NEW YORK (GenomeWeb) – Personal Genomics of Taiwan is developing an optoelectronic single-molecule sequencing technology that it says will be able to sequence a human genome for less than $1,000.
The company, a spinout from the Industrial Technology Research Institute (ITRI) in Hsinchu, is hoping to complete a prototype sequencer this year and to commercialize a sequencing platform in 2016.
Originally developed by engineering firm CrackerBio in collaboration with ITRI, the technology uses arrays of nanowells with integrated triple-junction photodiodes that are fabricated using complementary metal-oxide semiconductor (CMOS) technology. CrackerBio transferred the technology to Personal Genomics, which was founded in early 2011.
Personal Genomics, which is currently located within ITRI but plans to move into a new biomedical science park in Hsinchu a few months from now, currently has more than 40 employees, most of them scientists and engineers.
Last year, the company closed a $14.3 million Series A funding round from undisclosed investors in Taiwan and the US. According to Johnsee Lee, Personal Genomics' founder and CEO, investors included company founders, members of the semiconductor and high tech industry, and a medical group with relationships to hospitals and research groups.
Lee, a former president of ITRI and the first director of its life science unit, told GenomeWeb that the company converts an optical signal directly into an electrical signal on the chip, without the need for a microscope or a CCD camera, which are used by existing sequencing platforms from Illumina, Pacific Biosciences, and Roche's 454.
"We get rid of all that equipment," Lee said. "The signal is detected by a sensor immediately adjacent to the nanowell. We detect optical signals, but they are converted directly to electrical signals and can be differentiated," allowing for direct base calling.
This, he said, results in a less expensive and smaller sequencing platform, approximately the size of a laptop computer, and reduces the signal processing time because no image analysis is needed.
The company, he said, has filed patents that cover near-field detection by an optoelectronic sensor, meaning detection within a distance of 100 micrometers from the optical signal.
The only other commercial sequencing technology that relies on semiconductor chips is Thermo Fisher Scientific's Ion Torrent, Lee said, which uses pH sensors rather than optical sensors and cannot generate sequence data in real time because it needs to add the four nucleotides one at a time.
The other part of Personal Genomics' technology is its patented sequencing chemistry, which Lee is not ready to discuss in detail yet. He said it is a sequencing-by-synthesis chemistry that provides long single-molecule sequence reads and requires no amplification of the template DNA. It involves engineered polymerases and special nucleotides and measures four different signals in real time, one for each base. The chemistry has an embedded confirmation mechanism, a "clear and prolonged signal for every reaction," that increases accuracy, preventing spurious insertions or deletions.
While its sequencing chemistry is similar to Pacific Biosciences', the platforms would be very different. PacBio's RS II sequencer is "a big machine, very expensive," Lee said. "We're combining single-molecule [sequencing] with semiconductor detection. We're combining the advantages of PacBio and Ion Torrent."
The technology's long reads, low cost, and high speed would provide advantages for the clinical market, he said, which the company plans to target after the research market.
Lee said the company has already produced some sequencing data, which it might share publicly in the second half of this year. "We're still working on our prototype," he said.
The plan is to commercialize a sequencing instrument in 2016, possibly in partnership with another company. The instrument will likely cost about "an order of magnitude less" than Illumina's MiSeq, which has a price of about $125,000.
The greatest current challenge is the speed of development, as integrating the optoelectronic chip with the chemistry and sample preparation is challenging and time-consuming. "Time is our biggest enemy," Lee said.