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Scientific Instrumentation Symbiosis

Instrumentation firms are increasingly forging links with scientists in academic and nonprofit labs to tap into key research areas and develop new technology

by Ann M. Thayer
November 18, 2013 | A version of this story appeared in Volume 91, Issue 46

LARGE SCALE
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Credit: MRC-NIHR Phenome Center
Researchers at the U.K.’s MRC-NIHR National Phenome Centre conduct population-level phenotypic analyses using equipment from Bruker and Waters Corp.
Researchers at the UK’s MRC-NIHR Phenome center conduct population level phenotypic analyses using Waters’ and Bruker instruments.
Credit: MRC-NIHR Phenome Center
Researchers at the U.K.’s MRC-NIHR National Phenome Centre conduct population-level phenotypic analyses using equipment from Bruker and Waters Corp.

Instrument companies have many reasons to hunt for customers with deeper pockets than scientists in academic and nonprofit institutions. University, government, and other nonprofit laboratories make up less than one-quarter of sales for the industry. Perennially cash-strapped nonprofits are fighting for a shrinking pool of funding owing to cuts in government spending. In general, they buy instruments only every three to five years.

But academic customers offer benefits that better-funded industrial customers often don’t bring. One of them, according to Mark Cafazzo, senior market manager for the academic market at instrument maker AB Sciex, is a willingness to collaborate.

“We regularly poll our customers and have found that they don’t necessarily want a flat transactional relationship with their vendors,” Cafazzo says, “but really want to work regularly with us for mutual benefit.”

Working with top scientists at academic institutions is also a way for instrument companies to tap into cutting-edge research. Successful partnerships can pinpoint scientific questions and invent new equipment to help provide answers.

Instrument firms and academic scientists alike have warmed to the idea that collaborations, if structured well, will let them achieve their respective business and research goals without making major compromises. As a result, some long-standing industry-academic relationships are deepening into large-scale alliances.

Constant contact with academic collaborators helps firms develop products and validate technology. Not only are R&D leaders sounding boards for vetting new instruments, they are also training the next generation of scientists who may become customers. From these collaborators, companies get clues about what to invent, where to improve, and how research is evolving.

For their part, academic researchers frequently get early access to, or even help build, the newest technology to advance their scientific aims. In return for access, researchers may help develop methods and protocols for new equipment that a company can offer to other customers. Both sides have an interest in publishable results in which an instrument played a critical role.

Over the past several years, relationships between universities and industry have grown in number, size, and complexity. In fact, some people concerned about preserving academic freedom worry that scientists can get swept up in the tide and lose some independence. But a look at how three major instrument firms approach academic collaborations in general—and three marquee alliances in particular—suggests all parties can come out ahead if alliances are done right.

Separations and mass spectrometry firm Waters Corp. helps fund innovative research projects through its University Research Collaboration Program. Researchers may use the award to reduce the price of a Waters system. In return, the researchers agree to be available as expert references regarding the suitability of Waters’s products for addressing their research challenges.

Waters has worked with academia for more than 50 years, according to Scientific Director John C. Gebler. These interactions range from active collaborations that involve set milestones and the exchange of money or equipment to more passive relationships with informal communications. Either way, “we are very open about publication,” Gebler says.

Most of the work, he notes, focuses on demonstration and application of technology, which generally does not create patentable results. But advances do emerge.

“Many of the technologies that we have today, like ion-mobility spectroscopy, hydrogen-deuterium exchange MS, and ultraperformance liquid chromatography (UPLC), came from significant collaborative relationships,” Gebler explains. “We look to work in areas that we are interested in but that are new to us and where we don’t have the expertise in-house, or where there’s an opportunity to have additional market penetration.”

Waters also recognizes leading investigators through its Centers of Innovation Program. Launched in late 2010, the program has selected more than 20 scientists, labs, and research centers across a variety of fields. It provides them access to Waters’s scientists and technology, but it’s not a guarantee of funding or equipment and does not require researchers to purchase or use only Waters equipment.

Among the first recognized in the program was Jeremy K. Nicholson, a biochemist who heads the department of surgery and cancer at Imperial College London. He also directs the six-month-old MRC-NIHR National Phenome Centre, which conducts population-level phenotyping to uncover disease risk factors. Set up with the help of $16 million from the U.K.’s Medical Research Council and National Institute for Health Research, the center is a partnership among Imperial, King’s College London, Waters, and instrumentation firm Bruker.

Some of the fledgling center’s equipment was repurposed from the 2012 Olympic antidoping facility (C&EN, Sept. 3, 2012, page 40), but much of it is new, Nicholson says. The phenome center houses 16 Waters UPLC triple-quadrupole MS systems for exploratory profiling and targeted analysis and three Bruker 600-MHz nuclear magnetic resonance machines.

NEW DIGS
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Credit: Michael Barnes/UC Berkely
University of California, Berkeley, students work in a new analytical instrumentation lab equipped by Agilent Technologies.
Agilent Technologies has helped equip a new analytical chemistry undergraduate teaching lab at the University of California, Berkeley
Credit: Michael Barnes/UC Berkely
University of California, Berkeley, students work in a new analytical instrumentation lab equipped by Agilent Technologies.

Many of the 16 researchers now in the center “have been developing NMR- and MS-based platforms for biomarker discovery and analysis for at least 25 years,” Nicholson says. Because much of that work involved equipment from Bruker and Waters, “they were natural partners for the National Phenome Centre,” he adds.

Nevertheless, the instrumentation companies still had to pass muster. Nicholson notes that a proposal for the center was peer-reviewed and evaluated at high government levels. “We had to make a case for the scientific background and the benefits of what we are going to do and the business sustainability of the model,” he says.

Representatives from Waters and Bruker serve on an analytical development committee, and the firms provide engineering and technical support, but the center is free to set its own agenda. Under MRC policy, the center leases the equipment under a long-term agreement that provides for upgrades. At the same time, under an agreement with the instrument firms, “we have defined areas that we will work in and particular deliverables,” Nicholson says.

Such partnerships are more than just ways for an institution to get the best deal on expensive equipment. Choosing the right partner is critical to achieving a close interaction and to using technology in innovative ways, Nicholson says.

“For every sample, we have nine exploratory procedures,” he explains. “We are challenging the systems with different sorts of samples and also trying to make them high-throughput.” To increase productivity, center scientists push the equipment “until the rivets pop out,” he says.

Doing so is a way to identify weak links in a scientific system. “We have a very interactive program of instrument modification and enhancement to actually make the whole thing more fit for the ultimate purpose of large-scale phenotyping,” Nicholson says. “We are establishing what we consider to be extremely robust profiling and targeted methods that you can export anywhere if you have similar sorts of equipment.”

Nicholson says he believes instrument companies and their employees have a genuine desire to see their technology affect people’s lives. Not only is this “a very good place to be in ethically,” he says, but by generating deliverable results in a new field, they may be able to create a market where one didn’t exist.

Indeed, equipment suppliers have the opportunity to reach potential new customers through the phenome center. Support from Waters and Bruker includes donations of equipment for a training center for international students, scientists, and doctors. “There is a lot of opportunity where our technologies might be very valuable to a customer, but they don’t know how to use them,” Gebler says.

Better training and education are goals of another company-supported project: the Chemical Science Laboratories for the 21st Century at the University of California, Berkeley. As part of the $30 million undertaking, former College of Chemistry dean Richard A. Mathies wanted to update UC Berkeley’s chemistry curriculum and bring in modern equipment. Agilent Technologies helped with a deal that enabled the college to equip a new student lab with about $1 million worth of analytical instruments for about half the cost, Mathies says.

Agilent and UC Berkeley had connections long before the chemistry project. In early 2011, the firm made a multi-million-dollar commitment that included access to technology and company scientists to help UC Berkeley set up its Synthetic Biology Institute.

Because the school and the company knew and trusted each other, “everyone was pulling the wagon in the same direction to try to get to a deal that made sense, where you get a great facility at a price point that you can handle,” Mathies says about the student lab.

The connection with Agilent is “yet another example of how private industry can very appropriately work with public universities and make chemistry better,” he says. Although the proposal went through the usual university purchasing process, he says other suppliers were unlikely to match the significant discounts, grants, and donations Agilent offered.

Opened this fall, the student lab contains a collection of Agilent’s latest instruments and software. Included are gas chromatography, GC/MS, LC, infrared, and atomic emission systems to cover a range of teaching and experimental needs. Agilent doesn’t run the lab, but the company is interested in developing educational software, Mathies says.

MONEY SPENT
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In a survey of 48 academic research labs, most rank consumables as their top purchasing priority. NOTE: Survey respondents are labs in the U.S., U.K., Germany, and Japan and were asked, “What are your two highest purchasing priorities for your lab?” SOURCE: Goldman Sachs Global Investment Research
This bar graph shows the first and second priorities when it comes to purchasing.
In a survey of 48 academic research labs, most rank consumables as their top purchasing priority. NOTE: Survey respondents are labs in the U.S., U.K., Germany, and Japan and were asked, “What are your two highest purchasing priorities for your lab?” SOURCE: Goldman Sachs Global Investment Research

The lab is open to upper-level students to use directly, whereas students in introductory courses can submit jobs that lab staff will run. Students, even nonmajors, “can learn about these instruments, actually see what they can do, and are much better prepared when they go out in the workplace,” Mathies says.

Jack Wenstrand, Agilent’s director for university relations and external research, says he’s happy with how the lab partnership turned out. “The students are going to benefit, the faculty is going to benefit, and having a prominent lab at such an excellent university demonstrating the capability of our instruments is good for us.”

Agilent has particularly close relations with UC Berkeley, Wenstrand adds. “We have been doing research with them for a very long time. They are important customers, and many Berkeley graduates are employed by Agilent.”

Agilent has recognized UC Berkeley scientists among its early-career professor awardees and through its Thought Leader funding program. Over the past five years, both of these awards, made to universities on scientists’ behalf, have supported about 20 established and five young investigators.

“When we engage with a university, we do it intentionally,” Wenstrand says. “It’s important to our future to get a deep appreciation of how advanced research requires and enables new measurement solutions.”

In this way, academic collaborations, especially those involving basic research, complement Agilent’s internal R&D, which tends to be more proprietary and product-focused. “A very important part of our basic research program is accomplished through our work with universities,” Wenstrand says.

Still, companies aren’t the only ones taking the initiative to create partnerships. As part of the Xtreme Everest 2 Expedition this past spring, University of Cambridge researchers were going to analyze metabolic samples acquired at high altitudes using AB Sciex equipment already in their labs. Needing additional support, they reached out to a former university colleague, now an AB Sciex scientist, Cafazzo says.

“Our relationship went from strictly vendor and customer to our being a sponsor for a certain portion of their work,” he recalls. “We expect some really nice applications notes and publications to come out of that work on these irreplaceable samples.”

Indeed, AB Sciex gets numerous proposals every year from scientists looking for instrumentation or R&D support. Although the company evaluates them carefully, “we are a business, not a granting body, and we can’t fund everything,” Cafazzo explains. “We seek to partner with people who are really expanding the way MS is used and are positive advocates for us in terms of their publications and the conferences at which they like to speak.”

AB Sciex looks for key opinion leaders as well as “rising stars” through its two-year-old Academic Partnership Program. Grants to young investigators in the U.S. and Canada may include a partially or fully funded equipment system. Cafazzo says AB Sciex built the program to bring it closer to customers who buy instruments infrequently.

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The firm also has long-term academic collaborators who have been important to its technology development, such as Ruedi Aebersold, a professor in the Institute of Molecular Systems Biology at the Swiss Federal Institute of Technology, Zurich, also known as ETH Zurich. Aebersold helped develop SWATH Acquisition, an MS technique that can quantify nearly all detectable peptides and proteins in a sample from a single analysis.

FUNDING SOURCES
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A survey of 63 academic and nonprofit labs worldwide shows that most funding comes from governments. NOTE: Labs in the U.S. and Europe account for 80% of survey respondents, and labs in Asia and Central and South America account for 20%. SOURCE: Mizuho Securities USA
This pie chart shows where funding comes from for a select set of academic and nonprofit laboratories.
A survey of 63 academic and nonprofit labs worldwide shows that most funding comes from governments. NOTE: Labs in the U.S. and Europe account for 80% of survey respondents, and labs in Asia and Central and South America account for 20%. SOURCE: Mizuho Securities USA

Building on this work, AB Sciex formed a partnership with the Institute for Systems Biology, a Seattle-based nonprofit headed by Leroy Hood. In February, ISB and AB Sciex signed a three-year agreement to collaborate on developing MS methods and technology in proteomics, applying SWATH to build biomarker libraries.

ISB scientists have known people at AB Sciex for many years, says Robert L. Moritz, ISB’s research director for proteomics. “We have had very much aligned thoughts about advancing proteomics. The latest partnership was more formalized because it was much larger.” ISB uses AB Sciex instruments, and the two sides exchange people and expertise.

Although ISB’s charter calls for open-source research, Moritz says this isn’t an issue in the institute’s work with AB Sciex. “We develop the technology hand in hand with AB Sciex to solve the problems,” he says. “But we don’t work on the mass spectrometry—that’s what AB Sciex does. We work on methods and data interpretation and on being a public repository.”

His research group transfers its methods and data analysis directly to ISB’s Proteomics Core facility. Open to ISB faculty, staff, and outside collaborators, the fee-for-service facility is a “best test for wider public consumption,” Moritz says. The facility houses more than 20 MS systems from different suppliers. “We work currently on AB Sciex systems, but there is no reason why this could not be translated to other platforms as well,” he suggests.

Instrument suppliers say their relationships are not exclusive and that they compete for researchers’ attention through the performance and quality of their products. “It is a very fluid environment, and we are always hoping to catch the ear of someone who we consider to be a key opinion leader,” AB Sciex’s Cafazzo says. Working with scientists who use multiple instrument brands can actually yield valuable comparisons.

Making an academic collaboration succeed requires more than just intellectual alignment, company managers say. It’s important to understand each other’s capabilities and communicate well. For example, Waters’s Gebler says, “Academics are not held to the same time constraints and pressures that we are in industry, and so one has to go in recognizing that a fruitful collaboration is going to take time.”

At Agilent, the technical staff of both its Agilent Research Laboratories and its product lines can propose academic partnerships. “Virtually everything we do with universities involves a committed Agilent sponsor who cares about the specific work to be done and has detailed expertise in the area,” Wenstrand says. Each engagement must advance the interests of the university researcher and, through the participation of the Agilent scientist, provide opportunities for the company to contribute and learn.

Companies say they try to make it easy for academic researchers to pursue their research without interference. “We want them to draw the conclusions they hope to reach out of their work, and we support them in every way we can,” Cafazzo says. “The best experimental design is to accomplish what they are trying to do and show the power of the technology at the same time.”

Watching out for the interests of academic researchers in their dealings with the corporate world are groups such as the American Association of University Professors, which will soon publish principles to guide industry-academia relationships.

The principles are not intended to discourage relationships with industry, says Cary Nelson, an English professor at the University of Illinois, Urbana-Champaign, and former AAUP president. “It is to manage them so that they’ll survive public scrutiny, preserve the integrity of academic research, and serve at least those industries that really want honest research.”

Principles that relate to equipment purchases, for example, address conflicts of interest, decision-making authority, and the need to evaluate multiple vendors, Nelson explains. He warns against relationships that are exclusive, involve confidential work and prevent publication, or allow companies to set research or educational agendas.

Once industry support has been established, academic enterprises can become reliant on it to pay the bills, Nelson cautions. “The problem is, once you get onto a particular gravy train, there will always be a date—whether it is next year or three years down the line—when the decision arises whether to renew,” he explains. Knowingly or not, researchers can find themselves serving corporate needs to keep relationships going.

But it doesn’t have to be that way. Most companies, Nelson says, want “research that is unblemished, whose objectivity and disinterested character they can stake their business on, and they want a university that renders independent judgment on their products. And that’s a good industry-academy relationship because it benefits the public, it benefits the academy, and it benefits the industry.”

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