Liquid Handling for the Masses
Smaller, easier-to-use instruments move more labs from manual to automated.
Liquid handling plays a fundamental role in a wide range of biological research. In describing exciting trends in liquid handling, Kevin Keras, business unit manager for liquid handing and automation at Caliper Life Science, points out two applications: sample preparation for next generation sequencing (NGS) and analyzing recombinant proteins and antibodies. To achieve such application advances, liquid handling needs ongoing technological improvements.
“There’s a continuing trend toward miniaturization in liquid handling,” says Brad Nelson—senior director, product marketing & applications at Labcyte. “It enables applications and throughputs that weren’t possible before.”
Another key trend involves smaller, simplified platforms. “The trend targets customers transitioning from handheld pipetting to automated liquid handling,” says Kiara W. Biagioni—product manager, automation liquid handling equipment at Thermo Fisher Scientific.
That transition demands some simplification. “It shouldn’t take a software engineer to program the instrument,” says Aaron Bonk, product manager at Hamilton Robotics. “The software should be intuitive and friendly, so about anybody in the lab can use it.”
Increasing the Throughout
The trend of more researchers moving from manual to automated pipetting spawned the Thermo Scientific Matrix Hydra II and DT. The Hydra II fixed-tip system provides aspiration and dispensing of volumes down to 100 nanoliters for 96- and 384-well plates. The disposable-tip DT version transfers 96 samples to 96- or 384-well plates.
For researchers making the handheld-to-automated transition and also interested in an instrument that can scale up, Biagioni mentions the Thermo Scientific Versette. This automate liquid handler can work with single- to 384-channel pipetting, all across a volume range of 0.1–1,250 microliters. “In high-throughput screening,” Biagioni says, “the bottleneck can be upstream, so you can see that a smaller liquid handler like the Versette can be a complementary product to a high throughput–screening system.”
Any liquid used in biological preparations, must be free of contamination. That’s why Rainin—a Mettler-Toledo company—makes its BioClean tips. “These give researchers confidence that the tips are free of any DNA, RNA, pyrogens, endotoxins, and so on,” says Jim Petrek, Rainin’s chief technology officer. To ensure the contamination-free character of these tips, Rainin molds them in-house. “We need that level of control to be sure that every lot and batch is meeting our standards,” Petrek says.
As steps change, some of the hardware might too. If a researcher relies on a variety of plate formats, Rainin’s adjustable spacer multichannels can quickly adapt. “These manual pipetters can expand from 9 millimeters to a wide format—say, 24-well plates or tube holders,” Petrek says. “It increases the throughput and enhances the workflow.”
How an instrument handles a liquid depends in large part on what the liquid is. Instead of making a user adjust a handler for different fluids, Labcyte developed its Echo liquid handing system, which identifies the fluid being handled and makes any necessary adjustments. This instrument handles a wide range of fluids, including dimethyl sulfoxide–based fluids, aqueous buffers, protein, protein-crystallography screening sets, up to 60 percent glycerol, and others.
According to Nelson of Labcyte, the Echo “listens to the fluid, measures its characteristics, and dispenses accordingly.” In fact, it dispenses from nanoliter to microliter volumes very accurately—in just 2.5 nanoliter drops.
“We’ve seen this instrument adopted by labs with less familiarity with liquid handling,” says Nelson, “because they don’t need a liquid-handling specialist to fine tune for each liquid.”
It’s one thing to deliver a liquid and another to track the handling process. Caliper Life Sciences added a sensor for challenges like this. “For proteins—and some molecular biology kits—we have implemented a non-contact, clogged well–detection sensor called ‘PING!’,” says Keras. “PING! is an ultrasonic sensor that can interrogate filter plates in search of clogged wells.” He adds, “Clogged wells can result in lost samples—no data—or even worse, well-to-well contamination due to overflows during multiple filtration steps.”
Simplifying the Steps
When preparing a sample for NGS, Keras says that doing this manually “includes very tedious sample preparation that requires a great deal of pipetting skill and attention to detail.” In addition, it’s expensive. “We partnered with one lab in the U.S.,” Keras says, “who told us the cost of reagents to prep a 96-well plate could easily exceed $50 to 70K.”
To make this sample preparation faster and more economical, Caliper Life Sciences developed the Sciclone NGS Workstation. “All the programming and liquid-handling optimization has already been done for the user,” Keras explains, “and we even provide a highly graphical user interface to walk operators through every step of the assay setup and run.” He adds, “Regents for these assays are so expensive, a misstep anywhere along the way can result in low or no yield.”
User-friendly programming also makes some liquid handling easier and open to many more users. This summer, Hamilton Robotics will introduce new software for its MICROLAB NIMBUS workstation. Bonk says that this software will “let users work with many basic commands that are commonly used in various processes, such as serial dilutions.” He adds, “It’s all drag-and-drop, and the user adjusts the parameters.” To use this software, according to Bonk, a user only needs to know the manual liquid-handling process, and the software walks the user through the steps to automate it.
Integrating the Options
While liquid handling resolves some challenges, it generates others. For example, Bonk says, “One blood tube could lead to 20 different samples. What do you do with those samples and how do you keep track of them? As one instance of taking on such a challenge, Hamilton Robotics delivered a compound screening and storage system to the University of North Carolina at Chapel Hill. This system integrates –20 degree Celsius storage of a compound library with a 96- and a 384-channel MICROLAB STAR liquid-handing workstation. The Hamilton Rack Runner robot moves the tubes from storage to the screening platform.
Other collaborations will also enhance drug discovery by way of advanced liquid handling. In late March 2011, for example, Tecan Group announced that it would commercialize a product and accompanying consumables developed using HP’s high performance–inkjet technology. According to Wendy Lauber, director of product management, liquid handling robots and consumables at Tecan, “These products are able to dispense volumes ranging from 15 picoliters up to 5 microliters.”
The HP D300 Digital Dispenser provides direct digital titration technology. Lauber says that this technology “streamlines the laboratories titration workflows.” She points out that the intuitive easy to use experiment design software enables people to perform complex experiments with little need for training. The researchers can be performing their experiments in only a couple of hours. Furthermore, “The industry is moving toward smaller, bench-top systems,” says Lauber. “This product will support this type of use.”
The product is designed for use in research to speed the evaluation of how potential drug compounds impact biological agents at very low concentrations. This new capability can benefit research by significantly improving accuracy when evaluating drug effectiveness, testing drug interactions, and developing new drugs.
Overall, liquid-handling users keep expanding. In labs where scientists once handled a dozen or so steps with manual pipettes, small automated systems can now take over the process.