Automated Liquid Handling: A Primer

Imagine yourself entering a life sciences research lab. Imagine the benchtops with pipettes hanging on racks and containers brimming with liquid reagents. Your colleagues would be hard at work transferring liquids with those pipettors. Soon, you will start your own experiments with your own set of pipettors and tips.

Transferring small liquid volumes is a fundamental technique in the life sciences. Yet, despite being simple and repetitive, researchers are prone to making errors. These mistakes can ruin experiments. Errors in volume transfer represent the single largest source of inaccurate and imprecise data in biomedical research. Researchers also face a time crunch to process samples and produce data. 

As scientists work with microliter, nanoliter, or even picoliter volumes, they need machines that accurately and speedily handle small volumes. Having such systems will help scientists generate reproducible data, reduce human-derived errors, and enhance efficiency in research. By simplifying repetitive tasks, automation increases throughput, reduces cross-contamination, and enhances reproducibility. From genomics to drug discovery, automation is and will be essential for advancing medical research as a whole.

What Is Automated Liquid Handling?

Automated liquid handlers, or automated liquid handling systems, comprise hardware and software designed to transfer liquids with minimal human input. These machines comprise core components and module add-ons that maximize the handler’s functionality across several disciplines in biomedical research . Automated liquid handlers also come in diverse shapes and sizes depending on your experimental research needs. Irrespective of their form, automated liquid handling systems  must be capable of transferring small volumes down to microliters and nanoliters 

Components of An Automated Liquid Handler

All automated liquid-handling machines have the following core components that enable them to automate sample handling and transfer:

• Dispensing parts: These represent components of the liquid handler that move liquids from a sample around. These are found at the dispensing head, devices that dispense solutions to a mechanical receiver, a substrate, or into a container. Dispensing heads can be fixed or mounted with consumables such as disposable tips, pins that make physical contact with a surface, or needles that dispense fluids.
• Actuator: Actuators are components of the automated liquid handling platform that enable liquid flow. They are commonly composed of syringes or peristaltic pumps. The former have plungers that aspirate or dispense fluids and are most suitable for transferring smaller volumes for their accuracy. Peristaltic pumps have rotating heads with rollers that allow liquid to flow inside the tube. These pumps are more suitable for larger volumes because the liquid flow is not always uniform.
• Substrate: Substrates are any places where liquid can react or be placed to conduct experiments. They are commonly divided into three types. 

• Well plates: These plates contain wells where fluids can be placed. They can come in 96-well or 384-well plate formats, but there can be as many as 1536 wells in a single plate. These can also come as microplates. Irrespective of the form, these substrates are designed to handle microliter volumes.
• Solid slides or membranes: Solid slides and membranes are primarily used for microscopy experiments (insert link to Excedr article about microscopy). Automating the slide preparation process makes viewing slides easier and minimizes sample contamination.

• Robot: PIpetting robots are the most important part of the liquid handler as they confer automation. Every robot contains an x- and a y-drive that tells the robot where to put the volumes in terms of Cartesian coordinates. The robotic arms can also come equipped with a z-drive to control the rotation at its end effector.

Automated liquid handlers also come with a series of modules that confer additional functionality. Here are just a few of these modules:

• Barcode readers: With so many samples to track within a single run, the liquid handling robot needs a way to distinguish one sample from another. This lab automation module distinguishes samples within and across molecular assays by scanning unique barcode tags for each sample.
• Shakers: Most samples require some form of stirring and shaking to mix the reagents and samples together. These shakers can also come with heaters that control the temperature of the samples and solutions being mixed. 
• Magnetic bead separators and vortexes: Magnetic beads have been a staple of nucleic acid extraction protocols for decades. These coated beads bind specifically and reversibly to their targets, making nucleic acid purification easier. The magnetic bead separators and vortexes automate the bead processing steps, minimizing nucleic acid loss from washing and centrifugation steps. The process can also be done with microliter volumes, minimizing sample usage.

Applications of Liquid Handling Workstations

Each component of an automated liquid handling system plays a critical role in most aspects of life sciences research. How scientists apply these machines in research depends on the questions they are interested in answering. Here are just some of the applications where researchers stand to benefit from automation:

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• Protein characterization: The human body possesses tens of thousands of protein-coding genes, each of which can generate unique protein structures. Isolating these proteins requires a broad range of growth conditions to determine the environments through which functional proteins can be isolated and crystallized. Automation allows those conditions to be tested at a high-throughput rate. Automation also reduces variability when recovering extracellular vesicles through density separation in complex body fluids, making it easier to characterize proteins inside those structures. All these features make automation an attractive component for conducting proteomics research.
• Real-time (RT-PCR) and next-generation sequencing (NGS): RT-PCR and NGS are fundamental techniques in molecular genetics research. Both feature the study of nucleic acids like DNA and RNA sequences to characterize genomes. Amid these efforts, technical errors in sample processing, volume pipetting, and sample contaminants, can render qPCR data useless. However, automated liquid-handling tools like the MRD disk minimize the risk of these errors, enhancing reproducibility. These systems have also helped researchers in the UK assess patients for SARS-CoV-2 infections (processing 2000 samples per day for qPCR). 
• Drug discovery: Drug discovery remains a costly process where billions of dollars are spent to get novel therapeutics into the market. This process comes with the need to develop commercially viable drugs that meet regulatory standards. Maximizing the chances of drug development success requires a concerted effort to characterize multiple drug candidates that meet those standards. Automation makes that process easier. It streamlines compound synthesis and allows the drug to be assessed under many test conditions with precise pipetting and sample transfer. 
• Sample processing: Irrespective of the downstream research being performed, most research workflows require some form of sample preparation. Automated liquid handlers minimize cross-contamination by delineating samples by their position on the well and their associated barcodes. Liquid handlers also minimize technical errors in pipetting microliter volumes. These features allow the normalization of sample processing protocols.

Excedr Leases Automated Liquid Handling Systems

Excedr boasts a wide range of automated liquid handlers that will help you meet your research needs. Each of them provides scale but can also provide a small footprint to ensure researchers still have lab space to conduct research.

• Hamilton Corporation: Hamilton Corporation provides a series of Microlab automated liquid handlers, four of which are benchtop-sized (Microlab Prep to Microlab Star V). All Microlab systems contain a single robotic arm that can transfer sample volumes and reagents, conduct serial dilutions, pick hits of interest, and work with sample replicates. All systems come with Hamilton-specific software, such as Microlab Prep and the Microlab Venus five, where users input programs for the robot to follow. The Microlab Star handlers can also have multiple modules. These include a heat shaker for heating samplesand a cooling chamber to cool samples. Additionally, the compact Microbial NIMBUS is compatible with the 96-well and 384-well plate configurations. Hamilton also supplies their patented CO-RE II (Compressed O-Ring Expansion) pipette tips. These tips are fully compatible with all of Hamilton’s liquid handlers and allow for highly accurate automated pipetting. 
• Tecan Corporation: The Freedom EVO line comprises four automated liquid handlers that provide benchtop capabilities for automated liquid handling. The EVO 75 and 100 models have room for two mounted arms and 27 or 30 grids of worktable space, respectively. For large-scale automation, the EVO 150 and EVO 200 base units come equipped with three robot arms and up to 69 grids of worktable space. All four handlers come with PosID technology that identifies samples by their barcode. The machine can also find missing samples and note them with this system. Finally, the EVO lines can come with specific packages containing modules for specific scientific applications, from nucleic acid and protein purification to library preparations for sequencing.
• Perkin Elmer: G3 automated workstations are a diverse lineup of automated liquid handling tools that can be used for multiple operations. For example, the Zephyr G3 NGS iQ Workstation can handle liquids and includes a thermocycler, robotic arm, and other deck accessories to facilitate NGS assays. The Janus G3 BioTx Pro and Pro Plus provide 8-channel dispensing and a 96-channel multiple pipetting head. It can also sport a wide range of modules, such as a vacuum filtration system, for conducting plate-based purification and fraction collection. This feature minimizes contamination during protein and nucleic acid purification and maximizes efficacy in cell line selection and expression optimization experiments.

Selecting an Automated Liquid Handler to Lease

Excedr hosts automated liquid handlers from many companies to meet all your automation needs. To best help you lease the most applicable automated liquid handler, we recommend that you consider the following factors as you decide on an automated liquid handling system:

• How much throughput do you want? To answer this question, determine how many samples you’re working with or processing in a single run. You could consider the number of proteins you’re purifying, the number of biomarkers you’re testing with qPCR, or how many samples you’re processing for NGS experiments. 
• How much space do you have? A researcher only has so much space to work with most of the time. In this question, researchers should consider the dimensions of the liquid handler, how many samples you’re processing, and where the machine will be placed. Answering this question will help you identify an appropriate size that you can pursue for your automated liquid handler. 
• How easy to use and ergonomic is the automated liquid handler? Safety should be a top priority when using laboratory automation tools. Scientists should be able to access the equipment without risks to safety. Also, consider the possibility of using dangerous reagents or being exposed to pathogens if you’re working with clinical samples. Ease of use should also ensure the machine’s software is accessible and efficient.
• ‍How much volume will you work with per sample? Automated liquid handlers have varying capacities for transferring different sample volumes. The sets of disposable tips they can handle and the surface interfaces they use will each impact how much volume the robots can use. Also, consider the volumes of the reactions in which you’re conducting your experiments.

Establish Your Automation Pipelines with Excedr

Researchers are increasingly turning to automation to meet the growing needs of high-throughput experimentation. From nucleic acid diagnostics to protein-based assays, transferring the manual sample handling and processing steps to an automated liquid handler will only enhance biomedical research.

Excedr’s leasing program allows you to identify the best automated liquid handler for your research needs. After answering the list of questions we provide, we use our expertise to help you acquire the best automated liquid handling system for advancing your research. 

Interested in leasing an automated liquid handler? Let us know!