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Using automation to prepare sequencing libraries isn’t a new concept, and most researchers are aware that there are numerous benefits to automating this process. However, many labs are still hesitant to switch to automation and often believe that it’s not suitable for their lab. To combat these concerns, we’ll cover some of the key advantages, review the most important considerations, and get real-world advice from automation experts to remove any lingering anxieties.
Advantages of automation
“Number one is reducing human-associated errors,” says Calvin Cortes, Biomek NGeniuS Senior Product Manager at Beckman Coulter. Users who’ve spoken with Cortes have explained how human-associated errors have cost their lab significant time and money over the years, and anyone who has prepared sequencing libraries is aware that the process is delicate and often requires many precise manipulations.
“Library preps can be a long, drawn-out process and just a few seconds of lost focus/mental fatigue can mean the difference between high-quality results and a failure,” adds Jesse Cassidy, Director of Applications at Eppendorf. “Automation eliminates such potential for human error, ensuring the delivery of the correct reagent in the right amount to the selected location and at the appropriate stage of the process.” This advantage is the main reason why many labs have decided to make the switch to automated library preps.
Automation also allows labs to increase their throughput and frees up time. Researchers can put away their multi-channel pipettes and focus on other important tasks while the machine does all the work. John Fink, General Manager of Automated Liquid Handling at PerkinElmer, sums it up nicely, “In essence, automation relieves lab personnel from manual work, giving them more time to conduct analysis. Reduced failed samples (reruns) and hands-on time translates to cost savings for the lab.”
Hesitation to automation
Despite the clear benefits, many prospective users have a valid hesitation preventing them from switching their lab over to automation. Addressing these common concerns, along with guidance from our automation experts, can help remove some of the anxiety that researchers have when making this big change.
“A common fear I see in speaking to clients new to automation is the loss of control,” says Cassidy. “The samples that are being processed are precious and may be difficult or impossible to procure more of. Giving away control of such an important process to a device you aren’t yet familiar with can take some time and careful review of performance data.” To help clients with these concerns, Cassidy said that his team provides representative data to demonstrate the robustness of their system. In addition, his Field Application Support team gives hands-on training and optimizes the process to ensure they’re set up for success.
Another normal hesitation to automation is the cost. “Due to upfront capital expenditures, many labs think they cannot afford automation,” says Fink. “However, a well-designed automated library prep system helps generate cost savings from day one by requiring fewer consumables and can lower the rate of sample loss. Reagent rental models can also alleviate the upfront cost.” These automation costs can be further lowered when considering the reduced need for staff to perform all-day, hands-on work. Most automation instruments only require a brief setup before running an entire library prep workflow. The reduction in labor and sample loss are huge cost-saving measures.
The possibility of cross-contamination during the automation process is another major concern. Cross-contamination can invalidate the results of a sequencing study and is a nightmare for researchers. But modern automation systems have been designed to mitigate this problem through a variety of methods. As Cortes describes in one method, “the [robotic] arm of the system uses different paths to ensure it’s not moving over open tubes.” This method, along with the automated precision pipetting that can prevent drips, are examples of strong contamination deterrents.
A common misconception among prospective users is the belief that they need specialized training or coding skills to run one of these instruments. “You don’t need to program it or have engineers come in to make any changes or use new protocols,” says Cortes. This includes instances where edits or customizations are needed. Fink further highlighted this by saying, “For labs lacking in specialized library prep, automation, and/or scripting experience, pre-programmed, vendor-qualified, walk-away solutions exist already enabling these labs to access the promise of NGS.”
Selecting an automation system
The first step to finding your automation system starts with compatibility. “Find a system that can do the chemistries you’re going to use in your lab,” mentions Cortes. This means ensuring the instrument is equipped to prepare the different library preps your lab is using. Fink adds, “Labs need to consider both their existing and potential future NGS needs when choosing automation for their library preparation workflows as new library prep kits are continually released.”
Rob Grillmeyer, Senior Sales Manager at Beckman Coulter, elaborates “Future-proofing is a big concern for customers. They’re worried their instrument will become a paperweight.” This is why most modern instruments have increased modularity and the ability to add and customize protocols. Prospective users should choose a device that can allow changes in the current workflow but also adapt to new protocols in the future. Automation is an investment that should continue to be useful for many years regardless of changes in the lab.
“Throughput is another important factor to consider,” says Fink. “Labs should not only consider their current workloads, but also determine if future throughput will increase or decrease.” Smaller labs that benefit from the free time produced by automation can typically use this opportunity to increase their throughput. In addition, higher throughput labs may also need to run experiments with a reduced number of samples in the future. All of these changes to the workload should be kept in mind when choosing an automation system.
Cassidy acknowledges other important factors. “Make sure that you’re satisfied with the results of your library prep manually, before transitioning to automation. If the yields and/or quality are low by hand, it’s unlikely to improve drastically by automation. Once acceptable results are obtained manually, they can be used as a benchmark to assess the automated results.”
Prospective users should also remember that purchasing a library prep automation system is more than just buying a liquid handler. These instruments should account for different aspects of the library prep and the needs of the experiment. This can include onboard thermocyclers, proper storage of the samples and reagents, and mixing and aliquoting reagents prior to their use. Many devices can also detect problems like identifying low volumes of reagents or an insufficient number of tips. These features can accelerate workflows and make library prep automation systems much more valuable than standard liquid handlers alone.
With his parting thoughts, Cassidy explains that NGS requires “a large investment in the sequencer, personnel, and storage to run the workflow. I find that labs cannot truly unlock the full potential of most sequencers without automation. [It’s] a solution to the most tedious and error-prone portion of the sequencing process and is a very helpful step in maximizing the output of the sequencer.”