Advantages of Fully Integrated NGS Automation

Next-generation sequencing (NGS) continues to become more important in helping us to understand and treat disease. This means that proper NGS library preparation is more critical than ever before, as poor-quality libraries seldom yield reliable, high-quality results. But library preparation workflows are typically time-consuming and labor-intensive, involving many steps—dozens, or even hundreds— to prepare DNA or RNA samples for sequencing. 

Why prep samples by machine, instead of by hand?

Most labs still perform many library preparation steps manually, which requires multiple rounds of repetitive pipetting for diluting, mixing, loading, and pooling samples, as well as the need to physically move plates between various stations; each of these steps introduces opportunities for human error.

As many labs seek to make library prep more efficient and reproducible—while also alleviating some of the tedium—they are turning to automated, robotic liquid handling systems to take over. Robotic liquid handling platforms are highly effective at transferring precise amounts of liquid from one highly specific location to another; thus, automating significant portions of the NGS library preparation workflow can eliminate errors that occur due to variability and fatigue of human operators. Liquid handlers can also combine these operations with tasks such as plate moving and barcode scanning, and interface with other laboratory equipment such as mixers, heaters, and thermocyclers.

However, designing, adopting, operating, and managing automated NGS workflows is not trivial, especially for smaller labs and those not already accustomed to working with automated liquid handlers. Some of the challenges faced by labs attempting to create their own automated NGS sample prep system include:

• The need for highly trained automation experts. Most automation systems on the market are not designed for novice users, and require advanced training and automation experience to develop successful workflows and operate the instruments. This challenge is amplified when there is turnover of automation personnel; new operators must be trained on each instrument and workflow, leading to a lag in throughput and consuming additional resources. In some cases, training even requires travel to off-site locations.
• Operational challenges of open-platform systems. Many automated systems for NGS sample prep are “open-platform systems,” meaning that multiple automation components and other equipment are set up across an open deck.  For example, most NGS workflows involve components such as thermal cyclers, quantification modules, magnets, shakers, and other equipment—all of which need to be incorporated into the deck. In many open-platform setups, some components (such as heat blocks or thermocyclers) remain off-deck and require hands-on user intervention to transfer samples at specific workflow steps. 
• Lack of unified, consistent vendor support for components. While open systems can offer greater versatility than some “closed systems,” open systems are complex to set up, run, and maintain, thus increasing the need for in-house expertise—or increasing dependence on outside support. Since system components—including hardware, software, components such as thermocyclers and other modules, and application and reagent support—are often provided by different vendors, it can be difficult to get the right support for troubleshooting workflow challenges or modifying protocols, and to coordinate suggestions from the various vendors. This can be especially important when protocols require modification, such as for different input types/amounts, changes to reagent kits, or whole new library prep methods.

What are the advantages of fully integrated automation systems?

One way to minimize the challenges of setting up a new automated workflow for NGS sample prep is to use a fully integrated automated liquid handling system that is supported by a single vendor, including all components, software, protocols, and reagents.

And, choosing a system with on-board components for every step of the workflow provides even greater freedom—allowing even automation novices to walk away while samples are transformed from input nucleic acids into pooled, sequencing-ready NGS libraries.