Liquid Handling Buying Guide

Liquid Handling Buying Guide image

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

This buying guide provides you with information to help you make the right decision when selecting liquid handling equipment. Learn about key technologies, important considerations and the future of liquid handling.


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 repositioned. The fluid being transferred, often referred to as the sample fluid, is held in tips. These tips can either be permanent features of the liquid handler or disposable pieces.

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. Aspiration and dispensing of sample fluid is typically carried out in the microliter, milliliter and nanoliter range. However, it is now also possible to dispense volumes in the picoliter range and femtoliter dispensing may be possible for microarray applications in the future.

Automated liquid handling grew from the high throughput needs of medical diagnostic laboratories in the late 1980’s and through the 1990’s. Liquid handling systems continued to evolve during the decade long embrace of very high throughput drug screening by the pharmaceutical industry and received a further boost from genomic sequencing studies.

Today automated liquid handling systems are used within a variety of key industries including forensics, drug-discovery, pharmaceutical development, molecular biology, food and beverage, agriculture, materials science and clinical diagnostics. Automated liquid handling systems can now be optimized for a number of techniques including PCR, next generation sequencing, immunoassays, cell based assays, protein crystallization, high throughput screening, time resolved fluorescence, nucleic acid preparation, protein purification, blood analysis, solid-phase extraction and liquid-liquid extraction amongst others.

Automation has revolutionized the speed of scientific development, providing greater reproducibility and a saving of 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.

Key Liquid Handling Technology

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 creates the suction necessary to draw the sample fluid into a disposable tip. An air cushion separates the sample aspirated into a plastic tip from the piston inside the pipette. Upward movement of the piston produces partial vacuum inside the tip, causing the liquid to be drawn in. The air cushion moved by the piston acts like an elastic spring from which the volume of liquid in the tip is suspended. The liquid is dispensed when a push-button is pressed to the first stop point, moving the piston down and emptying the tip. Blow out, or complete emptying of the tip, is achieved by pressing the push-button to a second stop point. 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.

In positive displacement pipettes, which are often used for applications requiring greater accuracy, sample fluid is delivered by means of a Teflon-tipped plunger that fits inside the capillary, which can be glass or plastic. As the plunger tip and sample are in contact, such pipettes produce a high level of accuracy and reproducibility, and show minimal carryover of sample, allowing the capillary to be reused. Given the effects of an air-cushion are not applicable in these devices, positive displacement pipettes are suitable for liquids which can be seen as critical in conjunction with air-cushion systems. Such applications include liquids with high vapor pressure, high viscosity or high density. These devices are also suitable for applications such as PCR, which calls for an absence of aerosols to prevent cross contamination.

Fluid Drive Technology

Similarly to a pipette, pumping liquid in accurate measures is fundamental to automated liquid handling systems. There are a few types of pump which might be used, thus you should consider the dispenser type that best suits your requirements. When purchasing a liquid handling system you should ask the manufacturer which types of dispensing technology are employed?

The most common type of pump used in liquid handling systems is a piston pump, also known as a syringe pump. The piston fits snugly with an air tight seal in a tube. Withdrawing the piston creates negative pressure, which in turn creates suction, aspirating liquid into the tip. Advancing the piston creates pressure, which forces the sample fluid out of the tip. As with air-displacement pipettes there is usually an inherent volume of air or other liquid between the piston and sample fluid. This air or other liquid is known as the working fluid, as it is the medium through which the work of the piston or other pumping device is transferred to act on the sample fluid. In a small number of liquid handling systems capillary action creates initial suction and pre-aspirates the sample fluid to be in direct contact with the piston. This volume of fluid becomes the working fluid. As with positive displacement pipettes the piston then protrudes into the tip to control the aspiration and dispense of the sample.

In automated liquid handling systems, piston pumps can take many forms. Systems in which the syringe pump is connected directly to the working tip are often known as air displacement systems, as there is an inherent gap of air that functions as the working fluid. In some systems the syringe pumps are located at a distance from the working tip and are connected via tubing. In these systems a pre-loaded liquid usually acts as the working fluid. These systems are often described as liquid or hydraulic displacement systems. A single-piston pump has a fixed total displacement. While liquid can be ejected or drawn in, the total volume of liquid transfer is limited to the volume of the syringe. For continuous flow, piston pumps can still be used, but two or more pistons must be arranged so that some pistons are dispensing, while others are drawing in fluid. Devices known as check valves, properly arranged in line with the pistons are used to limit flow to one direction and provide continuous flow. Piston based pumps are used in the majority of modern automated liquid handling systems.

Some liquid handling systems utilize a variation of the syringe pump, known as a diaphragm pump. Unlike a syringe pump the seal is driven in a reciprocating manner, similar to a gasoline engine, alternately aspirating sample fluid, and dispensing fluid out. Check valves are used to maintain fluid flow in one net direction. Bi-directional pumping can be achieved by using two diaphragm pumps. Because a simple spinning motor can be used to generate the reciprocating motion required for this type of device, diaphragm pumps are very popular, and truly ubiquitous.

Other liquid handling systems utilize a pressure driven system in which small air pumps or pressurized reservoirs create the vacuum for suction or pressure for dispense. These pumps are typically mounted just above the tips. To achieve accuracy these systems include 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. The advantage of this arrangement is compactness and cost. Air pumps are inexpensive and come in a wide range of shapes and sizes. Electronic sensors are continuously becoming smaller and less expensive, making this relatively basic pumping system perfectly adequate for a large range of liquid handling applications.

The final type of pump used in today’s liquid handling systems is the peristaltic pump. This type of pump uses a roller to squeeze a liquid-containing flexible tube, thereby displacing the liquid in the direction of the roller movement. The main advantage of the peristaltic pump is the separation of the pumping mechanism (the roller) from the medium (tubing) that holds the sample fluid. It is therefore ideal for applications requiring minimal cross contamination. For precision liquid handling the main disadvantage of peristaltic pumps is lack of accuracy. Flexible tubes are elastic, which means their volume over a particular distance may vary. In addition, liquid is delivered in ‘packets’ consisting of space between the two roller engagement points. The flow tends to be pulsed. The rollers can be arranged to minimize this effect, and control loops that can handle such variable loading dynamics are a must, but compared to syringe pumps fluid output is not as constant.

Automated Liquid Handler Configurations

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 characteristics and technologies underlying each of these instrument types are outlined below.

Automated Dispensers

The simplest types of liquid handlers are automated pipettes or 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 1536 aliquots simultaneously. 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.

Multi-channel systems can have a small number of channels (4, 8, 12 or 16) or a large number of channels (96, 384 or 1536). Systems with a small number of channels 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. As microplates gained favor, automated dispensers were produced with matching numbers of channels to the most common plate formats i.e. 96, 384 and 1536. 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 automated liquid dispensers are routinely used for plate replication, in which liquids are taken from a source microplate and dispensed into a large number of destination microplates.

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. Capacitive sensors use the electrical property of "capacitance" to make measurements. Capacitance is a property that exists between any two conductive surfaces within some reasonable proximity. A weak electrical potential is created between the pipetting channel and the labware carrier. When using conductive tips and an ionic liquid the capacitance of the circuit is measured. Using this 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. In systems with pressure based liquid level detection a pressure transducer inside the air displacement channel measures the pressure inside the barrel during pipetting. The data from this sensor changes as the tip approaches the liquid surface, touches the surface and drives below. This data can be used to control pipetting in real-time. Pressure level sensing is the only way to determine the level of non-ionic liquids.

Robotic Workstations

Even in environments where labor is relatively inexpensive, as in academic laboratories, a scientist’s time is generally better spent designing experiments and analyzing data rather than performing repetitive, error-prone pipetting procedures. Automated dispensers, which enable the transfer of liquids between tubes, microplates etc, constitute the simplest type of liquid handler. More complex systems with built in robotic functionality have been developed to manipulate the position of the dispensers and/or containers. Typically the portion of the liquid handling system that aspirates and dispenses sample fluid moves, while the containers that store and receive the liquids stay stationary. 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. Whatever their size, the wider the motion range and the heavier the load, the greater the importance of minimizing vibration. Vibration can have a detrimental effect on reliability and accuracy. 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.

As with automated dispensers, robotic workstations will differ mechanistically and will employ different pumping strategies. You will need to carefully consider which mechanism best suits your application and requirements. Liquid handling robotic workstations also differ in number and configuration of features such as robotic arms and pipetting heads. In addition, the functionality of the probes and the availability of accessories will also differ among different robotic workstations. Such factors ultimately determine the versatility and flexibility of your system.

Fully Integrated Workstations

A wide range of automated liquid handlers offer greater functionality than the simple liquid dispensing offered by the more basic models. Integrated liquid handling workstations are capable of fulfilling a number of roles with minimal input from staff. For example, you may want to ask the manufacturer whether plate handling is automatable. Manual plate handling can slow productivity. Automating the process with a compatible microplate stacker increases throughput and walk-away operation.

Fully integrated workstations may enable the integration of additional laboratory devices, such as centrifuges, microplate readers, PCR instruments, colony pickers, heat sealers, shaking modules, bar code 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.

Some automated liquid handling systems are designed to fulfill a specific application. The most common functions of integrated liquid handling workstations include nucleic acid preparation, PCR, next generation sequencing, ELISA, time resolved fluorescence, high-throughput screening, assay automation, protein crystallography, solid-phase extraction and liquid-liquid extraction. Multi-functional workstations allow a number of different applications to be performed and provide even greater flexibility. When choosing an automated liquid handling system it is therefore extremely important to consider both your current and future application requirements. Given that every automated liquid handling workflow is distinctive, the greatest challenge facing the industry is providing the average laboratory with customization at a reasonable cost.

General Considerations for Liquid Handlers

General Considerations for Pipettes

The complexity of automated liquid handlers makes them the main focus of this buying guide, but the factors that should be considered when purchasing a standard pipette have also be addressed. You will firstly need to decide whether an air displacement pipette or a positive displacement pipette best suit your applications. Air displacement pipettes are more common in standard laboratories and are designed for general laboratory procedures. Positive displacement pipettes are commonly used for heavy liquids or ones that are too viscous to be displaced accurately by air, as well as dense, volatile, radioactive or corrosive samples.

You will need to 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. Electronic pipettes require less force and fewer hand movements, which reduces the risk of repetitive strain injuries. Accuracy and precision is often enhanced with electronic pipettes, as there is less chance of human error. It is important not to underestimate the importance of ergonomic design. The chances are you will be using the pipette almost daily for several years, so you should ensure it is both practical and comfortable.

Another factor you will need to consider is whether you require an adjustable or fixed volume pipette. The most common type of pipettes can be set to a specific volume within its 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.

Depending on the number of pistons in a pipette, there is a differentiation between single-channel pipettes and multi-channel pipettes. 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 8 wells can be handled in parallel as this type of pipette has 8 pistons in parallel. Repeaters are specialized pipettes, optimized for repeating working steps. For example, a repeater pipette 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 which do not fit on normal pipettes, although some electronic pipettes are able to perform this function using standard tips.

For sustained accuracy and consistent operation, pipettes should be calibrated at periodic intervals. The frequency of calibration will depend on the skill and careful handling of the operators, the type of liquid dispensed by the pipette and the accuracy required by the instrument. Typically pipettes should be calibrated semi-annually. Calibration is generally achieved by gravimetric analysis. When buying a pipette you should discuss calibration protocols with the manufacturer.

General Considerations for Automated Liquid Handlers

Bringing an automated liquid handler into your lab will require reflection to determine your goals, research to decide which liquid handler is right for your lab and time and effort to implement the system. While automated liquid handlers are powerful and popular tools throughout the scientific industry, they can be quite costly, so it is important to ensure you are purchasing the right one for you. Speed is perhaps the most cited advantage of automated liquid handling systems. However, when purchasing liquid handling equipment there are many other factors that need to be carefully considered. These factors will be addressed in the remainder of this section in the guide.

Once you have chosen one of the dispenser types listed in the previous section of the guide, you will need to consider the volume range you require in a liquid handler. The volume range you require, like many of the considerations discussed here, will depend on your applications. Many modern liquid handlers are capable of delivering a wide range of volumes, making them suitable for several applications. When discussing the volume range of an instrument with its manufacturer you should also ask what different vessel types the equipment can handle.

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 occur when dispensing low volumes can become proportionally magnified.

In order to ensure high-quality results, it is paramount to achieve reproducibility, accuracy and precision across all volume ranges. For the majority of applications accuracy and consistency of results are far more valuable assets than speed or throughput. This is not to say that these factors should not be taken into consideration. You will need to carefully evaluate the throughput needs of your laboratory. Very high throughput liquid handling systems are most common in drug discovery, pharmaceutical and clinical labs. Medium to low throughput instruments are likely to be adequate for applications such as cell based assays, chromatography and protein crystallization.

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.

Automated liquid handlers can dramatically change the way a laboratory functions, thus taking on new liquid handling equipment can be a daunting experience. Whether you are purchasing liquid handling equipment for the first time, or upgrading an existing instrument, it is important to make sure that adequate after sales technical support and training is available. Whilst everything is operating well, this may well seem like the last consideration, but in the event that support is required, it is important to know how this will be achieved. On a similar note you should consider the potential need for equipment maintenance and repair. 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.

Another factor that contributes to the successful implementation of new liquid handling technology is the instruments ease of use. The ease of use of an automated liquid handler is in part determined by its software. 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. 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 for beginners and experienced technicians alike. Software that enables scheduling of the workflow may be beneficial for very high throughput procedures. 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 bar code readers, shakers and incubators. Some software packages support FDA regula¬tion requirements for multilevel user management, full audit trail, electronic records and electronic signatures. When purchasing an automated liquid handler you should enquire as to whether software upgrades are available free of charge.

Most users of automated liquid handling want a system that operates at the push of a button, but is flexible enough to incorporate changes in method or workflow. While many users create their own workflows, some manufacturers supply methods for certain applications with their systems. The ability to automatically optimize protocols is important, as it effectively reduces instrument wait time.

When purchasing an automated liquid handling system it is important to establish just how flexible you need the system to be. Most researchers seek a system the can grow with the laboratories needs, for example, with regard to changes in throughput and application. In order for a system to grow with your changing requirements you will need to investigate the potential for upgradability. 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 compatability with the manufacturer. While many manufacturers offer a full solution using their own equipment, others will happily interface with third party devices. If you wish to use equipment or instruments you already own you will need to research this in some detail. It is often advisable to look for a manufacturer that has experience with a wide range of equipment.

Specialized consumables, such as microplates and pipette tips, are used within liquid handling equipment. In addition to considering the technology you wish to use, you should research which consumables are required for your applications and ensure these can be used with your instrument. 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. Collaborations between liquid handling manufacturers and reagent providers have led to validated protocols being developed. These protocols are designed to produce results that are comparable to manual methods, while using less reagents and saving considerable time.

Liquid handling error can be caused by many sources, including operators, environmental factors, and the device itself. 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 high throughput screening 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. When purchasing liquid handling equipment you should also 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.

Cross contamination is an important consideration for many laboratory applications. 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 what washing procedures are 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 high force loads typically required for tip injection. It is recommended that you speak with the manufacturer about any cross-contamination concerns that you may have and find out what steps they have taken to avoid this occurring.

Liquid handling equipment ranges in size from small instruments that can fit inside a fume hood, to large room-sized systems. You will need to carefully evaluate how much of your laboratory space can be dedicated to your new instrument. The good news is that liquid handling manufacturers appreciate laboratory space is extremely valuable and consequently are trending towards smaller, more compact systems. Benchtop friendly systems that do not compromise on complexity or handling capacity are becoming more readily available.

The final, and perhaps one of the most important considerations, is cost. You may choose to compare the expected cost and time savings of a potential liquid handler with the actual cost of the system. If you do choose to take this approach be sure not to overlook invaluable assets such as improved quality of data and reproducibility.

When approaching liquid handling vendors you should have a thorough idea of your current and future needs. Contact multiple vendors and have a list of questions prepared. Explore all of the available options and where possible request a demo before purchasing.

Application Specific Technologies and Considerations

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.

As previously mentioned some of the most common applications for liquid handling systems include PCR, next generation sequencing, immunoassays, cell based assays, ELISA, protein crystallization, high throughput screening, time resolved fluorescence, nucleic acid preparation, protein purification, blood analysis, ADME, solid-phase extraction and liquid-liquid extraction amongst others. Some instruments are completely dedicated to one of these applications, while others are capable of performing multiple applications. Some of the most popular applications are discussed in more detail below.

Cell Based Assays

Cell based assays are a versatile and powerful tool in many research laboratories. Cell based assays refer to any of a number of different experiments based on the use of live cells. 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 cell culture is currently gaining popularity, as it enables cells to be studied in a more physiologically relevant environment. If you intend to automate three dimensional cell culture you will need to check that your system is capable of handling the specialized plates and consumables required for this application.

As with other types of assays, test volumes are reaching microscopic proportions. Many vendors are selling high density plates with microliter working volumes suitable for live cell work. It is best to choose a system which is modular in design and allows the implementation of new assays and hardware in the future. 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 an important factor that needs careful consideration. Completing the protocol before resident cells have the opportunity to change through growth, senescence, or death is critical for obtaining reliable and accurate results.

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

Sample preparation for next generation sequencing (NGS) involves many steps that can be tedious and error prone. Most steps involved are highly amenable to automation that 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.

NGS liquid handlers are now emerging as valuable tools in providing large amounts of genetic information in a single run, increasing throughput and reducing sequencing cost. Laboratories adopting automated sample preparation often report significant reduction in hands on time with increased efficiency and throughput resulting in sequence ready library samples.

There are many different liquid handling systems on the market capable of automating NGS sample preparation procedures and consequently choosing the right instrument for your requirements can be challenging. When choosing an automation platform, users should consider the technical performance of the liquid handler and its proven performance for NGS sample preparation. Selecting a system that is highly versatile and customizable is recommended as it can help ensure applicability across a range of sequencing applications. It is important that you verify exactly which steps of the NGS process the system is capable of automating.

Because the sample preparation protocols for NGS are rapidly evolving, an ideal automation system should be compatible with reagents for various applications on leading sequencing platforms.You should enquire about the compatibility of the liquid handling workstation with other suppliers NGS kits and reagents. Similarly you should check with the manufacturer whether the kits you currently use are amenable to automation.

If you are choosing a system solely for NGS sample preparation you will probably want a small, compact benchtop system to allow enough room in the laboratory for the actual sequencers themselves. Given the rapid pace that NGS is evolving, you will need to ensure that your automation solution can expand and be upgraded to meet your future needs.

Polymerase Chain Reaction

The polymerase chain reaction (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 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 you experiments. Automating PCR can reduce human error, costs, the risk or repetitive strain injuries and enable better reproducibility.

Before purchasing a liquid handler for PCR automation you will need to clarify your objective. Determine exactly what you intend to accomplish by adopting automation in your lab. You will need to consider what sections of your 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.

In addition to considering factors such as compatibility, upgradability, speed and accuracy, you will also need to determine if the system contains a thermal-regulatory module that will ensure temperature regulation in the heating blocks. Other additional modules that may be required include those for plate sealing and centrifugation. Prevention of contamination is critical for successful PCR and you will need to make sure that workstations can protect your samples against cross contamination from previously amplified DNA templates. You should pay particular attention to the deck layout of liquid handlers designed for PCR automation and ensure that the system is versatile in terms of accepting a variety of PCR plate formats.

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. The crystallization of proteins is a multi-factorial process that depends on the interplay of several independent parameters, such as temperature, protein concentration, crystallization agent concentration, and the presence and nature of impurities or additives. To determine the optimal crystallization conditions, special screens for testing various conditions can be developed, and ready-mixed precipitate solutions can be applied. It is often highly desirable to test several conditions at any one time to get faster results. 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.

There are several liquid handling systems available that are dedicated to protein crystallization. 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. You should however check what, if any, setup changes are required for each of these different approaches.

A modular system, which can be configured to a wide range of requirements, is the usually the best option for protein crystallographers. Once you have purchased a system you may find you wish to enhance its capabilities in the future with modules for plate storage, imaging and sample tracking for example.

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 high-throughput screening, 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 emphasises how automated liquid handling is maturing as an industry.

In the future scientists will continue to demand more walk-away time, higher throughput, smaller volume ranges, increased speed, more compact systems, improved software and greater accuracy. Automated liquid handling will be 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.

One of the most exciting technologies and developments in the industry is acoustic liquid handling. Acoustic liquid handling, or acoustic droplet ejection, is a non-contact technique that uses acoustic energy to precisely transfer liquids. Sound waves propel specific sized droplets from a source onto a microplate, slide or other surface suspended above the source. Acoustic liquid handling eliminates the need for pipette tips, therefore reducing cross contamination and speeding up the process by avoiding time consuming washing steps.

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.

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 be a much easier task.

Visit the SelectScience product library 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.

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4 out of 5

"Plate is very useful, it is not supplied in this quality by any other vendor."
Martin Lemmerer, Novartis





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VIAFLO 384 (Integra)

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4 out of 5

"Simple, sleek and highly efficient design. Impressive accuracy across a range of volumes…"
Grant Eastman, Novartis Institute for Biomedical Research


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