Helicos BioSciences Corporation traces its roots to a paper published in April 2003, in the Proceedings of the National Academy of Sciences (PNAS), by Cal Tech professor and primary author Dr. Steve Quake. The paper described the preliminary development of a technique for single-molecule DNA sequencing derived from the Sanger method for sequencing-by-synthesis. Using the new technique, fluorescent signals were utilized to detect labelled nucleotide triphosphates incorporated onto DNA templates bound to a quartz slide.
Despite limitations in the sensitivity, speed and the size of obtainable sequence, the new sequencing method described in PNAS was novel and showed sufficient promise to catch the eye of venture capitalists who approached the professor about investing in his technology. There must have been something about the technique that was what venture investors are looking for as this was a first, according to long-time staff member and Senior Director of Research, Dr. Timothy Harris...venture investors don't usually approach the scientists, it's the other way around!
The PNAS publication was released on April 1, 2003, the first round of financing for a new company was initiated Dec. 19, 2003 and on Jan. 2, 2004, Helicos opened its doors with 5 employees, including Dr. Harris, a specialist on measurement science and single molecule technology. Helicos is currently situated in Cambridge MA, USA and, after 2 rounds of investment financing, and as of an IPO on May 27, 2007, it is now publicly traded under NASDAQ: HLCS.
Helicos specializes in genetic analysis technologies, in particular a True Single-Molecule Sequencing (tSMSTM) technology, validated with the sequencing of the M13 virus genome as described in Science Magazine in April 2008. The specialized tSMSTM platform uses the HeliScopeTM Single Molecule Sequencer. According to Dr. Harris, this particular project was begun in January 2004 and by June 2005 they had successfully sequenced the M13 virus, a medically relevant sequence, described in the Science paper.
How Does tSMSTM Work?
A strand of DNA about 100-200 base pairs is cut into smaller fragments using restriction enzymes and polyA tails are added. The shortened strands are then hybridized to the Helicos flow cell plate, which has billions of polyT chains bound to its surface. Each hybridized template is sequenced at once, therefore billions per run can be read. Labelling is performed in "quads" consisting of 4 cycles each, for each of the 4 nucleotide bases. Fluorescent-labelled bases are added and a laser in the instrument illuminates the label, taking a read of which strands have taken up that particular labelled base. The label is then cleaved and the next cycle begins with a new base. After the flow cell has been treated with each base (4 cycles) the quad is complete and a new one begins again with the initial nucleotide base.
Currently the HeliScopeTM can read DNA fragments of about 55 base pairs in length. The more bases in the sequence, the lower the percentage of strands that can be used in a sample, because some strands cease to elongate during the process. For reads of 20 or so bases, about 86% of the strands can be used. For longer reads (55+ base pairs) this percentage drops to about 50%.