Helicos True Single Molecule Sequencing (tSMS) technology has a device that images billions of single molecules per run and produces over 2 Gigabases of sequence data per day – a throughput performance almost 100X greater than Sanger methods, and faster than any of the “next-generation” methodologies.
To achieve a higher level of sequence accuracy unmatched by any other technology. Helicos has developed a method for sequencing each single molecule template multiple times. This novel sequencing approach enables researchers to generate data sets with a high degree of accuracy.
With the Helicos technology, the DNA to be sequenced is first chopped into short pieces about 200 bases long and injected into a flow cell, a specialized glass slide. The flow cell is coated with tiny snippets of DNA that are designed to snag the fragments as they float by, anchoring them in place. The immobilized pieces of DNA are fluorescently labeled so that their position under a fluorescence microscope can be recorded by a camera. Nearly a billion pieces of DNA can be analyzed in a single sequencing experiment, compared with about 400,000 to 50 million for other technologies.
The flow cell is then nestled into the HeliScope, where the microscope sits ensconced in 400 pounds of Vermont granite.
Other advanced sequencing methods use a similar approach, known as sequencing by synthesis. But unlike those technologies, the HeliScope can distinguish the unamplified fluorescent signal of a single base taking its place on a growing DNA strand. One key to that ability is a nonstick material that the company developed, which coats the surface of the flow cell and allows it to be washed clean between reactions: residual fluorescent bases would make it more difficult to accurately detect individual sequencing reactions.
It takes five to ten days to read all the DNA that can be loaded into two flow cells; for sequencing, that’s 400 million strands of DNA per cell, which can generate 20 billion bases’ worth of usable sequence.
Helicos is still tinkering with the technology, developing chemistry that could boost the speed of the sequencing reactions and allow more pieces of DNA to be anchored to a flow cell. Along with the other major players in the field, the company hopes to deliver a complete genome sequence for $1,000, an accomplishment that would mark the beginning of something totally new in medicine: individuals’ ability to access their own genomic information
A Jan 2008 article that compares several leading DNA sequencing approaches The Helioscope is estimated to cost $75,000 to $100,000 and take six to eight weeks to sequence an entire human genome. The price of the Helicos Genetic Analysis System, including the HeliScope, is $1.35 million.
In April 2008, researchers were indicating the need to develop chips with many more channels, so that multiple genomes’ worth of DNA can be sequenced simultaneously and being able to quickly place long dna sequences in those channels.