing pore. An array of nanopores can test all possible probes. By to precisely position the probe through the pore, a researcher lining up their appearances in time, researchers can reconon the strand. Ideally, one probe would be able to read the base struct the DNA sequence. should pass through the pore sequence. Unfortunately, the only every few milliseconds, giving the many pores on a single chip,” states technique didn’t work. The problem researchers time to obtain a clear signal. Ling. Now, his group has figured out is that the pore is too big, and several To slow down the sample, “we put a how to do it at low cost. They took a bases can fit inside simultaneously, avermagnetic bead onto the tail of a DNA silicon chip and sliced several long, aging out the signal. and use a magnet to pull on the bead. straight canals into the surface. They Ling believes it’s impossible to make But we keep the electrical field on, so etched one side of the chip with a solua pore small enough to fit just a single it keeps exerting force on the DNA, base. Instead of lamenting the girth of a tion of KOH; the other side was impulling the DNA downward through mersed in KCl. nanopore, Ling decided to exploit it. In the pore. So we have a tug-of-war. The The electrochemical potential differ2005, he and his group patented their DNA’s speed is determined by the balence between the KOH and the KCl idea of using 6-to-8-base DNA probes ance of the forces,” says Ling. caused a spontaneous electrical current that would latch on to a strand of DNA Currently, Ling and his colleagues to flow through the chip, like in a batto be sequenced wherever there was a are applying the magnetic-bead techmatch. A double strand passing through tery. When a pore opened, the current nique on a long piece of DNA with cusjumped. By carefully monitoring the a pore blocks 2 as many ions as a sintomized sequences designed for matchcurrent, Ling and his colleagues could gle strand, making an obvious dent in ing probes. Ling expects to see DNA the current. But to thoroughly sequence judge when enough nanopores had probes with his team’s nanopores “pavformed. Previous attempts to keep tabs a strand of DNA, a researcher would ing the way for demonstrating sequencon pore growth by monitoring the curneed to test every possible probe—for ing next year.” an 8-mer, that would mean 65,536 pos- rent were foiled by the steady hum of 3486
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