Technique

Dispense modes: free, contact-wet, and contact-dry, and when to use each

Whether the tip free-falls the liquid, touches a wet well, or touches a dry surface changes accuracy, contamination risk, and speed. A practical guide to the three modes.

Two liquid classes can share every flow rate and air gap and still behave differently, because the last centimeter of the transfer is not the same. How the liquid leaves the tip, whether it free-falls, meets liquid already in the well, or touches a dry surface, is its own decision inside the class, and it trades accuracy against contamination risk against speed. Here is how the three common modes differ and when each earns its place.

Free dispense

In a free dispense the tip stays above the well and the liquid free-falls in. Nothing the tip touches gets contaminated, which is what makes it possible to reuse one set of tips to dispense into many wells, and to keep a sterile transfer sterile. It needs enough speed, and often a blowout of a leading air gap, to detach the last of the liquid cleanly. The weakness is small volumes and viscous liquids: a droplet that will not fall, or one that clings and strings, shows up as a short or missing dispense.

Contact-wet dispense

In a contact-wet dispense the tip touches liquid already in the destination well, so cohesion pulls the volume out rather than force. That lets you dispense slowly and accurately, with little aerosol or bubbling, which is why it is the mode of choice when the volume has to be right and the well already holds liquid. The trade is contamination: the tip has touched the well contents, so you cannot reuse it across wells without carryover, and typically change tips between transfers.

Contact-dry dispense

A contact-dry dispense touches the tip to a dry well wall or bottom and lets the liquid wick off against the surface. It is the way to place small volumes reliably into an empty well, where a free dispense would leave a droplet hanging on the tip. It usually pairs with a tip-touch to shed the last of the liquid. Because the tip meets a dry surface rather than pooled liquid, cross-contamination risk sits between the other two modes, but a tip that touched one well should still be treated with care before it touches the next.

Multi-dispensing builds on free dispense

Aliquoting one aspiration into many wells, sometimes called multi-dispense, relies on a free dispense so the tips never touch the wells. It is fast and thrifty with tips, but the first and last aliquots from a single aspiration are the least accurate, so a well-built multi-dispense class discards a lead and trailing volume rather than delivering them. When each aliquot must be exact, a single well-by-well transfer still wins.

Choosing the mode is really choosing what you are optimizing: reuse and speed point to free dispense, accuracy into filled wells points to contact-wet, and reliable placement into empty wells points to contact-dry.

Pick the dispense mode before you tune the numbers. Half the parameters in a class only make sense once you know whether the tip touches the well.
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