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Bio-Rad, Bruker Deal Links SELDI and MALDI-TOF/TOF Platforms

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This story has been updated from an earlier version

Bio-Rad Laboratories and Bruker this week announced they will co-develop and co-market a new product that combines elements of Bio-Rad's SELDI platform with Bruker's MALDI-TOF/TOF platform.

The deal will combine SELDI chips and software with the MALDI mass spectrometer for a platform that "will provide new solutions for biomarker discovery, in particular, for the detection and high-confidence identification of intact peptides and proteins under 30 kilodaltons" — which current technologies have difficulty identifying, the two firms said in a joint statement.

Brad Crutchfield, vice president and life-science group manager at Bio-Rad, told ProteoMonitor this week that while SELDI allows researchers to rapidly screen proteins, for fingerprinting and identifying spectra "you really need a full-function MALDI platform, and that's just not what SELDI was designed for."

By combining the SELDI technology with the MALDI mass spec, "you can essentially in one platform … move [from screening] right into trying to identify those specific peaks to see if you can find them" in a database, he said. "It really gives us an opportunity to offer that full range of screening and identification."

Bio-Rad also will continue to sell the full SELDI system as it has in the past, and each company will market the other's technology as standalone platforms.

"We never had an interest in being a full-time participant in the mass-spec market … and we really looked at this as an extension of our traditional business, which is in the area of protein separation, expression profiling," he said. "At this stage we felt that it was much better to partner with somebody than try to develop our own companion mass spec to the SELDI technology."

Bruker referred requests for an interview to Bio-Rad, but in a statement, Gary Kruppa, vice president for business development at Bruker Daltonics, the division that develops and houses Bruker's mass-spec business, said that its instruments will "bring a new dimension to protein profiling and identification, expanding the capabilities of [the] SELDI technology.

"New products based on this combination of technologies will allow access to new technical capabilities and new market segments in applied proteomics, enabling researchers to better identify and characterize new biomarkers."

Crutchfield declined to disclose the financial terms of the deal.

New Life?

In a highly competitive field where deals linking two mass spectrometry technologies from different vendors are unusual, the agreement may be a way for Bio-Rad to make relevant a technology that has failed to capture the interest of the research community.

Bio-Rad bought the SELDI technology from Vermillion, formerly called Ciphergen Biosystems, in 2006 for $20 million and has since been evaluating its strengths and limitations [See PM 08/03/07] and exploring new applications for it, which Crutchfield said the firm continues to do [See PM 03/13/08].

Originally developed by William Hutchens at Baylor College of Medicine and commercialized by Ciphergen, the technology has had a checkered history. SELDI, which works similarly to MALDI, allows researchers to capture proteins on a chip for analysis on a mass spec. One difference is that in MALDI, a biological sample is mixed with a matrix and then spotted on a surface before it dries. By comparison, SELDI spots the sample on a surface that binds with certain proteins. The remaining sample is washed away, resulting in a cleaner analysis with less background noise.

The platform was once seen as a potential breakthrough technology for biomarker discovery. For example, in 2002 Lance Liotta and Emanuel Petricoin, then co-directors of the joint National Institutes of Health/US Food and Drug Administration proteomics program, used the SELDI platform to identify protein biomarkers for ovarian cancer for the first time, sparking a charge of excitement around the tool.

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Two years later, though, researchers at the University of Texas MD Anderson Cancer Center, led by Keith Baggerly, reported they could not reproduce Liotta and Petricoin's results. Though the criticism was not about the SELDI technology as much as Liotta and Petricoin's sample preparation and data analysis, it nonetheless tainted the platform. As a result, the research community has generally regarded SELDI with some skepticism.

Recently, Matthias Mann, a professor and center director in the department of proteomics and signal transduction at the Max Planck Institute for Biochemistry, said the ensuing controversy is one reason for the backlash that proteomics has faced in recent years from funders [See PM 02/12/09].

Today, SELDI is a marginalized research tool. A PubMed search using keywords "SELDI" and "surface elution laser desorption ionization" brought up 165 research articles in 2008. By comparison, keyword searches using "MALDI" and "matrix-assisted laser desorption ionization" resulted in 4,555 hits; and searches using "ESI" and "electrospray ionization" returned 4,615 results.

For their part, Bio-Rad officials in the past have acknowledged the platform's limitations, including its inability to support MS/MS sequence analysis commonly used for protein identification, and its unsuitability for some post-translational modification analysis.

Hoping to improve the technology, the company has upgraded its electronics, temperature variations, and overall mechanics, and has also worked to make the software more user-friendly.

This week, Crutchfield said that "what we've really tried to do is focus on what SELDI does well, and, in some respects, [it] is exactly what this deal [with Bruker] does."

However, he stressed that joining up with mass-spec manufacturers is not part of Bio-Rad's strategy for the SELDI instrument, and that the firm is not actively pursuing similar partnerships with other vendors.

Crutchfield declined to disclose how many of the instruments Bio-Rad has sold since acquiring the technology from Ciphergen, though another company official said a year ago that it was a "significant number." In 2006, shortly before Bio-Rad closed that acquisition, Vermillion revealed that since the company's inception it had sold about 670 SELDI mass specs. The disclosure came in court documents pertaining to a lawsuit between Vermillion and Health Discovery that was eventually settled [See PM 07/12/07].

Bio-Rad and Bruker said their collaboration would benefit research into protein and peptide biomarkers smaller than 30 kilodaltons. But according to Zheying Zhu, a research associate in the division of investigative science at Imperial College in London, larger proteins may in fact be a bigger target for Bio-Rad and Bruker.

"What I would like to see [improved] in SELDI, or SELDI with MALDI-TOF, in the future is increased sensitivity to detect proteins with large molecular weights, more than 20kDa, which would be a wider platform in use of SELDI," Zhu said in an e-mail to ProteoMonitor this week.

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