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Successfully Maintaining Automated Liquid Handlers

Liquid handlers require regular maintenance for consistent, reliable results

by
Sachin Rawat

Sachin Rawat is a freelance science and tech writer based in Bangalore. He holds a master’s degree in biotechnology. Find him on X (Twitter) at @sachinxr.

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Most operations in a laboratory involve moving around various amounts of liquids. While manually doing this is practical for smaller experiments, biology is increasingly high throughput. Experiments in fields like omics, pharma, and systems biology involve parallel handling of hundreds or thousands of samples.

Unlike manual pipetting, automated liquid handling systems can do this quickly, allowing researchers to spend more time on other tasks. Capable of sophisticated operations like reformatting, cherry-picking, and aliquoting, they are also cost-efficient and offer high repeatability and precision. 

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However, automation doesn’t necessarily mean error-free, and care needs to be taken to ensure the reliable operation of automated liquid handlers (ALHs).

Common problems with ALHs

Over time, wear and tear lowers the accuracy of liquid handling systems. These are often visible on closer inspection as kinks or bends in the tubings, loose fittings, uneven heights of the pipette tips, and obstructions to moving parts. Otherwise, uneven dispensing or errors in liquid transfers along the edges or in particular rows or columns of microtiter plates could hint at malfunctioning of certain parts. 

Errors in liquid transfer also show up as random or periodic variability in data or loss of signal over time. If unnoticed, these errors could propagate to downstream operations, wasting time and resources. Routine maintenance can prevent these errors from creeping in.

Contamination is a major problem with automated liquid handling systems.

Contamination is a major problem with automated liquid handling systems. Reagent residues may build up on pipette tips, or some liquid may carry over from one step to the next. Another common problem is that they might aspire or disperse incorrect volumes. This could be due to prolonged shear forces on the pipette tips, reagent build up, or environmental factors. For example, humidity, temperature, and vibrations can alter liquid properties, leading to variations in measurements from different batches or machines. Minimizing these disturbances in the laboratory space and following best practices in handling ALHs are key to extracting the most value from them.

Best practices for maintaining ALHs

To prevent contamination from the residual reagents, permanent pipette tips should be cleaned regularly. In protocols that require sequential dispensing steps, adequate cleaning between the transfers prevents carryover contamination. If the liquid handler uses disposable pipette tips, choosing the appropriate pipette tip based on the properties of the liquid lowers the risk of contamination.

Pipetting parameters should also be adjusted according to the type of sample. For example, using a lower flower rate when aspiring high-viscosity liquids prevents the formation of air bubbles, ensuring accurate volumes. Likewise, a higher blowout air volume ensures that sticky liquids don’t remain in the pipette tips.

To ensure that liquid handlers are transferring the correct volume, it’s important to monitor their performance. Two common methods are gravimetric and photometric measurements. The gravimetric method involves measuring the weight of the liquid to verify if the correct volume has been transferred. On the other hand, photometric methods involve adding a dye and measuring its fluorescence to verify the volume. The latter method has the advantage of testing directly in the labware.

Lastly, to prevent costly repairs, moving parts of liquid handling systems should be routinely inspected, and components like tubes, valves, and pumps replaced when necessary. Following best practices and regular maintenance ensures that automated liquid handling systems deliver reliable and reproducible data.