CHROMATOGRAPHY · 1.7-micron particle chemistry edges company forward in the race to supply the most powerful LC equipment

By John Russell

December 15, 2004 | Generally reticent Waters Corp. held its "first ever" media day last month to indulge in a bit of chest-thumping around its new Acquity Ultra Performance LC (UPLC) systems, and to clarify the company's strategy following a string of acquisitions in recent years — most recently, two software companies: NuGenesis Technologies (scientific data management) and Creon Lab (LIMS specialist).

The new Acquity system, Waters says, represents a giant leap forward. Launched at Pittcon, Acquity features 1.7-micron particulates — far smaller than the 3- to 5-micron particles most widely used today — and backpressures up to 15,000 psi, far greater than the 6,000psi pressures that are common now. The net result, the company says, is higher resolution, greater sensitivity, and faster throughput.

In a show of marketing bravado, Waters has dubbed the technology "ultra performance liquid chromatography," and Waters Division president Art Caputo told the gathering that Acquity's dramatic performance inspired the company to hold the event. Waters began shipping the new instruments in August.

ULTRAMODERN: Waters' new Acquity liquid chromatography system, one analyst says, will be a boost to proteomic research and biomarker discovery.

Waters trotted out an AstraZeneca researcher, Ian Wilson, to sing Acquity's praises, which he did almost giddily. Wilson is a principal scientist engaged in metabonomics work, and his group used Acquity UPLC paired with mass spectrometry (MS) to identify biomarkers in urine of rats. They were able distinguish three genetic flavors of Zucker rats (+/+, +/-, -/-) at various stages of their life cycle, and they were also able to distinguish nude, black, and white strain rats, all based on urine markers.

"UPLC/MS is the future for [analyzing] complex biological sample metabonomics," Wilson said. "All of these [techniques] generate oceans of data. To get around that, it makes sense to use pattern recognition, and we all hope that the urine will provide the sum of the things going on inside you for the past couple of hours."

"If you were to give me the urine from an adult of any one of these [rats], we could UPLC/MS the urine and with pretty good confidence say which type of animal it was. I don't know if you're impressed by that, but I certainly am," Wilson continued.

"I don't know how many compounds you think there are in urine," he said, "but HPLC/MS shows you 2,000; UPLC in the same time shows you 10,000. How many components are there in urine? One hundred thousand? We've still got a way to go."

Waters isn't alone in pushing chromatography's envelope. In 2003, Agilent Technologies introduced 1.8-micron particles.


Reducing Separation Anxiety 
"Traditional separations would take at least 15 minutes, if not 30 or even 45 minutes," said Helmut Schulenberg-Schell, Agilent's LC product marketing manager. "Moving to smaller-particle column technology allows you to do separations on a second-to-minute scale, so basically you can have separations in a minute, or even less than a minute ... saving as much as 95 percent of the time per sample."

Waters Corp. Business: Liquid chromatography, mass spectrometry, and thermal analysis instruments and their consumables; related informatics software; and services Employees: 3,900 Headquarters: Milford, Mass. Markets: Pharmaceutical, life science, biochemical, industrial, academic, and government 2003 sales: $958 million (product: $723 million; services: $235 million) 2003 income: $223 million (pre-tax) SOURCE: THE WALL STREET JOURNAL

However, Schulenberg-Schell cautioned, "Smaller particles and higher pressures are not of value to customers by itself. We have seen customers using several parameters like particle size and size distribution, temperature, pressure, column ID, or using multiple dimensions in HPLC in order to increase throughput, separation efficiency, or sensitivity."

Agilent, like many instrument manufacturers, is working feverishly on microfluidic chip technology and has just introduced a new HPLC chip, which, Schulenberg-Schell said, "will take HPLC to a new level of convenience and reliability, especially the combination of HPLC chip technology with mass spectrometry. The performance we currently see — for example, with proteomics applications — is outstanding."

Waters' newest offering got strong marks from one analyst. "Advancements such as Waters ultra performance liquid chromatography will certainly enhance proteomic research and biomarker discovery. Rapid protein separation tools that increase resolution and require less sample are critical; however, much research remains to determine which protein peaks are to become validated disease-related biomarkers," said Zachary Zimmerman, senior research analyst, Life Science Insights.

Acquity required improvements on several fronts. New chemistry (ethane-carbon-silicon) was developed for the particles. The column was strengthened to withstand higher pressures, and detectors were also improved. Waters says Acquity is five to nine times faster than conventional HPLC.

The Acquity system consists of a binary solvent manager, sample manager, Acquity column chemistry, column manager, and either tunable UV or photodiode array detectors. It has an optional sample organizer with a capacity for up to 21 microtiter plates or up to eight vial racks.

"This the closest we've come to producing a universal column. Now we all understand [the need to show] separation on different ligands, so we will produce another series of these columns in the next few months with a choice of two or three more types of chemistry, but we think that this will take care of 90 percent of separations," said Brian Smith, Waters' senior director, pharmaceutical business development.

Waters has grown steadily in recent years, and revenue is expected to top $1 billion in 2004. HPLC and MS products constitute roughly 90 percent of Waters' business, with thermal analysis accounting for the remainder. Caputo said customers are eschewing "best of breed" tools for integrated solutions — a trend, he said, that in part drove Waters' strategy of selective acquisitions with informatics playing an increasingly important role.

Waters is striving to create "a singular information management environment," said Pat Martell, direct of informatics product marketing, comparing the Waters suite to Microsoft Office for the lab. Major informatics offerings include MassLynx (GC/MS), NuGenesis SDMS (scientific data management system), Empower (chromatography), and Waters' Q-DIS/QM (LIMS) and Q-DIS/R (analytical workflow).