by Laura Lane
Independence Day inspires many Americans to consider their freedoms to act, speak, think, and worship as they choose. This month, you may also want to think about the freedom granted by automated liquid handling devices. Just as these instruments have brought breakneck speed to high throughput screening operations in industry, liquid handlers are starting to liberate academic researchers from the oppression of repetitive, manual pipetting. Without such burdens, researchers are now free to make leaps and bounds in the life sciences.
The wide variety of automated devices that are now available has evolved over the last 25 years. With the sudden and swift spread of the AIDS epidemic in the 1980s, the world received a glimpse of the sluggish drug discovery process. Regulations and approvals of the U.S. Food and Drug Administration notwithstanding, the urgency to find a treatment spurred the development of expedited methods of research. Today, those technologies are still crucial. While researchers are just as desperate to treat a barrage of diseases, the enthusiasm and importance of studying genes and proteins also play major roles in the development of high throughput technologies. Projects that would otherwise require excruciatingly protracted time periods now operate on timelines more in line with the fast track uncovering of the molecular and cellular worlds.
The bottom line, of course, is a major driver in the move toward automation, according to the market analysis report, “World Drug Discovery Technologies Market Outlook,” published by Frost & Sullivan. “Major goals for research facilities include improved efficiencies and reduced overall research and development costs,” says Jessica Patel, an industry manager at Frost & Sullivan, explaining that cost-cutting means reducing spending on reagents, consumables and instruments.
Automated liquid handlers are central to accomplishing these common goals. The devices are crucial to downsizing experiments to miniaturized formats, which reduce the use of reagents and consumables. Robotic arms and multi-probe dispensing heads can dispense nanoliter volumes with a precision not possible with the inherent faults of human performance. This capability allows assays to be miniaturized and modified for higher density plates. Whereas 96-well microplates were once the norm, 384- and 1536-well plates are quickly becoming the standard, says Nance Hall, vice president and general manager of automation and detection solutions at Perkin Elmer. “People are still trying to determine how far we can go.”
The savings snowball from there. Decreasing the use of reagents and consumables will reduce how much you spend on disposal. Automation also allows you to spend less on labor, as the robotics take over the manual tasks of dispensing, aspirating and mixing fluids, and changing and/or washing pipette tips. You also get more for your money as you “free highly paid PhD-level researchers from feeding and watching instruments,” Hall says. “With the instrument approach, the instrument does the research and the scientist can analyze the results.”
Fortunately, automated liquid handlers are more affordable than ever. Decreasing prices and smaller units have both improved the accessibility of the instruments. “Overall, cost has come down for entry level systems,” says Marc Goldstein, PhD, product platform manager of Beckman Coulter’s automation business center.
In addition, many companies have adopted the modular approach, which allows researchers to purchase liquid handling functionality by itself. Instead of the prohibitive cost of large systems that provide start-to-finish features, purchasing individual modules makes the move to automation more realistic and less intimidating. You can buy “as much automation as needed, leaving open the door to further expansion,” Goldstein says.
“It’s not only easy on the customer to make the transition [to automation], but also gives them the confidence that if their needs change someday, they’re not being locked into something designed for one thing and one thing only,” he says. “They can reconfigure the instrument for another application.”
The latest software is making that programming endeavor less daunting. Packages accompanying instruments usually come with preset programs for common protocols. You’ll also find user-friendly pictorial interfaces that simultaneously attempt to offer maximum flexibility and optimal simplicity. This includes drag-and-drop tools and the familiar point-and-click of a mouse.
“Software is becoming a driving factor for selling equipment,” says Luke Roenneburg, product manager for high phase liquid chromatography at Gilson. “People are now less focused on hardware and are more focused on how efficient and feature-rich the software is.”
Another big draw is the individualized service that many companies now offer. This can mean anything from recommending appropriate specific instruments to pre-programming them before delivery. Labs that employ lower-skilled technicians to operate the instruments can especially benefit from such service.
“Some markets want plug-and-play capability so they don’t have to worry about programming,” says Mike Halvorsen, product manager of sample preparation stations at Gilson. “We can pre-design the software for very specific applications so the customer can just hit the ‘run’ button.”
The demand for such ease reflects the overall trend toward liquid handlers that are unencumbered by the many features of flexibility. This is becoming most evident with nucleic acid sample preparation and solid phase extraction. Researchers in this segment of the market “are less concerned about fancy technology,” says Marc Feiglin, the Tecan Group’s chief technology officer of life sciences. “They care much less about technology and flexibility and are much more interested in quickly obtaining reliable and reproducible results.”
In fact, the call for simpler, plug-and-play instruments is reflected in the approximate one-third of liquid handlers that already cater to the needs of genomics researchers, Feiglin says. While they still prize the speed of fancier devices, the priority is obtaining high quality results, which can be efficiently obtained with instruments developed for specific applications. These include devices for DNA purification, RNA isolation, microaarray hybridization, PCR clean-up and set-up.
“The simpler devices will also appeal to researchers who perceive automation as being expensive and complex to use,” he says. “Without the complexity of unnecessary flexibility, the instruments can be more affordable and less intimidating.”
Despite the apparent trend toward simplicity, the technology for both multipurpose and application-specific liquid handlers is certainly advancing. Sophisticated tubes can detect and report clots. Pipette tips can provide verification of the volumes dispensed and/or transferred. Increasingly, instruments can respond to the input and act accordingly. Called closed-loop systems, the capability can improve the efficiency of assays and screening efforts.
For example, researchers can program the instrument to respond to the downstream reader. Upon recording specified types of data, the instrument can pay special attention to the pertinent samples, such as retrieving them and performing further analysis. “Systems are becoming smarter,” Hall says.
They can also become much cleaner, according to Mark Robillard, vice president of sales and marketing for CerionX, which has introduced a new method for washing dispensing probes and tips. Their microplate-like device is equipped with two dielectric plates. By repeatedly reversing their polarities, electrons form a plasma that “breaks apart contaminants at the molecular level,” Robillard says. “When you’re using water to wash, you’re really only diluting out the contamination.”
Readily integrated into most liquid-handling systems, the company’s tip charger device can also help save money and the environment. Circumventing water rinse can reduce water usage and the cost of disposal. And, with the tip charger’s ability to both clean and sterilize, researchers can forgo the cost and waste of disposable pipette tips.
Such advancements could find use in many labs. Still, many researchers are simply looking to “replace the hand-held multi-pipetters” to dispense liquids into plate after plate, says BioTek Instruments product manager Jason Greene, pointing to his company’s bulk dispensers. “Instead of depending on a technician’s pipetting skill, customers are looking for robust products that continue to perform, reduce down time, while also providing broad volume ranges and faster processing.”
Who can argue with that?
