3 Innovations in Next-Generation Sequencing Sample Prep

Next-generation sequencing (NGS) has revolutionized the fields of genomics, oncology, and infectious disease. Sanger sequencing paved the way for NGS, enabling the complete sequencing of the human genome, a project which took almost 30 years to complete^1,2. In contrast, NGS offers much faster and more cost-effective solutions. However, manual NGS sample prep has several challenges, including labor-intensive pipetting, sample variability, and reagent waste, all of which can create bottlenecks in modern research and laboratories.

This blog outlines three key innovations in NGS sample prep and highlight how emerging technologies have utilized automation to transform NGS sample prep workflows.

Innovation #1: End-to-End Automation of Library Construction

Emerging technologies can automate key steps in NGS workflows, including library construction, allowing for precise reagent dispensing, magnetic bead-based purification, and the integration of thermal cycling^3,4. When using NGS in clinical applications, such as cancer and population genomics, data reliability and reproducibility is essential to ensure regulatory compliance. During the COVID-19 pandemic, automated NGS played a pivotal role in the global response, with automation allowing rapid and reproducible SARS-CoV-2 sequencing, which aided in timely public-health decision making and identification and tracking of SARS-CoV-2 variants^5–7. 

The G.STATION NGS Workstation from DISPSENDIX is an automated end-to-end system that includes instruments such as the I.DOT Liquid Handler and the G.PURE NGS Clean-Up Device, providing all you need to automate DNA-seq, RNA-seq, and targeted sequencing workflows. NGS sample prep automation enables consistency in results, improves throughput, and eliminates human error and hands-on time. These automated systems can provide confidence in NGS workflows, ensuring precision and consistency across runs and enabling traceability for regulatory compliance. 

Innovation #2: Sequencing-Ready DNA Prep Platforms

Automated systems can be integrated into the entire NGS workflow, including DNA and RNA extraction, library preparation, magnetic bead purification, and quantification and quality control, all in one platform^3,4. Studies have shown that sequencing-ready DNA preparation platforms can reduce hands-on time from 3 hours to less than 15 minutes, making them highly efficient and high-throughput, requiring minimal intervention and reducing human error⁸. Fully automated, sample-in, library-out workflows have demonstrated high reproducibility and quality outputs, making them valuable in population genomics, cancer genomics, and metagenomics⁹.

The G.STATION NGS Workstation from DISPENDIX is a fully walk-away platform that includes all the essential instruments for NGS sample prep (Fig. 1). The G.PURE NGS Clean-Up Device is included in the G.STATION NGS Workstation and runs at rapid speeds, able to perform bead-based clean-ups in 96- or 384-well plates in minutes, allowing for fast, consistent, high-throughput results.

Figure 1. The G.STATION NGS Workstation from DISPENDIX includes all instruments needed for high-throughput automated NGS sample prep, including the I.DOT Liquid Handler and G.PURE NGS Clean-Up Device. 

Innovation #3: Non-Contact, Low-Volume Reagent Dispensing

Inefficiencies are common with manual NGS sample prep, including low signal-to-noise ratios, sequencing errors, low-quality input material, and difficulty achieving consistent results, often due to its time-consuming, error-prone nature. These errors and inefficiencies lead to poor quality results that may need to be repeated, using more time, money, samples, and resources.

The I.DOT Liquid Handler from DISPENDIX dispenses in the nanoliter range, allowing for assay miniaturization, which can lower plastics use, preserve reagents and precious samples, and be cost-efficient (Fig. 2). The I.DOT Non-Contact Dispenser can also be used for scalability due to its compatibility with 96-, 384-, and 1536-well plate formats. The I.DOT eliminates the risk of human error and ultimately leads to more efficient NGS sample prep. 

The I.DOT Liquid Handler has been used to automate and streamline multiplex sequencing library preparation, such as the COVseq protocol, from low-input samples. This approach enabled large-scale genomic surveillance, as thousands of samples could be processed weekly at less than $15 per sample¹⁰. 

Figure 2. The G.PURE NGS Clean-Up Device and I.DOT Liquid Handler from DISPENDIX can fully automate NGS sample prep, providing reproducible, precise, and traceable results at rapid speeds. 

Why These Innovations Matter Now

NGS is essential in many workflows, especially in clinical diagnostic settings, such as identifying genetic variations, diagnosing infectious diseases, and identifying cancer mutations. Not only is there a rising demand for high-throughput NGS sample prep due to its speed, but there is also a need for its ability to provide reproducible and reliable results, ensuring cost-effectiveness and compliance with regulatory guidelines. Emerging innovations like the G.PURE NGS Clean-Up Device and the I.DOT Liquid Handler from DISPENDIX align with advanced laboratory needs, providing reproducible and cost-effective results at speed.

Conclusion: Future-Proofing NGS Workflows with DISPENDIX

As the need for NGS grows exponentially, there is an equally increasing need for high-throughput, efficient, and reliable workflows. Automated NGS sample prep is the solution for fast, reliable NGS sample prep. The G.STATION NGS Workstation from DISPENDIX includes the G.PURE NGS Clean-Up Device and I.DOT Liquid Handler, providing an end-to-end automated system for NGS workflows, leading to precise, accurate, reliable, reproducible, and traceable NGS sample prep. 

Download the I.DOT Liquid Handler brochure or the G.STATION NGS Workstation brochure to transform your NGS sample prep workflows!

References

1. Giani AM, Gallo GR, Gianfranceschi L, Formenti G. Long walk to genomics: History and current approaches to genome sequencing and assembly. Comput Struct Biotechnol J. 2020;18:9-19. doi:10.1016/j.csbj.2019.11.002
2. Hutchison CA. DNA sequencing: bench to bedside and beyond. Nucleic Acids Res. 2007;35(18):6227-6237. doi:10.1093/nar/gkm688
3. Akutsu J, Tojo Y, Segawa O, et al. Development of an integrated automation system with a magnetic bead‐mediated nucleic acid purification device for genetic analysis and gene manipulation. Biotechnol Bioeng. 2004;86(6):667-671. doi:10.1002/bit.20049
4. Hoffmann A, Timm A, Johnson C, Rupp S, Grumaz C. Automation of customizable library preparation for next-generation sequencing into an open microfluidic platform. Sci Rep. 2024;14(1):17150. doi:10.1038/s41598-024-67950-6
5. Rachiglio AM, De Sabato L, Roma C, et al. SARS-CoV-2 complete genome sequencing from the Italian Campania region using a highly automated next generation sequencing system. J Transl Med. 2021;19(1):246. doi:10.1186/s12967-021-02912-4
6. John G, Sahajpal NS, Mondal AK, et al. Next-Generation Sequencing (NGS) in COVID-19: A Tool for SARS-CoV-2 Diagnosis, Monitoring New Strains and Phylodynamic Modeling in Molecular Epidemiology. Curr Issues Mol Biol. 2021;43(2):845-867. doi:10.3390/cimb43020061
7. Coope RJN, Matic N, Pandoh PK, et al. Automated Library Construction and Analysis for High-Throughput Nanopore Sequencing of SARS-CoV-2. J Appl Lab Med. 2022;7(5):1025-1036. doi:10.1093/jalm/jfac054
8. Ott O, Tolppi S, Figueroa-Cruz J, Myagmar K, Unurbuyan K, Tripathi A. Leveraging the fundamentals of heat transfer and fluid mechanics in microscale geometries for automated next-generation sequencing library preparation. Sci Rep. 2024;14(1):12564. doi:10.1038/s41598-024-63014-x
9. Kim H, Jebrail MJ, Sinha A, et al. A Microfluidic DNA Library Preparation Platform for Next-Generation Sequencing. Orlando L, ed. PLoS ONE. 2013;8(7):e68988. doi:10.1371/journal.pone.0068988
10. Simonetti M, Zhang N, Harbers L, et al. COVseq is a cost-effective workflow for mass-scale SARS-CoV-2 genomic surveillance. Nat Commun. 2021;12(1):3903. doi:10.1038/s41467-021-24078-9