Laboratory Automation – Moving More of Less

Techniques for handling ever smaller amounts of liquid change the scale and speed of scientific discovery. In basic research, biotechnology, and pharmaceutical studies, scientists benefit from automated assays that require smaller amounts of sample. Smaller samples also allow for higher throughput experiments, which require sophisticated software to keep the work flowing smoothly.

by Mike May and Gary Heebner

ADVERTISERS Leica [Germany] instruments and systems for imaging analysis, including microscopes and digital cameras +49 6441 29-0 http://www.confocal-microscopy.com Leica [USA] 847-405-0123

CONTENTS • Standardizing multiwell plates • Modifying microwell surfaces • Robotic liquid handling • Higher density microarrays • Integrated microfluidics • Watching workflow

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Anyone who used sterile technique with stacks of tissue-culture plates knows how tedious such a process gets. It can take hours to change medium, and keeping track of which plates received what operation demands special care. To handle fluids more efficiently, scientists wanted a connected group of containers, the ability to use smaller volumes of reagents, and simpler methods to keep track of how each sample gets treated.

The 96-well microplate fulfilled many of those desires. Multiwell plates also triggered advances in laboratory automation and miniaturization. As the following experts reveal, handling fluids more quickly and efficiently plays a fundamental role in pushing basic and applied research to ever faster speeds.

Lowering the Levels
Today, scientists can also purchase 384- and 1,536-well plates. Despite the increasing number of wells, the overall plates take up the same size. According to Michael McFarland, business technology manager at Corning Life Sciences, “Every industry needs standards to enable automation platforms to evolve cost effectively. The SBS [Society for Biomolecular Screening] footprint microwell plate enabled different equipment manufacturers to design to a single standard, and the concept was scaleable simply by changing the number of wells within that footprint.”

Moreover, different experiments demand wells of different shapes and made of different materials or coated with different treatments. Companies like Corning, Nalge Nunc, and Greiner Bio-One offer a range of plasticware products. For example, Corning offers microwell plates with modified polystyrene surfaces. McFarland says, “Some cells like to grow on a surface, and others prefer growing in suspension. Some assays—such as ones involving microscope imaging—need cells to stay in place.”

Corning also offers its CellBIND surfaces for cell based assays. McFarland says that this treatment encourages many cell lines to attach faster and proliferate more quickly. He adds, “This is also very useful in any situation where a scientist needs a way to get more cells, such as producing cells for high throughput screening assays or when using cells to produce biotherapeutics.”

Relying on Robotics
As the wells increase in microplates, scientists need automated techniques for routine and repetitive tasks. Automated work stations from companies including Beckman, Caliper Life Sciences, Hamilton Company, PerkinElmer, and Tecan can deliver small volumes of reagent or wash the samples in microwell plates around the clock.

According to Joerg Pochert, director of the pharma and biotech group at Hamilton, scientists seek increasing reproducibility and process stability. This is why Pochert’s company developed the Microlab STAR liquid-handling work station. Pochert says, “The STAR is something that has not been available so far. There are no syringes, no pumps, and no tubing.” Instead, this system works like automated, hand-held pipettes. Pochert adds, “This technology also allows us to monitor each pipetting step, therefore achieving previously unknown process stability.”

Micro Spots and Micro Flows
Although multiwell plates handle small volumes, microarrays and microfluidic devices go even smaller. Both of these technologies attract many companies, including Affymetrix, Febit AG, and NimbleGen for microarrays and Agilent Technologies, Caliper Life Sciences, and Cepheid for microfluidics.

In microarrays, advances often revolve around more genes on an array or processing arrays more quickly. Stephen Fodor, chairman and chief executive officer of Affymetrix, says, “The GeneChip Mapping 100K Array Set is capable of genotyping over 100,000 SNPs [single nucleotide polymorphisms].” He adds, “Jeffrey Friedman, Markus Stoffel, and Jan Breslow of the Rockefeller University are using this array technology to genotype approximately 200,000 SNPs per individual for the complete adult population of the Micronesian island of Kosrae.” This population is especially interesting because it developed obesity following dietary changes—receiving Western foods—after World War II. Fodor says, “Rockefeller scientists are using genotyping microarrays to identify the exact genetic variations that might explain why only some individuals developed obesity, cardiovascular disease, and diabetes.”

Scientists can combine biological assays with microscale plumbing to build what is known as a lab-on-a-chip. Kevin Hrusovsky, president and chief executive officer of Caliper Life Sciences, says, “Our LabChip technology uses miniature volumes of sample to run tests that have multiple advantages over traditional assays—accurate, information-rich data being the most important of these advantages.” The microfluidic chip brings together the target and reagents, separates the analytes or cells of interest, and then the reaction can be detected directly on the chip. Hrusovsky adds, “Our LabChip 3000 Drug Discovery System, which was launched in February 2004, is gaining rapid acceptance as a very proficient way to do drug screening and drug discovery.”

Tracking the Workflow
As new automation techniques allow more samples to be processed and analyzed faster, scientists need better tools to keep track of the process. A variety of companies—including Accelrys and MDL Information Systems—provide products to track data.

According to Scott Kahn, chief scientific officer at Accelrys, “The most fundamental challenge in lab automation is how to develop a workflow that doesn’t just collect data but acts on it and does necessary analysis on the fly to drive the result to its ultimate destination.” In other words, the analysis software helps a scientist decide how to run an experiment in real time.

Accelrys provides several new approaches to automation. Its Accord HTS manages high throughput experiments, Accord Inventory manages libraries of compounds, and Pipeline Pilot links disparate data and creates a processed result. Osman Güner, Accelrys’s executive director of cheminformatics and rational drug design, says, “These tools enable a scientist to make better informed decisions, and there are lots of very expensive decisions in discovery, design, and development of a new product.”

The combination of handling smaller samples in higher numbers and keeping track of the process with intelligent tools will change the experiments that scientists and clinicians can do. “To improve human health,” says Fodor of Affymetrix, “we need to shift the paradigm from diagnosing and treating an existing disease, to one in which we predict disease susceptibility, determine individual response to drugs, and focus on earlier detection, more accurate diagnosis, and therapeutic management.” Making more automated laboratories will help scientists push toward this arena of so-called personalized medicine and other achievements in basic research and biotechnology.

Mike May (mikemay{at}mindspring.com) is a freelance writer and editor based in Madison, Indiana, U.S.A. Gary Heebner
(gheebner{at}cell-associates.com) is a marketing consultant with Cell Associates in St. Louis, Missouri, U.S.A.

WEBLINKS ADVERTISERS Leica [Germany] instruments and systems for imaging analysis, including microscopes and digital cameras +49 6441 29-0 http://www.confocal-microscopy.com Leica [USA] 847-405-0123 FEATURED COMPANIES and ORGANIZATIONS Accelrys – a subsidiary of Pharmacopeia bioinformatics software http://www.accelrys.com Affymetrix DNA microarrays http://www.affymetrix.com Agilent Technologies, Inc. microfluidic devices http://www.agilent.com Beckman Coulter, Inc. automated work stations http://www.beckmancoulter.com Caliper Life Sciences automated work stations http://www.calipertech.com Cepheid microfluidic devices http://www.cepheid.com Corning Inc. – Life Sciences Division plasticware for lab automation http://www.corning.com Febit AG DNA microarrays http://www.febit.com Greiner Bio-One International plasticware for lab automation http://www.gbo.com/bioscience Hamilton Company automated work stations http://www.hamiltoncomp.com MDL Information Systems, Inc. bioinformatics software http://www.mdl.com Nalge Nunc International plasticware for lab automation http://www.nalgenunc.com NimbleGen Systems, Inc. DNA microarrays http://www.nimblegen.com PerkinElmer Life and Analytical Sciences automated work stations http://las.perkinelmer.com Tecan automated work stations http://www.tecan.com

Note: Readers can find out more about the companies and organizations listed by accessing their sites on the World Wide Web (WWW). If the listed organization does not have a site on the WWW or if it is under construction, we have substituted its main telephone number. Every effort has been made to ensure the accuracy of this information. The companies and organizations in this article were selected at random. Their inclusion in this article does not indicate endorsement by either AAAS or Science nor is it meant to imply that their products or services are superior to those of other companies.

This article was published as a special advertising section in the 28 January 2005 issue of Science