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BioTrove s Bob Ellis Targets Business Space Between Arrays and PCR

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At A Glance

Bob Ellis, CEO, BioTrove

Experience: 2001-2003 — Executive vice president, Affymetrix.

1998-2001 — President, Genometrix.

1995-1998 — Business unit manager, Applied Biosystems, Perkin Elmer

1993-1994 — Vice president, general manager of Far East, Perkin Elmer ABI.

 

During a 30 year career in the analytical instruments business, Bob Ellis, 57, has made stops at Applied Biosystems, Perkin Elmer, Hewlett Packard, and Affymetrix— where he was executive vice president — as well as startup Genometrix. Now, he is three months into a job as president and chief executive officer for BioTrove of Woburn, Mass., a seven-year-old firm that is commercializing a microfluidics-based analytic platform.

With his resume alone, Ellis is an executive to watch in this industry. But just last week, he and his team at BioTrove announced that they had raised an additional $10.9 million cash infusion. This second tranche of investment came from previous investors, and followed the company’s August 2002 Series B funding round of $5.25 million.

BioArray News spoke with Ellis to learn about how the company will use this war chest of some $16 million to commercialize its technology, which includes the Living Chip, a developmental nano-scale fluidic chip technology for biological analysis.

Will you describe the Living Chip technology?

We have seen an opportunity to really combine nanofludics technology — the nanotiter plate technology — and the field of real-time PCR.

Right now, we have two product concepts, one with 3,072 holes, which is in a 1 by 3 format, a microscope slide. Then we have a second format, a 25,000-hole nanotiter plate, which is in a 3 by 5 format. As a side note, we can make the nanochips in any configuration. Internally, we use 10 by 10 [nanotiter plates] for development. Down the road, they may make a great diagnostic chip.

But the point is, you can do real-time PCR in these, and it’s extendable into proteins, so we have done ELISA assays, a lot of different assays, including cellular, so it’s a true platform. We are just focusing, initially, on doing SNP analysis and transcript analysis using PCR. It’s a great platform to do lots of things.

We see the attributes of the volume of 25 nanoliter holes and the intrinsic savings that can bring to doing real-time PCR. And then you take the parallelism of the chips and, all of a sudden, I think you are in an area that really combines the attributes of the microarray world and the real-time PCR world. Clearly people see real-time PCR as the gold standard for transcript analysis. Affy does a great job with their whole genome arrays, and we see this technology as being able to straddle a lot of the needs and requirements of people in the microarray world, in particular, the validation, while at the same time, being able to make real-time PCR more far more affordable, allowing people to do far more experiments, and look at more transcripts simultaneously. So we see a bridging of those two worlds. The opportunity is take our platform, [where] you can do SNPs or do transcripts, in the same nanoarray. And be able to do 3,000 [tests] per chip, and eventually that will be expanded up to 25,000 holes, which you will see in our second-generation chips.

It’s like a DVD, which is one analogy that I use. Basically, it is a substrate [and] you can put movies or music on it. The analogy is the test tube, the microtiter plate, 384, 1,536, to our 3K and our 25K. Again, it [is] a substrate that you can put a lot of things in: you can put cells in it, RNA, DNA, lots of things. So, as the density goes up, the cost goes down. It’s not technically Moore’s law, but it is analogous to that.

When do you expect the Living Chip to be commercially available?

We are going out to our first test sites next week with some local people who will be trying out our 3K chips. The first application that we can do with that fairly easily is [SNP] end-points. So we will be getting customer feedback right away on that. We are giving a workshop at the Tri-Genome conference at the end of March and we will be presenting data from alpha test sites. So, we are literally just starting. We expect to have the SNP chips commercially available in the June time frame.

You can actually almost do SNP analysis almost out of the gate — there is very little barrier to entry on that. You can just buy a chip from us and try it, if you have a flatbed thermal cycler and scanner. So if you have a flatbed thermal cycler, the old in situ thermal cyclers, you can basically load these [chips] up with Taqman or some other endpoint SNP analysis. You can amplify them offline and then just stick them into an array scanner, the standard array scanners that use the 1 by 3 [inch] microscope slides.

To do transcript analysis, you need an instrument. Because there is no real-time imaging thermal cycler that can read a 500 micron pitch, we plan to have beta units of that [instrument] this summer, in the July, August time frame, hopefully with full commercial launch for the transcript chips in the late fall, early winter, towards the end of this year. That is pretty much on track. Once we have the instrument for them, people can do both SNP and transcript [analysis] on our technology.

How long were the negotiations for the funding?

I was appointed CEO in October and that’s about when we started. It’s an inside round, so it went pretty quickly.

With your experience, reputation, and knowledge, would it be fair to say your coming on board clinched the deal?

No, we are a team here. I think what really convinced [investors], was coming up with a really compelling reason why people will adopt this technology and articulating that.

As I have been here, we have kind of changed the direction of the ship. We have moved from using our Living Chip for high-throughput screening, to basically focusing on genomic applications. And, the technology guys have really pulled through in adapting what we have developed there and I think this is indicative of a real, true platform. It has been a combination of being able to demonstrate we can do these things, along with just focusing everybody on the objective and articulating a cogent market development plan.

How will you use the funds?

It will put us in good position to have these products commercialized and give us a good shot at moving forward, looking down the road to either a mezzanine round for growth capital or hopefully, depending on the markets, taking a shot at the public equity markets. I don’t want to be too specific, because we can set expectations and things can change, and you know how fickle the IPO market is, but that is certainly something we want to set our sights on, audacious as that is.

Where is the company today?

We are extremely competent in the invention and product development area. We have a very strong team. So out of the 30 employees we have now, 27 are either engineers or biologists to support that profile. As we move into the next phase the key use of funds is to build up manufacturing capability to make the chips, and then the commercialization side, to build the sales and distribution, the sales and technical support. That’s the next level. That is something we will be putting in place over the next four or five months. We have the technology working very well. We have demonstrated this to a number of key people and we have good external input on it. We need to take it into manufacturing, and develop the commercialization part. I’ve felt that it’s: Let’s get the tech up and working. Now, the next level, is: Okay, let’s get serious about making and selling it.

Given the ability to do real-rime PCR massively in parallel, does this do away with the need for microarrays?

That’s the whole proposition we are testing. This is something I’ve always felt — and you are getting a little personal philosophy here — that that is something that would pull together analytic requirements for transcript analysis and the parallelism. Because even the maximum 384-well plates from our friends at ABI, you are still pretty limited in the number of simultaneous transcripts. Our starting product does 3,072. It’s quantitative. And, because they are holes, the key thing we have figured out is how to get things in and out. In the microfluidics domain, people have had trouble [with that], and that’s what we have figured out how to do.

How so?

What allows us to do this are the holes. Their dimensions vary a little bit, depending on the thickness of the substrate. But basically, they are 300-micron-diameter holes. You have a hydrophobic surface on the outside, and on the inside of the holes, it’s hydrophilic. So you have this surface-tension differential. You can fill these just by dipping them in the liquid. The good news is that it fills up to 25 nanoliters, and [the results] are very reproducible with strong CVs. The bad news is, you’ve got to have to have 25 nanoliters. But, at that level, it is just such a tremendous savings in terms of sample usage, or reagent usage, that it makes doing lots of Real-Time PCR very, very affordable.

Will you take us through your career?

I started in the industry with Finnegan Instruments, in sales. My boss went over to HP, and I ended up at HP Scientific Instruments, with the mass spec group. There I did product development and marketing. The group of people that started ABI were originally from HP labs. Elaine Herron, who is [now] the CEO of Picoliter, recruited me up to ABI and that was 1986. So I started with the synthesis product line, and then I took over all the DNA products. The sequencer had just got on the market, and I was the marketing manager. It gave me great experience marketing something that was the first of something on the market, and that, of course, is what ABI is great at. I did the subsequent revisions of the sequencer and some of the other synthesizers that we co-marketed at the time. Then, I got a chance to go over to Japan and managed Applied Biosystems Japan and the whole Asia-Pacific area for about five years. And then, I came back and managed some business units in applied genetic analysis for food testing and forensics, [and] put together a subsidiary for agriculture. Then I had a chance to go to a startup called Genometrix. I thought arrays were where really where we needed to go. It was kind of the thing in 1998 to go and find your own company, so I went down there, and we were going great guns, and almost got out, but we got caught up in the big bubble burst, and, of course, we had a very unpleasant outcome. But before that collapsed, I was offered a position at Affymetrix to head up their product development quality. So I was there, and I decided that there was a lot of things out there that I could take a look at and I came across BioTrove, and it was something that I felt that what the world needed — massively parallel single analysis stuff. I saw the technology when I was over at Berlin, it was, I think at a show called Nanotechnology meets Biology. I was giving a keynote speech [when] I first saw the this technology. Some of the guys at Aventis were one of the test sites for BioTrove at the time. Personally, I thought that was what the world needed because if you can get the advantages of doing one thing really well, and just parallelizing it, you can extrapolate that. That really intrigued me. Obviously the team here is very good and we have brought in some molecular biologists with experience with PCR to enhance that on the application side.

Is ABI a training ground for executives for this field?

I cut my teeth at ABI and learned a lot. I went from a product manager, marketing manager, vice president, general manager role. They were roughly $30 to $40 million when I joined them and a lot smaller than HP, where I would never have been given those opportunities. I think as a company goes through its normal life cycle and being really successful, I think it just naturally will spin off people. I enjoyed doing that when I left ABI and went off to Genometrix. I just had another opportunity and I said, well, you know, I’ve got to do it one more time. So I think that is the normal thing. There can only be one boss, so you can choose to be supportive or try your own ideas. I think, naturally, that as you are looking out, and you can see opportunities, sometimes you see a good match and some technology that can solve a problem.

Are you in competition with Affymetrix?

No, we are not. We are in a completely different domain. They have wonderful products and they are following Moore’s law to a T. We are there to fill in the gap between the whole genome and doing Real-Time PCR in a 384-well plate. And my daughter is a senior product manager there.

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