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Bio-Rad, Continuing Work on SELDI, Eyes Applications Beyond Biomarker Discovery

Bio-Rad Laboratories continues to refine its SELDI platform, making improvements to the instrument and exploring new applications beyond biomarker discovery, company officials told ProteoMonitor.
Since purchasing the surface enhanced laser desorption ionization system in late 2006 for $20 million from Ciphergen, now called Vermillion, Bio-Rad has quietly been at work smoothing out kinks in the instrument while exploring new business opportunities.
Last summer, the company said in a conference call that it had evaluated the platform and identified areas for improvement, while making reassurances that though the platform has limitations, it remains a valuable tool for biomarker identification [see PM 07/26/07].
This week, company officials said that the improvements are ongoing, and during the course of the year new software, starter kits, and iterations of the SELDI chip will be available.
On the engineering side, the company is working to improve the hardware, “upgrading the electronics, making it more stable, [and improving] things like temperature variations and … the mechanics,” according to Scott Conradson, manager for the protein detection business unit. Bio-Rad is also redesigning the Enterprise edition of the platform to resolve chip-jamming problems reported by customers, he added.
Concurrently, Bio-Rad is trying to make the software “more intuitive and user-friendly,” said Julie Hey, marketing manager for the company’s protein-detection business unit. Some of the improvements will be on the back end and will not be apparent to users. Other changes will be reinstating overlay plots after receiving requests by some existing SELDI users.
In addition, Bio-Rad will add wizards and more statistical-analysis tools to the software. The company is also looking at new applications and “incorporating new modules for those new applications,” Hey said, though she declined to elaborate because they are still in development.
On the applications front, while other mass specs are used for research areas outside of proteomics, including metabolomics or lipidomics, Bio-Rad is focusing SELDI exclusively for protein research, at least for now.
“At this point, we still haven’t looked at those markets,” Hey said.
Regaining Relevance?
These and other improvements to the SELDI platform are part of continuing work by Bio-Rad to reinvigorate and make relevant again a platform once seen as a potential breakthrough technology for biomarker discovery. More recently, however, it has been largely pushed to the margins of proteomics research.
In trying to revitalize the platform, Bio-Rad has an uphill climb ahead of it. In 2007, there were about 150 scientific articles in which work was conducted on the SELDI platform, according to a keyword search on PubMed. By comparison, there were about 2,300 experiments conducted on the MALDI platform and 2,800 experiments performed on electrospray ionization mass specs.
It is unclear how many experiments on the MALDI and ESI platforms were proteomics focused.

“One way that we’ve positioned the instrument is to be used for high-throughput profiling.”

Bio-Rad officials have acknowledged the limitations of the instrument saying it does not support MS/MS sequence analysis commonly used for protein identification, and is not suited for analysis of some types of post-translational modifications.
According to Hey, “One way that we’ve positioned the instrument is to be used for high-throughput profiling.” The instrument, she said, does not do protein-sequence identification, though the company is exploring solutions for that type of work. She declined to say specifically whether that would include SELDI.
“We do want to incorporate the SELDI technology in some sense,” she added.
Diane McCarthy, global manager of the company’s Bio-Marker Research Centers, reiterated that as with other platforms, proper study design with the SELDI is crucial to getting the right results.
“It’s really how you set up your designs and any of these proteomics technologies are very sensitive and can pick up on artifacts that may be associated with the site of sample collection, or the day that you ran the experiment,” she said. “And so it’s really understanding what all the pre-analytical biases are.”
The company in December released an “extensive” user guide on experiment design, how to go through the SELDI experimental protocol and “really helping people to understand how to set up their experiments appropriately so [that] at the end of the day, they can get robust biomarkers out of the process,” McCarthy said.
Throughout the year, Bio-Rad said it will release starter kits intended for new SELDI users to “ensure that they can establish their own techniques properly before actually embarking on any experimentation, which we found in the past was an issue,” Hey said.
Chipping Away at Inconsistencies
Along with work on the instrument and accompanying software, the company is also trying to improve the SELDI chip, particularly the manufacturing process. One common complaint from customers is the chip’s high variation coefficient, particularly from lot to lot, Conradson said, which the company attributed to the manufacturing process.
Bio-Rad has been working with their manufacturer to “improve those processes for consistency and also improve our [quality assurance],” he said.
Overall, Hey said, the company has been “actively” seeking feedback from customers for ideas on how to improve the SELDI platform.
One such customer, Jenny Eriksson, a researcher in the department of medical sciences at Uppsala University, told ProteoMonitor in an e-mail that while she and her colleagues received their new instrument only recently and haven’t had time to evaluate it, she found the older software easier to use and to learn.
In particular, she would like to see a read-only version of the software: Because her department has five licenses being shared by 12 users, many of whom use the instrument sporadically, a read-only version of the software would allow them to work with their data at their own computer, rather than having to sit by the instrument, she said. 
“Also, since you can control the instrument from your own computer if you have the full version of the software, I think it would be reassuring to new and insecure users to have a read-only version to minimize the risk of mistakes,” Eriksson added.
According to Conradson, Bio-Rad has sold a “significant number” of SELDI instruments worldwide since it purchased the platform a year and a half ago, though he declined to give specific numbers.
“We’re quite happy with how the business is going, particularly in the last couple of quarters as customers and users have recognized what Bio-Rad is doing in terms of support and improvement,” he said this week.
The client base for the instrument is largely in the clinical research area, though there are a number of pharmaceutical clients, particularly for the Bio-Marker Research Centers, Hey said.