IBM scientists are developing microchips for genome sequencing.




This has certain potential for archaeology, especially those sites
where the objects and subjects have become suspect of being mixed.


Tuesday, October 06, 2009
Big Blue's DNA-Reading Chips
IBM scientists are developing microchips for genome sequencing.
By Katherine Bourzac

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.

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.

http://www.technologyreview.com/biomedicine/23589/?nlid=2407
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