Precise Automation for High-Throughput Liquid Handling

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 Precise Automation for High-Throughput Liquid Handling

Please see our Liquid Handling Robotics (Automated Systems) to find manufacturers that sell these products

Automation in the lab improves productivity and throughput. Automated liquid handling systems save time, increase precision, and contribute to quality control. These labor-saving devices also minimize strain injuries by automating repetitive work.

An automated liquid handling system prepares tubes or trays of samples and reagents. The system is frequently used in high-throughput contexts for precision sample preparation.

Many manufacturers offer a range of automated liquid handling systems. Simple systems are standalone units that automate sample delivery to tubes or plates. More complex workstations are designed for specific applications such as sample preparation for chromatographic analysis. Fully customizable systems incorporate a range of accessories such as coolers, shakers, barcode readers, and robotic arms for plate management and labware manipulation. These systems are highly programmable and can be incorporated into a full through-lab automation system.

Applications of automated liquid handling systems

Automated liquid handling systems are widely used wherever precision sample preparation or compound management is required for high-throughput assays. They are widely used in the pharmaceutical and biotech, cosmetics, food and beverage, forensics, and chemicals industries.

Liquid handling systems are commonly used for sample preparation for high-throughput pharmaceutical screening; cell-based assays; solid-phase extraction; catalyst synthesis and processing; genomic and proteomic studies such as PCR setup, peptide mapping, and immunoassay protocols; and chromatographic techniques such as HPLC, LC/MS, GC, GC/MS, and NMR.

Automated systems are also used for compound management, e.g., liquid and powder weighing for library compounds; serial dilution procedures; and microplate replicating, reformatting, and pooling. The Thermo Scientific™ Matrix PlateMate Plus Automated Pipetting System from Thermo Fisher Scientific (www.thermoscientific.com) offers full plate dilutions and full plate reformatting from 96-source plates to 96- and 384-assay plates, or from 384-source plates to 384-and 1536-well assay plates.

Liquid handling technology

The pipet technology for automated liquid handling systems can be air displacement or positive displacement. Air displacement pipets are suitable for a wide range of laboratory liquids. Positive, or liquid, displacement pipets are suitable for volatile or viscous liquids. The Thermo Scientific Matrix PlateMate Plus Automated Pipetting System offers a choice of eight pipetting heads. It is capable of pipetting resins and beads, caustic solvents, and high-vapor-pressure liquids.

Consider also the risk of cross-contamination, especially when dealing with biological samples. Disposable tips reduce the risk of cross-contamination and different systems have different techniques for changing pipet tips. The Alchemist from Rigaku (www.rigaku.com) eliminates the risk of cross-contamination through its BirdFeeder technology. With BirdFeeders, each chemical is stored in a self-contained vessel, and off-the-shelf bottles and pipets are used for on-deck storage and noncontact dispensing.

MICROLAB® STAR Liquid Handling Workstations from Hamilton Robotics (www.hamiltonrobotics.com) are based on air displacement pipetting technology. This increases accuracy and repeatability while providing chain-of-custody with pipet condition monitoring and recording

Precision at microvolumes

The precision of liquid handling systems varies with volume. Automated liquid handling systems typically work in the microvolume range for low-volume, high-throughput work. Check the manufacturer’s precision and accuracy tables for the volume with which you will most frequently work.

The pump in the Micro10x™ from Hudson Robotics (www.hudsonrobotics. com) comes in two different sizes (0.25” and 0.375” barrel) to maximize accuracy at low and high volumes. The Micro10x features a positive-displacement pump head and tip-touchoff capability to ensure consistent results, despite differences in fluid viscosity and surface tension.

The PiP Precision Dispenser from Fluid Metering, Inc. (www.fmipump. com) uses valveless technology to deliver very precise volumes for pipetting, syringing, and diluting. The PiP micro π-petter® delivers in the range of 0–100 μL per dispense; the model QC216 delivers 0–1.28 mL per dispense.

VERSA liquid handling modules from Aurora Biomed (www.aurorabiomed.com) include a nanopipettor for low-volume aspiration and dispension.

Throughput

Throughput is important for high-volume labs. It depends on both dispensing speed and labware manipulation capabilities.

The ReagentDrop module in Aurora BioMed’s VERSA system presents high-speed dispense functions from on-line reagent bottles. Neutec Group’s (www.neutecgroup.com) Dosi-pump by Biotool Swiss (www.biotoolswiss.com) has high flow rates of up to 1000 mL/min.

Pump dispensers

Most liquid handling systems use pipets to deliver precise volumes of sample and reagent. However, some liquid handling systems incorporate a pump.

For example, the Perimatic Premier from Terra Universal (www. terrauniversal.com) is a heavy-duty, microprocessor-controlled precision dispensing pump, suited for rapidly and reproducibly filling a variety of containers including vials, bottles, test tubes, and Petri dishes.

Container range

The GX-241 Liquid Handler from Gilson (www.gilson.com) can hold hundreds of samples ranging from 2-mL vials to 100-mm test tubes. It can also hold up to four shallow or deep-well 96-well microplates.

Figure 1 – The Moss Liquid Handling Platform from Zinsser performs high-speed liquid handling to microplates and storage vials. The two vortexers in the center of the platform can be tilted as shown, allowing the probes to access the maximum amount of liquid at the bottom of the vials.

Customizing your liquid handling platform

Many systems go far beyond simple liquid handling in order to achieve the automation of entire processes. For example, Zinsser Analytic’s (www.zinsserna.com) Moss system (Figure 1) performs high-speed liquid handling to microplates and storage vials. It can be customized to include vortexers that may be purged with nitrogen or argon to create an inert environment; a sonification bath; a high-throughput capper/decapper tool; and a barcode scanner. It also includes powder handling capabilities.

Sterile dispensing is essential for laboratories involved in culture media preparation. The MEDIAJET from INTEGRA Biosciences AG (www. integra-biosciences.com) is an automated medium dispensing system that fills Petri dishes of various sizes. VacuSafe from Inotech Biosystems International, Inc. (www.inotechintl.com) can dispense liquids for general wash protocols, or sterile liquids can be dispensed for tissue culture media changes.

Figure 2 – The Freedom EVO platforms from Tecan offer liquid handling systems for different scales and throughputs. They can be combined with a wide choice of robotic arms, liquid handling tools, and application options.

The Tecan (www.tecan.com) EVO® workstation (Figure 2) is completely customizable and can be fitted with shakers, mixers, vortexers, plate readers, plate washers, separation devices, heaters and coolers, centrifuges, thermocyclers, plate and tube sealers, cell counters, incubators, barcode technology, and labware handling options. The PipetMax platform from Gilson can be customized to use any reagent and any protocol.

Robotic arms—extending the reach

Robotic arms are the key to integrated lab automation. They can be programmed to move tubes and plates and also other labware such as cameras and probes. Agilent’s (www.agilent.com) Encore Multispan Liquid Handling System has a built-in robotic arm that reaches up to 53 cm (21 in.) off-deck, making it easy to automate entire work flows.

Freedom EVO liquid handling workstations from Tecan can be fitted with up to three independent robotic arms. For example, with the Robotic Manipulator arm and the Liquid Handling arm, the system can pipet while the robotic arm simultaneously moves the next piece of labware.

MICROLAB STAR Liquid Handling Workstations from Hamilton Robotics feature the CO-RE gripping tool that enables the pipetting channels to act as a gripper, picking plates from a stack or moving plates around the deck. Since the software determines positions from the rack definition, it does not require positional teaching.

The robotic gripper option for Zinsser liquid handling platforms can handle loads up to several kilograms. It can move an entire aluminum reactor block with vials and lid, which is a critical step used in solid-phase synthesis automation.

Software

Table 1 – Liquid handling system manufacturers

Automated pipetting systems often have simple touchscreen operation to set the dispensing volumes. More complex customizable liquid handling systems are controlled by highly programmable software, allowing the user to specify a sequence of precise steps to automate complex assays.

Most systems come with preprogrammed settings for commonly used functions. Effective software will increase precision, quality control, and operator walkaway time.

The tracking and reporting options will vary between systems. The Flow-Web™ software for the YSI Flownamics SEG-FLOW from YSI Life Sciences controls the system internally and logs data and information for each vessel or stream. If you have existing lab management software, check that the manufacturer’s software can be easily integrated.

Footprint

System footprints vary from benchtop to floor-based units, depending mainly on the system capabilities. For larger systems, some manufacturers recommend a minimum room size that is larger than the space required by the system. Some benchtop devices will fit into hood space. The Agilent Bravo Automated Liquid Handling Platform is available in two models: The standard model fits in most laminar flow hoods, while the SRT model is three inches shorter, providing extra clearance for shorter hoods.

Other considerations for liquid handling systems

In addition to the purchasing cost, consider the ongoing operating overhead for your chosen system:

  • Will your system accept reagents and tips from any supplier or only from the manufacturer?
  • How often does the system need to be recalibrated?
  • Can calibration be carried out in-lab?

Consider also how easy it is to use the system: Will users require training, and if so, how long will it take? The intuitive software for the epMotion Automated Pipetting System from Eppendorf North America (www. eppendorfna.com) takes half a day for an operator to learn.

A list of manufacturers of liquid handling systems is given in Table 1.

Please see our Liquid Handling Robotics (Automated Systems) to find manufacturers that sell these products

Katriona Scoffin, B.Sc., is a freelance science writer; e-mail: [email protected]