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PacBio Aims to Boost Throughput of SMRT Technology with Microchip Co-development Deal

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Pacific Biosciences and Imec, a Belgian non-profit nanoelectronics research firm, have partnered to develop advanced microchips for highly multiplexed single-molecule genetic analysis, the firms said this week.

The goal of the multi-year research collaboration is to scale the capacity and throughput of PacBio's single-molecule real-time technology, PacBio's president and CEO Michael Hunkapiller said in a statement.

Imec will help to identify ways to bring greater economies of scale to PacBio's technology through nanoscale semiconductor fabrication, said Luc Van den hove, president and CEO of Imec.

The partners plan to combine PacBio's zero-mode waveguide technology and Imec's expertise in nanophotonics, complementary metal oxide semiconductor sensors, technology integration, and fabrication.

Imec, headquartered in Leuven, performs research in nanoelectronics and has international partnerships in the areas of information and communications technology, healthcare, and energy. The company has a staff of almost 2,000, including more than 600 industrial residents and guest researchers. Last year, Imec reported about €300 million ($363 million) in revenue.

PacBio declined to disclose details about the semiconductor chip technology to be used in the collaboration, or what parts of its existing technology, which includes a camera to record fluorescent signals, the new technology might replace.

The company also declined to specify by how much it plans to increase its technology's capacity and throughput. According to Sejal Sheth, vice president of strategic marketing at PacBio, the goal is to scale the throughput "significantly" beyond the near-term improvements that the company is making to its existing PacBio RS platform.

Any product development based on the new technology would be "in the medium- to long-term timeframe," Sheth told In Sequence via e-mail.

PacBio said two years ago that it was working on a new, highly multiplexed version of its technology that would integrate the sequencing chemistry, optical detection, and signal processing into a microchip and get rid of the camera (IS 2/23/2010).

At the time, the company said the so-called V2 technology was going to multiplex several million zero-mode waveguides and increase the polymerase speed to up to 50 bases per second, resulting in a throughput of more than 100 megabases of sequence per second. PacBio said it planned to commercialize two FDA-certified sequencing systems based on the new chip technology, starting in 2014.

Sheth said that the company no longer uses the term "V2 technology" but that the collaboration with Imec is consistent with the objective of that technology to "harness the advantages of the [single-molecule real-time] technology across a very large number of ZMWs."

Peter Peumans, director of Imec's Life Science Program, which the PacBio collaboration is part of, told In Sequence that his company is "good at the integration of optics and electronics and all kinds of structures on a single chip" and will use that knowledge to help design a new generation chip for PacBio that will increase the SMRT technology's capacity and throughput.

While he declined to disclose details about the planned chip design, he said that "it's logical that the optics, which is today a central part of PacBio's technology, would be a prime candidate for going toward a more integrated technology."

Imec will provide PacBio with access to state-of-the-art semiconductor technology as well as life science expertise, a combination that he said is "fairly unique."

"We translate a life science problem into a technology problem. We then look at whether we can solve the technology problem, and then we test out whether the technology actually functions as projected," Peumans explained. "It's that translation step going both ways, translating and then testing it out, that's really important for these companies. They usually can't find a place like it to do this kind of translation."

"Our basic message is, if you can draw it on a whiteboard, on a piece of paper, we can build it here," he said.

Imec, which was founded in 1984 with support from a government program that aimed to strengthen the microelectronics industry in Flanders, offers contract research to industrial partners in a number of areas. Its Life Science Program currently has partnerships with about 10 companies, including Panasonic.

With Panasonic, Imec is working on several projects, including a PCR-on-a-chip system, Peumans said. The PacBio collaboration is the company's first public contract with a DNA sequencing company, he noted.

Ion Torrent has already adopted semiconductor technology for its sequencing platform, and Roche's development partnership with DNA Electronics is pursuing the same strategy. Peumans noted that this trend is in "recognition that life science problems can be improved in important ways by using semiconductor technology. It's not always easy to see the opportunities because you need people who are versed both in technology and in the life sciences."

It is unclear, though, why the two industries are only getting closer now, having co-existed for many years. "I think the reason is that both the life science industry and the semiconductor industry were comfortable where they were. They were both earning a living comfortably, but now both of these industries are facing challenges," he said.

While the healthcare industry, and by extension the life science industry, is facing increasing drug development costs, for example, and is looking for new ways to make the process more efficient and cheaper, semiconductor companies are also "facing an uncertain future where the further scaling of chips is no longer guaranteed … so they need to figure out what they are going to do next," he said.