Automated liquid handlers (ALHs) are one of the truly enabling technologies of modern life sciences, particularly in medical testing, biological research, and high high-throughput screening. Applications in combinatorial chemistry and materials investigations were considered emerging a decade ago, but these markets remain small.
Liquid handlers use robotically controlled pipettes to deliver precise quantities of liquid reagent to reaction vessels, often to microtiter plates.
“Automated” is the functional word in ALH markets. Once a method is entered, robots are expected to deliver fluids continuously and precisely (both in terms of location and quantity), with extremely high reproducibility, often nearly continuously.
Manufacturers of ALHs are feeling pressure to simplify, to offer products that resemble workstations rather than stand-alone instruments. “That doesn’t mean they want simplified capabilities,” says Isaac Meek, technical specialist at Caliper Life Sciences (Hopkinton, MA). “They want the features and functions, but they also want to be productive without having to be programming experts.”
Caliper and other vendors therefore “encapsulate” or standardize methods to liquid handler configurations, thus multiplying the instruments that can benefit from specific methods.
Another significant trend is shrinking instrument size and discrete systems. “Users want desktop-sized instruments that will not interfere with other equipment,” Mr. Meek says. With more-compact footprints have come software improvements that positively affect usability.
True walkaway automation is also increasing in importance along with the ability to track and monitor samples as they wind through the workflow. Pipetting accuracy and calibration, which go hand in hand, are significant operations or features, depending on one’s perspective, in automated liquid handling.
Calibration is usually done gravimetrically, but the weakness of this approach is that by weighing the entire plate (the standard method), one obtains the average volume delivered but no inkling of tip-to-tip variability.
“When we introduced our first liquid handler in 1990 for emerging high-throughput screening applications, there was greater concern for coefficient of variation than for absolute accuracy,” says Tom Astle, president of Tomtec (Hamden, CT). “Users wanted and expected all samples to be the same. Today, with the emphasis on bioanalysis, accuracy is king.”
Issues in delivery accuracy vary depending on the type of displacement used. Air displacement, which uses disposable tips, creates the most pipetting variation, according to Mr. Astle.
With positive displacement pipetting, the piston plunges to the bottom of the tip’s orifice, so there is no air gap or dead air volume that can affect dispensing. Positive displacement delivers superior tipto- tip reproducibility, Mr. Astle says, but it requires tip cleaning, another possible source of error.
Mr. Meek mentions three factors that buyers should consider when shopping for an automated liquid handling system:
• Software versatility and ease of use: How easy is it to learn? Does the instrument come with useful software content or methods? How steep is the learning curve?
• Instrument size and configuration: Liquid handlers should not require special tables or space, or dedicated hoses or power supplies.
• Flexibility, expandability, and ability to integrate with other systems if needed. These benefits are important if labs expect increased throughput needs or if methods change.
- Enables the user to automate a single work stage or a whole application
- Features a robotic dispensing module that guarantees the results are accurate
- Includes a drag-and-drop function for easy programmability
- Racks feature a spring mechanism allowing the use of a wide range of tubes in the same rack
Automated Liquid Handler
- Handles tubes and vials up to 100 mm
- Performs automatic vial decapping and recapping
- Scans and decodes 1D/2D barcodes
- Features a rack/plate transfer station
Precision™ Microplate Pipetting System
- Unique XY transport design provides effortless 96- to 384-well plate transfers with the same pipette mechanism
- Configurable multi-station platform and powerful onboard software allow for customized applications
- Offers a variety of fluid transfer operations
- Features 19 self-interchanging and quick-swap options and a total volume range of 0.1 to 1,250μL
- Supports various procedures, from automated serial dilution and cherry picking to 96/384 plate replications
- Compact size enables the Versette to be placed virtually anywhere, from a benchtop to an enclosure
Thermo Fisher Scientific