Rapid and Cost-effective NGS Workflows through Automated Liquid Handling

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Modern automated liquid handling solutions make the most of vertical space for a smaller footprint in the lab.

by Paul Lomax, Head of Genomics, SPT Labtech

Next-generation sequencing (NGS) has changed the face of research, giving scientists deeper insights into the most challenging problems. As the cost of sequencing continues to decrease, NGS technology is becoming more accessible, subsequently appearing in diverse research applications from disease-specific panel development to the creation of personalized medicines. However, the broader utility and accessibility of NGS comes with a corresponding growth in the number of samples that labs are required to handle.

Historically, NGS sample preparation has been a demanding process. Traditional workflows can be time-consuming and challenging, with small volumes of difficult-to-handle liquids, and protocols that require meticulous pipetting, dispensing, incubating, and shaking of samples. Owing to such complexities, scaling NGS protocols effectively and reproducibly to accommodate the influx of samples can be a significant hurdle.

Automating liquid handling is a promising solution to streamline the NGS workflow, enhance efficiency, and enable labs to handle larger numbers of samples more consistently. But not all automated systems are created equally. To leverage automation in a way that truly adds value to your NGS experiments, you must consider certain key factors.

In this article, we explore the role of automation in NGS workflows, how it can address common challenges in sample preparation, and highlight the crucial elements you should consider to get the most from your NGS experiments.

Manual processes hinder the true potential of NGS

NGS holds enormous potential, but the steps involved in sample preparation often impose significant constraints. Manual library preparation, for instance, demands lengthy, intricate protocols that are not only time-consuming but require high levels of precision. Maintaining a consistent level of accuracy across different days and operators is therefore highly challenging. Liquid handling brings additional complexity as some liquids are highly viscous, making precise sample and reagent transfer difficult.

Such labor-intensive and complex manual processes often lead to bottlenecks in the workflow, which invariably result in longer processing times and higher operational costs. Furthermore, these become difficult to scale and it is hard to maintain consistency, especially when dealing with an increasing number of samples. This, in turn, monopolizes lab personnel time, anchoring their time in data generation instead of higher value data analysis.

So, how do labs unchain themselves from the restrictions of manual processes and make full use of the potential offered by NGS technology? One promising approach is through the introduction of automation into liquid handling and library preparation.

Automate your way to highly effective and consistent workflows

Automation, for example pipetting robots, holds the key to transforming the way NGS workflows operate:

  • Throughput is greatly increased
  • Hands on-time for lab personnel is drastically reduced
  • Procedure consistency, and therefore results reliability, are boosted — even when performed by different users

Some automated liquid handlers — particularly those that use positive displacement technology — can also transfer very small volumes with high accuracy. With this technology, systems can handle various types of liquids, including viscous samples and reagents which are notoriously challenging to work with, on a small scale. Consequently, automation paves the way for miniaturization in library preparation.

Despite the dramatic reduction in sequencing costs, the expense associated with library preparation remains high. Miniaturization, or the practice of reducing the volumes of samples and reagents used in each well, can significantly bring down the cost per sample, thereby improving the feasibility of more complex experiments.

The importance of miniaturization goes beyond cost efficiency. It also plays a crucial role in the emerging field of single-cell genomics. Such studies require library preparation on each individual cell — a process that would be logistically impractical if done manually. An automated system with positive displacement technology enables these studies to be completed in hours rather than months, making single-cell genomics more accessible and practical for labs around the world.

Optimize your workflow with the right automated solution

Automated systems can vary significantly from one supplier to another, so it is crucial you choose the solution that is right for your lab. Four factors can be considered to ensure you select the option that best optimizes your workflow: the number of instruments, instrument size, system usability, and connectivity.

The number of instruments

Often, workflows involve multiple instruments, each contributing to different steps of the process. However, a multi-setup approach has its drawbacks. For instance, transferring samples between instruments can be time-consuming and poses the risk of errors or cross-contamination. Furthermore, multiple instruments occupy valuable lab space.

Fortunately, new automated systems integrate all critical steps — pipetting, dispensing, incubating, and shaking — into a single, unified instrument. Some even include a built-in thermocycler for added efficiency. Combining steps into one instrument streamlines the workflow, eliminating the need for transfer and thereby saving time and reducing potential errors.

Instrument size

Not all automated systems are designed with compactness in mind; many are single-layered and can occupy a large area within your lab. Some modern solutions, however, make efficient use of vertical space through multi-layered designs, thereby reducing their footprint (Figure 1). Not only does a multi-layered solution free up lab space for other valuable tasks, but it can also eliminate the need to expand facilities or prioritize instruments based on their size.

System usability

Automated workflows often don't directly mimic their manual counterparts, and instruments will need to be programmed to achieve your goal. Many labs don’t have the luxury of dedicated in-house programmers, so choosing a system that is easy to use is vital. Otherwise, the lab may need to bring on an automation expert, incurring additional personnel costs and training time. What’s more, if your automation workflows depend on a single expert, your lab risks productivity bottlenecks whenever they’re away, and ultimately you risk losing this expertise if they leave.

Modern automated solutions aim to be highly accessible and intuitive, requiring no prior coding expertise. As such, these solutions can significantly limit the amount of training needed, enabling lab personnel to be ready to write their own protocols after as little as half a day of training.

Connectivity

In an increasingly interconnected scientific community, having cloud-enabled automated systems is vital. The ability to share data and protocols easily is fundamental to nurturing collaboration, and speeds up the adoption and roll-out of new workflows within an organization or even across the broader community.

A cloud-enabled solution allows users to share updates or improvements to protocols instantly, minimizing the time needed to implement changes and consequently accelerating the overall pace of research. Moreover, cloud capabilities ensure that your data and protocols are securely stored and backed up, providing an extra layer of data protection, and allowing you to retrieve them easily in case of local hardware failures.

What does your future hold with automation?

NGS holds the potential to dramatically advance our understanding of biology and diseases, paving the way for innovative treatments and therapies. But the key to fully harnessing NGS lies in the improved efficiency and reliability of sample preparation workflows gained through automation.

Automated liquid handling solutions enhance consistency, reduce the time needed for sample preparation, provide valuable walk-away time for lab personnel, and lower the potential for human error. Solutions that use positive displacement technology also lay the groundwork for future advancements in genomics research, making traditionally expensive experiments more cost-effective through miniaturization.

Ultimately, when thoughtfully integrated, automation has the power to transform NGS experiments from a cumbersome, time-consuming process into a streamlined, efficient, and scalable workflow. By using advanced all-in-one automated liquid handlers, we move a step closer to unlocking the full potential of NGS and realizing its promise of driving significant advancements in biological research and medicine.

 

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