Applied Biosystems preparing to go SOLiD

Applied Biosystems (ABI) are preparing to release their next generation genetic analysis platform to test sites in June this year. The new 'supported oligo ligation detection' (SOLiD) system enables ultra-high-throughput DNA analysis promising dramatic time and cost savings. The instrument will be launched into a highly competitive market that has recently seen the release of Roche Diagnostics' / 454 Life Sciences' Genome Sequencer FLX system and Illumina's / Solexa's 1G Genome Analyser. Dr Dennis Gilbert, chief scientific officer and vice president for research at Applied Biosystems, told LabTechnologist.com: "The next generation technologies do the upfront chemistry in a massively parallel manner, doing close to a billion reactions at the same time. This means that one next generation instrument could replace between 50 and 100 of the current instruments." ​ "The major driver for next generation sequencing is for faster and cheaper results. Our new SOLiD technology is between 10 to 100 times faster than standard sequencing techniques enabling us to fundamentally open up new applications,"​ he continued. "We spent two years looking at both our own technologies and others which led to the Agencourt technology purchase. We were sure that the properties of the fundamental chemistry would lead to getting great results."​ The SOLiD system, based on 'sequencing by ligation' technology was bought by ABI during their $120m (€91.6m) acquisition of Agencourt Personal Genomics in July 2006. The intellectual property rights to the 'sequencing by ligation' technology are currently in dispute​. How it works​ The technology works by first amplifying DNA fragments using a water in oil emulsion polymerase chain reaction (PCR) technique that amplifies the DNA onto polystyrene beads. When the emulsion is broken the beads float to the top of the sample and are then placed on an array. Sequencing primers are then added along with a mixture of four different fluorescently labelled oligo probes. The oligo probes are eight bases long and bind specifically to the fifth base in the sequence to determine which of the four bases (A, T, C or G) it is. After washing and reading the fluorescence signal from the first base, a ligase is added, not a polymerase as in standard Sanger sequencing. The ligase cleaves the oligo probe between the fifth and sixth bases, removing the fluorescent dye from the strand of amplified DNA. The whole process is repeated using a different sequence primer, until all of the intervening positions in the sequence are imaged. The process allows the simultaneous reading of millions of DNA fragments in a 'massively parallel' manner. This 'sequence-by-ligation' technique also allows the use of probes that encode for two bases rather than just one allowing error recognition by signal mismatching, leading to increased base determination accuracy. "The cost savings are enormous as you don't need complex robots or as many researchers to do the same task. Currently it costs between $5m and $10m to sequence a human genome; the next generation technology is allowing us to get closer to $100,000,"​ said Dr Gilbert. Applications​ Current techniques are limited by time and cost issues meaning that some applications are just too costly to undergo using one to one mapping of results to search for differences between DNA or RNA samples, for example, when looking for cancer causing gene mutations. Dr Gilbert said: "Currently its almost a signal to noise problem, where there may be only one mutation that causes the cancer to grow - using current techniques these studies are not doable as they are prohibitively expensive."​ "The goal is to be able to identify a couple of hundred things that may be the cause of a problem, not to have a database of every variation. The problem then becomes the validation of those changes and finding out if it applies to multiple people and multiple disease states." ​ Dr Gilbert also said that Applied Biosystems has been optimising the acquired technology and was "on-track"​ to deliver its first test instruments in July. He said: "The success of any technology is driven by the results that the customers get; it's not just about having the best technology but using the technology to understand biology. Because of Applied Biosystems extensive commercial organisation we have a huge number of sequencing specialists that can help our customers to quickly get started with a new technology."​ Dr Gilbert said that Applied Biosystems were yet to put a final price on the instruments, but did say that it will be comparably priced with other instruments. "Sequencing is everywhere already so we don't have to educate people about what the technology can do; the next generation technology will allow the expansion of the applications into agriculture, gene expression etc." ​ "The most important thing is to get the technology into the scientist's hands and give them new tools. This should bring a whole new wave of biological understanding. To be able to analyze DNA at such high throughput will really impact the way people look at biological problems,"​ he concluded.