IBM researchers are developing a chip for cheaper, faster DNA sequencing using fabrication techniques refined through semiconducting manufacturing. The chip uses layered electrodes to control the movement of individual DNA molecules and exploits a technique called nanopore sequencing. The approach could allow DNA to be passed through a sensor that would rapidly read off its genetic code.
Nanopore sequencing is attractive because, unlike existing sequencing methods, it could read long stretches of DNA without the need for labels or chopping and amplifying enzymes. “If this works, you should be able to read tens of thousands of bases with no labels, making it cheap and fast,” says Jeffery Schloss, program director for technology development at the National Human Genome Research Institute. Being able to read long stretches of DNA without chopping it up would also make the data-processing side of genome sequencing simpler. “If you can do long reads, you don’t have to make assumptions about the sequence or match it to existing sequences” in order to put it back together, says Schloss.
Several research groups are developing their own approach to nanopore sequencing. All involve the movement of DNA molecules through a tiny pore one base at a time; as the bases move through the pore, they can be read using various techniques. But one of the biggest obstacles to making a practical nanopore sequencer has been controlling the rate of the movement of the DNA. This is the problem the IBM group is working on. “The DNA goes through the pore too fast,” says Gustavo Stolovitzky, manager of functional genomics and systems biology at IBM’s T. J. Watson Research Center in Yorktown Heights, NY.
For the past two years, Stolovitzky’s group at IBM has been developing chips arrayed with “DNA transistors” that use layered electrodes to control the movement of the DNA. The electrodes are built on the company’s research fabrication line using the same technology employed to make silicon integrated circuits.
The IBM researchers first deposit conducting and semiconducting materials that will act as electrodes onto silicon wafer layers each about three nanometers thick. Then they use a transmission-electron microscope to blast a hole as small as one nanometer in diameter in the stack. A chip is cut from the wafer and placed in the middle of a container of potassium chloride, like a partition. DNA molecules are placed on one side of the solution, and a voltage is applied across the chip. Because DNA has an electrical charge, the IBM researchers can control its movement through the pore by using the electrodes to create electrical fields.