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Gary Valaskovic on How to Make a Mass Spec Startup Firm Succeed

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At A Glance

Name: Gary Valaskovic

Age: 37

Position: President and co-founder, New Objective

Prior Experience: Postdoc, Cornell University, 1995-97. Studied with Fred McLafferty.

PhD, Cornell University, 1989-95

 

How did you get into mass spec?

I got into mass spectrometry through a postdoctoral appointment with Fred McLafferty at Cornell University. As a graduate student at Cornell, I was doing my research in scan probe microscopy. Fred was on my thesis committee, and after my defense, he invited me to join his group as a postdoctoral associate. I was surprised and pretty pleased because I knew that he was top in the field. I knew that biological mass spectrometry was gaining a lot of momentum. This was the place you wanted to be as a scientist [if you were] interested in both solving biological [and] analytical chemistry problems.

I wasn’t really sure what I was going to work on, but Fred had casually left a preprint of Matthias Mann’s original nanospray paper on my desk. I looked at this and thought, ‘this is really exciting.’ The next day I went back into his office and told him that all the instrumentation that I worked on for graduate school actually applied to nanospray. Then the quest of my postdoc became answering the question, ‘What’s the smallest possible sample we can analyze?’ using Fred’s FTMS machine. Almost every month we would reach a new milestone in sensitivity. That work culminated in a paper in Science (Valaskovic et al., 1996; 273(5279):1199-1202) where we were able to generate MS/MS data on a 29kDa intact protein and identify it at the attomolar level.

 

How did you reach that sensitivity?

We developed a system to perform capillary electrophoresis and interface it with nanospray mass spectrometry. We used a 5 micrometer ID column and directly coupled that to the mass spectrometer. We were able to get a stable spray at a flow rate of about 4 nanoliters per minute, which was at least a factor of five lower than what had previously been demonstrated. That opened my eyes to the analytical power of mass spectrometry as applied to protein analysis.

 

How did you decide to start your own company?

From the time I was a teenager, I had this idea that being a professor was my calling. I expressed this to Fred, and he [supported my idea], so we started out to develop a research proposal. [But during one of our meetings] I came up with reason after reason why [this or that school] wouldn’t work for me. For every school I shot down, I could see Fred was getting a little more frustrated with me. At the end of the meeting, Fred looked me in the eye and said, ‘Gary, I don’t think you realize it, but you don’t want to be a professor.’ So I left his office, I was pretty upset. [But] I realized that he was right. Where I got satisfaction from in scientific research was developing new things, and seeing those new ideas, new tools, and new technologies used by other scientists. There was no more effective way to do that than to start a company. At that point, I set to work on starting New Objective.

 

That’s not what you learn as a scientist...

From the age of 13 until about 22 I had the good fortune of working for a scientist by the name of Walter McCrone. He was the world’s leading light microscopist, and he was also an entrepreneur; he started at least four companies over his career. I saw that a scientist could be a businessman, and that you didn’t necessarily have to have formal business education to do it. The greater part of running a business was common sense. I admired his entrepreneurial spirit, and I really learned from that.

I knew that I did not want to go the usual venture capital funding business model [route, so] I started the company with founders’ capital, with the addition of a small amount of seed money from an angel investor. My goal was to make it sustainable based on that seed capital. We started out with three people. At the time, there were two or three areas in the country that were centers of excellence in proteomics, and Boston was one of them that had a great deal of appeal to myself and to my wife. There were some really great academic groups, [for example] at Harvard, at Millennium Pharmaceuticals, and at the Genetics Institute, which was later acquired by Wyeth. I started calling these people up and telling them that I started this company, New Objective, and [that] we were going to provide consumables for nanospray and protein analysis by LC/MS. They were all kind enough to invite me into their labs, and give me a chance to see what they were doing, how they were doing it, what their needs were, and where they thought their needs were unmet in terms of other commercial products. I then tailored the first generation of New Objective’s consumables based on what I learned from these groups.

We had glass nanospray needles and fused-silica nanospray needles. Based on the methods that I developed at Cornell, we were able to make tips to a particular size. At the time in the field, it was very common to use tips that you had to break to open. That of course is a very technique-dependent operation. One of the principal goals of New Objective has been to make nanospray available to everyone, so that the average protein chemist who has some familiarity with mass spectrometry can run a nanospray experiment and get the kind of sensitivity that they expect.

 

How did your business develop?

The demand was strong at the start, and we have had more or less exponential growth in sales since then. At this point, we have well over 1,000 customers. Probably there is not a major pharmaceutical or biotech company, if they are doing proteomics by LC/MS, that is not using our products. We were profitable by year three.

 

Was keeping up with demand a challenge?

That was a huge challenge. It was great to see the orders grow like that, but it did catch us by surprise, it was faster growth than we anticipated. We had started up in a rather small space in Cambridge and had really met the limitations of that space; we were running double and triple shifts. About two years ago, we moved to a larger facility in Woburn, Mass., and we were able to buy more equipment, hire more people, and be much more efficient in what we do. We now have 15 employees.

 

Do you have any alliances with large vendors?

We do. We have been an OEM vendor to many of the larger firms that are involved in mass spectrometry and liquid chromatography.

 

You later developed chromatography products?

When I was working with customers, I realized that the nanospray was only half of the equation in terms of sensitivity and analyzing a complex sample. The other half was chromatography. Based on that, we developed a nanobore LC column, which we call a PicoFrit column. In that column, the reverse-phase material is integrated directly into the nanospray emitter. It’s a very efficient transfer of material, so you maintain high sensitivity. If you make the column the right way and use the right materials, you can also get a very high resolution separation. That enabled a whole new set of applications, culminating in multi-dimensional separations for doing shotgun [proteomics]. Up until that time these devices were being made by hand by what are now a lot of our customers. Probably our biggest competitor has not been another company but the customers themselves, making their own consumables for nanospray.

 

How do you market your products?

We sell direct, [but] we also have a number of distributors. Our principal means of marketing has been going to trade shows; we do on the order of about a dozen a year, which is hard work for a small team of people. Our customers are usually our best sales people because the vast majority of them are very happy with our products.

 

Are you developing new technologies?

We have an exciting new technology, an automated control system for electrospray. In one of our nanospray sources, we have a spray visualization system, so you can actually see the spray that is coming off. Based on this, you control different experimental parameters. We are developing a system to automate that process, a machine-vision based approach. We are hoping to have alpha-testing done in the 4th quarter of this year.

We believe that the ramifications for nanospray will be to bring new applications to the format. The next generation of problems in proteomics will almost certainly be quantitative, [but] the quantitative analyses tend to be very repetitive and you usually have a lot more samples. It requires much more experimental control to get a good quantitative number with a low standard deviation. Kind of the dirty little secret of nanospray is, it provides very good sensitivity, but it can be hard to control. [With our new product], each time you run an experiment, you are going to have the same spray conditions.

 

Will proteomics remain the cornerstone of your business in the future?

Certainly proteomics is a market that continues to grow. It’s perhaps not the heady days of 2000 and 2001, where it was busting at the seams, but it’s still a very healthy growth. If you can compare proteomics to genomics, the analysis of the genome was a sprint; the analysis of the proteome, that’s a marathon.

 

What is your secret to success for a startup company?

One, you do have to have an area where you excel, whether you are starting a company to provide a new tool, like New Objective does, or a new service. The second requirement is that you have to be customer-focused and customer-driven, not technology-driven. You can’t turn your back on the customer.

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