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Hal, Open the Refrigerator Door

By Mark D. Uehling

July 20, 2005 | Can a humble refrigerator make your high-throughput screening (HTS) campaigns more productive?

Yes, Eli Lilly discovered. The Indiana company once needed half of a full-time employee to manually consolidate 300 HTS hits a week from the company’s 96-well plates. After the installation of a TekCel Plate Management System — more or less a laboratory information management system (LIMS)-enabled, automated, robot-friendly refrigerator — the pharma reduced staffing needs for that chore by 90 percent. Best of all, the TekCel system would pay for itself within two years.

Business is good, says TekCel CEO Robert Rosenthal: “The trend is to higher-quality storage. We are not in the situation of the late 1990s, where people threw money at any technology they could. They have to justify the expense.” TekCel customers include AstraZeneca, CuraGen, Procter & Gamble Pharmaceuticals, Wyeth, and TIGR. The inefficiencies and bottlenecks of drug discovery are so numerous that it may not be immediately obvious that the industry’s refrigerators need to be increasingly networked and automated every day.

TekCel Plate Management System
COLD COORDINATION: All processing steps of the
LIMS-enabled TekCel Plate Management System are
fully automated and contained within a controlled,
inert environment.

TekCel users need not worry about buying a freezer and connecting it to a LIMS or laptop. It’s already tightly integrated, and scientists can boss the TekCel system around by e-mail. “The end user can sit at a PC and say what they want,” says W. Steven Fillers, VP and chief scientific officer. Before joining TekCel, Fillers tried to build similar systems from scratch at Sandoz and Biogen. Then he realized TekCel had already solved some of his problems. One was how to reliably keep track of, say, a million compounds.

Killer App, Chiller Appliance

Another issue, especially in academia: a small footprint. “Some of our competitors have to build buildings to get theirs in,” Fillers says. TekCel’s PlateStore requires a mere 37 square feet of floor space and fits through traditional office doorways. Impressively, it can be transformed into a battery-powered hovercraft, allowing it to be moved by a lab technician down hallways or onto a loading dock. Some organizations are acquiring such large libraries that they may want to put one unit into really deep storage. “You can send one away,” Fillers says.

Indeed, the sheer size of compound libraries is creating opportunities for storage and refrigeration concerns. “Everybody can own big libraries,” says Fillers. “What they can’t do is keep them live and keep that quality level up.”

It helps to monitor the temperature at which samples are stored. Even tiny amounts of condensation in the dimethyl sulfoxide storage medium in microplates can affect the sample concentrations when opened for handling. When a machine does the job, errors moving tiny tubes or transferring a few droplet-sized aliquots of sample are greatly reduced. And because everything is bar-coded, TekCel users don’t have to squint to read a frost-covered number written in ballpoint ink.

Cold, Hard Data

As Rosenthal and Fillers take a visitor on a tour, a rumpled, elderly man tinkering with one of the machines explains a few of the nuances of various databases and robotic arms. He turns out to be Julian Warhurst, the company’s founder and chief technical officer. “Our customers want to do their screens, they don’t want to wait for this thing to deliver,” Warhurst says. “This maximizes the time you’re working on what you want to be working on, not waiting.”

The TekCel robots, of course, can deliver plates (and data) more quickly than humans, at the rate of several hundred samples per hour, around the clock. Thought has also gone into the relatively obscure art of selecting which tubes or plates in a vast freezer are selected when. That’s a complex logistical challenge: A variety of project teams may be clamoring for their samples to run first. TekCel customers report that vice presidents have an occasional but well-documented tendency to bump their HTS runs to the front of the queue. TekCel’s software can accommodate that, too.

Such tricks are partly enabled by TekCel’s Adaptive Process Technology, software that prioritizes and assembles the optimal schedule for all the jobs. One key task is pulling tubes or plates for different jobs at the same time and arranging them for maximum efficiency later. If a plate goes missing, or something goes awry, the system can send an e-mail or text message via cellular phone. This is not your grandfather’s Frigidaire.

TekCel is not alone in the networked refrigeration market. Other companies are also combining sample storage and IT. Thermo Electron, for example, recently introduced its Forma line of ultra-low-temperature storage products, with storage capacities from 329 to 572 liters. Thermo’s RapidStak plate stacker and BioBank sample library system can both be managed with Microsoft .NET tools. With all of its robotics outside the cold compartment, the BioBank can store and fetch 1,000 microplates at 80 C below zero. Storing samples for drug discovery, it would appear, is a globally warming market.

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