A requirement for higher throughput is often the main reason for researchers to consider using automation. However, another critically important property of automated platforms is their capacity to improve the consistency of results. By vastly outperforming humans in terms of both repeatability and reproducibility, automated liquid handlers streamline laboratory workflows through greater data accuracy and precision. It is this superior consistency that, in turn, enables researchers to scale up throughput. This article explains why you should think about using an automated liquid handler, how these instruments work, and suggests some key features to look for when choosing an automated liquid handling platform to support your research.
Regardless of the level of throughput, automation can always improve experimental consistency. Manual pipetting is associated with a high risk of operator-related variability that can be monitored by two key performance indicators, namely repeatability: the comparability of results when an assay is run by one individual over time; and reproducibility: the comparability of results when an assay is run by different individuals. By using an automated liquid handler to perform and keep track of the different steps in a method, operator-related variability can be reduced or completely removed, saving researchers time, money, and sample material since experiments no longer need to be repeated.
The level of automation that is introduced will depend largely on the nature of the workflow. Where a workflow is of moderate throughput, semi-automation offers a way for researchers to incrementally scale up production and improve the consistency of results. Full automation is instead most valuable in applications that benefit from completely removing human movements. Here, it allows for processing of hundreds of samples at a time by following complex methods without deviation, while also reducing the likelihood of repetitive stress injuries and providing protection against hazardous or infectious material such as SARS-CoV-2.
A typical automated liquid handler comprises hardware to physically transfer liquids between different types of labware that have been placed on the instrument’s deck, and software to control and direct the various movements. Fundamental to this are the channels—pipettes equipped with high precision motors and electronics that pick up disposable tips (or can be fitted with reusable needles) before aspirating a liquid from its source and dispensing it to the relevant labware. An automated liquid handler can have anywhere from one independent pipette channel to 384 pipette channels on a probe head, with channel size varying from <1 µL to 5 mL; these can usually be alternated to meet diverse user requirements. Although many automated pipetting channels are liquid-filled, systems based on air displacement are preferred as they prevent carryover.
In addition to air displacement pipetting, another way of reducing the risk of cross-contamination is to choose an automated liquid handling platform that offers sensor-based capacitive liquid level detection. By ensuring pipette tips are inserted into liquids at the correct depth during aspiration and dispense steps, this avoids the accumulation of droplets on the tip surface that can subsequently be transferred to other samples.
For easier integration into laboratory workflows, it is sensible to select an automated liquid handling platform equipped with pre-defined liquid classes. By leveraging information about the properties of different liquids, and how those properties are affected by environmental conditions such as temperature, humidity, or atmospheric pressure, such platforms are more likely to achieve a successful transfer. For instance, an instrument programmed to transfer a high viscosity liquid such as glycerin may employ a lower flow rate, whereas a pre-aspiration mix step might be performed where liquids with different densities have been combined in the same well.
A further use of the liquid class is to dictate the method settings—clearly defined parameters for every aspiration and dispense step in a method that control the physical approach of the channel and tip based on the requirements for each individual transfer. Method settings include liquid level detection, liquid following, pre-wetting, anti-droplet control, and single versus multiple use of tips; used in conjunction with the liquid class data, they provide researchers with a strong starting point from which to set up their particular workflow.
Image: Monitored air displacement (MAD) offers real-time detection of clogs and pipetting errors
Image: Total aspiration and dispense monitoring (TADM) verifies the sample transfer with a traceable digital audit trail.
Another valuable feature to consider when selecting an automated liquid handler is whether it includes process controls such as monitored air displacement (MAD) or total air displacement monitoring (TADM) for assessing liquid transfers. These are especially useful for setting up challenging liquid handling activities like low volume pipetting, multi-dispensing/aliquoting, and serial dilution since they provide proof that transfers have taken place as expected.
To learn more about automated liquid handling and how it can benefit your workflow, visit hamiltoncompany.com