IBM which began the project in 2007, aims use its considerable semiconductor manufacturing expertise, combined with computing and material science, to design an integrated sequencing machine that will offer advances both in accuracy, speed, and lower the cost.

“More and more of biology is becoming an information science, which is very much a business for IBM,” said Ajay Royyuru, (right) senior manager for  the computational biology center at the New York Thomas J. Watson Laboratory.

DNA sequencing began in the 1970s with the original Human Genome Project  which sequenced the first genome in 2001 at a cost of roughly $1bn. 

In the last few years,  sequencing cost has been falling at a rate of tenfold annually says Harvard geneticist  George M. Church (left) who expects industry to hold that or some fraction of that improvement rate, for the foreseeable future.

Some 17 startup and existing companies are now in the sequencing race, pursuing a range of third-generation technologies. Sequencing the human genome now costs $5,000 to $50,000. Dr. Church emphasised that none of the efforts so far had been completely successful. No research group had yet sequenced the entire genome of a single individual.

Sequencing power and speed essentials
The IBM approach uses a “DNA transistor,” hoped to be capable of reading individual nucleotides in a single strand of DNA aspulled through a nanopore. The system would consist of two fluid reservoirs separated by a Si membrane with up to 1m nanopores array  to sequence vast quantities of DNA at once.

The goal is to build a machine with the capacity to sequence an individual genome of up to 3bn bases, or nucleotides, “in several hours." This power and speed is essential if progress is to be made toward personalised medicine say  researchers.

Central to the system is nanoscale electric tweezer mechanism, repeatedly pausing a neutrally charged strand of DNA,  while an electric field pulls the strand through the three nanometers diameter nanopore.
 
Researchers have successfully used a transmission electron microscope to drill a hole through a semiconductor device intended to “ratchet” the DNA strand through the opening, stop for perhaps a millisecond to determine the nucleotide base order — adenine, guanine, cytosine or thymine — that make up the DNA molecule. The project can now reliably pull DNA strands through nanopore holes. But sensing technology to control the movement rate and read specific bases has yet to be demonstrated.

“DNA strands seem to have a mind of their own,” Elaine Mardis,  (right) co-director of the genome center at Washington University in St. Louis is quoted, noting that DNA often takes a number of formations other than a straight rod as it passes through a nanopore and previous efforts to create uniform silicon-based nanopore sensors had been disappointing.

Crucial  to improve the quality of DNA analysis is ability to read longer sequences. Current technology is y in the range of 30 to 800 nucleotides. The goal is to be able to read sequences of as long as 1m bases, according to Dr. Church.

Other approaches to faster, cheaper sequencing include a biological nanopore approach pursued by UK Oxford Nanopore Technologies,  and an electron microscopy-based system being designed by Halcyon Molecular, a Silicon Valley start-up with a technique for stretching DNA single strands  on thin carbon film. The company may be able to image strands as long as one million base pairs, says Dr. Church, who acts as adviser to Halcyon and others.