**2.3. Changeable-tip transfer devices**

Based on the way the reagent is being transferred, these instruments can follow two dis‐ pensing modes: contact or non-contact (Kong et al. 2012). Contact-based devices allow the fluid to be transferred to touch the surface of the destination container or solution, offering a simple and dependable alternative to sub-microliter fluid handling. Non-contact devices uti‐ lize additional force other than gravity to eject liquids, as minute volumes cannot be dis‐ pensed efficiently with gravity alone (Kong et al. 2012). The process is faster than using permanent tips or pins (Fig.1), because there is no washing step between delivery, while re‐

**Figure 1.** Various types of liquid handling tips, pins and heads from A) washer B) pintool C) peristaltic pump-based bulk dispenser D) liquid handler with single and 8-channel pipettors E) pipettor with 8-independent channels.

The peristaltic pump is used for bulk reagent dispensing in conjunction with a nozzle head (Fig.1C) and a flexible tubing cartridge. The tubings stretch around a set of rollers connected to a motor. With the rotating motion of the motor, the rollers compress the tubings creating

Typically, this type of dispenser is capable of handling volumes as low as 5 µL, offering a fast dispensing option for 96-/384-/1536-well plate formats. The disposable tubing cartridge is pre-sterilized, and the entire liquid path can be autoclaved. Additionally, these devices are normally equipped with programing capabilities that allow discrete column-wise dis‐ pensing, variable rolling speed settings and adjustable dispensing volume. The pump can roll both forward and backwards to execute priming and emptying functions, respectively.

Fluid handlers that utilize fixed-tips (Fig.1E) are usually efficient at transferring relatively small volumes (100 µL or above) and have been largely used for compound pipetting ("cherry picking") and serial dilutions. They incorporate 2-/ 4-/ 8-channel expandable liq‐

A major limitation is the lack of capabilities to dispense into individual wells.

ducing cross-contamination and evaporation (Dunn and Feygin 2000).

**2.1. Peristaltic-based devices**

178 Drug Discovery

**2.2. Fixed-tip transfer devices**

a continuous fluid motion due to positive displacement.

The use of disposable tips (Fig.1D) is a simple alternative to avoid washing steps required for fixed-tip based systems, while eliminating completely the risk of cross-contamination. These instruments employ a conventional air displacement mechanism. A wide array of commercially-available tip sizes, materials and molding qualities offers the scientist great flexibility. There are even specialized tips with nanoliter-scale transfer capabilities that can be used in any conventional pipettor (Murthy et al. 2011; Ramírez et al. 2008).
