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Robotic Workstations and Automation in Drug Discovery

Robotic Workstations and Automation in Drug Discovery

What would a manager in a drug discovery lab like to see in automation products?

by
Angelo DePalma, PhD

Angelo DePalma is a freelance writer living in Newton, New Jersey. You can reach him at angelodp@gmail.com.

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High-throughput screening (HTS) for drug discovery was conceived through the nearly simultaneous industrialization of combinatorial chemistry and the emergence of affordable laboratory automation, but its success ultimately depends on integrating factors related to chemistry, assay design, and informatics. Combichem enabled the creation of compound libraries with millions of compounds, while laboratory robots, plate handlers, liquid handlers, and supervisory information systems allowed their study.

Today, drug discovery remains a game of big numbers. John Unitt, director of bioscience at Sygnature Discovery (Nottingham, UK, and Cambridge, MA), notes that deep-pocketed companies routinely investigate libraries in the one-to-two-million-compound range, while smaller discovery organizations use much smaller libraries of only 200,000 to 400,000 molecules.

Robotics have more than kept up with the compound flow, so automation vendors now differentiate on the basis of accessibility, breadth of assay (i.e., instrument and method flexibility), and software, while library vendors focus on creating collections of original chemical scaffolds. Meanwhile, a whole separate industry works on automating and—perhaps more importantly—standardizing optical readouts, liquid handling and dispensing, and background tasks like cell culture and preparation.

For low-throughput routine automated liquid handling, Sygnature relies on the Biomek NXp Automated Workstation, a small-footprint system with two pipetting options and built-in flexibility. “We picked the Biomek system for its throughput, breadth of assay, and walk-away time,” Unitt says. Sygnature uses one NXp for assay construction and another for metabolic, pK, and ADME studies.

For liquid dispensing, Sygnature uses the Labcyte Echo acoustic dispensers to prepare assay test plates using nanoliter volumes of compound solutions. “This assay automation setup conserves highly valuable compound stocks and also optimizes liquid-handling performance by using the excellent accuracy and precision of the Echo,” Unitt says.

For their robotics platform, Sygnature relies on systems from HighRes Biosolutions (Boston, MA), a vendor Unitt worked with while in a previous position at a large biopharmaceutical company. The ACell benchtop automation system provides entry-level, deploy-anywhere automation and easy integration with HighRes plate storage units. “A typical drug discovery laboratory will also want to invest in the storage unit and maybe cell culture as well, plus informatics to communicate and capture all data generated during screening,” Unitt says. “With the ACell system modular, you can grow and expand in terms of assay readouts, end points, and capacity.”

Despite still relying on huge molecule collections, HTS is no longer merely about compound library size. The emphasis, Unitt notes, is on quality versus quantity. “For our projects, senior medicinal chemists assess all structures for chemical diversity and lead-like structures while emphasizing synthetically novel scaffolds.”

Quality has become a priority for library developers because, in the past, compound collections included entries with significant side products and impurities. False positives and negatives resulting from unanticipated, unknowable interactions between impurities and targets can thwart the potential for mining a collection of hits for structureactivity relationships, which discovery scientists use to generate lead molecules and eventually drug candidates.

What would a manager in a drug discovery lab like to see in future automation products? “We’re always looking for ways to do things faster,” Unitt says. “Accuracy and precision of existing automated systems are already very good, so the emphasis should be on customer support to minimize downtime.”

One key to the success of HTS is the application of assays that ask the right questions of the right compound library. “If an identifiable bottleneck exists, it is adapting a standard laboratory test—immunoassay, enzyme inhibition, etc.—to microplate formats and successfully marrying that assay to the robotic workstation,” Unitt explains. Assay developers have made great strides in this area, “but over the years, HTS has overcome problems like these as more and more screening platforms have been adapted to it.”


For additional resources on robotic workstations, including useful articles and a list of manufacturers, visit www.labmanager.com/robotic-workstations