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Jun 15, 2013 (Vol. 33, No. 12)

Liquid Handling Needs a Helping Hand

  • Click Image To Enlarge +
    Arrayed pipette tips on a liquid-handling robot. [Nantela/iStockphoto]

    Whether it’s dispensing reagents, washing plates, or plating out bacteria, moving things around is at the core of biomedical R&D and production.

    The task is increasingly done in high-throughput using robotics and automation, which take care of everything from the individual steps to coordination of the processes.

    How all of this can be done better, smarter, and more accurately—starting with a common vocabulary with which to begin the discussion—and put together into productive workflows was discussed at Select Biosciences’ “European Lab Automation” held earlier this month in Hamburg.

    A common language helps to facilitate discussion and move a field forward. Stefan Bammesberger, R&D engineer at the laboratory for MEMS applications at IMTEK, University of Freiburg in Germany, felt that in order to compare liquid handlers, he first needed to establish a way of categorizing them, and to find a vocabulary to discuss their performance.

    He first separated dispensing technologies into those that use contact as a way of dislodging the dispensed liquid and those that do not. Because contact is a potential source of cross-contamination, a dispensing method that rather ejects the liquid may be preferable, especially for biomedical applications. Among the noncontact dispensers, two types of technologies predominate for the nanoliter to microliter range: valve-based and positive displacement, each with its own advantages and disadvantages.

    Having delineated dispensing mode, Bammesberger set out to establish a terminology that could describe performance characteristics. Discussions always come down to precision (how close dispensed volumes are relative to each other) and accuracy (how close the dispensed volumes are relative to the target volume).

    Yet, “when you look at how the different manufacturers characterize volumetric precision and accuracy, everybody does it somehow differently from the others, so it’s not really comparable. No standard has prevailed in the industry, and it’s really hard to compare the performance of different dispensing systems,” he said. What are necessary are parameters at once generic enough to be utilized for many different applications, yet meaningful and objective enough to allow comparison of very different liquid handlers.

    Take filling a 384-well plate with an eight-channel dispenser. Usually manufacturers fill a plate and measure the volumes dispensed, but this doesn’t give insights into where the deviation from the ideal might come from.

    “So I try to break it down into the very basic elements you do with a liquid handler, the most basic of which is the intra-run approach, where you have just one channel doing one thing—dispensing aliquot after aliquot,” Bammesberger explained. “Let it do the same thing several times and measure how it deviates.” He terms these “intra-run” measurements.

    Building up from there, measurements looking at the reproducibility between runs are “inter-run.” On the other hand, “tip-to-tip” measurements look at deviations made when dispensing from multiple channels.

    Bammesberger went on to demonstrate the applicability of his categorizations and terminology, using them as the basis with which to evaluate five commercial noncontact liquid dispensers. His sampling found that intra-run and inter-run CVs tend to be significantly smaller than the corresponding tip-to-tip CVs for a given target volume and liquid handler, prompting him to suggest that for high-precision applications, it may be beneficial to use only a single tip of a liquid handler.

  • Learn to Work Together

    Joe Liscouski, executive director of the Institute for Laboratory Automation, also promotes the benefits of communication and standardization—such as the introduction of microtiter plates—as means to help fuel growth within the industry. With automation playing an increasingly larger role in the laboratory, researchers need to better communicate with technologies, and the technologies must also communicate and work with each other. It’s important to step back and have a look at how the whole process can be made more productive.

    Right now, most lab automation is the result of custom-developed, purpose-driven systems. They’re put together piecemeal from different components—dispensers, washers, readers, and sealers—made by different manufacturers, interacting through made-to-order software. Frequently, the equipment was designed for use by human beings, not by automated methods. It’s a far cry from the USB plug-and-play connectivity enjoyed by the personal computer market today.

    Liscouski said we need to start thinking about how the processes in the lab as a whole can be made more productive, and not just component by component. “In some cases that means re-engineering the processes,” he said.

    Among his recommendations, “instead of having people act as robots, have robots act as robots. …It’s a matter of making better use of people. Instead of using them as a means of transferring materials from one place to another, it’s allowing the equipment to do that and allowing the people to spend more time doing analysis, doing thinking, doing research.”

    These are all components of what Liscouski calls scientific manufacturing, in which the automation process is designed—or redesigned—as an entire system. To make full use of the concept, users who will need to be involved in the planning and facilitation must demand from vendors that their hardware and software will talk with others’ hardware and software. Those who are designing and building the systems should focus on “understanding how labs work, instead of the science people learning about how to talk in bits and bytes,” he said.

    Liscouski was concerned that budding researchers are being trained in the sciences but not necessarily in the automated tools that are being used to do science. “When they come out of undergraduate education, they go into laboratories and there are all these tools that they’ve never seen before, and yet they’re expected to work with them and understand them,” he said. “The gap needs to get filled.”

    A large emphasis of the nonprofit Institute for Laboratory Automation is education. The organization provides live, video, and online courses for both lab personnel and IT support.

    “We probably have the only life sciences-based course for IT professionals that talks about what labs are, how they work, what goes on in them, what kinds of things they bump into, and then also talks about what’s necessary to provide the day-to-day support in those kinds of environments,” Liscouski notes.



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