The Single-Molecule Advantage
While several other companies offer various sequencing-by-synthesis technologies with high throughput platforms, various different reagents, at comparable costs, and for short reads of 25-40 base pairs, only Helicos reads the DNA sequence one nucleotide at a time with their patented labeling technique that is sensitive enough to allow reads on a single molecule. Other methods require that the DNA be amplified (using PCR) to make multiple (millions) of copies prior to sequencing. This introduces the potential for a significant degree of inaccuracy due to processing errors by polymerase enzymes during amplification.
As of April 2008, the HeliScopeTM was reportedly able to sequence billions of nucleotide bases per day. Helicos is a member of the Personalized Medicine Coalition and has received "$1000 genome" grant funding. The $1000 genome in one day is a projected goal that would require the sequencer to process billions of bases per hour. Currently, the prototype sequencer would take years to identify an entire genome, which would cost much more than $1000.
The applications for tSMSTM technology are many, including detection of genetic variants in humans and other species for determining causes of disease, antibiotic resistance in bacteria, virility in viruses and more. The ability to detect a single gene without amplification has many potential uses in environmental microbiology, as genetic techniques are often used to detect viable, non-culturable microorganisms or those found in soil and other matrices that prohibit isolation by current methods. Furthermore, the nature of environmental samples often presents difficulties for gene amplification using PCR, due to contamination issues. However, these difficulties would also have to be overcome in order for the polymerase enzymes used in tSMSTM to function without interference.
The theory behind single-molecule sequencing is fairly basic and you might wonder why no one has thought of it before. Although it sounds simple enough, there are many technical components involved in developing such platforms, and plenty of challenges to keep Helicos busy, including the development of new chemical reactions and reagents, plates and high throughput readers. The ability to detect fluorescence of a single label on a single base requires highly sensitive instrumentation, and the chemistry for labelling and detecting signals needs to be just right to minimize interference and optimize fidelity of the DNA polymerase as it is applied to immobilized templates and labelled nucleotides. These are some of the challenges faced by Helicos as it continues to develop this technology in hopes of someday delivering the $1000, 1-day human genome.