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ABI's David Hicks on the Challenges to Mass Spec, Proteomics Market


David Hicks
Senior director of the proteomics mass spectrometry business group
Applied Biosystems
Name: David Hicks
Position: Senior director of the proteomics mass spectrometry business group for Applied Biosystems
Background: Director of proteomics marketing for ABI; senior marketing director and product line manager, PerSeptive Biosystems, 1994 to 1998

David Hicks oversees mass spectrometry at Applied Biosystems. ProteoMonitor caught up with Hicks at the American Society for Mass Spectrometry conference in Indianapolis this week to talk about that part of the company’s business and where it’s heading.
Below is an edited version of the interview.
What’s your message to proteomic researchers at this year’s ASMS?
We’re continuing to show the innovations and the new workflows that are available for biomarker research and protein quantitation, specifically. Those are high-growth areas of proteomics and there’s been a lot of rapid change in technologies, products, et cetera, that fuel the adoption of these things.
If you look through the ASMS program, there’s a real uptick in protein quantitation in general, and in that application applied to biomarker research specifically. Some of those things are iTRAQ reagents, for example. Last year we introduced the 8-plex. This year, there were a number of customer presentations [by] early users of the 8-plex that showed its applicability across a wide range of samples
The adoption of iTRAQ in general as a label technique has continued to have great impact on this. There have been over 65 peer-reviewed papers at this point. There are a large number of posters. As a matter of fact, there’s almost a whole poster session primarily around iTRAQ. You can see a number of competitors talking about the use of iTRAQ technologies. So clearly, it’s starting to have an impact.
We’re committed to the continued advancement on that. That includes increasing the multiplexing on that from four to eight as well as other innovations in that chemistry family.
Are you moving beyond eight?
Potentially, but there are places where we can apply iTRAQ to things like the [multiple reaction monitoring] workflow, so now we can use what we call mTRAQ, which is a technology we have talked about scientifically, where it uses an iTRAQ-like moiety. We actually add it to the peptide to use it in a way to do absolute quantitation, using MRM workflows.
Not only do I want to look at relative changes, which is what iTRAQ does in biomarker discovery — cancer versus normal, or relative changes over time — but in the MRM workflow when using an mTRAQ reagent, you have the capability to do absolute quantitation. [You can see] exactly how much is my peptide or protein of interest going up or down in a wide range of samples.
That’s why we call that workflow a biomarker verification workflow. Once you’ve discovered the biomarkers with a population of normal versus disease, a key next step is to move toward validation: Does that really hold up when we look at hundreds and even thousands of patient samples across a variety of sub-segmentations and things?
It doesn’t make sense for most researchers to repeat those big discovery experiments where you’re looking at many, many analytes across many, many samples when only a few have proven to be changing significantly during the discovery experiment.
There, you want to switch to a method that’s going to let you do quantitation, but do it under a much larger population of samples and do it as accurately as possible, And using labels like mTRAQ would allow you the capability to do that. And if you use the MIDAS or MRM workflow, you’ve got the capability to look at five, 10, 50 putative markers and be able run those plus hundreds of samples cost effectively fairly rapidly and quantitatively.
Has R&D for proteomics shifted to the consumables side away from instruments?
No, no, it’s a balance of investment. It’s an investment in new platforms, and software and reagents, and some of the applications work needed to create these whole new workflows.
The 4800 [Plus MALDI TOF/TOF] was a substantial new platform project for us. QSTAR Elite was a very significant platform project. We continue to have platform projects like that in our development. We just talked about the FlashQuant as a platform technology that at some point we’ll commercialize into a proteomics configuration.
But it’s not just limited to that because the innovations aren’t just coming from new pieces of hardware, new forms of mass spectrometry. A case in point is LC MALDI. It’s the LC that you’re so familiar with as a separation technique before you go to mass spec. But here, rather than going directly to a mass spec, you’re actually depositing it onto a MALDI target, mixing it with matrix, and thereby freezing the sample in time including the separation.
It hadn’t escaped our attention many years ago that if you could freeze that separation in time, by mixing that stream of chromatographic media with a matrix, it freezes that sample in time. And what we do is we move the plate and collect spots or tracks of the chromatography. So when you finish a one-hour chromatography and you’ve collected a spot every two seconds, you’ve literally got the whole chromatographic separation on your MALDI target and all the complex peptides are separated from each other.
That gives you the ability to dive deep down into the sample and not be worried about the time of chromatographic elution because if you get an area, for example, that has a lot of peptides in it, some in high abundance, some in low abundance, you can go back and keep shooting the MALDI target at that particular area and dive deeper into the sample.
What are the growth markets in mass spec?
Right now, there’s growth actually in all those segments. CROs are growing, especially in places like China and India, but also in the United States now. The applied markets, the use of mass specs for food, environmental testing, and even forensics is a high-growth area. And proteomics is also growing right now.
Yes, new instrumentation, and new technology are driving replacement or expansion in core labs. But there’s also an adoption of mass spectrometry techniques in places like the biology laboratories.
A lot of biologists, the majority of biologists do some form of protein research or protein analysis along with DNA, small molecule, cell [work]. Cell biologists, cancer researchers, a molecular biologist — at some point, you’re probably going to look at or study a protein, whether it’s via Western blot or whether it’s a 2D gel experiment or whether it’s going to be a whole iTRAQ analysis.
A lot of them traditionally work with core labs. They’ll take their biological problem to a mass spectrometry core lab and partner with them to get a solution. It still happens, but there’s an ever-growing population every year of customers buying their first mass spec and putting it into these applications.
One of the drivers there is biomarker research. You really cannot pick up a science magazine or [other literature] and not see some new initiative like the NCI fueling growth in biomarker research.
What are some of the challenges in mass spec technology that you think the field has not really addressed properly and completely, and what is ABI doing toward that?
I won’t say that it hasn’t been addressed properly; it’s all complex stuff. But a couple of the challenges that are out there [are related to] sample prep across the wide variety of samples that we’ve got. Whether it’s dealing with the challenges of plasma samples — a big source for biomarker discovery, but one that contains an incredible dynamic range; proteins expressed at grossly large amounts like albumin; to proteins expressed in fleetingly small, in some cases almost immeasurable, quantities.
A dynamic range of somewhere between 10 and 12 magnitude — that’s a huge challenge for anybody. That’s like trying to look at Mt. Everest and a microscopic bug at the same time.
Things like depletion columns and enrichment strategies are new approaches to that sample prep. And there’s still a lot of activity going on in that space — so the whole field of sample prep and how we can process these samples, how we can deal with the challenges.
Over the past year or so, some of your competitors, such as Agilent and Waters, have looked to grow their mass spec business. How is ABI responding to this?
The mass-spectrometry market — and we’ve been in it for 21 years — has always been competitive. Nobody’s backing away from the mass-spectrometry market, and there are others that are spooling up and there’s a constant rate of new products and challenges.
We actually focus our energies on responding to unmet customer needs. As an innovator and a leader in the field, our focus has never been on beating our competition. More importantly, it’s been on meeting unmet customer needs. That’s where the growth of the market’s going to come from, where our growth is going to come from. And our focus on that and our strategy continues to be innovation. We’re not stopping the innovation that’s required, we believe, to meet those unmet customer needs.
A few of your competitors like Agilent and Thermo Fisher Scientific are moving to expand their LC business. But we haven’t heard anything from ABI in terms of the LC space. Why is that?
LC is a part of the solution to the customers’ needs. In some cases, that solution is best achieved by making our software on our mass specs compatible with the LCs that the customers already have or prefer to use. In a number of places, you’ll find that it’s really customer preference that’s going to drive it. The most important thing that we can do is make our software powerful enough and integrateable enough with the variety of LCs that are out there.
One thing that we’ve talked about is the fact that our software is now compatible with the Waters UPLC, also with the Agilent 1200, also with the Shimadzu high-speed separation techniques. Some of those customers, they need that kind of open architecture.
In other cases, it’s important to bring an integrated solution, so we build partnerships with some vendors or in some cases, with the Tempo line, actually commercialize with Eksigent as our partner a specific ABI-branded, ABI/MDS Sciex-branded product that specifically matches up to our system.
We’re not approaching the LC market as a one-strategy issue. It’s matching up what the best solution for LC is to our specific customers that we’re going after, bringing them a mass spec solution, or integrating an LC-MS/MS solution.
So we’re not trying to be LC for LC’s sake.

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