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Danley of CombiMatrix Discusses Future of Microarrays in Biodefense


CombiMatrix, a microarray provider based outside of Seattle, Wash., is working on an integrated pathogen-detecting chip for the US Department of Defense that will be able to conduct testing for biological and chemical threat agents using both microarray and microfluidic technology.

Retired US Army Colonel David Danley has been directing CombiMatrix’s homeland security and defense program since he retired from the armed forces in 2003, and he brings nearly 40 years of experience in the biological sciences, and 25 years of government service to his role at the company.

Danley recent spoke with BioArray News from his company’s headquarters in Mulkiteo, Wash. to discuss CombiMatrix’s efforts and the developing marketplace for pathogen-detecting, microarray-based technology.

How big was the grant from the Department of Defense and what are they expecting in return?

The grant itself was a multi-year contract for ‘05-‘06, and the initial contract was for about $6 million. We are expecting additional funding this year for a total of about $8 million.

What we will be developing for them is actually a portable system — we will start off with a lab bench, a small desktop system that they can use to develop the different probes that they need for detecting biothreat agents. Then we’ll work to make the system smaller, more compact, portable, and we’ll base the system on electrochemical detection so we won’t be using optical at all. So we will eliminate fluorescence detection.

Will you use microfluidic-based testing like Agilent’s ALP or is this completely different?

Well, we are looking at a number of different ways to amplify threat agents in a mixed sample, a complex sample — PCR is one of them, we are looking at whole-genome assays. There are a number of approaches that we can take and it’s not entirely clear which the best approach is going to be.

But will you be using microarray technology?

Oh,yes, we’ll be using microarrays. It will be microarray, electrochemical detection, no fluorescent reagents, and we are not sure which format for amplification we will be applying.

Are you aware of any other technology similar to yours that has been made available or is in development for biodefense applications?

I suspect there are a lot of companies that are working on this technology. Clearly the program down at Sandia laboratories that uses bead technology is a standalone system with air sampling that uses both antigen and antibody. I believe they’ve got some limited PCR capabilities as well.

Do you see this as a trend combining all these tests or options into one technology?

Well I think what the user community wants, and I am not sure what it will ultimately look like because there’s going to be cost trade-offs as the users want to get rid of redundant systems or systems that are incompatible. In other words, in the military, where you’ve got to deploy something to the field and you’ve got to support it with logistics to have two or three or four different agents to detect biothreat agents is not logistically sound. So they would like to have one format, one system that does everything — you know chemical detection, biodetection, viruses, bacteria, toxins.

But is that achievable?

I believe that it is. Is it going to be cost effective, though? That’s hard to say. In some respects it will be extremely cost effective because you’ll be able to detect through genomics all of the threat agents as well as virulence factors and other indicators that an organism may have been genetically modified, but that’s not going to be an inexpensive tool.

But that’s definitely an issue isn’t it?

Well that’s definitely the issue. So right now what we are trying to do is to find that sweet spot where we can provide a maximum amount of information for the most reasonable price.

Is this going to be ready this year? When will you send the prototypes back to the DoD?

Well, we will have prototypes to the DoD in this year, definitely. Whether we will have the ultimate product to them? That’s going to take a little more time.

How developed is the DoD on their side of the equation? Do they have their own in-house people that are working on this technology, or do they subcontract all of that work out?

Well, the United States Army Medical Research Institute for Infectious Diseases [part of the DoD] has a microarray program with their own technicians in developing probes and assays. We are working with them and we provide information and they provide information under a cooperative research agreement. So we have a sanctioned relationship with a government laboratory to develop our technologies. They see a great benefit in electrochemical detection and getting away from expensive optical readers that can cost tens of thousands of dollars. Our first prototype will be small and relatively inexpensive.

How much do you anticipate your technology will cost?

Several thousand dollars.

Is the government the main client here or are there other people in private industries that are also looking to pick something like this up and integrate it into one of their systems?

There are defense contractors that are looking at integrating our technologies into defense biodetection systems. I think from a commercial standpoint that what we are doing — developing for the government has definite commercial applications, not for biodetection but for the same reason that one uses microarrays. This will be dual-use technology. In many respects that benefits the government because by being commercially available it brings the cost of the product down.

How much money has the government made available to invest in this kind of technology?

That’s hard to say and I don’t have a good answer. In terms of stark investments I can’t say because there’s money going to laboratories to look at these technologies, so we’ve got different Army, Navy, and Air Force laboratories looking at microarrays. We have them looking at biodefense, gene expression, and human performance — so the spectrum of activity is so wide that I couldn’t hazard a guess as to how much is involved, but I would assume tens of millions of dollars will be invested in this technology, trying to bring it to fruition, and when they see it coming to fruition there will be quite a bit of funding available.

Ultimately, where will this technology wind up and who will be using it in the field?

The product will initially be restricted to field laboratories, which might be associated with environmental monitoring labs, or hospital labs, or they might be part of chem-bio monitoring teams that are currently fielded by different [armed services].

Ultimately we believe our product can be made small enough and automated so that it can be incorporated into stand-alone autonomous systems so that it would provide comprehensive monitoring and validation. So we see a progression of products staring with bench-top units evolving towards a smoke detector — a very small handheld unit. They can be autonomous, which means that somebody can hang them on a wall, but in all likelihood they will be the responsibility of your chemical and biological specialists who are assigned to each unit.


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