Contamination occurs when droplets are formed at the end of a tip, when aerosols are formed during the application and so on.
The droplets are a problem that can and must be prevented. The way to do this is by aspirating a transport airgap when traveling across the deck with liquid in the tip. This is a standard point in optimization as the transport airgap varies in size depending on a few factors (type of liquid in the tip, volume in the tip, volume to be dispensed etc.).
Aerosol formation is harder to prevent, especially in very sensitive applications. However, most liquid handlers can be equipped with a HEPA filtration unit, UV lights and other additional features to keep the system as clean as possible.
In a system, contamination is formed when the sample is aspirated into the system. A liquid handler using disposable tips will only aspirate samples in that tip. This ensures no samples in the system itself. From a manual experience, many users are persuaded to use filtered tips, also on a liquid handler. However, opposed to working manually, if the system is optimized and used correctly, there is no need for filtered tips for 99% of the applications.
In systems without a disposable tip, needles or nozzles are used to aspirate and dispense. There is a higher risk of contamination using this technique, but it does make washing easier. In regards to using nozzles, the main source of contamination is found in all connection points and especially in valves if not washed correctly.