When it comes to sample management, particularly large libraries of compounds, automated liquid handling is proving to be a “go-to” solution. Automated systems provide efficient, accurate, reproducible and trackable results that translate into time and cost savings. 

In addition to underpinning the workings of high-throughput (HTP) screening operations such as drug discovery, automated liquid-handling systems are becoming more common in smaller-scale research laboratories.

These labs often require more throughput than manual methods can provide, thus the shift toward more automated workflows.

Tara Jones-Roe, marketing manager at Beckman Coulter, shares the view that automated liquid-handling solutions provide powerful tools for reducing the inherent variability of manual pipetting techniques, helping to ensure methodology consistency, optimize accuracy and reproducibility and simplify sample-ID traceability—all essential functions for increased throughput. “Because they eliminate the need for laboratory staff to perform routine, repetitive and mundane tasks, liquid-handling systems can be found worldwide in labs that focus on genomics, cell biology, proteomics, drug discovery, forensics and related research areas,” says Jones-Roe.

Out-of-the-box solutions

For companies like Agilent Technologies Inc., market insights show that many researchers working in the areas mentioned above are looking to invest in an automation platform that can handle application-specific workflows, without necessarily needing to become automation experts themselves. “Many companies now offer ‘out-of-the-box’ solutions that are application-focused where high-throughput sample preparation is needed,” points out Chad Whitman, product manager of next-generation sequencing (NGS) automation and consumables at Agilent. Two prime examples of such solutions are sample prep for NGS and antibody characterization. “Overall, researchers in these areas want a system that is easy to use, provides consistency and increases walk-away time,” Whitman adds.

Although quick, convenient installation and familiarization is one draw, another is modularity: the ability to add functions and volume-handlingcapacity later on. “A scalable approach enables a researcher to build on a stand-alone device by adding modular transport and storage units as workload increases; therefore, his or her initial financial investment is never out of date or wasted,” explains Debra Conway, director at CyBio Northern Europe Ltd., a subsidiary of Analytik Jena. For example, a researcher could start with a CyBio® benchtop FeliX™ and later add a CyBio® QuadStack and CyBio® Carry (plate handler) to transform a 12-position, deck-based pipettor into a 160-plate batch processor on the lab bench. 

The possibilities for augmenting workstations are vast in terms of what is available in today’s liquid-handling market, with the only limitations being perhaps cost and bench space.

“There are literally hundreds of tools that can be used to efficiently automate liquid handling,” says Jones-Roe. At the recent SLAS meeting in Washington DC, Beckman Coulter unveiled their Biomek i-series automated workstation which provide complete workstation workflow solutions for scientists. Expanded deck capacities—as demonstrated by Beckman Coulter’s i-Series Biomek i7 workstation—enable integration of multiple components and devices that researchers require for their evolving priorities. Such complementary hardware options include devices; heat, cool, tip and shake samples; barcode readers; and labware feeders.

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Interchangeable components like the dispensing head of the workstation itself create even more versatility. CyBio’s FeliX platform comes with a range of swappable heads, offering up to 384 channel parallel pipetting and volumes ranging from 0.5 µl to 1 ml With its CyBio Vario 1,536 programmable air-displacement pipette head, volumes as low as 100 nl can be dispensed for further analysis in applications like MALDI.

According to Dave Donofrio, director, business development at BioNex Solutions, “The major cause for loss of accuracy and precision in liquid handling equipment is due to the fouling of the fluid path by the sample.” With the Nanodrop Automated Pipettor from BioNex Solutions, “contamination risks are greatly reduced as the flow-regulating solenoid is isolated from the sample flow path,” shares Donofrio and “this is a major step forward in terms of improved dispensing reliability and robustness.”

Keeping track

Yet it’s not just the convenience and longevity of a workstation that attracts those looking for solutions for compound library management to their chosen liquid-handling solution. When managing thousands of compounds, the traceability of each of these is crucial. Jones-Roe explains: “Tracking well ID and compound information is critical for downstream processing. Efficient HTP screening requires maintaining the integrity of sample data from the source plate to the end of the workflow.” He points out that mismatched data can result in hours of nonproductive time spent poring over text files (and often hand-written notes), which wastes money and can delay important discoveries.

Instead of relying on manual labeling and tracking of samples, which is time consuming (even when error-free) and often falls foul of the aforementioned pitfalls, researchers can now leave these tasks to the machines. For instance, Agilent’s BenchCel Workstation range includes an Automated Barcode Labeling Workstation that can be used alongside the BenchCel Microplate Handler. Analytik Jena also brings a fairly recent offering to this space in the form of the CyBio® QuadPrint, which features flexible barcode labeling on all four sides of the microplate as well as an automatic label-height adjustment.

Using automation to manage library compound samples makes it much easier to accurately trace data throughout an entire workflow, which helps maximize the operational efficiency demanded by HTP screening and increases walkaway time.

Supporting software like Beckman Coulter’s Biomek software automatically ensures reportable traceability for literally every movement of every sample during every step of a workflow. Most platforms produce a data log that records all transfers and is coupled with onboard barcode checking to ensure flawless traceability.

At SLAS, BioNex Solutions launched a next-generation laser-based marking system to provide direct, indelible marking on microplates, tubes, vials and other labware. This instrument eliminates the risk of adhesive-backed labels which can get damaged or lost under normal storage and handling conditions.

Being picky

Another liquid-handling innovation that has revolutionized compound library management is ability to perform complex hit picking. In addition to speeding up the screening of potential drug candidates—consolidating the hits from the various “source” plates into “destination” plates to simplify further analysis—many hit-picking technologies accommodate nanoliter-scale volumes, meaning a given amount of sample can go much further. The mosquito X1 from TTP Labtech is an example of a single-tip, nanoliter hit-picking system that’s compact enough for benchtop installation. Analytik Jena’s CyBi®-FeliX platform’s interchangeable SELECT™ head features automated tip change to provide fast, accurate, contamination-free hit picking.

According to Donofrio, “the integration of liquid handling routines into laboratory automation systems for the execution of hands-free assay protocols will be a continuing trend—as researchers want to spend their time focused on science, not performing routine pipetting tasks, serial dilutions, plate replication etc.”

Other innovations that have improved the repeatability and reproducibility of liquid-handling workflows include things like positive-displacement disposable tip heads, which enable better flow control; and improvements to the precision and accuracy of volume transfers, such as acoustic dispensing to allow for picoliter volume transfers, and liquid-level sensing.

Supporting software

Realizing the efficiency benefits of all the hardware mentioned here requires powerful but easy-to-use software tools. “This software must support a wide spectrum of needs, from sample-ID tracking and scheduling of multi-day methods (e.g., for cell-culture workflows) to simplifying the creation of complex process cascades,” explains Jones-Roe. In most cases, software tools must also provide connectivity with widely used laboratory information management systems (LIMS). “Beckman Coulter’s SAMI EX software saves hours of time by streamlining all types of workflows, while calendar-formatted SAMI Process Management software cuts time and costs by enabling users to automate and monitor multiple complex workflows over periods of days or weeks,” says Jones-Roe.

The graphical user interface (GUI) in CyBio’s software is used to load and manage the systems’ interchangeable heads; the systems are self-aligning, and no teaching of head positions is required after a “head swap.” Conway also points out the collaborative capacity of CyBio’s software: “Our open-source software allows for sharing of protocols across multi-users using different devices. … This is particularly recognized within the synthetic biology arena.”

Final word

Liquid handling is now mainstream in many research settings, from academic labs and start-up companies to ultra-HTP drug-discovery screening operations in biotech and large pharma companies. As Donofrio shares, “cost and features are vitally important in selecting a workstation, but at the end of the day, it’s about reliability and a system researchers can trust.”  The benefits of automation, accuracy, reproducibility and time savings are being captured by tool providers in an array of workstation options that address the liquid-handling needs of even the most fastidious researcher.

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