As collections of compounds and biological samples expand, biotechnology and pharmaceutical companies seek more-efficient ways to keep track of these libraries, and that requires improved automation. “The size of compound libraries has grown and grown,” says Peter Cavallo, sales manager at Denso Robotics (Long Beach, Calif.). “Some are now over a million, and automation of some sort is almost mandatory to manage that.” That automation, though, must be flexible, fast, and effective.

With a background in high-throughput screening, sample management, and information technology, Sue Holland, PhD—site director for sample management technologies, molecule discovery research at GlaxoSmithKline (GSK) in Research Triangle Park, NC—understands the needs of this field. She says that these systems must provide environmental control while facilitating rapid access of material.

Before buying or upgrading automation, a user must assess what is needed. “Analyze the project,” Holland encourages, “and then adjust the automation accordingly.” In high-throughput screening, for instance, Holland recommends a compromise between the best storage conditions and rapid access. To meet that balance, GSK uses a custom system. “We can provide several million samples for high-throughput screens in a few days,” Holland says.

click to enlarge The modular design of The Automation Partnership’s Polar system offers flexibility for different inventory sizes. (Image: The Automation Partnership.)

She also points out that technologies must work well together. For example, she says, “You can have the best automation, but if the labware has some issues then the whole system fails.” She adds, “Information technology systems underpin all of this.” Only a few years ago, says Holland, most of the information technology was developed in-house at GSK. “The commercial offerings weren’t out there,” she says, “but now that is changing.”

For many companies, chemical library management is more advanced than biological samples. Consequently, lessons learned from managing chemical samples can lead to better choices for biological ones. At GSK, explains Holland, “We are looking at using some of our existing chemical library automation with biological samples.”

Smoother moves
Automating sample storage requires liquid handling, which should be flexible. Consequently, Kiara Williams, product manager, automated liquid handling at Thermo Fisher Scientific (Waltham, Mass.), points out that the Thermo Scientific Matrix PlateMate 2x3 “has different types of interchangeable pipetting options, and one is a 96-channel piercing tool.” She adds, “This can eliminate steps and move samples from storage tubes to assay plates.” This device, says Williams, can be integrated into larger robotic systems.

click to enlarge The UK Biobank uses The Automation Partnership’s Polar automated repository. Liquid nitrogen is used to maintain –80°C storage conditions for millions of sample tubes. (Image: The Automation Partnership)

In general, says Cavallo, pharmaceutical companies ask for a range of characteristics in robotics systems, including long life, increased time between failure, and spare parts available for many years. He adds, “In essence, robotics move things around, and we don’t want to be the most complex thing in your system. So we make it easy to program the desired movements into the robots.”

To make automation more reliable, some companies turn to new methods of movement. As one example, Agilent Technologies (Santa Clara, Calif.) uses direct-drive robots. That means that a motor drives a joint, and there are no gears. In some of the systems from Hamilton Storage Technologies (Hopkinton, Mass.), sister company to Hamilton Robotics (Reno, Nev.), external magnetic couplers located in ambient temperatures drive the ultra-low-temperature internal robotics.

Some companies have developed entirely new approaches. “We moved away from robotics,” says Ben Schenker, U.S. sales and support manager at TTP LabTech (Cambridge, Mass.). “Pneumatics can be used reliably at sub-zero temperatures.” So the TTP system works somewhat like the pneumatic tubes at a bank drive-through. Like a deposit pushed by air to a teller, samples can travel from storage to a lab. “We blow out tubes one by one,” Schenker adds, “which is quicker than sending racks of tubes that must be picked through at the bench.”

Sample stability
Beyond being stored in an orderly fashion, systems must also maintain sample quality. “A big issue for people with compound libraries,” says Dave Harding, sales and marketing director at RTS Life Science (Manchester, UK), “is precipitation of compound. Then, the concentration of the sample is not what they thought it was, and that leads to screening errors.” To detect precipitate in a tube and to identify the liquid level, RTS is introducing a tube auditor, which will work without removing a tube’s cap.

click to enlarge An A3 SmaRTStore is used as part of a larger system for the biorepository at the Broad Institute. (Image: RTS Life Science)

For biological samples, long-term quality requires lower storage temperatures. Moreover, automation for managing biological samples is less mature than chemical storage. “It’s an up-and-coming area,” says Ian Yates, global sales support manager for automation solutions at Agilent Technologies. He adds, “Lots of biological samples must be stored at –80° Celsius and below.”

Several companies, including Hamilton Storage Technologies, make automated –20°C and –80°C sample storage systems. For example, Matt Hamilton, vice president at Hamilton, says, “Our automated storage systems require minimal or no infrastructure changes and work well in distributed and satellite labs.” In addition, Hamilton’s –80˚C Sample Access Manager (SAM) storage systems include integrated sample management software that supports chain of custody and 21 CFR Part 11 requirements.

RTS Life Science also makes systems for biological samples. For example, the biorepository at the Broad Institute (Cambridge, Mass.) uses an A3 SmaRTStore. According to RTS, this storage device works in a larger system, and overall it stores about 300,000 DNA samples. Moreover, the complete system can pick a sample every six seconds.

Focusing on flexibility
As collections grow larger, researchers need easy ways to log samples into a laboratory information management system (LIMS). At Thermo Fisher Scientific, the recent VisionMate HighSpeed 2D barcode reader takes on that challenge. According to Kacey Wiley Pouliot, Thermo Fisher’s product manager, sample storage and microplates, “This device reads a two-dimensional bar code on the base of a tube and loads the sample information into a LIMS, which tracks the sample through its entire life cycle.” She adds, “This device is friendly with many other automation systems.”

Contract Storage Facilities If space is at a premium, external storage contractors can keep samples safe. BioStorage Technologies, Indianapolis, Ind. (www.biostorage.com) provides sample storage, inventory management and cold chain logistics for the biotechnology and pharmaceutical industries throughout the research, clinical trial, and commercialization phases of drug development. The company offers secure, temperature-controlled storage; real-time tracking of stored biological samples; and next-day return of biomaterials. BioStorage Technologies operates facilities in the United States and Europe. Facilities comply with Good Laboratory Practices (GLP), Good Manufacturing Practices (GMP) and Good Tissue Practices (GTP). A proprietary, Title 21 CFR Part 11 sample inventory management system (ISISS) designed specifically for compliant biomaterial storage, tracks and reports sample status. SeraCare of Milford, Mass. (www.seracare.com) has more than 25 years of sample management experience and stores over 20 million biological samples for government and commercial customers in its biobank. To lower risk, there are two repository locations comprising over 80,000 square feet. SeraCare provides both short- and long-term sample storage from room temperature to -196˚C. Services include: clinical trial support, viral culture and molecular services; contract research services in molecular biology, virology and immunology; and custom bioservices. SeraCare offers logistical expertise to manage samples from the point of collection to downstream applications; prepares and distributes visit specific kits; can act as a central processing laboratory for research and clinical trials.

Automated storage systems must also grow with a customer’s needs. For such a challenge, Hamilton offers a modular active sample management system for large, microplate applications, such as high-throughput screening and compound libraries. These systems feature server and storage modules. According to David Camp, PhD, director of Queensland Compound Library in Australia, “The modularity of the Hamilton plate management systems is ideal for our facility. We are not only growing rapidly, but we also have hundreds of research users in different settings. We must provide everything from open access to some parts of our library to very limited access to other samples.”

Beyond growing collections of samples, customers also need systems that adapt to improved or even new instruments and variations in the kinds of samples in a library. “Users need modular configurations,” says Yates. “You can start small with our products and then mix and match components as needed. As a result, a company can fine tune a system to manage samples across its entire supply chain.”

To further simplify sample access, Hamilton enhanced its active sample management systems with SealTite technology, which automatically lids and unlids microplates. Easily integrated with Hamilton STAR liquid-handling robotics, SealTite’s stainless steel lids form a liquid-tight seal.

Systems must also give users options. VWorks from Agilent, for instance, provides an event-driven scheduler for automation control. “Throughput is one of the big demands in sample libraries of a million or more,” explains Yates. VWorks can intersperse large jobs with small ones, such as slipping a small job into the ongoing flow of a larger task. Users can also configure this software to automatically handle some errors, such as loading the wrong labware for a particular assay. VWorks would set aside the wrong tray, for example, and go on to other tasks.

Other companies also develop storage systems that let users manage collections of jobs. As an example, the Coda system from The Automation Partnership (TAP) in Hertfordshire, UK, can work with as many as 2,500 plates as large as 1,536 wells. “But multiple jobs come to the system in pieces,” explains Ian Ransome, TAP’s sales director. With its Concerto software, Coda efficiently juggles those orders. “This provides very flexible scheduling software and a large library of instrument drivers,” says Ransome.

Speeding ahead
Beyond being flexible, companies want consistency. At GSK, for example, Holland mentions, “If we put a new system at one site, it goes into all of our sites for the same purpose. That minimizes costs in terms of integration, reduces our R&M (repair and maintenance) burden, and leverages our purchasing power.”

Although Holland believes that sample management has really come a long way, she sees more to do. For one thing, she’d like to integrate quality assurance of the samples into the entire process. “We have the ability to measure purity and concentration of stock material but want the ability to measure the purity and concentration of what we give out for bioassays,” Holland explains. “Right now, there’s no easy way to do that.”

The companies that find the best ways to incorporate automation into sample management could produce tomorrow’s most profitable products. In addition, the right automation could even develop products that we can’t imagine today.

About the Author
Mike May is a publishing consultant for science and technology based in Houston, Texas.

This article was published in Drug Discovery & Development magazine: Vol. 12, No. 10, November/December, 2009, pp. 14-16.