The IBM researchers are now performing simulated experiments to refine the chip’s design. The properties of the system can be varied by, for example, changing the thickness of the layers that make up the electrodes and the size of the pore. The movement of the DNA can also be altered using different voltages in the electrodes. Instead of fabricating every potential chip design and testing every voltage, however, the researchers are modeling the nanopore system using an IBM Blue Gene supercomputer. The software running on this machine can calculate the physics of tens of thousands of atoms in the DNA molecule and in the chip every picosecond. A version under development will enable them to model 200,000 atoms at this rate, says Stolovitzky.
The IBM group is working on methods for sensing each base as it passes through the pore. With modifications, Stolovitzky says, the same electronics used to control the movement of the DNA could also be used to measure electrical properties that distinguish the bases making up the genetic code.
“We look at this as a data problem,” says Stephen Rossnagel, a researcher at IBM Watson. Sequencing a genome today, Rossnagel says, involves making sense of three gigabits of data that’s “mixed up” and has to be put back together. Directly reading pieces of DNA without chopping them up simplifies this problem, and the DNA transistors could be made in large arrays, each reading the same sequence. The more times the same stretch of the genome is read, the better the quality of the resulting sequence. Rossnagel says the approach IBM is pursuing should be simpler to integrate with the microelectronics needed to crunch the resulting data.
According to Schloss, the IBM nanopores, which could be fabricated in large arrays, could prove more practical than previous efforts. “The ways this has been done before don’t lend themselves to sequencing,” he says. Some groups have slowed the movement of the DNA across a pore by attaching a bulky molecule to it that must be pushed down the strand as it passes through the nanopore. Others have stationed an enzyme at the pore that cuts the strand and passes the bases through individually. Controlling the movement of the DNA with microelectronics might prove more practical, and it seems to allow for better control, says Schloss.