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Taiwanese Team Developing Single-Molecule Real-Time Optical Sequencing Tech Registers for X-Prize

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By Julia Karow

A team of researchers in Taiwan that is working on a single-molecule real-time optoelectronics-based sequencing technology has recently entered the competition for the Archon X Prize for Genomics, the X Prize Foundation said this week.

The group, which started in 2007 and calls itself "Cracker," is based at the Industrial Technology Research Institute in Hsinchu, Taiwan. ITRI provided initial funding for its research.

According to its website, the team is getting ready to spin off its technology and staff into a privately held company. It is currently "passing through initial development milestones" and plans to "report publicly about them in the near future."

The researchers aim to sequence single DNA molecules in real time using a fluorescence-based sequencing-by-synthesis method.

According to the website, their patent-pending method uses arrays of up to a million nanowells on a composite "sTOP" chip — short for "sequencing on top of a photodiode" — that consists of three layers: a light-emitting tier in which the nanowells are embedded, a filtering tier, and a photo-sensing tier.

Strongly reminiscent of Pacific Biosciences' zero-mode waveguides, the observation volume within the nanowells is confined, allowing the researchers to record single fluorescent tags. "One fluorescent molecule can be detected when present locally in the reactive volume, and be singled out from an environment highly concentrated in fluorophores," according to the website.

As light of a particular wavelength emanates from the sides of a nanowell, fluorescent tags in the well are excited and emit light, which passes through the filter tier and is converted into an electric signal by a photodiode at the bottom.

The Cracker team, which registered for the X Prize on Oct. 1, is the eighth team to enter the competition, joining VisiGen Biotechnologies (now part of Life Technologies), Roche's 454 Life Sciences, the Foundation for Applied Molecular Evolution, Reveo, Base4 Innovation, the Personal Genome X-team, and ZS Genetics.

The winner will be the first team to sequence 100 human genomes to certain specifications within 10 days for less than $10,000 per genome.

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