Waters Corporation: Fifty Years of Innovation in Analysis and Purification

I was present at the symposium on natural product synthesis held in 1971 at the 23rd Congress of the International Union of Pure and Applied Chemistry in Boston. Before such luminaries as Derek Barton, Alan Battersby, Karl Folkers, and Gilbert Stork, Woodward, in a nearly four-hour lecture, recounted the B₁₂ story, punctuating it frequently by declaring, “We could not have done this without liquid chromatography.” Nearly every organic chemist of note was in the audience of close to 5,000, and although Woodward cited neither company nor brand names in his talk, the cognoscenti spread the word like wildfire. Following Woodward’s example, a single HPLC peak soon supplanted a single thin-layer chromatography spot as a criterion for chemical purity in organic synthesis.

To take advantage of such excellent publicity James Waters himself quickly assembled a bold direct mail campaign. He compiled a list of 900 names and addresses from an American Chemical Society directory of chemistry faculty and mailed each a promotional kit that included a glossy photo of himself with Hamburger and Woodward and a letter with the simple message, “Look what we did for Woodward. We can do the same for you!” Following up on the 100 replies to his first foray into marketing catalyzed phenomenal growth for Waters Associates.

The Next Generation of Innovation

Although his company’s reputation was built on dedication to making customers successful, Waters and his team recognized that their LC systems used many components made by other companies. They foresaw the importance of becoming self-reliant if they were to deliver state-of-the-art technology and continue as a market leader. Over time, each component of an LC system—pump, injector, detector, column, fittings, stationary and mobile phases—was rethought and redesigned. A commitment to materials science began when Styragel polymer technology was used to create Porapak packings for gas chromatography columns, and a 1969 collaboration with István Halász in Saarbrücken led to the development of Durapak— the first commercial bonded-silica phases for gas chromatography and liquid chromatography— and a new standard for efficiency: Corasil, the first pellicular silica HPLC packings.

Waters Associates introduced the first dual-reciprocating piston, 6000-psi pump for HPLC, the M6000, in 1972, developed by R&D director and engineer Burleigh Hutchins and a craftsman and machinist named Louis Abrahams. This precision-volume solvent-delivery device used noncircular gears, a step motor, and feedback control circuitry to drive small-diameter parallel plungers sequentially for nearly pulseless flow. When the M6000 hit the market it was considered revolutionary; it proved so reliable that many continued to be used for decades. The M6000 was to be the last R&D project that Waters would oversee, and it inspired a succession of innovations destined to alter the HPLC landscape forever. Competitors soon retired pressurized vessels and other primitive pumping means and sought to imitate the wildly successful M6000. Cottage industries sprang up to supply replacement parts. All this activity spurred rapid acceptance of HPLC in labs worldwide and accelerated the growth of the nascent HPLC industry.

The first 6000-psi compatible septum-less high-pressure injector for HPLC, the Model U6K, with its novel valve and fluid circuit technology, soon followed. The U6K and the M6000 had been developed in parallel with another landmark chemistry project, led by Richard Vivilecchia, to create the first commercial small-particle (10-µm) packing materials for HPLC. These were µPorasil silica and the first monofunctionally bonded silica, µBondapak C18, developed by using a unique, proprietary homemade silane. Columns packed with the latter, introduced in its present form in 1974, became the best-selling columns in history.

The first generation of HPLC users were frustrated by poor-quality solvents. In the late 1960s a Waters Associates applications chemist, William Dark, worked with Malinckrodt to stabilize chloroform with nonpolar amylenes rather than ethanol so as not to wreak havoc on retention-time reproducibility in normal-phase separations. This success led to the development of other HPLC-grade solvents. Waters Associates itself entered the solvent business for a few years in the late 1970s, during which time it developed specifications and analytical protocols that led to major improvements in the quality of methanol, acetonitrile, tetrahydrofuran, and other key mobile phase components, especially water. When Waters Associates exited the solvent business, it shared all its test procedures and demanding requirements with the industry, thereby creating a competitive environment from which users ultimately derived significant quality and performance benefits.

In 1977, commissioned to find “new, faster, more convenient ways to do traditional sample preparation operations,” I teamed with my colleagues, Waters Associates researchers Vivilecchia and David Lorenz, to invent the Sep-Pak cartridge by using triaxial bed compression and hermetically sealed individual packaging to maintain bed integrity, performance uniformity, and adsorbent activity. Three months later, in January 1978, Waters Associates shipped the first commercial, disposable, miniature silica-based adsorbent liquid chromatographic columns for sample enrichment and purification via solid-phase extraction (SPE). Almost three years passed before a competitive product came to market. Explosive growth followed in the application of SPE to a full spectrum of sample preparation problems in every lab around the globe. Thirty years later SPE is still growing rapidly and stands as a predominant technique for removing interfering substances in samples prior to analysis.

James Waters sold his company to Millipore in 1980, thereby ending his relationship with Waters Associates. Millipore, in turn, divested the Waters Division in 1994. Waters Corporation became a publicly traded company again in 1995. A year later new high-purity silica Symmetry HPLC columns, Alliance HPLC systems, and patented Oasis polymers raised the respective bars for column, flow rate, and SPE reproducibility to amazingly high levels. Also in 1996, Waters morphed from a minor player to a major leader in mass spectrometry by acquiring Micromass Ltd., of Manchester, England.

Several times in the past 50 years Waters has introduced equipment designed expressly to operate new column technology, creating a dramatic increase in separation power with the potential to alter the course of science. The most recent of these system innovations, introduced in 2004, has pushed the limits of separation science from high to ultra performance and was inspired by investigations into materials science. Zhiping Jiang and his team won awards for the first generation of hybrid-particle technology (HPT) packings, polymerizing a pair of monomers (tetraethoxysilane and triethoxymethylsilane) so that organic functionality may be distributed throughout a spherical silica particle’s backbone. HPT offered, for the first time, the possibility of designing tailored particle surfaces, even deep within micropores. By incorporating an ethylene bridge into one of the comonomers, Kevin Wyndham and his team were able to make 1.7-µm particles with an order-of-magnitude-higher resistance to hydrolysis at pH extremes and surprisingly high pressure resistance. This latter discovery, in turn, inspired Waters Corporation engineers to design the Acquity UltraPerformance LC System, capable of operating at 15,000 psi. Its dramatic order-of-magnitude increases in speed, sensitivity, and resolution herald the dawn of a new era in separation science.

A Legacy of Innovation

Although published contributions from academia are often placed in the limelight, so many of the important achievements in chromatography have been made almost invisibly by industrial scientists and engineers. Crossing the boundaries of physics, chemistry, mathematics, and engineering, separation science has been perfectly mated to the interdisciplinary teamwork vital to entrepreneurial endeavors that are focused on uniting resources to solve problems and create products that meet customers’ needs. James Waters exercised his inborn drive to succeed and, through his enterprises, brought these forces together to create revolutionary tools for analysis and purification.

As Waters Corporation approaches its golden jubilee, Waters and the company he started can take pride in the legacy of innovation and vision its first 50 years will leave. Although nearly 30 years have passed since James Waters sold his company, his name remains over the door, and the company continues to follow his simple formula for success: “innovation, a good attitude, and hard work”.