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Icons of Progress
 

The DNA Transistor

IBM100 The DNA Transistor iconic mark
 

Hopes were high for major advances in medicine when the US$2.7 billion Human Genome Project was launched in 1990, by the US Department of Energy and the National Institutes of Health. There was a tremendous sense of accomplishment when the mapping of the genome was declared to be finished in 2003.

Yet, even today, fewer than 50 people in the world have had their entire genome sequenced and made available for research. Until the procedure is done for large numbers of individuals, medical scientists won’t be able to achieve major breakthroughs in disease diagnosis and personalized medicine. The primary issue is expense. While the cost of sequencing DNA has dropped dramatically over the past decade, it’s still expensive—about US$10,000 per individual. Scientists say the cost will have to drop to near US$100 before the full potential of the advances in genomic research can be realized.

That’s where IBM Research comes in. By combining genetics with semiconductor technologies, at the Watson Research Lab in New York in 2007, scientists Gustavo Stolovitzky and Stanislav Polonsky invented a mechanism, which they called the IBM ® DNA Transistor, designed to make it possible to sequence genetic material accurately and cheaply—eventually, they hope, for a few hundred US dollars per person. Their project is among a handful of promising initiatives that could bust open the field of genetics in the relatively near future. “How low can we go in price?” asks George Church, a professor of genetics at Harvard Medical School. “There are all sorts of applications where computing and sample preparation aren’t limiting and the price can keep going down.”

Here’s how the DNA Transistor works: A silicon membrane is placed vertically in a solution-filled chamber, dividing it in two. Strands of genetic material are placed in one side of the chamber, and electrical charges are applied—negative in the part of the chamber where the genetic strands reside, and positive on the other side. The positive charge draws a strand of genetic material into a tiny opening, or nanopore, in the membrane. As the strand passes through the opening, the combination of the electrical charges and the composition of the membrane have the effect of ratcheting the strand through one bead of genetic material at a time. This mechanism makes it possible to accurately and quickly read the genetic makeup of the strand.

The invention came about through serendipity. In 2007, Stolovitzky, who specializes in genomics, and Polonsky, who specializes in semiconductors and physics, had a chance meeting in a corridor at the IBM Research building in Yorktown Heights, NY. They began talking about some of the challenges in biology. Stolovitzky said great things could be accomplished in medical science if researchers had the ability to sequence an individual’s entire genome quickly and inexpensively. The two discussed the possibility of using semiconductor technology to help create a quick and inexpensive gene sequencing machine. Within a few weeks they came up with the idea for what we now call the DNA Transistor.

The project took a major step forward in July 2010, when IBM and Swiss pharmaceutical giant Roche announced a joint effort to develop a commercial gene sequencer based on the DNA Transistor. There are plenty of challenges remaining. The IBMers have shown through simulations and experiments that the ratcheting effect should work. Now, with Roche scientists, they have to do more inventing to put the concept into practice. The goal is to have a functioning prototype soon. “We are working toward this goal and, so far, physics hasn’t been screaming against us. There are engineering problems but they’re the kinds of things we can solve,” says Stolovitzky.

The DNA Transistor is an example of how the interdisciplinary nature of IBM Research can yield scientific breakthroughs that are unlikely to come from academics or corporate researchers who concentrate on a single domain. By combining expertise in genomics, physics and high-performance computing, IBM is helping to produce major advances in genetics research. “Technology has opened the aperture of what you can observe, so it’s inviting us to comprehend more and more of the universe that surrounds us, the genomic universe,” says Ajay Royyuru, who heads the Computational Biology Center at IBM Research.

Thanks to such advances, for the first time in our 200,000-year history, we humans are at last coming to truly know ourselves.

Now the race is on to exascale computing—a thousand-fold increase to be achieved by using new technologies like light pulses or nanoscale carbon tubes to move beyond today’s chips and interconnects.

Recent announcements from IBM Research around CMOS Integrated Silicon Nanophotonics may help IBM take the lead in that race. This new exascale technology integrates electrical and optical devices on the same piece of silicon, enabling computer chips to communicate using pulses of light—instead of electrical signals—resulting in smaller, faster and more power-efficient chips than is possible with conventional technologies.

By integrating optical devices and functions directly onto a silicon chip, enabling 10 times the current processing power, the current rules and limitations concerning processing power and speed will be rewritten. A new generation of high-performance computing is being born, with IBM once again breaking new ground in the intersection of science and business.

 

Selected team members who contributed to this Icon of Progress:

  • Ajay Royyuru Senior Manager of the Computational Biology Center at IBM Research in New York
  • Gustavo Stolovitzky IBM Researcher, Manager of the Functional Genomics and Systems Biology Group
  • Stanislav Polonsky IBM Researcher, Circuit Test and Diagnostics Technology, Device Physics
  • Stephen M. Rossnagel IBM Researcher, Materials Science, Semiconductor Applications
  • Hongbo Peng IBM Researcher, Physics, Nanopore DNA Sequencing
  • Roche / 454 Life Sciences Team Global healthcare company and co-developer of DNA Transistor