How Automation Can Support Increasing Demand for Next-Generation Sequencing

The demand for next-generation sequencing (NGS) is growing quickly, with the market expected to grow at a compound annual rate of 15.7% to hit $27 billion by 2027. Advancements in NGS technology, coupled with declining costs of genome sequencing, are fueling this demand across a range of therapeutic areas, including cancer, infectious disease and the study of inherited disorders.

But this exploding interest in NGS increases the pressure on researchers to find new ways to improve the efficiency of the process. NGS library preparation is a prime candidate for improvement – and automation is the key to making this process more efficient.

Complexities of NGS library preparation

Library preparation is often a very long, complicated process. First, the genetic material that has been extracted for sequencing must be converted into a readable format for the sequencer that will be used. Purified genetic material must be fragmented through physical, enzymatic or chemical cleaving, after which the fragments are converted into a library by a variety of enzymatic and amplification techniques that add sequencing adapters and molecular barcodes.

In targeted sequencing workflows, libraries are further enriched by amplification or hybridization techniques. Bead-based cleanups and size selection are frequently performed throughout the workflow to refine the library and remove preparation by-products such as adapter dimers. Accurate liquid handling is vital at every step, and the whole process may span several days.

Automation can dramatically reduce both the amount of hands-on time and associated processing errors, allowing data scientists to set up library preparation with a few simple steps and then walk away. This promises to free up researchers so they have more time to focus on meaningful tasks such as data analysis. In other words, automation allows scientists to do actual science, rather than focusing on tedious tasks like manual pipetting.

Automation of reproducible processes

There are several emerging technologies for automating library preparation, including automated liquid handling platforms that are specially designed for high-throughput applications. These tools combine pipetting heads, robotic arms, integrated devices such as thermal cyclers, and software to automate complex workflows.

Newer liquid handlers designed specifically for low- to medium-throughput applications can process up to 24 samples, with hardware and consumables innovation enabling them to retain walk-away functionality despite having a small footprint.

One major advantage of automation is that it can reduce errors; however, even traditional liquid handlers leave room for user error in several parts of the process. Mistakes such as misplacing or using the wrong reagents and consumables are common and can lead to errors and failed library preparation.

A study comparing an advanced automated library prep system to a traditional liquid handler found that the number of interactions required after starting the run for the traditional handler was six, versus zero for the new automated system.

That’s because the new automated system could accommodate more consumables, verify reagent volumes with liquid level sensing and incorporate novel optics technology to monitor the deck during setup. This monitoring ensured reagents and consumables were present in sufficient quantity and placed correctly before processing.

Shrinking the sequencing workflow

Another NGS library preparation method that’s growing in popularity is miniaturization, which involves the use of acoustic dispensing and other miniaturization technologies to shrink the sequencing workflow. Miniaturization offers the potential to reduce the amount of reagents and samples needed, increase the speed and throughput of experiments and lower the overall cost per sample.

Moving towards precision medicine

NGS technology is playing an increasingly important role in everything from the development of diagnostics to personalized medicine. It’s a technology that could greatly improve our understanding of complex human diseases, our ability to combat emerging pathogens and more.

In oncology, NGS can guide customized treatments based on individual patients’ genomic data or distinct molecular changes in tumors. Embracing automation in NGS research will improve the efficiency of laboratory processes to help scientists and data analysts get these innovations to patients faster than ever before.

About the author:

Alexander Sahm brings more than 15 years of robust experience in automation engineering and process development, and he is part of the NGS global product development team at Beckman Coulter Life Sciences.