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The Helicos Genetic Analysis System platform was the first commercial NGS implementation to use the principle of single molecule fluorescent sequencing, a method of identifying the exact sequence of a piece of DNA. It was marketed by the now defunct Helicos Biosciences.

The fragments of DNA molecules are first hybridized in place on disposable glass flow cells. Fluorescent nucleotides are then added one-by-one, with a terminating nucleotide used to pause the process until an image has been captured. From the image, one nucleotide from each DNA sequence can be determined. The fluorescent molecule is then cut away, and the process is repeated until the fragments have been completely sequenced.

This sequencing method and equipment were used to sequence the genome of the M13 bacteriophage.

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