How to Buy Liquid Handling Technology



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Liquid handling options span the range from simple or automated pipettes to room-sized multifunctional workstations. Consequently, choosing the right equipment for your requirements can be challenging.

In this guide, learn about the key technologies, important considerations to take into account when planning your purchase, different applications and the future of liquid handling.

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1. Introduction

Precise and accurate delivery of samples and reagents is fundamental for many sensitive techniques employed in today’s laboratories. Liquid handling devices draw in (aspirate) a given volume of liquid from a source container and deliver (dispense) this liquid to the destination container once it has been appropriately re-positioned. The fluid being transferred, often referred to as the sample fluid, is frequently held in tips. These tips can either be permanent features of the liquid handler or disposable pieces.

PAdvancements 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. Aspiration and dispensing of sample fluid is typically carried out in the microliter, milliliter and nanoliter range. However, it is also possible to dispense volumes in the picoliter range, and even femtoliter dispensing is being used, for microarray applications.

Automated liquid handling has evolved rapidly since its first use in the late 1980s and 1990s, with the need for very high throughput drug screening by the pharmaceutical industry and genomic sequencing studies.

Today, automated liquid handling systems are used within a variety of key industries, including forensics, pharmaceutical drug discovery and development, molecular biology, food and beverage, agriculture, materials science, and clinical diagnostics. Recent optimizations of liquid handling technology, often with add-on features, enable a number of different techniques to be performed in these industries, as shown in Table 1. Some of these are discussed further in the ‘Application Specific Workflows’.

Table 1. Technique Optimizations of Liquid Handling Technology
Industry Techniques
Pharmaceutical – Discovery & Development ADME-Tox Screening
Bioprocessing
Cell Based Assays
Chromatography
Compound Management
High Content Screening
High-Throughput Screening
Imaging- Fluorescence / Microscopy
Immunoassays
Mass Spectrometry
Next Generation Sequencing
PCR
Nucleic Acid Preparation
Protein Purification / Crystallization
Solid-Phase Extraction
Clinical Diagnostics / Forensics Blood Analysis Blood Analysis
Chromatography
Immunoassays
Mass Spectrometry
Next Generation Sequencing
Nucleic Acid Preparation
PCR
Molecular Biology / Basic Research Chromatography Cell Based Assays
Cell Culture
Chromatography
Next Generation Sequencing
Nucleic Acid Preparation
Protein Purification / Crystallization
PCR
Transfection
Analytical Chemistry (Forensics, Food & Beverage, Environmental, Material Science, Pharmaceutical) Chromatography
Mass Spectrometry
Next Generation Sequencing
Nucleic Acid Preparation
PCR
Processing
Solid-Phase Extraction
Titration

Automation has revolutionized the speed of scientific development, providing greater reproducibility and saving time and laboratory resources. While every automated liquid handling experiment is unique, for example in terms of throughput, reagents, volumes, order of addition and readout, there are several features that are central to all liquid handling technologies.

2. Key Pipette Technology

Pipettes have long been used for the accurate handling of liquids in scientific research and development. The introduction of automatic pipetting devices has revolutionized liquid handling procedures in the laboratory, and they offer many advantages over traditional glass pipettes, including improved reproducibility, speed, safety and ease of use. A considerable variety of pipettes are currently on the market, ranging from the fixed-volume, single-channel, manually operated pipettes to the latest electronic multi-channel instruments with fixed- or variable-volume settings. The majority of pipettes function according to one of two dispensing principles:

In air-displacement pipettes, which are used for standard applications, a ‘piston’ (see section on ‘fluid drive technology’ below) creates the suction necessary to draw the sample fluid into a disposable tip. The influences of temperature, air pressure and humidity must be minimized with an air-displacement pipette through design measures to ensure the dispensing accuracy is not impaired.

Air-displacement pipettes are commonly found in standard laboratories and are designed for general laboratory procedures.

In positive displacement pipettes, which are often used for applications requiring greater accuracy, sample fluid is delivered by means of a syringe-like system in the pipette tip. In these pipettes, the piston and sample are in direct contact, enabling high levels of accuracy and reproducibility, as well as minimal liquid carryover. As the piston is a disposable part of the pipette tip, the risk of cross-contamination is eliminated.

Positive displacement pipettes are commonly used for liquids with too high a vapor pressure, viscosity or density to be displaced accurately by air, as well as volatile, radioactive or corrosive samples. These devices are also suitable for applications such as polymerase chain reaction (PCR) protocols.

TIP: What type of liquid are you trying to dispense? What accuracy is required? Consider contamination - do you need to switch between applications, liquid types etc.?

Manual or Electronic Pipettes?

Consider whether a manual or electronic pipette is more appropriate for your needs.

Generally, manual pipettes are more robust and are therefore well suited to everyday use. They are often very easy to calibrate and most suited to research labs that do not require high-throughput processing. The latest manual pipettes are made with comfort and reliability in mind, for example Acura® manual micropipettes from Socorex Isba SA. In addition to ergonomic design, the Acura® manual pipettes incorporate an integrated calibration system to greatly facilitate this process, and a patented adjustable tip ejection mechanism that enables tips from various manufacturers to be used. Other examples of manual pipettes include the new Tacta range of mechanical pipettes from Sartorius Group and the ultra-light Eppendorf Research® plus pipette. 

Flexibility should be considered when purchasing your pipette: is it easy to switch between different applications or solutions? Is the pipette autoclavable? Do you need a single-channel, multi-channel or fixed volume pipette? Which pipette tips are compatible?

Electronic pipettes require less force and fewer hand movements, which reduces the risk of repetitive strain injuries. Accuracy and precision are often enhanced as there is less chance of human error. The Socorex Acura® electro series of electronic pipettes, shown in Figure 1, is highly versatile, with 27 different interchangeable volumetric modules available for single and multichannel pipetting in a number of different working modes. In addition to the traditional working modes such as forward, reverse, step and dilution, the Acura® electro series offers tactile mode, which enables you to monitor aspiration and distribution and is useful for titration or measurement of unknown sample volumes. These pipettes also offer easy battery charging. 

Figure 1: The Acura® electro 926/936/956 by Socorex

Another example of an electronic pipette is the PIPETMAN® M from Gilson, Inc. The recently updated version of this pipette range features a personalized pipetting mode that enables users to create pipetting protocols easily and rapidly for applications including qPCR, ELISA, next-generation sequencing (NGS) and cell culture, among others. Bridging the gap between a handheld electronic pipette and a fully automated system is the VIAFLO range of dispensers from INTEGRA Biosciences. These systems give labs the flexibility to automate certain processes without the need for purchasing a huge fully integrated multi-modular system. Learn how the VIAFLO ASSIST is used to automate assay development in the video, Figure 2.

Figure 2: Dr Lisa Stehno-Bittel, President & Co-founder of Likarda, discusses how the company employs the VIAFLO ASSIST in early stage drug discovery

TIP: Consider ergonomic design and the frequency of use.

Adjustable or Fixed Volume Pipette

Another factor you will need to consider is whether you require an adjustable or fixed volume pipette. This consideration will very much depend upon the accuracy required. The most common type of pipettes can be set to a specific volume within their operational range and are known as adjustable pipettes. These limits must be adhered to, as these pipettes are prone to damage if they are adjusted too far above or below the volume range. The volume of a fixed volume pipette, as its name suggests, cannot be changed. Because the mechanisms within fixed volume pipettes are less complex, they often result in more accurate volume measurements as volumes cannot be changed in error.

Green Sub-Heading for Use Within Sections

The decision of whether to purchase a single-channel pipette or multi-channel pipette is dependent upon the volume to be dispensed and the number of repeats. For manual high-throughput applications, such as preparing a 96-well microtiter plate, most researchers prefer a multi-channel pipette. Instead of handling well by well, a row of eight wells can be handled at the same time as this type of pipette has eight pistons (see section on ‘fluid drive technology’ below) in parallel. Many models incorporate simple mechanisms to adjust tip spacing on the pipette, to enable pipetting between plates, tubes and other labware of different sizes. The new generation of VOYAGER II pipettes from INTEGRA Biosciences incorporates motorized tip spacing to optimize this process.

There are also specialized pipettes available that are optimized for specific applications such as sample dilution or repeating working steps. The Acura® manual 810 from Socorex is an example of a dilution pipette. This unique straw pipette has two pre-calibrated steps that enable subsequent pipetting of 1 and 0.1 mL of the same liquid, ideal for performing serial 1:10 dilutions in bacteriology. Repeater pipettes can dispense a specific volume, such as 20 µL, several times from a single aspiration of a larger volume. In general, they have specific tips that do not fit on normal pipettes, although some electronic pipettes are able to perform this function using standard tips.

Bottle top dispensers are also available to meet the needs of a broad range of applications in biology, pharmaceutical, clinical, chemical and forensic labs. These simple dispensers are designed for safe and reproducible handling of liquid reagents, including acids, bases or solvents, from a variety of bottles and flasks. Socorex’s Calibrex™ range of bottle top dispensers, for example, contains a number of different models capable of dispensing volumes between 0.1 mL and 100 mL. To ensure optimum working conditions, it is critical that you routinely maintain and clean your dispenser, the Calibrex™ dispenser can be fully disassembled without any tool to simplify this process.

TIP: Consider how easily the pipette can be calibrated, a method usually achieved through gravimetric analysis. When buying a pipette, you should discuss calibration protocols with the manufacturer.

3. Automated Liquid Handler Technology

In order for liquid handling solutions to meet the demands of today’s laboratories, automation of pipettes has led to the development of large workstations using a number of core technologies. Fundamentally, liquid handling systems can be categorized as automated dispensers, robotic workstations or fully integrated workstations. The technologies and considerations underlying each of these instrument types are outlined below.

Bench-Top Semi-Automatic Pipettors

There are many bench-top semi-automated pipettors available; these offer a more efficient method than manual pipetting that can also help to reduce the risk of repetitive strain disorder. These systems aim to bridge the gap between manual pipettes and a fully automated system, and are designed to provide fast and precise processing of 96- and 384-well microplates, without the requirement of a computer. For example, the CyBio® SELMA semi-automatic pipettor, from Analytik Jena Life Science, is designed to fill 96 and 384-well microplate formats in seconds. Another option is the Eppendorf epMotion® 96, shown in Figure 3, which has a large volume range between 0.5 µL and 300 µL using only one head or system, eliminating the need to switch pipette heads or employ a second device to achieve all volumes. Semi-automatic pipettors also have the open flexibility of linking to external devices such as shakers, heating adapters, etc. See more in the SelectScience pipette directory.

Figure 3: The Eppendorf epMotion® 96 semi-automatic pipettor

Automated Dispensers

Automated dispensers are designed to deliver precise and measured quantities of liquid to a receptor vessel, such as a microplate. These instruments range from single-channel devices, which dispense one volume at a time, to multi-channel devices, capable of dispensing up to 1,536 aliquots simultaneously, such as the CyBio® Well Vario from Analytik Jena Life Science.

Single-channel instruments were the original automated liquid handling systems and are still commercially available today. The main advantage of single-channel instruments is flexibility, but as a result of only having one channel, they do have throughput limitations. Currently, multi-channel systems make up the majority of automated liquid handlers produced.

TIP: Consider the volume range you require in a liquid handler. Many modern liquid handlers are capable of delivering a wide range of volumes, making them suitable for several applications.

Multi-channel systems with a small number of channels (4, 8, 10, 12 or 16) are generally more flexible than systems with a larger number of channels. This is because the spacing between the channels can usually be adjusted, making them suitable for more applications. These channels are built into a structure known as a ‘head’, with permanent spacing matching the spacing of the wells in the microplate. In drug discovery, low volume automated liquid dispensers are routinely used for high-throughput content and compound screening. For example, TTP Labtech’s latest offering, the dragonfly® discovery, Figure 4, uses novel liquid handling technology to address the drug discovery workflow, from assay development and validation to high-throughput screening (HTS), hit-to-lead (H2L) and lead optimization. The system can dispense non-contact volumes of 200 nL to 4 mL of any liquid class from positive displacement disposable tips into 1536, 384 and 96-well plates, enabling complex gradients, randomized dispensing patterns and dilutions to be performed.

Figure 4: Joby Jenkins, TTP Labtech, explains the features of the new dragonfly® discovery liquid handler

The majority of automated dispensers employ a piston or syringe pump for operation, but other types of fluid drive technology can be used. Liquid level detection is an important component of all of today’s liquid handlers. Traditional capacitive liquid level detection is still most commonly used to determine when the tip is submerged in liquid. Data software can determine the height of the liquid surface and take appropriate action. An alternative to capacitive liquid sensing is pressure-based liquid level detection, which can be used to determine the level of non-ionic liquids. Using this method, data from the pressure sensor changes as the tip approaches the liquid surface, touches the surface and drives below. This data can then be used to control pipetting in real time. Other pipetting systems utilize optical sensor technology for liquid level detection.

Robotic Workstations

More complex systems with built-in robotic functionality have been developed to manipulate the position of the dispensers and/or containers of liquid handling systems. It is the ability to move and carry out additional functions that differentiates these systems from automated dispensers. Robotic workstations allow for more automation than can be achieved with a static liquid handler.

Systems that can move slides, tubes or microplates, for example, tend to be more mechanically complex and consequently can be quite sizeable. While large, complex liquid handlers still dominate large industrial and academic projects, the industry is moving towards more compact, modular automated liquid handling systems. Larger systems with more complex functionality often create issues around movement and vibration, which can have a detrimental effect on reliability and accuracy.

TIP: Consider how much of your laboratory space can be dedicated to your new instrument and whether you will need space for additional modules.

TIP: Most manufacturers will have undertaken stringent procedures to ensure vibration is kept to a minimum, but it is worth discussing this with the supplier before purchasing an instrument.

Fully Integrated Workstations

Fully integrated workstations may enable the integration of additional laboratory devices, such as centrifuges, microplate readers, PCR instruments, colony pickers, heat sealers, shaking modules, barcode readers, spectrophotometric devices, storage devices and incubators. More complex liquid handling workstations can perform multiple laboratory unit operations, such as sample transport, sample mixing, manipulation and incubation, as well as transporting vessels to/from other workstations.

When purchasing an automated liquid handling system, it is important to establish just how flexible you need it to be. Most researchers seek a system that can grow with the laboratory’s needs, for example, in response to changes in throughput and application. In order for a system to meet with your changing requirements, you will need to investigate the potential for upgradability. The Freedom EVO® Workstation series from Tecan, Figure 5, for example, offers a number of different base units and flexible workflow options.

Figure 5: The Tecan Freedom EVO® Workstation can be upgraded to meet current and future laboratory needs

The most common functions of integrated liquid handling workstations include nucleic acid preparation, PCR, next-generation sequencing, ELISA, time-resolved fluorescence, HTS, assay automation, protein crystallography, solid-phase extraction and liquid-liquid extraction. Multi-functional (modular) workstations enable a number of different applications to be performed and provide even greater flexibility.

TIP: When choosing an automated liquid handling system, it is important to consider both your current and future application requirements. If you intend to customize your liquid handler and integrate other modules, such as microplate readers and PCR instruments, you will need to discuss its compatibility with the manufacturer.

Other General Considerations for Automated Liquid Handlers

In recent years, assay miniaturization, which provides a number of cost and time-saving benefits for the research and drug discovery industry, has been a real driving force in the evolution of liquid handling systems. Such benefits include a reduction in the amount of valuable compounds and reagents per assay, which enables an increase in the assay range and size to be achieved, providing a greater amount of information per screen. Microliter-size assays are now routine, with PCR often employing nanoliter or picoliter reaction volumes, and microarraying striving for femtoliter dispensing.

Reduced volumes increase an assay’s volumetric complexity, and inaccuracies that may occur when dispensing low volumes can become proportionally magnified. The development of acoustic liquid handling also provides a solution to inaccuracies that can occur when dispensing low volumes. These automated systems use acoustic energy, through sound waves, to eject precisely-sized droplets from a source onto a microplate, slide or another surface suspended above the source. The Labcyte Inc. Echo® 500 Series of liquid handlers utilizes ultrasonic acoustic energy technology for accurate liquid transfer and is suitable for applications in compound management, genomics, proteomics, and diagnostics.

Liquid handling quality assurance is an extremely important factor to consider for most applications, and is particularly important for critical drug discovery processes. Due to the minute volumes typically handled during HTS and other drug discovery phases, inaccuracies of just one microliter can affect the integrity of the process by producing false positive and false negative results. Identifying and correcting any liquid handling error can save scientists in any field time, money and resources. New technologies are now available for rapid and reproducible assessment of the accuracy and precision of volumes dispensed from automatic instrumentation.

TIP: Ensure you have stringent quality assurance procedures in place. In addition, you should ask the manufacturer what assay validation data is available for a specific liquid handler. This will provide you with proof that the instrument performs as indicated.

Another important consideration that should be investigated when choosing a liquid handler is its flow rate spectrum. Most liquid handlers will have adjustable flow rates that cover a relatively large range. It is important to ensure that this range covers the flow rate you require for your applications. Higher flow rates are likely to be required for applications such as sensitive cell based assays, while slower flow rates may be necessary for viscous fluids or chromatographic assays.

TIP: How sensitive is your application and operation to downtime? If you need constant operation, you may want to consider purchasing more than one liquid handler.

Robust software that does not crash is essential for walk-away liquid handling. Most robotic software has a consistent and intuitive graphical user interface to control all movement and pipetting procedures of your workstation.

TIP: You should look for software that is user friendly and versatile, but does not require any extensive programming skills. Start-up screens or wizards to guide users through their daily routines can be extremely helpful. Free software upgrades are also essential.

TIP: Also consider the location of the manufacturer. Adequate support for your liquid handler in your country is an essential requirement.

Software that enables scheduling of the workflow may be beneficial for very high throughput procedures and walk-away liquid handling. Some applications may benefit from features such as tip touch, multi-target dispensing, timing procedures and complete control over accessories. The software should be able to be integrated with other software and allow interaction with peripheral devices such as barcode readers, shakers and incubators. Some software packages support FDA regulation requirements for multilevel user management, full audit trail, electronic records and electronic signatures. Being able to ‘walk-away’ and leave your instrument to do its required handling job, and trust that it is not contaminating samples or losing tips and is dispensing accurately, is essential.

Specialized consumables, such as microplates and pipette tips, are used within liquid handling equipment. Consider which consumables are required for your applications and ensure these can be used with your instrument.

Cross-contamination can occur when the sample fluid is not sufficiently emptied from the tip. Some automated liquid handlers use fixed tips, which significantly reduce consumable costs. However, if you choose to use fixed-tip transfer devices, you will need to investigate washing procedures recommended for the instrument. An alternative to fixed tips is the use of disposable tips, which removes the need for time-consuming washing steps. Many manufacturers claim that disposable tips completely eliminate cross-contamination, but this should be read with caution. During tip ejection, disposable tips can produce aerosols, which potentially lead to cross-contamination. Aerosol production results from displacement of residual liquid in the tip by the high force loads typically required for tip injection.

4. Fluid Drive Technology

Pumping liquid in accurate measures is fundamental to all automated liquid handling systems. There are a few types of pump that might be used, thus you should consider the dispenser type that best suits your requirements. The most common type of pump used in liquid handling systems is a piston pump, also known as a syringe pump. In automated liquid handling systems, piston pumps can take many forms. Table 2 below provides details of the different types of pumps and their features and considerations.

TIP: When purchasing a liquid handling system, you should ask the manufacturer which types of dispensing technology or pumps are employed.

Table 2. The different types of pumps used in liquid handling instrumentation and their features
Pump Types Displacement System Features / Considerations
Piston (Syringe) Pumps Air-displacement System Inherent gap of air that functions as the working fluid (see air displacement pipettes)
Liquid or Hydraulic Displacement System Connected via tubing
Pre-loading liquid acts as the working fluid
Continuous Flow (Check Valve) System Two or more pistons are arranged so that some pistons are dispensing, others are drawing in fluid. Uses check valves to limit flow to one direction and provide continuous flow
Diaphragm Pumps Single directional pumping Check valves are used to maintain fluid flow in one direction
Simple spinning motor can be used to generate the reciprocating motion
Bi-directional pumping (two diaphragm pumps) Two diaphragm pumps
Peristaltic Pumps Roller squeezes a liquid-containing flexible tube Minimal cross-contamination
Lack of accuracy
Pulsed flow – use control loops that can handle such variable loading dynamics
Fluid output is not as constant as piston pumps
Pressure Driven Pump Systems Small, inexpensive air pumps or pressurized reservoirs create the vacuum for suction or pressure for dispensing
Pumps are typically mounted just above the tips
Active valve and pressure-sensing technology with advanced feedback-control algorithms that utilize the data collected from the pressure sensors to control the valves and pumps
Next-Generation Sequencing

Piston-based pumps are used in the majority of modern automated liquid handling systems.

5. Application Specific Workflows

Many of the general considerations highlighted in the previous section of the guide, including required volume range, flow rate and throughput, will be largely dependent on your application. Although these considerations will be influenced by your application, they are applicable for all scientists looking to purchase liquid handling equipment. This section of the guide takes a more in-depth look at specific applications performed by liquid handling equipment and discusses some of the factors that should be considered when implementing technology for a specific application.

Biological Samples

The need to handle biological samples in small or large quantities is an increasing requirement for liquid handling instrumentation. As described above, miniaturization of samples for specific screening, PCR, assays, chemical analyses and mass spectrometry is now used in many different labs.

The main requirement for handling biological samples is avoidance of cross-contamination. Most research-based labs are moving towards using automation in their sample preparation, and there are many labs that have migrated towards the semi-automated pipettor systems which are helping to bridge the gap between handheld dispensers and fully automated systems. The use of positive displacement and disposable tips, as well as the development of acoustic liquid handling, helps to reduce the cross-contamination issues of moving between samples and also to ensure precise dispensing of the liquids involved.

Cell-Based Assays

Cell-based assays refer to any of a number of different experiments based on the use of live cells; they are a versatile and powerful tool in many research laboratories. In drug discovery, for example, cell-based assays can be used to measure various parameters, including cell proliferation, toxicity, motility, formation of a measurable product, and morphology. Although still widely used, in traditional cell-based assays, the cells are cultured in a two-dimensional format. Three-dimensional (3D) cell culture is currently gaining popularity, as it enables cells to be studied in a more physiologically-relevant environment.

TIP: If you intend to automate 3D cell culture you will need to check that your system is capable of handling the specialized plates and consumables required for this application.

In cell-based assays, automated liquid handlers can be used for applications such as cell plating, compound addition and reagent addition. While automation does provide consistency for cell-based assays, speed is another important factor that needs careful consideration. In cell-based assays, timing is everything: completing the protocol before resident cells have the opportunity to change through growth, senescence, or death, is critical for obtaining reliable and accurate results. Hear how advances in acoustic liquid handling, in combination with mass spectrometry, have helped scientists at AstraZeneca to develop a method for ultra-high-throughput screening, in the video interview, Figure 6.

Figure 6: Hear about a breakthrough method for ultra-high-throughput screening

Just as there is no one way to accomplish a cell-based assay, there is no one way to automate a cell-based assay. Depending on the structure of the experiment, as well as the available time, space and budget, it might be best to automate a single, small portion, automate several portions and link them together manually, or automate an entire assay.

Next-Generation Sequencing (NGS)

Sample preparation for NGS involves many steps that can be tedious and prone to error. Most steps involved are highly amenable to automation, which standardizes the process and provides greater consistency in results. Consequently, several manufacturers have developed liquid handlers that provide a walk-away solution for NGS sample preparation applications. See examples of automated solutions for NGS sample preparation in Figures 7 & 8. Technologies that miniaturize sample preparation for NGS, offer cost savings and lower sample input are especially useful for high-throughput applications.

Figure 7: Watch this presentation to learn how the Beckman Coulter Biomek FXP workstation is optimized for preparation of challenging samples

Figure 8: The JANUS® G3 NGS Express Automated Liquid Handling Workstation from PerkinElmer, Inc. is a compact, flexible and easy-to-use solution for efficient sample preparation of up to 24 NGS libraries

TIP: When purchasing an NGS liquid handling system, check for reagent compatibility, plus consider the space in your lab and the potential for expansion and upgrades of the machine.

Polymerase Chain Reaction (PCR)

PCR is a cornerstone technology for genetic research and many molecular diagnostic-based tests. As projects become larger and more laboratories and clinics adopt PCR, consistency, speed and performance become increasingly important. If your lab is routinely processing several PCR plates, you may wish to consider automating the procedure. If your PCR applications are few and far between you may find a multi-channel, electronic pipette is sufficient for improving your experiments. Automating PCR can reduce human error, costs, the risk of repetitive strain injuries and enable better reproducibility. Regardless of your throughput, there are many things to consider when performing PCR, such as sample integrity, reaction mix components, or following the MIQE guidelines (Minimum Information for Publication of Quantitative Real-Time PCR Experiments). Products such as Gilson, Inc.’s qPCR Assistant and Normalization Assistant software for the PIPETMAX® liquid handling workstation, Figure 9, are designed to eliminate error and cross-contamination.

In large liquid handling systems, consider the deck layout and ensure that the system is versatile in terms of accepting a variety of PCR plate formats.

Figure 9: The PIPETMAX® Normalization Assistant software from Gilson

TIP: Consider what sections of your PCR workflow you are interested in automating. You may wish to automate DNA extraction, isolation and quantitation, in addition to automating PCR set-up. You should also determine what level of operator intervention you require and the timeline for your projects.

TIP: Consider compatibility, upgradability, speed and accuracy. Determine if the system contains a thermal-regulatory module that will ensure temperature regulation in the heating blocks, and consider including modules for plate sealing and centrifugation.

Protein Crystallization

The protein crystallization process involves long wait periods of weeks or months, during which the actual protein crystals are formed under controlled conditions. Robotic dispensing instrumentation can be used to rapidly set up large numbers of protein crystallization conditions. In general, automation improves throughput, decreases error within and between experiments, and organizes the data by generating reports of the steps performed.

Several available liquid handling systems are dedicated to protein crystallization, such as the Freedom EVO® Protein Crystallography from Tecan and the TTP Labtech dragonfly® Screen Optimisation Liquid Handler, which is designed to complement the TTP Labtech mosquito® in the protein crystallization workflow. It is recommended to choose a workstation that is capable of dispensing small sample fluid volumes, probably in the nanoliter range. This will enable you to use smaller volumes of your precious protein samples and test more crystallization conditions. Most liquid handlers for protein crystallization will be capable of automating the most popular protein crystallization techniques including hanging drop, sitting drop and microbatch.

A modular system, which can be configured to a wide range of requirements, is usually the best option for protein crystallographers.

TIP: Check what, if any, set-up changes are required for each of these different techniques involved in crystallization. Also consider modules for plate storage, imaging and sample tracking.

6. The Future of Liquid Handling

>Given the cost, complexity and reliability of early systems, very few people would have predicted a bright future for automated liquid handling or for laboratory automation in general. However, the demands of certain applications, including HTS, medical diagnostics and genomic sequencing, created a necessity that made automation commonplace. Automation has enabled laboratories to perform routine tasks in a much faster time and with much better results. The future of automated liquid handling now looks extremely bright, with manufacturers continuing to invest in the development of new systems to better meet the needs of today’s scientists. The recent expansion beyond traditional reagent and solvent dispensing emphasizes how automated liquid handling is maturing as an industry. Manufacturers are also responding to the need to reduce the waste associated with consumables required for these high-throughput experiments. For example, Biotix Inc. is focused on ways to save space and reduce packaging for robotic tips and other pipetting consumables.

In the future, scientists will continue to demand more walk-away time, higher throughput, smaller volume ranges, increased speed, more flexibility, more compact systems, improved software and greater accuracy. Automated liquid handling will become routine in more scientific industries in the future and will be applied to even more scientific procedures. Automation companies will continue to work with reagent manufacturers to develop larger numbers of validated protocols. These collaborations will offer greater diversity and more choice. Furthermore, such walk-away protocols will add value and flexibility to the workstation.

There may be an increase in the demand for miniaturization and the need to handle ever smaller volumes more efficiently and more accurately, with systems handling microfluidic and nano-sample preparation, plus single-cell analysis, pushing the boundaries of sample handling. There is also a growing need for liquid handling technologies in the automation of cellular workflows, with particular demand for 3D cell culture solutions for the drug discovery industry. The need to analyze large volumes of blood in the areas of diagnostics, clinical trials and forensics labs is also becoming increasingly important.

The automation of NGS has become a particular focus for the clinical industry, with a demand for the use of this technology in a number of areas, including infectious disease and cancer. Progress in microfluidic liquid handling will also aid synthetic biology, used, for example, in the development of lab-on-a-chip technology. Learn more about organ-on-a-chip technology and its potential for drug discovery and toxicology research in this video interview with Professor John McLean, of Vanderbilt University.

In the future, straightforward laboratory tasks will become more automated, simplifying everyday procedures. Liquid handling systems will become more customizable, with external devices being interfaced with systems, and automation will become globalized and standardized, offering limitless choices for the modern lab.

7. Summary

There are many different types of liquid handling system on the market and choosing the correct one for your applications may be challenging. By understanding the technology and applying a few simple considerations, selecting the right instrument can become a much easier task.

Visit the SelectScience product directory to find out about the latest liquid handling technology from leading manufacturers and read user reviews. Watch the latest videos and use the SelectScience application note library to keep up-to-date with the latest liquid handling methods.

Editor's Picks

Editor ImageKerry Parker
Editor-in-Chief

Digital Reading Micropipettes - Acura® Manual 825/835/855 (Socorex Isba SA)

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5 out of 5

“This product is good value for money. It is compatible with most tips available in the market.”
Christos Shammas, CING

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Echo® 500 Series Liquid Handlers (Labcyte Inc.)

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4 out of 5

“The Echo Liquid Handler has completely transformed the way I carry out my experiments.”
Amanda Loshbaugh, University of California, San Francisco

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Tecan Freedom EVO® Workstation (Tecan)

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4 out of 5

“We have a 384-well pipetting head that we find very robust and reproducible.”
Aurianne Lescure, Institut Curie

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MVS® Multichannel Verification System (Artel)

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5 out of 5

“The supporting team staff are very knowledgeable and friendly.”
Zhenhua Gu, Pfizer Inc.

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Biomek FXP Laboratory Workstation (Beckman Coulter)

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4 out of 5

“Very good instrument in terms of robustness and the results it gives to us.”
Javier Burgueno, Laboratorios Esteve

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Microlab STAR Line Liquid Handling Workstations (Hamilton Company)

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4 out of 5

“The after-sale assistance of Hamilton technicians was always rapid and useful.”
Stefano Bonacci, Gsk

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