At first, an automated liquid handling system might seem complicated and overwhelming. But once you have started working with these devices, you will realize how they simplify your workflow. Engineers have developed many different features to facilitate challenging applications.
When handling small volumes with automated liquid handling systems, it is possible to aspirate all reagents needed for the reaction in one tip, separated by an air-gap. This technique is widely discussed, especially in terms of contamination of the different liquids by drops on the outside of the pipette tip. Some manufacturers recommend this anyway to save time and effort1. The systems can aspirate the water first, followed by reagent A, then reagent B, etc. Each liquid layer is separated with an air gap to prevent mixing or the reaction starting inside the tip. When the liquid is dispensed, all reagents are mixed directly and the smallest volumes are washed out of the tip by the larger volumes in the tip. The tip should be changed after every pipetting step.
A better option is to use special tools optimized for small volumes, e.g., for transferring volumes of 1 µL in free-jet dispensing. This increases speed and avoids cross-contamination. If volumes below 1 µl are pipetted, it is better to dispense directly into a target liquid or against the vessel surface to dispense the whole volume. Dispensing small volumes with liquid contact is also recommended when challenging liquids such as viscous liquids are pipetted.
Another very helpful feature of automated liquid handling systems is tip dipping. When only 1 µL sample is aspirated into the tip, the liquid drop often sticks to the outside of the tip during dispensing. It is possible to program the tip to dip into the liquid in the well so that drops and micro-drops on the outside surface of the tip reach the reaction.
Furthermore, setting the aspiration and dispensing speed as well as the blow-out volume and speed helps too. The perfect speed for each type of liquid and volume can be programmed. And setting these parameters leads to highly reproducible results because we pipette at different speed every day depending on our personal performance. Automated liquid handling can ease your mind and increase trust in challenging applications by taking over the annoying parts.
1 Astle T W, Small Volume Pipetting, technical report. 1998. Journal of the Association for Laboratory Automation. Vol. 3 No 3, July 1998