Making DNA sequencing cheap enough for everyone on the planet would reap immeasurable benefits to individuals by identifying their genetic predispositions, pinpointing medicines that are likely to help and drugs that are likely to cause adverse reactions. The treasure trove of data reaped could also harvest a bounty of new gene therapies that cure diseases that have been resistant to traditional treatment methods. Now IBM has pooled its resources in nanofabrication, microelectronics, physics and biology to make this dream a reality.
IBM is solving the technological problems of "personal genome sequencing" in a new project unveiled today by its chairman, Sam Palmisano, at the Medical Innovation Summit (Cleveland Clinic, Oct. 5-7, 2009). Palmisano will describe a project that harnesses IBM's state-of-the-art 8-inch semiconductor fabrication equipment to simultaneously manufacture hundreds of gene-sequencers-on-a-chip. Each chip would then power a genome sequencing device that identifies every base in a person's entire 3 billion-nucleotide DNA sequence in about an hour.
"Our goal is to sequence a person's DNA with our chip at about a megahertz [a million nucleotide bases per second], which would take about an hour per person to sequence all 3 billion bases in their DNA," said Steve Rossagel, a researcher working on the project at IBM's T.J. Watson Research Center, in Yorktown Heights, N.Y.
IBM's data processing prowess makes it a good candidate for tackling this task because even though each person's DNA will need to be sequenced just once, there will be an endless need for massive subsequent data processing tasks that scan, analyze and design gene therapies for curing the maladies identified.
"Since there are billions of people on the planet, you begin to appreciate the magnitude of the task of collecting and processing all that data," said Rossagel.
To meet the challenge, IBM is repurposing its previously reported "DNA transistor" to automate the genome sequencing procedure. The DNA transistor, which IBM revealed last year, was fabricated with a traditional metal gate, but with liquid electrodes for the transistor's source and drain in two small chambers on each side of the chip. This architecture was adapted to the DNA sequencer project by adding two more layers of metal (for three total, each separated from the other by an insulator), then drilling a 3-nanometer hole—called a nanopore—through the stack to connect the two liquid chambers.
When DNA strands were put in one chamber that was negatively charged, they were attracted to the positive charge applied to the other liquid chamber. As the DNA strand was sucked through the hole by the electric charge, it traversed the three electrodes lining the nanopore, which IBM plans to use to sense each base on the strand as it passes.
"What we are doing is using an electric field to control the flow of DNA strands in the nanopore," said Stas Polonsky, another IBM researcher working on the project. "By applying voltages to the metal layers lining the nanopore, we create potential wells, which interact with the charges along the backbone of the DNA strand, moving it along one base at a time."
IBM says that within three years it will have solved most of the technological problems. If all goes well, IBM predicts that personal genome sequencers will reduce the cost of the task to under $1,000, and possibly to as low as $100, compared with the $3 billion spent by the Human Genome Project to sequence the first human DNA strand.
