The development of automated liquid-handling systems was originally driven by pharma to boost throughput for drug screening. But today liquid handlers are increasingly used in smaller labs to accomplish routine work even at lower throughput. Liquid handlers remove human error and add traceability to pipetting processes. Researchers in labs big and small will continue to use manual pipetting—but how do they know what to look for to find an automated system that fits their needs? Here are some key considerations about choosing automated liquid handlers.
Adapting throughput
Even 20 years ago, most liquid handlers were designed for process automation and high throughput screening (HTS)—and that was it. The fastest systems with the highest throughput—such as those offered by Agilent Technologies, Beckman Coulter, Hamilton Robotics and Thermo Fisher Scientific—are crucial tools for high-throughput screening and drug-development research. However, while throughput remains an important issue, it is the ability of the system to handle workflow challenges that needs to be balanced alongside simply addressing throughput. This trend has developed as system adoption is driven more by scientists than simply automation specialists.
But these sophisticated, high-throughput platforms are overkill for smaller labs—as well as prohibitively expensive and complex to operate. “There was a huge chasm between manual liquid handling and the big, sophisticated liquid handlers,” says Kevin Barrett, senior vice president of strategic business development at Gilson.
Companies like Gilson are attempting to address the challenges faced by smaller research labs that have lower-throughput needs but still require more throughput than manual methods can provide. Gilson’s Pipetmax is an automated pipetting station designed as an extension of the company’s Pipetman manual line. Similarly, Hudson Robotics’ SOLO is an automated, handheld pipettor adapted to an arm that moves in three dimensions and can reach other equipment, such as spectrometers and thermocyclers, says Hudson’s chief scientific officer, Alan H. Katz. Eppendorf’s epMotion® line of automated pipettors are designed to handle one to 384 sample workflows. A system which addresses both workflow complexity and has the ability to service both high and lower throughput applications is Beckman Coulter’s Biomek® 4000 Workstation, which is geared to “specific applications and dedicated workflow solutions” that adapt to researchers’ needs, according to Andreas Hahn, senior manager in global product management and strategy at Beckman Coulter Life Sciences.
Adding value
Considering throughput level is a great first step, but then consider whether a system will be adding value to your research, Barrett advises. Here, value refers to several factors: freeing researchers from routine work to do higher-level functions, such as analyzing data or planning experiments; removing human errors in pipetting and sample movements; and adding reliability and traceability to liquid movements. “Once something becomes routine, you’re no longer adding value to that process [by doing it manually], and that’s where a simple pipetting station could free the user to do more valuable things, like concentrating on experimental design or interpreting the data you’ve just generated,” says Barrett.
Reproducibility is especially important for experiments that might be run over several weeks, for example, or in different parts of the world. How features can add value—in traceability and reliability—is apparent in the Thermo Scientific™ Multidrop™ Combi SMART dispensing system, which automatically tracks each sample cassette throughout its lifetime. Tecan’s Adaptive Signal Technology detects liquid levels to minimize dead volume and use all the sample in a vessel, says Ian Shuttler, head of strategy and portfolio management for the life science business at Tecan.
Applications
Liquid handlers are used in a wide range of applications today. In addition to general tasks such as serial dilutions, common uses include PCR, nucleic acid purification and sample preparation for mass spectrometry (MS) and—increasingly—next-generation sequencing (NGS). But some liquid handlers include features for particular applications, such as cell-based assays. Thermo Fisher’s Multidrop™ Combi dispenser is especially suited for dispensing intact, viable cells. Eppendorf’s epMotion instruments have internal sterilization features that lend themselves to cell-based assays, says Jesse Cassidy, Eppendorf’s manager of application support. The company’s new advances include the CleanCap, an integrated UV lamp and HEPA filter module. “This allows users to quickly and effectively sterilize their instrument between uses,” says Cassidy. Tecan’s Fluent platform, which began with HTS applications around cell-based assays has expanded to support compound management, says Shuttler.
Labcyte’s Echo® liquid handlers use acoustic energy to transfer fluids without the use of pipet tips or pin tools. Sound waves eject precisely-sized droplets of 2.5 or 25 nanoliters from the source liquid to a microplate, microscope slide or other surface. Larger volumes are transferred at the rate of hundreds of droplets per second. “Our customers benefit from the ability to miniaturize assays, which reduces reagent costs, conserves rare samples and improves data quality,” says Chris Grimley, vice president of marketing at Labcyte. “Also the ability to rapidly cherry pick samples and reagents from libraries can be used to generate highly complex, multiplexed assay designs, or to create highly multiplexed single pools for next generation sequencing. This increases throughput and often enables experiments that couldn’t reasonably be performed using conventional liquid handlers.”
Ease of use
Ease of use is an important feature of any system, as researchers value their time and are adopting faster, turnkey solutions. Ease of use also minimizes costly mistakes, giving more reliable results. Tecan’s new platform, Fluent, builds on the company’s Freedom EVO platform by making it simpler—and simply easier to use. “With our teach-free capabilities, the system software knows where everything is, so it’s ready to go out of box—there’s no teaching robot arms where to go,” says Shuttler.
Labs of all sizes appreciate instruments that are easier to use. But in contrast to big labs performing high-throughput screening, smaller labs today have different needs—their throughput is lower, yet increasingly they are generating multidimensional results. “Now we are seeing the focus more on increased content and data interpretation, then just throughput,” says Hahn. The increasing complexity of their experiments and results means that they want more simplicity when it comes to instrumentation. “The goal is to take the complexity out of the workflow,” he says.
With the quickening pace of research, many don’t have time to develop programs for their liquid handlers, or to train new lab personnel to use one. Gilson is removing complexity with turnkey, application-focused methods called assistants. “Someone with no liquid-handling experience at all can use it, because the assistant asks about the design of their experiment, then uses expert logic to determine variables such as what speed to aspirate at,” says Barrett. He expects to see more turnkey applications that do exactly what the customer needs them to do, and very simply.
Similarly, Agilent recently made changes to its software, creating application-focused interfaces to run samples “these do not expose the individual protocol steps to the user but rather the experimental conditions,” says Louis Murray, product manager of genomics automation solutions at Agilent Technologies. “[Customers should ask,] can it do what I need to do, and can I do it reasonably easily?”
Flexibility
Because different researchers have different needs for different types of research, says Patrick Pfenninger, senior product manager for the VANTAGE Liquid Handling System at Hamilton Robotics, Hamilton customizes its systems to accommodate individual labs. “For some customers, repeatability is more important than throughput, and [for] others it’s vice versa,” he says. For example, you can add multiple channels or multi-probe heads and parallel processing to increase throughput, and add barcode scanning and activate total aspiration and dispense monitoring to improve traceability.
Among the many factors to consider when looking for a liquid handler, the ones that matter most are the ones that affect your particular research. Remember to account for possible future needs for throughput, adding value to your research, focused applications support, ease of use and flexibility. With the range of choices available today, you’re likely to find a liquid handler that’s right for you.
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