Underneath the tips, liquid handlers come in two fluidic architectures, and which one you are on decides what a liquid class can and cannot do. One moves liquid with a cushion of air behind a disposable tip. The other fills the whole path with a liquid and pushes on that. They aspirate the same microliters but they fail in different ways, and they demand different habits.
Air displacement
Air displacement is the familiar case: a disposable tip, a column of air between the plunger and the liquid, and a plunger that moves a measured volume. The air cushion is a spring, which is both the strength and the weakness. It covers a wide volume range and, because the tip is disposable, it eliminates carryover by throwing the contamination away. But the compressible air also means viscous and volatile liquids need careful tuning, because the cushion lags behind the plunger just when you need the volume to be exact.
Positive displacement and system liquid
The other architecture fills the tubing, valves, and often a fixed steel tip with a continuous liquid, the system liquid, and drives the transfer by moving that liquid with a syringe. There is no compressible air cushion, so the response is direct and repeatable, which helps with hard liquids. The cost is that the sample now shares a fluidic path with the system liquid, separated only by a small air gap, and fixed tips must be washed rather than discarded, so carryover becomes something you manage instead of something you avoid by default.
Living with system liquid
System liquid, usually degassed water, is part of the instrument, and treating it carelessly undermines every class you build on it.
- Degas it: dissolved air forms bubbles in the line, and a bubble is a spring that ruins volume accuracy exactly like an unwanted air cushion.
- Keep it clean and fresh: the system liquid touches every transfer through the fluidic path, so contamination or growth in the reservoir reaches your samples.
- Mind the transport air gap: the small air gap between system liquid and sample stops them mixing, and its size is part of the class, not an afterthought.
- Prime and wash deliberately: bubbles trapped at startup and residue between samples are both defeated by proper priming and wash steps, which belong in the method.
Which to reach for
Air displacement with disposable tips is the safer default when cross-contamination is the enemy and your liquids are reasonably behaved across a wide range of volumes. Fixed tips with system liquid earn their keep when you want the directness of an incompressible path, high-throughput washing is acceptable, and the consumable cost of disposable tips at scale is a real concern. Many labs run both, and the important thing is to know which one a given class was built for.
A class tuned for an air cushion does not transfer to a system-liquid path, and vice versa. The fluidic architecture is part of a class context, not a detail.