Highlights

'Post-light' genomes shape sequencing for the future

July 2011

As the price of genomic sequencing continues towards the $1,000 genome, innovative new technologies are ensuring the rapid progression in speed of sequencing genomes. Enabled by a new technology that allows sequence data to be generated via semiconductors, this new chip- based technology ensures that the speed of genomic data will continue to keep track with, and possibly even exceed, Moore's Law, changing the way genomic research, and eventually healthcare, move forward.

First described in Nature in July 2011, semiconductor sequencing involves "gathering sequence data by directly sensing hydrogen ions produced by template-directed DNA synthesis, offers a route to low cost and scalable sequencing on a massively parallel semiconductor-sensing device or ion chip" according to an editor's note.

Traditional optical-based genomic sequencers generate data via a sensitive system of lights and optics that detect fluorescently-tagged base pairs in the genome. These systems are inherently complex and require increasingly intricate imaging technologies, electromagnetic intermediates and specialized nucleotides or other reagents.

By developing a technique that reads DNA information electronically, semiconductor sequencing is able to bypass these imaging requirements, instead harnessing the trillions of dollars of investment in the fabrication and design of semiconductor foundries and brings those advancements to bear on the rapid decoding of genomic information.

The Ion Personal Genome Machine, the first instrument to employ semiconductor-based sequencing, was launched in December 2010, and has established itself as the fastest selling genetic sequencer in the world.

The desktop-sized system uses a disposable chip at the heart of its sequencing engine, and is thus upgradable for higher throughput and faster sequencing times as newer, more advanced sequencing chips are introduced to the platform. The 314 chip, the chip the system was introduced with, uses 1.2 million sensors to generate approximately 25 million bases in a two-hour sequencing run. Subsequent chips have show ten-fold increases in output, with the 316 chip producing 100 million bases and the 318 chip expected to produce one gigabase, all operating in a two-hour sequence run.

The rapid deployment of semiconductor sequencing has allowed for first-of-its kind sequencing in global pandemic situations, highlighted by the use of this technology in the recent E.coli outbreak in Germany.

As the virulent outbreak became more widespread, separate teams in China and Germany set out to solve the genome of the bacteria. After two hours of sequencing and three days of analysis, the Chinese team, centered at BGI, immediately published their data to the Internet, the first time ever in an outbreak that researchers around the world were able to study the bacteria's genome in real time.

The German team, centered at University Münster, Münster, Germany, subsequently published their full analysis of the exceptionally virulent Shiga toxin (Stx)-producing Escherichia coli O104:H4 in PLoS ONE, proving semiconductor sequencing technology is an important new tool to protect public health during public outbreaks.

"As soon as we finished sequencing the DNA of this strain, we made the results public, like any ethical company would" says Nir Nimrodi, head of food safety at Life Technologies told Technology Review at the time. Life Technologies was able to use this data to immediately deploy a PCR-based test for the bacteria as well

New research published in the journal Nature describes the semiconductor sequencing technology underlying the Ion Torrent Personal Genome Machine sequencer and demonstrates the robustness of the machine by sequencing three bacterial genomes and a human genome. The team, led by Jonathan Rothberg, Head of Ion Torrent, sequenced the genome of Gordon Moore, co-founder of Intel.

The publication Moore, the creator of Moore's Law, which declares that the number of transistors per square inch on integrated circuits will double every year, signals the path and progression forward semiconductor sequencing can take.