Low volumes are where a liquid class is most easily embarrassed. Asking a channel built for a milliliter to place a couple of microliters means resolving a tiny fraction of its range, and at that scale every small error becomes a large percentage. Handling 0.5 to 20 microliters well takes deliberate choices, not just a smaller number in the volume field.
Match the tip to the volume
The single biggest help is a smaller tip. Dispensing a few microliters from a 1000 microliter tip wastes the resolution of the instrument; a 50 microliter tip brings the target back into a range the hardware can actually control. If a protocol spans a wide range, accept using more than one tip and more than one class rather than forcing the largest tip to do delicate work.
Dispense to the surface, and single-dispense if you can
At low volume a free-falling drop may never leave the tip, so a surface-empty dispense that touches the liquid or well is more reliable. A single dispense, rather than aliquoting, also removes a source of variability you do not need when the volumes are already hard.
Turn off liquid following, keep the tip close
Following the liquid level down can do more harm than good at these volumes, so it is often best turned off. Keep the distance between the tip and the pipetting surface small, without blocking the tip, so the short transfer stays controlled.
Give it time, and mind capillary action
Small volumes benefit from a longer settling time so the tiny column can equalize, and from slow swap speeds on the way out. Watch for capillary action, too: at 10 or 50 microliters a liquid that wicks up the tip on its own can pull in more than you asked for, so tune the blowout to prevent capillary over-aspiration.
- Use 50 microliter tips rather than large channels for 0.5 to 20 microliters.
- Prefer a single, surface-empty dispense.
- Turn liquid following off and keep the tip near the surface.
- Lengthen settling time, slow the swap speed, and tune blowout for capillary effects.
At low volume, the tip matters more than the setting. Right-size the tip first, then tune, and the small transfers stop fighting you.