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ArrayIt s Todd Martinsky On the Development of Protein Microarrays

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At A Glance

Name: Todd Martinsky

Position: Vice president and co-founder of TeleChem International; leader of ArrayIt division

 

How did you get into the microarray business?

How I got started is kind of an interesting story. My brother-in-law is Mark Schena, and Mark Schena was the first author on the first microarray paper that was published back in October of 1995. He was a postdoc at Stanford at the time. And so he writes this blockbuster paper, and my experience back then was in the database consulting industry.

So initially, my involvement with microarrays was helping Mark negotiate consulting arrangements and set up milestones and do that sort of thing. We did a lot of consulting way back then to various organizations — Molecular Dynamics, Johnson & Johnson, places like that. What became really clear to us was that while the consulting was important, what the customers really needed were products to be empowered to do their own experiments. That’s what everybody was after — to implement microarray technology. Through the consulting that we were doing, we could tell people these are the kind of tools you need to use microarrays, but at the time there were no commercial products. This was back in 1995, 1996. That was primarily DNA back then. For us, we’re kind of a unique microarray company in that our core technology can be used for both DNA and protein microarrays — that’s not necessarily true for companies like Affymetrix.

So that’s essentially how I got started, through helping Mark with his consulting, I ended up getting deeply involved with the technology itself.

What were some of the problems you were asked to solve as consultants?

One of the first problems back then was just getting microarrays manufactured. There really wasn’t good technology to do that in a robust way. You can really see what a family business this is when I tell you that my father invented Telecam’s famous spotting technology. And that technology has been installed nearly 2,500 times now worldwide on a number of robotic systems manufactured by PerkinElmer, BioRad, Harvard Biosciences. So really microarray technology really got off the ground with the percolation of commercial products. So my dad invented the spotting technology. A company that has since gotten bought out by Harvard Biosciences called Cartesian Technologies had the robotic system that we used to move the spotting technology. Then General Scanning, which is now owned by PerkinElmer — they released the ScanArray 3000. So with Cartesian Technologies, us with the spotting and the ScanArray 3000, really the key essential tools for people to be empowered to do microarrays were established, and everything started snowballing from there. Prior to that, everyone had to reinvent the wheel in their own lab.

What was your role in all of this?

My role was more in business — commercialization, to get the product out there and widely used. If there’s an area that I know most about it’s the actual manufacturing of different types of microarrays. Because our organization has provided the key microarray manufacturing technology for all these years, I’ve ended up talking to literally thousands of users under a variety of applications.

Speaking of protein microarrays, the first protein microarray data I ever saw was generated by a guy named Thomas Joos out of NMI in Germany back in 1998. He’s a pretty famous guy at this point. This was an autoimmune disease serum-based microarray.

What did you do with the data?

We just presented his results to show that other types of biomolecules such as proteins could be printed in microarrays. And we’ve always thought microarrays as essentially universal biochemistry platforms. That was kind of the crux of an article that I wrote for this Pharmagenomics supplement that was published in September where we talked about carbohydrate microarrays, peptide microarrays, artificial receptors, small molecules, oligos, cDNAs, bacterial artificial chromosomes. All of these things are finding their ways into the microarray format.

Can you give some insight into the protein array field now in terms of leaders in the field and companies that have innovative technology?

It’s interesting, I don’t think there’s really a clear-cut leader at this point. I don’t think there’s one company that’s standing above the rest.

Would you agree that bead-based arrays are growing at a faster rate than planar arrays?

That’s a pretty fair statement. You look at companies like Cell Signaling Systems and R&D Systems — they’ve really adopted that bead-based platform, and there’s a lot of companies developing platforms around it. It’s flow cytometry — it was developed in the 1980’s — if people want to use 1980’s technology in the 21st century, that’s up to them. I think that when you print samples in columns and rows on glass like we do, there’s a distinct advantage there to go back and to really look at raw data and judge how well the experiments are working — it’s a lot harder to do that with flow cytometry. So why have beads expanded more than planar arrays? I’m not really sure. I think in research we’re seeing a lot more arrays on slides than Luminex systems.

What projects has your company been involved with lately?

We’ve been doing surface chemistry projects for Dr. Robertson’s and Dr. Utz’s lab at Stanford. We did a nice peptide microarray project at UCSF screening a phage library that they’ve developed. And then we’re deeply involved in a microarray project with an autoimmune disease company that has traditional ELISA-based assays and plates and tubes now. They want to stay in stealth mode at this point; they don’t want to get scooped. But this project is slated for FDA approval in 2005.

Can you describe more about the autoimmune microarray?

It’s a multiplexed assay that’s going to be used for diagnostics. I think it’ll be the first FDA-approved product in the protein microarray field. A lot of these ELISA assays are very easy for us to miniaturize with our current detection and manufacturing technologies — it’s just a matter of doing the work. There’s a tremendous amount of tests there to miniaturize and multiplex. And it’s not hard. And maybe Luminex has been successful because you can still buy antigens and antibodies and use them as analyte-specific reagents and just run it on a Luminex system. That isn’t so clear once you start printing microarrays into columns and rows — it looks like the FDA is going to say that’s a device, and no longer an analyte-specific reagent. And a device puts the product in a different classification, and it’s going to need more approvals from the FDA. But we’re learning more and more about that as we go through the process for this autoimmune array.

What is your company looking to focus on in the future?

Our real focus now — we’ve been a technology development company for the past eight years, perfecting our microarray manufacturing technologies, our spotting buffers, our robotic systems, our spotting technology — we really feel like we have that dialed in real well now. So we’re transforming from a tools, kits, and reagents business to a content business. So the goal is to have focused microarrays of both DNA and proteins for different pathways or different experimental applications. For example our first protein microarray release will be antibodies commonly used in cancer research. We’ll take this set of antibodies normally used one at a time and we’ll print all 120 antibodies into an a microarray and provide that on a slide for somebody to use for whatever study they want. That’ll probably be released in January.

Are you working on other protein microarrays?

There’s that one in the diagnostic area that we’ve already talked about. That won’t be distributed by us, it’ll be distributed by the autoimmune disease company developing the test. That’s in the pipeline for FDA approval. Everything’s working really great with that.

What are some of the biggest challenges of protein microarrays?

For us, it’s content. It’s developing relationships with the companies that have the content for us to use and produce the pre-made microarrays. The other challenge is what pre-made microarrays do people want? We came up with this list of cancer antibodies and showed it to some people at Merck and other places, and they said, ‘Oh, well, this is a really interesting chip, but can we get this antibody and this antibody on it?’ So everybody’s got their own applications and things that they want to look at. Producing a microarray that everybody wants to use isn’t that simple. That’s why you see so many companies in the kinase microarray area — cytokines are a really popular area of study, so when you make a product like that you have a pretty good size customer base. So the challenge is what microarrays does the field want to buy? What content goes on the chip? What’s the content, and where do you get the content?

The future of microarrays is really as diverse as biology itself. So our future goals are really to leverage our core manufacturing technologies and push into different sample types, like peptides and antigens and antibodies and focused content arrays — that’s where our business is headed.

 

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