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A Synchrotron Beamline Right on Your Lab s Desktop? Stanford Start-Up Says it Can Do it

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Mass spectrometers are not the only large proteomics instruments to be shrinking in size these days: The equivalent of a giant synchrotron light source used in high-throughput protein structure determination can now fit on a laboratory desktop, according to Palo Alto, Calif. start-up Lyncean Technologies.

Lyncean, founded in 2001 by Stanford professor Ronald Ruth and two staff members from the Stanford Linear Accelerator Center, developed the technology based on research that Ruth conducted at Stanford, where he is now on a part-time leave of absence.

Ruth, who is the president of Lyncean, announced at the Keystone Symposia on Structural Genomics in Snowbird, Utah, this week that the company will begin in-house testing early next year of a pre-production prototype for a tabletop X-ray source.

Ruth told ProteoMonitor that the source, which he says is roughly 100 times more intense than common laboratory sources, boasts flux capabilities “comparable to some of the most highly productive beamlines” at synchrotron facilities such as the Advance Photon Source at Argonne National Laboratory; and resolution capabilities comparable to many such beamlines, as well. He said that the instrument is being targeted to “the entire X-ray science community,” but that academic laboratories will likely make up the bulk of the initial customers. Lyncean will begin taking orders for the instruments during the testing process, and will accept “inquiries” prior to that.

The X-ray source combines an electron beam and a laser beam to get essentially the same effect as the bright traditional synchrotron sources, but without using the giant magnets employed in larger sources, according to the company’s website. The total X-ray power is also much smaller, a characteristic that simplifies the complex heating and radiation shielding required for the larger instruments.

The work at Lyncean was funded entirely by founder money and SBIR grants courtesy of the National Institute of General Medical Sciences’ Protein Structure Initiative — which earlier this month released funding details for its $75 million per year, five-year production-phase projects (see PM 2-13-04, 4-9-04). Ruth said that the company has so far received $1.4 million in SBIR Phase I funding and over $6 million — spread out over two years — in Phase II funding from the PSI funding pool.

NIGMS staff scientist Charles Edmonds told ProteoMonitor that the institute was interested in Ruth’s technology because NIGMS already funds scientists, particularly through the PSI, who rely on synchrotron radiation. “The prospect of being able to have that advantage, if not in a home laboratory setting, at least in a more distributed fashion … would have been of interest to [NIGMS] no matter what,” Edmonds said. “Plus, I can speak personally: I think this is really neat!”

One of the PSI’s goals is to increase the throughput of protein structure determination, and Ruth said his instrument does that by dramatically increasing access to beamline-quality X-rays. “The flux is high, but more importantly, it’s yours 24 hours a day. … All of the techniques that are being developed for high throughput structural genomics can be applied with this source,” he said.

Indeed, access to high quality beamlines has been cited as a major bottleneck in the structural proteomics pipeline. James Holton, who operates the Advanced Light Source at Lawrence Berkeley Laboratory told ProteoMonitor in February that he felt “the bottleneck for the data collection part of things is that synchrotron visits are too long and too infrequent” (see PM 2-6-04). Edmonds commented that the NIH “has worked hard to fill in what was recognized as a gap, and it’s not such a bad thing now.” He added, however, that structural proteomics is a growing field, so current facilities may not always be adequate. “What’s OK, or tolerable, or even sort of good right now, many not cover it tomorrow,” he said.

Ruth said that the tabletop synchrotron was not meant to replace the larger beamlines, so much as complement them with a more accessible X-ray option. “You should think of this as the PC of X-ray science,” he said. “If you think of the APS at Argonne, you should think of that like a supercomputer of X-ray science. And you should think of the X-ray sources that people use in their labs now like handheld calculators.” While “supercomputers” like APS have “state of the art” equipment and can handle larger volumes of people, “you can also do a lot of work on your own workstation,” he said. Traditional laboratory X-ray sources, on the other hand, are “typically not tunable, they’re typically low-plex, they’re not very bright — they don’t emerge from a tiny spot, and if you do, the flux is very low.”

Ruth said that, in addition to its core technology, Lyncean will also market “add-ons” to the source, and “will be working with other companies and scientists to develop X-ray optics and that sort of thing.” He said the company has not yet set up collaborations, but is currently in discussions with several scientists.

— KAM

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