Choosing the Right Liquid Handling System for NGS Applications

Next-generation sequencing (NGS) is a powerful technique that has revolutionized multiple industries and fields of research by allowing for the accurate decoding of DNA and RNA sequences¹. NGS involves complex and technically demanding workflows that are prone to error and contamination, especially when performed with manual liquid handling techniques². Automated liquid handling systems remove much of the tedium, cost, and risk associated with manual methods for performing NGS. This is achieved through accurate dispensing of tiny volumes, reduced contamination, and lowered expenditure on consumables^3,4. This article will cover key factors to consider when choosing a liquid handling system for NGS workflows, including the available options and advanced features to watch out for.

Key Considerations for Choosing a Liquid Handling System

Throughput Requirements

The number of samples you need to analyze simultaneously plays a big role in choosing the optimal system. Automated systems allow far more samples to be prepared and analyzed simultaneously than manual methods, making it easier to compare data between multiple samples during analysis⁴.

Precision and Accuracy Needs

Many NGS applications require precise identification of single base changes within long DNA sequences. High accuracy is especially important when sequencing data is used to drive clinical decision-making⁵.

Sample Volume Ranges

Environmental and clinical samples often come in limited quantities, meaning researchers must use incredibly small volumes to obtain usable data⁶. Automated liquid handlers can accurately dispense at the nanoliter scale to ensure even low-volume samples are not wasted.

Contamination Prevention Features

Contamination is a massive problem with NGS experiments, making data difficult to analyze and interpret⁷. Automated liquid handlers are inherently less prone to contamination because they remove the need for manual input.

Types of Liquid Handling Systems for NGS

Several types of liquid handling systems can be used for NGS workflows, each with distinct features, advantages, and limitations.

• Manual pipettes. Depending on the model, manual pipettes typically have a volume range of 0.1 microliter to 10 milliliter and are prone to dispensing errors and contamination^2,8.
• Electronic pipettes. These have a similar volume range to manual pipettes and perform repeated dispensing more accurately with less strain on the operator.
• Automated liquid handlers. These liquid handling systems range down to 0.1 nanoliters and provide faster, more accurate dispensing without manual input^3,9.
• Integrated workstations. These systems incorporate multiple instruments to perform different tasks within automated NGS workflows, such as library preparation, PCR setup, and normalization.

The G.PREP NGS Automation system combines the I.DOT Liquid Handler and the G.PURE NGS Clean-Up Device to provide an integrated and fully automated NGS workflow (Fig. 1).

Figure 1. The G.PURE NGS Clean-Up Device ensures optimal NGS workflows and high quality by providing automated tip-free clean-ups.

Matching Liquid Handling Systems to NGS Applications 

Library Preparation

Library preparation involves fragmenting DNA or RNA and adding adapters to make the fragments compatible with sequencing platforms¹. This process requires the accurate dispensing of tiny volumes, often across a long workflow, making automated liquid handlers a fantastic option.

PCR setup

PCR setup for NGS involves amplifying targeted DNA regions using specific primers to enrich and prepare samples for sequencing analysis¹⁰. This requires adding multiple reagents at small volumes with a high risk of contamination. Once again, automated liquid handling systems shine in this application.

Normalization and Pooling

These steps involve adjusting DNA concentrations to ensure uniform sample input and combining multiple samples for simultaneous sequencing¹¹. Manual and electronic pipetting have a high potential for cross-contamination between samples and inaccurate dilutions, making automated liquid handlers another great choice for this application.

Advanced Features to Look For

Barcode Scanning and Tracking

Barcodes make it simple for automated systems to track large sample quantities of diverse types, ensuring they are stored, processed, and handled appropriately.

Integration with LIMS

Automated liquid handlers can be integrated with laboratory information management systems (LIMS) to ensure all samples are accounted for and their progress through the NGS pipeline can be monitored effectively.

Error Recovery

Built-in error recovery systems help prevent errors during the NGS workflows from impacting results. The I.DOT Liquid Handler has patented DropDetection technology that verifies dispensing volumes to ensure accurate dispensing and more reliable results (Fig. 2).

Figure 2. DropDetection accurately detects errors in liquid dispensing and helps to tailor dispensing protocols for increased accuracy.

Cost Considerations and ROI

While automated liquid handling systems require an upfront investment, they can provide significant savings in the long term. Check out our G.PREP ROI Calculator to see how much you could save with an automated liquid handling solution for NGS.

Conclusion

Selecting the right liquid handling system is crucial for optimizing NGS workflows. Automated systems offer significant advantages, including enhanced precision, reduced contamination, and the ability to handle large numbers of samples efficiently. Researchers can choose a system that best suits their needs by carefully considering factors like throughput, accuracy, sample volume, and contamination prevention. Investing in automation ultimately improves data quality, speeds up workflows, and provides long-term cost savings for NGS applications.

Ready to optimize your NGS workflow?

Download our G.PREP NGS Automation brochure and take the first step towards faster, more accurate sequencing results. Get your copy now!

References

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