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Jun 15, 2011 (Vol. 31, No. 12)

Dispensing with Manual Pipetting

Automated Systems Trump the More Labor-Intensive Methods in Almost Every Situation

  • Maximizing Productivity

    Reed Kelso, co-founder and application scientist at Bionex Solutions, and his colleagues identified “a gaping hole in lab automation” in that available devices do not do any work while consumables are being loaded or unloaded and product is recovered. Bionex scientists call this “idle time.”

    In contrast, automated systems operating in modern industrial settings typically do not stop working except for maintenance. Every minute a tool is not doing work, the company is losing productivity. Kelso’s group set out to apply the concepts underlying Lean Six Sigma material handling to automated liquid-handling processes in life sciences labs, which led to the development of the Hive™ automation platform.

    The Hive is built around a Lazy Susan design, providing simultaneous-access plate storage that enables continuous operation. While one side of the carousel is accessible to the robot arm, the other is accessible to a technician for loading and unloading. The only downtime, explains Kelso, is the 2–3 seconds it takes for the carousel to rotate from one side to the other. Transfer of source and destination plates takes place outside of the pipetting space, and pipetting is not interrupted as plates are moved around on the deck.

    Kelso reports that a customer using the Hive has documented its ability to do the work previously done by six machines, and to complete it three times faster, resulting in an 18-fold increase in throughput. This application involves transferring randomly distributed hits from 96-well collection plates to a 384-well plate format for additional screening.

    Early adopters of the technology are expected to be looking for a system that can perform as many as 50,000 picks in an 18-hour day—laboratories that are doing very high-throughput applications such as cell culture screening, monoclonal antibody development, screening of synthetic molecules for drug or biofuels discovery, massively parallel PCR reactions involving a large selection of primers, or SNP analysis, for example. At this scale, hit recovery/cherry-picking becomes the bottleneck and cannot keep pace with screening technology.

    The ability to reduce sample transfer time by as little as 0.1 seconds over a process that requires 40,000 picks will allow laboratories to increase the scale of screening by as much as eightfold, contends Kelso.

    Each of the Hive’s pipetting channels moves independently, and the architecture of the system is designed to maximize the number of channels that can access a source plate at one time, with a minimum of two channels being able to access any combination of wells on a plate in parallel. A high-speed barcode reader and tip-exchange system, and a plate rotator that can change the plate orientation from landscape to portrait as needed contribute to the speed and flexibility of plate-processing operations.

  • Automating Workflows

    Click Image To Enlarge +
    One of the benefits of Agilent Technologies’ BenchBot Robot is the ability to “train” the robotic arm. The operator moves the arm to each position and presses the training button to program the system.

    For large-scale genomics research, Promega  offers a workflow for isolating genomic DNA (gDNA) from large volumes of whole blood using its ReliaPrep™ HT gDNA isolation system integrated on Hamilton’s MicroLab® StarPlus liquid-handling workstation.

    To avoid the inherent limitations of centrifugation-based methods for gDNA preparation—mainly the need to balance sample numbers and weights, and additional restrictions related to centrifuge capacity and operation—Promega developed ReliaPrep chemistry, explains Cristopher Cowan, manager, integrated solutions and engineering.

    It requires no centrifugation step to remove red blood cells or other plasma components, allowing ReliaPrep to capture all of the nucleic acid in a whole-blood sample. Storage and transport of blood samples prior to processing may expose the samples to freeze/thaw cycles or other conditions that can compromise the sample, lysing white blood cells.

    “You may have already lost much of your DNA yield before you even get to the precipitation step,” says Cowan. Rapid processing of 32 3–10 mL samples at a time takes place on the ReliaPrep’s HSM 32 LV device, which performs heating, shaking, and magnetization functions in one location. Automated liquid-level sensing allows the control software to scale the chemistry in each processing tube based on the volume of individual samples.

    In a poster presentation at “LabAuto”, Promega illustrated the efficiency of DNA recovery on ReliaPrep compared to a precipitation-based method using 10 mL samples of both fresh blood and blood samples exposed to two freeze/thaw cycles. The results show improved yield and purity based on UV absorbance spectroscopy data measured after elution of the gDNA or resuspension of the DNA pellets.

    According to Cowan, the ReliaPrep system uses a minimal amount of plasticware for gDNA isolation. Each blood sample is processed in a single 50 mL conical tube using two pipette tips—one for the elution and one for the removal of waste.

    The Hamilton MicroLab StarPlus can integrate with three 32-sample ReliaPrep HSM devices. The Promega/Hamilton method can process 96 samples in less than 8 hours, with an average yield of about 300 µg of DNA per 10 mL of blood.

    The concept of a benchtop robotic workstation designed to maximize the number and types of devices with which it can integrate, while maintaining a relatively compact perimeter to preserve workspace, was the central theme of a poster presented at “LabAuto” by Agilent Technologies.

    Seeing a gap not only in its own product line—between the small-scale BenchCel Microplate Handler and the Direct Drive Robot (DDR)—but also in the broader market for robotic liquid-handling systems, Agilent envisioned an instrument that would be applicable across multiple workflows, including genomics and sample preparation for next-gen sequencing, cell-based assays, maintenance of cell stores, sample management for high-throughput applications, and ELISA-based assays.

    Agilent’s BenchBot, introduced at “LabAuto” and set to begin shipment to customers this month, offers customers a midsize robotic system from which they can build a customized workstation and is sized to operate inside a standard fume hood. It can accommodate up to 10 devices at a time, has a vertical reach of 20–420 mm, a radial reach of 590 mm, a 270° work space, five degrees of freedom (z-axis, shoulder, elbow, wrist, and gripper), and an average pick-and-place transfer time of five seconds.

    The goal, says Marc Valer, product manager, integrated systems, is to enable customers to “create larger workstations in a smaller footprint, encompassing a whole workflow with one system.”

    The software includes a menu of operations for more than 140 different devices, allows for remote monitoring of robot status, and includes the One Touch Teaching function, with which users can manually place a plate at a desired position, press a button, and the software will record the information needed to instruct the robot to dispense at that position.

    The Benchbot’s gripper can grasp microplates in either portrait or landscape orientation, and the robotic arm can access various types of labware housed in a plate hotel or plate stack storage device or a unit that enables random access.

  • Catering to the NGS Market

    Recent improvements in throughput and in the multiplexing capabilities of second- and third-generation sequencing technologies have created a need to automate the up-front sample-preparation workflows that allow researchers to realize the full potential of these next-generation sequencing (NGS) platforms. Caliper Life Sciences just launched the Sciclone NGS Workstation to address these demands.

    According to Jeremy Lambert, automation applications and genomics marketing manager at Caliper, the Sciclone NGS Workstation is a fully featured automated liquid handler specifically designed to accommodate the rapidly changing protocol requirements of the NGS market, including modifications for single-molecule sequencing workflows.

    The Sciclone NGS Workstation can process a range of NGS methods including TruSeq protocols from Ilumina, RNA-Seq protocols from NuGEN, and multiplexed sequence capture methods from Roche NimbleGen. The Sciclone NGS Workstation also supports workflows for the Life Technologies Solid and Ion Torrent sequencing platforms as well as the Pacific Biosciences RS system.

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