Hasta La Gadget!

Researchers at IBM have found a way to meld biology and computing to create a new chip that could become the basis for a fast, inexpensive, personal genetic analyzer. The DNA sequencer involves drilling tiny nanometer-size holes through computer-like silicon chips, then passing DNA strands through them to read the information contained in their genetic code.

“We are merging computational biology and nanotechnology skills to produce something that will be very useful to the future of medicine,” Gustavo Stolovitzky, an IBM researcher, told Wired.com.

The “DNA transistor” could make it faster and cheaper to sequence individuals’ complete genomes. In so doing, it could help facilitate advances in bio-medical research and personalized medicine. For instance, having access to a person’s genetic code could help doctors create customized medicine and determine an individual’s predisposition to certain diseases or medical conditions.

Such a device could also reduce the cost of personalized genome analysis to under $1,000. In comparison, the first complete sequencing of a human genome, done by the Human Genome Project, cost about $3 billion when it was finally completed in 2003. Since then, other efforts have attempted to achieve something similar for a much lower cost. Stanford researcher Stephen Quake recently showed the Heliscope Single Molecule Sequencer that can sequence a human genome in about four weeks at a cost of $1 million. Services such as 23&me offer DNA testing for much less, but only do partial scans, identifying markers for specific diseases and genetic traits rather than mapping the entire genome.

Because of the expense, so far only seven individuals’ genomes have been fully sequenced. IBM’s personalized DNA readers, if successful, could extend that privilege to many more people.

“If there’s a chance that this could go behind the counter at hospitals, clinics and someday even a black bag then it would change how we approach medicine,” says Richard Doherty, research director at consulting firm Envisioneering Group. “All it would take is a simple test to look at anyone genes.”

DNA, or Deoxyribonucleic acid, contains the instructions needed for an organism to develop, survive and reproduce. A gene comprises the set of instructions needed to make a single protein. For humans, the complete genome contains about 20,000 genes on 23 pairs of chromosomes.

IBM scientists hope to change that by taking advantage of current chip-fabrication technology. Researchers took a 200-millimeter silicon-wafer chip and drilled a 3-nanometer-wide hole (known as a nanopore) through it. A nanometer is one one-billionth of a meter or about 100,000 times smaller than the width of a human hair.

The DNA is passed through the nanopore. To control the speed at which it flows through the pore, researchers developed a device that has a multilayer metal and dielectric structure, says Steve RossNagel, a researcher at IBM’s Watson lab in New York.

This metal-dielectric structure holds the nanopore. A modulated electric field between the metal layers traps the DNA in the nanopore. Since the molecule is easily ionized, voltage drops across the nanopore help “pull” the DNA through. By cyclically turning on and off these gate voltages, scientists can move the DNA through the pore at a rate of one nucleotide per voltage cycle –- a rate the researchers believe would make the DNA readable. IBM hasn’t specified how fast a strand of DNA can be read, though researchers say a fully functional device could sequence the entire genome in “hours.”

Ultimately, several such nanopores can run parallel on a chip to create a complete genomic analyzer.

Though researchers have figured out the basics, it could still take up to three years to get a working prototype. The challenge now is to slow and control the motion of the DNA through the hole so the reader can accurately decode what is in the DNA.

They also need to determine exactly how the DNA will be decoded when it passes through the nanopore. It’s an area of “intense research” within and outside of IBM, says Stolovitzky. One way to do it would be to measure the electrical properties of the different DNA bases such as capacitance and conductivity.

“This is a knowledge that most people would like to have,” says RossNagel. “If we could have a big enough database of human genomes then you can see the interplay of genetics. That would change how we approach medicine.”

Top Photo: A cross section of IBM’s DNA Transistor simulated on the Blue Gene supercomputer shows a single stranded DNA moving in the midst of invisible water molecules through the nanopore/ IBM

See Also:

• DNA May Help Build Next Generation of Chips
• Slideshow: DNA Spirals Into Artists’ Medium
• DNA Tests May Flunk African History

In the video below, IBM researchers explain how they came up with the idea for the DNA Transistor. The video includes an animated simulation showing a DNA strand moving through the nanopore.