Aspiration and dispensing of a sample fluid is carried out via a series of precise and accurate volumes in the microliter, milliliter and nanoliter range. Advancements in technology have resulted in the evolution of liquid transfer solutions, from the dispensing of sample fluid from an individual tip to large scale automated liquid handling, involving many tips, channels, robots and large workstations.

Automated liquid handling solutions are used within a variety of key industries including forensics, next generation sequencing, clinical reference, food and beverage, agriculture, drug discovery, materials, and pharmaceutical development amongst others. Automation has revolutionized the speed of scientific development, providing repeat reproducibility and a saving of time and lab resource.

Pipettes have long been used for the accurate handling of liquids in scientific research and development. Various designs enable the dispensing of liquids from smaller amounts (micropipettes) to larger volumes using syringe pumps. This technology is used in both manual and automated systems. Air placement and positive displacement pipettes are most common in manual systems, where piston air placement pipettes are used to dispense an adjustable amount of liquid from a disposable tip. Pipetting syringes handle larger volumes and are more popular in titrations and transfer of liquids.

The fundamental technology for automated is varied with pressure based liquid level detection more widespread in modern equipment.

Liquid Level Detection

Specialized consumables such as microplates and pipette tips are used within liquid handling equipment. It is important to consider the technology you wish to use, alongside researching the consumables needed to facilitate this. For example, if you wish to use a specific type of microplate, it is wise to confirm that this will interface with any new equipment, or if you wish to use disposable pipette tips – choose a liquid handling workstation that accepts these.

In order for liquid handling solutions to meet current demands, automation of pipettes and dispensers has led to the development of large scale workstations using a number of core technologies. Fundamentally liquid handling equipment can be summarized as follows:

Types of Liquid Handling Equipment

There are a number of key features/requirements to look for when purchasing new equipment. These features affect day to day liquid handling procedures, and manufacturers work to address these issues and support customers.

Key user requirements:

• accuracy
• optimal flow rate
• precision/repeatability
• ability to dispense low volumes
• minimal waste
• time and money saving
• avoidance of cross contamination
• overall speed of operation
• ability to purchase modular equipment
• consideration of space limitations (within the lab)
• high throughput facilitation
• error free solutions
• ability to track samples e.g. barcode reading and recording information
• integration with current equipment
• workflow optimization
• flexibility
• walk away capabilities

There are a number of application areas for liquid handling. For example protein crystallization, high throughput screening, high content, cellular screening, siRNA, nucleic acid preparation, PCR, ELISA, serial dilutions, time resolved fluorescence, DNA sample prep and extraction, protein separation, blood analysis and screening, ADME and SPE methods for chromatography amongst others.

Manufacturers aim to address these application areas and many offer complete solutions for specific application areas. Systems can be modular, enabling you to benefit from more than one technology listed above. Syringe pumps coupled with peristaltic flow through, for example, is popular for use with bulk microplate dispensing liquid technology. A manufacturer would design an instrument which could offer the two methods of liquid detection, and allow for the possible addition of modular components in the future, ideal for both uniformity and cost.

Simple Liquid Handling Procedures

Workstations can be used for simple procedures such as serial dilution, plate replication and reagent addition. Software is programmed to facilitate this task. Consider whether you would need an instrument solely for one procedure, such as serial dilution, or whether a larger workstation with this procedure as one option would be more appropriate. A larger workstation would take up more bench space and would be a greater investment, but may perform all the current and future tasks you would require in one instrument.

Specialized techniques

Consider whether your application would benefit from groundbreaking technology, such as ’touchless’ liquid handing. By eliminating the use of pipette tips and the adsorption of compounds during transfer, liquids can be moved by the use of sound. This acoustic technology provides a new solution for automated liquid handling, enabling increased accuracy where precise measurements are critical. Interpretation of results can be greatly relied upon using this technology as cross contamination of samples is avoided as there is no physical contact with the sample.

Collaborations between liquid handling equipment manufacturers and reagent providers

Some manufacturers have developed and validated leading protocols from reagent manufacturers on an automated platform. Examples of this are in DNA library preparation or compound dilution for pharmacokinetic studies. Sequencing sample prep solutions have been automated and adapted to enable parallel processing, whilst reducing the amount of initial sample required. Results are equivalent to that of manual methods, using less reagent and saving a great deal of time.

Integration

This is a key factor when purchasing new liquid handling equipment. Many manufacturers offer a full solution using their own equipment, and others will happily interface with third party devices. Research the various leading manufacturers to find out exactly what experience they offer with other equipment/instruments you already own such as barcode readers, cell analyzers, cell culture instruments, microplates, centrifuges, dispensers, dryers, enclosures, imagers, shakers, sealers, sample storage or microplate readers. Look for a manufacturer that has experience with a wide variety of equipment.

Sample tracking is made easier with automation. Barcoded and pipette volume data are automatically stored in files for easy access. Modular solutions can also be integrated into this process, however verify that if you add modular components to your system, that all information is recorded and stored. Manufacturers are designing these features as standard with the knowledge that as systems grow and develop, external components can be integrated with ease if necessary.

Consider your applications

Do you want to perform a specific procedure i.e. protein crystallization, or are you looking to perform a variety of procedures within a topic, e.g. next generation sequencing: sample prep, library prep, sequencing etc? There are solutions available which can perform all procedures, and software is constantly being developed to allow room for future opportunity and scope. There are also extremely specific solutions, where opportunity to develop is more limited given the parameters of the protocol. Ensure that you check these parameters and the future vision of the provider before you purchase.

Automation has enabled laboratories performing laborious tasks to achieve results in a much faster time. The future will see automation companies working with leading reagent manufacturers to automate applications. Collaborations will offer diversity and choice. Walk away solutions will develop further. Where before the user was required to monitor and carry out a process, now an automated solution can be adapted to suit individual requirements. This will enable the use of protocols which would otherwise have been impractical, adding value to the workstation and offering a new solution for the user.

Software will allow for more flexibility, enabling the customization of an instrument to meet assay requirements. Workstations are supplied with integrated software which is often upgradeable by the supplier for future requirements. However do verify the situation with software upgrades, such as whether they complimentary or paid-for.

In the future, straightforward laboratory tasks will become more automated, simplifying everyday procedures. External devices will interface with other devices and automation will become globalized and standardized, offering limitless choices for the modern lab.