**2. Types of liquid handling devices**

A whole array of liquid handlers has been developed for every aspect of drug discovery. These instruments encompass different technologies for distinct purposes. In terms of appli‐ cation, they are broadly classified as bulk liquid dispensers, transfer devices and plate wash‐ ers (Rudnicki and Johnston 2009).

© 2013 Chai et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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

uid handling arms in addition to 96- and 384-channel heads. This type of liquid handling device functions based on air displacement mechanism. The dilutor or syringe plunger pulls system liquid from the pipette tubing to aspirate the sample, with an air gap sepa‐ rating both fluids. The plunger speed, syringe size and resolution are factors that affect

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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

Pintool is a contact-based dispensing method widely used for handling volumes at the nanoliter scale (Cleveland and Koutz 2005). It consists of a set of stainless steel pins (Fig. 1B) carefully crafted for consistent dimensions. The bottom end of the pins can be solid, grooved or slotted, with the option of having a hydrophobic coating to prevent non-specific binding (Dunn and Feygin 2000; Rudnicki and Johnston 2009). Solutions are transferred through a combination of capillary action and surface tension, with the volume being highly depend‐ ent on the contact surfaces and solution properties (Dunn and Feygin 2000). The pin array is normally assembled in a floating pin cassette to ensure soaking of all the pins amid uneven surfaces, which also minimizes pin damage. After liquid transfer, the pins have to cycle

The piezoelectric dispenser is a non-contact technology, where solutions are delivered as multiple tiny drops of defined size (Niles and Coassin 2005). This technology has been uti‐ lized in contemporary inject printers and refined to be implemented in the biological scien‐ ces. Various biochemical solutions (DNA, RNA, proteins) and bacterial suspensions have been tested with no negative effects (Schober et al. 1993). The system is composed of a capil‐ lary tube made of quartz or steel, with one end connected to the reagent reservoir and the other end ending in an orifice from which droplets are ejected (Niles and Coassin 2005). A piezoelectric crystal collar is bound to the capillary, which is filled with solution. Upon volt‐ age application, the piezoelectric element contracts causing pressure on the capillary to gen‐ erate fine drops. The ejection is at high acceleration with minimal wetting of the nozzle (Schober et al. 1993). Several thousand drops can be dispensed per second, with attainable drop sizes spanning the picoliter and nanoliter range (Schober et al. 1993). Droplet volume depends on several factors, including bore diameter, solution viscosity and the voltage pulse

be used in any conventional pipettor (Murthy et al. 2011; Ramírez et al. 2008).

through washing steps to prevent cross-contamination.

amplitude and frequency (James and Papen 1998; Kong et al. 2012).

pipetting flow rate.

**2.3. Changeable-tip transfer devices**

**2.4. Pintool transfer devices**

**2.5. Piezoelectric devices**

**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.

#### **2.1. Peristaltic-based devices**

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 a continuous fluid motion due to positive displacement.

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

#### **2.2. Fixed-tip transfer devices**

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‐ uid handling arms in addition to 96- and 384-channel heads. This type of liquid handling device functions based on air displacement mechanism. The dilutor or syringe plunger pulls system liquid from the pipette tubing to aspirate the sample, with an air gap sepa‐ rating both fluids. The plunger speed, syringe size and resolution are factors that affect pipetting flow rate.
