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Bruker Pens Alliance with Nanosys to Develop Chips That Can Perform Certain LC Functions

This story originally appeared in Biocommerce Week, a newsletter that has been discontinued.
Bruker Daltonics this week entered into a research and development and distribution agreement with Nanosys that will couple Nanosys' NALDI target plates with Bruker's mass spectrometers.
The primary goal of the exclusive deal is to develop chips that can perform some of the functions currently done on larger, more expensive liquid chromatography instruments. Through the alliance, Bruker joins other BCW Index firms, such as Agilent Technologies and Bio-Rad Laboratories, which have sought to migrate some research functions previously done on larger instruments to chip-based platforms.
Under the agreement, Nanosys will supply Bruker with its nanotechnology-enabled matrix-free target plates, called NALDI chips, which Bruker will market with its laser desorption ionization time-of-flight mass spectrometers.
According to Bruker, the NALDI chips enable sensitive analysis of drug compounds, small peptides, natural products, pesticides, and other low-mass molecules that are otherwise difficult to analyze with mass spec. The NALDI chips are “a special target for a laser desorption-type of mass spectrometer, [which] would typically be a MALDI-TOF instrument,” said Catherine Stacey, director of applications for Bruker Daltonics.
“The technology is very appropriate for all types of small-molecule analysis, which is an area where MALDI-TOF has not traditionally been so strong,” said Stacey. “The NALDI technology is not for big proteins, where a lot of MALDI is done. So, it covers a whole different area of molecules.
“Obviously, a lot of the small molecules are traditionally done by LC-MS methods, so we see this as being able to be a very fast and easy way of analyzing small molecules, some of which are currently done by LC-MS,” said Stacey. “It’s not going to replace those very well-established technologies, but it could offer an opportunity for very high-throughput analysis, or quick analysis that doesn’t need demanding quantitation.”
Bruker does not manufacture any LC systems, but it partners with several LC vendors that link their instruments with Bruker’s mass spectrometers and related software.
The NALDI technology would also be useful in experiments where you don’t have “very complex mixtures of molecules that need separation, so any time you prep for or ID a molecule, whether it’s a synthetic molecule, you’re looking for particular drugs, drugs of abuse, forensic screening, all of those sort of areas,” Stacey said.
Nanosys does not sell the targets on its own, said Stacey. She said Nanosys’ expertise is in the nanowire technology, and the company has been looking for partners.
Stacey said Bruker is actively developing the product and could release it in the near term, but she declined to provide a more specific timetable.
She also said it was too early to say what role, if any, the NALDI technology would play in Bruker’s molecular diagnostics strategy going forward, though the technology could be applied to that field. Company officials have said in the past, including at the recent Pittcon meeting in Chicago, that the firm intends to apply its mass spectrometry technology to developing molecular diagnostic products.
“This is very much in the exploratory phase of seeing where some of the really hot applications will be for this technology,” said Stacey.
Thinking Small
Bruker is not the only firm in the BCW Index that is thinking small when it comes to protein research and diagnostic tools.

“The technology is very appropriate for all types of small-molecule analysis, which is an area where MALDI-TOF has not traditionally been so strong. The NALDI technology is not for big proteins, where a lot of MALDI is done.”

Bio-Rad, which has beefed up its protein tools portfolio considerably over the past year and a half but does not sell any mass spec equipment, is selling chips for protein-research purposes. Those chips are based on the surface enhanced laser desorption/ionization (SELDI) technology developed by Ciphergen and sold to Bio-Rad last year (see BioCommerce Week 8/16/2006).
Unlike the NALDI technology, though, SELDI is particularly suited for separating and identifying proteins from complex samples. Bio-Rad could also pair the technology with MALDI mass spectrometers, such as those made by Applied Biosystems, Thermo Fisher Scientific, Agilent, Waters, and even Bruker, but has yet to announce any such collaborations.
Although the NALDI technology is “nothing like” the SELDI chips, said Stacey, “There are competitive silicon surfaces on the market, but this one, I think, is superior to those that are out there at the moment.”
In addition to Bruker, Agilent also is working on methods of migrating applications currently done on LC instruments to a chip format, even though Agilent has invested heavily in building its LC product portfolio to challenge market leader Waters.
A couple of years ago, Agilent introduced its HPLC-Chip platform, which the firm believes has the potential to eventually displace LC instrumentation. “Right now we are building more and more capability in the Chip-LC platform, which will eventually allow us to move all of the functionality of the standard LC onto a chip,” said Chris van Ingen, president of Agilent’s Bio-Analytical Measurement business, on the sidelines of the Pittcon meeting in Chicago a couple of weeks ago (see BioCommerce Week 2/28/2007).
“If you can integrate the whole sample prep and separations workflow into one integrated chip you can enhance the sensitivity [and] improve the repeatability,” he told BioCommerce Week.
However, Bruker’s Stacey said “it’s just too early” to say whether more companies will pursue the migration of their technologies down to the level of chips.
“I think anytime you can replace the complex LC system — solvents, pumps, the whole expensive complexity of an LC — if it can be replaced with spotting a sample onto a target, that would be wonderful,” she said. “How much you can really do [with] that remains to be seen, but clearly we need to be in this technology and explore what it can do to keep our options open.”

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