High-Throughput Technology Picks Up Steam

There's no stopping this train. High-throughput sample processing has become the hot topic in the biotechnology and pharmaceutical industries. Clearly, the demands for faster, more efficient, and cheaper methods of drug discovery have taken the forefront as automated assays move from 96 to 386 and higher density microplates. In turn, faster and faster methods to process these plates follow. For example, in a recent press release, Zymark Corporation of Hopkinton, Mass., announced the successful processing of a thousand 96-well plates in 24 hours by one of its Allegro™ automation platforms. All together, the system processed 96,000 tests involving an advanced, 15-step assay for drug candidates that inhibit src kinase activity. Not one to sit still, Zymark plans to expand the Allegro system's capabilities to handle up to 400,000 tests per day. Robbins Scientific's Hydra® AP-Microdispenser Jim Stanchfield of Robbins Scientific sums up high-throughput science this way: "The technology keeps improving. It's very difficult to take a snapshot to see what's happening at any one time." Indeed, a recent report1 tells of the development of 3,456-well plates by Aurora Biosciences of San Diego, Calif. Populated with wells having a volume range between one and two microliters, these plates have the same footprint as a 96-well plate, but their use raises concerns about liquid handling at that scale. As it is now, systems like the Assay TekBench from TekCel Corporation of Martinsville, N.J., are equipped with up to four independently operated 384-channel pipettors. Certainly, drug discovery tools are headed toward ever-increasing sample processing capabilities. Of course, high throughput is not limited to just drug discovery. Amersham Pharmacia Biotech's new MegaBACE® DNA Sequencing System is a high-throughput, fluorescence-based DNA sequencer designed around capillary electrophoresis technology. The MegaBACE runs 96 capillaries in parallel. With a turnaround time of about 2 hours per run, the MegaBACE can process up to 1,100 templates, or 550,000 base pairs, in a 24-hour period. The MegaBACE accepts samples in a 96-well format. The thermal cyclers needed to generate enough reactions to supply it fall in the high-throughput realm. MJ Research's PTC-225 DNA Engine Tetrad™, for instance, has a maximum sample capacity of 1,536 independent reactions. Along similar lines, Intelligent Automation Systems manufactures a 16-block thermal cycler. Called the TC1600, this machine sustains large-scale, high-throughput industrial applications. High-throughput sequencing technology has been put to good use. Myriad Genetics Inc. of Salt Lake City, Utah, developed its own high-speed sequencing methodology to discover the first major breast cancer gene, BRCA1, in 1994 by analyzing DNA from large, multigenerational families with a history of this disease.2 Since then, the company has discovered other genes with important medical implications. High throughput shows up in other places. The EPICS ALTRA® flow cytometer from Beckman Coulter features the optional HyPerSort® High-Performance Cell Sorting System. According to Lew McAllan, manager of technical support for cytometry at Coulter headquarters in Miami, Fla., the HyPerSort uses pressures up to 100 psi to drive fluids through the ALTRA cell sorter system at 25 meters per second. This results in a processing rate of nearly 30,000 cells per second. A typical application involves the separation of a specific subclass of cells from a stem cell population for therapy and reinjection. Genetix Limited of the United Kingdom manufactures the 'Q' BOT III. A multitasking robot, the 'Q' BOT handles colony picking in addition to liquid handling and other applications. As an automated colony picker, the 'Q' BOT uses a CCD camera to identify appropriate colonies and then picks them with a 96- pinpicking head. After all the pins have picked colonies, it transfers them to 96- or 384-well plates in excess of 3,500 clones per hour. High-throughput applications and the accompanying robotics have also found their way into clinical settings. QIAGEN Inc. of Valencia, Calif., has introduced the new BioRobot 9604. Designed initially for the automation of QIAGEN's QIAamp viral RNA kits, the BioRobot 9604 performs tests such as HIV and hepatitis C viral load studies. According to Fred Siegman, automation group product manager for QIAGEN, the BioRobot 9604 is the industry's leading robot for these types of applications. Siegman also says that QIAGEN plans to use the same platform for automated RNA purification and other applications in the research setting. High-throughput systems and laboratory robots are expensive. Prices often reach several hundred thousand dollars, making purchases difficult to justify in the academic environment. Linda F. Bonewald, president of the Association of Biomolecular Resource Facilities (ABRF), an organization created to promote and facilitate communication between core facilities and research laboratories, explains: "Scale is often the problem. Academic labs usually don't have the sample sizes needed to support these systems. Industry core facilities are much more involved." She does see some movement in that direction, however, as a handful of academic core facilities have begun higher-throughput screening on a limited basis. The core facility that Bonewald operates at the University of Texas Health Science Center in San Antonio, for example, now performs bead library receptor binding assays. In the automated liquid handler market, Mark Engelhart, national sales manager for robotic systems at Hamilton Company, notes that "academic labs are not a preponderance of our business. They typically don't have the necessary sample numbers. Those labs that have the money buy automated liquid handling systems because they may want to automate for accuracy and convenience." One of the major problems facing the pharmaceutical industry is secondary testing of potential drug candidates mined from the high-throughput screening systems. These drug candidates need to go through tests such as toxicity, hydrophobicity, and uptake studies like CACO-2 assays before they move farther along the drug development pathway. According to Hamilton Company's Engelhart, there is not much standardization for automating these kinds of tests. Furthermore, he's noticed the "ripple effect" in the industry as companies begin looking for labware, equipment, and personnel. Solving these problems, he says, "is the next big challenge for these companies." V. Glaser, "Trends in Drug Discovery," Genetic Engineering News, 18 (21):12, Dec. 1998. B. Howard, "Life science enterprise in Salt Lake City, Utah," Biotechnology Laboratory, 16 (13):36, 1998.

High-Throughput Technology Picks Up Steam

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