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Stratos Develops Biochip as Alternative To ELISA for Biomarker Validation

Life science startup Stratos Biosystems has developed a technology that can validate proteins and biomarkers, and that it says is both quicker and less expensive than the standard ELISA method.
The enzyme-linked immunosorbent assay procees can take up to two years and cost up to $2 million. Stratos’ approach, which it calls immunoaffinity mass spectrometry, takes about half the time to develop at a fraction of that cost, according to company co-founders, Allan Stephan and Mark Stolowitz.
The device, called the EC-Affinity Biochip, is an antibody-based assay that enables researchers to analyze results directly on the mass spectrometer, thus eliminating the need for a second antibody for detection purposes. The company is hoping to have the chip commercially available in a year.
“We can put a capture antibody on the surface of the mass spectrometer plate, and capture from biological solution, from plasma or serum, a target antigen [that] is a potential biomarker,” said Stolowitz, who acts as Stratos’ chief scientific officer.
Because this can be done by parallel processing, hundreds, even thousands of patient samples can be examined. “And then we can reach each of those sites on the mass spectrometer and look for the mass corresponding to the intact antigen,” he said.
“It’s a very rapid assay test, and it’s a parallel, high-throughput approach to biomarker validation. It fills this immediate unmet need for biomarker validation,” he added.
Additionally, the technique differentiates post-translational modifications. While ELISA captures antibodies, researchers can’t be sure of what is being captured because ELISA doesn’t have the power to differentiate such modifications, Stolowitz said, since the antigen can be present in different isoforms. 
“There may be post-translational modifications on the antigen [and] it could be one thing, it could be six things,” he said.
Because of the ability of the EC-Affinity Biochip to differentiate isoforms, it can provide more information than a colorimetric or fluorescence-based ELISA, Stolowitz said.
Being able to detect the antigen in different isoforms is now increasingly seen as an important characteristic in biomarker discovery and validation, he said, because specific isoforms are being associated with specific disease states.
“For example, for a given biomarker that may be up-regulated in response to a specific cancer like breast cancer or ovarian cancer, it may turn out to be one or two of the isoforms that are specifically up-regulated,” Stolowitz said. “And now we have the ability to not only see to what extent the protein concentration is up-regulated or down-regulated, but to say, ‘You know in breast cancer, this specific isoform is the one that’s changing.’”
The chip, he said, offers the advantages of a surface enhancement laser desorption ionization platform, such as ease of use, without its drawbacks, such as poor sensitivity, mass resolution, and reproducibility.
The chip has been configured for use on a MALDI mass spec, though Stolowitz and Stephan said work will be done in the future to develop a chip compatible for electrospray instruments. Stratos has developed a proprietary surface chemistry that allows for analysis to be done on the instrument.
No Interest in a Life Science Tool
Created in 2004, Seattle-based Stratos is a two-man shop with Stephan running the business side and Stolowitz operating as the entire R&D and scientific staff. They first became acquainted when Stephan and a holding company for which he is CEO, the Stratos Group, invested in an earlier company Stolowitz started.
When Stolowtiz approached Stephan about his idea for the EC-Affinity Biochip, Stephan was intrigued. That enthusiasm was not shared by the venture capital community, however. No one, they said, was interested in investing in a life-science tool.
Plus, “the realities of [the venture capital] environments are that the technical founders are extensively diluted out by the time the company is well into the marketplace,” Stolowitz said. “We were trying to find a model where we could maintain significant equity and move the technology forward.”

“It’s a very rapid assay test, and it’s a parallel, high-throughput approach to biomarker validation. It fills this immediate unmet need for biomarker validation.”

To date, Stratos has filed three patents for the Biochip technology. It has received $2.1 million in funding, the first $1 million from Stephan and the Stratos Group, and $1.1 million from Don Listwin, a former technology executive who has funded numerous proteomics initiatives targeted at cancer research [See PM 05/31/07].
Eventually, Stratos approached Paul Lampe, a member of the Fred Hutchinson Cancer Research Center, who arranged to have Stolowitz appointed as a visiting scientist at his lab.
Lampe’s group is using proteomics methods to look for cancer biomarkers in the hopes of developing a diagnostic tool, and Lampe felt that Stratos’ work could benefit his own research, Lampe told ProteoMonitor this week.
“I felt that what they were doing sounded potentially interesting to what we’re doing,” he said. “It’s scientifically that we were looking for the interaction.”
In return for having access to the laboratory, Lampe’s group will be able to use the chips before they go on the market and retains the rights to any discoveries made using the chips.  
Stratos retains all intellectual property rights to the technology.
The company is speaking with several laboratories to further validate the technology and to pilot-manufacture the chip, Stolowitz said. Last week at the American Society of Mass Spectrometry Conference on Mass Spectrometry in Indianapolis, Stephan and Stolowitz began meeting with vendors about possible licensing and manufacturing deals, though they declined to identify the companies they had targeted.
They said they hope to have in place a distribution deal by the end of the year so they can scale up manufacturing and possibly launch the chip in time for ASMS next year.
In late May, the National Institute of Standards and Technology granted an exclusive license to Stratos for patent number 5,514,501 titled, “Process for UV-photo patterning of thiolate monolayers self-assembled on gold, silver, and other substrates.” The patent pertains to a method of manufacturing densely arrayed biochips for mass spectrometer-based identification of proteins.
The company’s main focus, though, is on further development of the EC-Affinity Biochip. While he doesn’t see it ever completely replacing ELISAs, Stolowitz said the chip could be an alternative to them, particularly for biomarkers that have already been well-characterized by mass spectrometry.
“Mass spectrometry is the only analytical method that is available to the protein chemist today that can differentiate post-translational modifications … so it will certainly be the alternative to ELISA in any instance where you’re trying to quantitate or characterize post-translational modifications or transcript variance,” he said.

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