The excitement about and focus on genomic sequencing stems from the high sales growth and untapped potential of massively parallel sequencing technologies, or next-generation sequencing (NGS).

The current generation of sequencers employs similar chemistries, yet utilizes unique strategies. Roche’s Genome Sequencer FLX and GS Junior systems use a combination of emulsion PCR, and sequence by synthesis via pyrosequencing. The systems produce longer read lengths than other NGS systems.

Illumina’s Genome Analyzer IIx is similar to Roche’s sequencer in that it employs a sequencing-by-synthesis strategy. However, instead of emulsion PCR, the Genome Analyzer II employs a cluster amplification process by which clonal clusters are automatically generated on a flowcell (a glass slide that contains eight channels). DNA fragments are attached to the flowcell, and the reagents containing the four bases and amplification enzymes flow through the channels to produce thousands of copies of the DNA fragment.

Like Roche’s Genome Sequencer, Life Technologies’ SOLiD system uses emulsion PCR. However, it employs a sequence-by-ligation strategy using a two-base encoding chemistry. While sequence by synthesis measures one base at a time, sequence by ligation measures two bases at a time for increased accuracy.

These three companies dominate the rapidly growing NGS market. In the short time since the first massively parallel systems were commercialized, the firms have expanded their portfolio of sequencers to address different segments of the market. Illumina, Life Technologies and Roche’s high-end sequencers, with a price point north of $400,000, remain the firms’ flagship products, particularly for genomic research centers. However, manufacturers are also introducing systems that are more suitable for other types of labs. Illumina, for example, offers five sequencer systems, including the recently launched MiSeq personal sequencing system, which is priced under $125,000.

The DNA sequencing market is an attractive business in terms of growth and size. As progressive as the latest sequencers are, the birth of the next generation of sequencing technologies is just around the corner. With a strong impetus to lower the cost of sequencing, companies are exploring novel approaches, including the use of non-optical technologies. Current systems rely on laser detection, which is an expensive component.

Ion Torrent, which was acquired by Life Technologies (see IBO 8/31/10), offers the Ion Personal Genome Machine (PGM) sequencer. Like other sequencers, the system uses sequence by synthesis. However, the Ion PGM measures the voltage or changes in pH on a semiconductor chip as bases are added. Other promising non-optical approaches include the use of electron microscopes and nanopores. The total market for NGS is expected to top $1 billion by 2014.

Next-Generation Sequencing at a Glance:

Leading Suppliers

• Illumina

• Life Technologies

• Roche Applied Science

Largest Markets

• Genomic Research Centers

• Academia

• CROs

Instrument Cost

• $125,000–$600,000