Biotechnology laboratory automation and NGS
“Automation” calls to mind enormous factories and huge machines, from the steam engines, spinning jennies, and power looms of the Industrial Revolution to twentieth century automotive assembly lines. Or perhaps in the present day, we think of computer chip factories and warehouse robots for picking commercial goods. However, automation benefits nearly all industries and the biotechnology industry is no exception.
Biotechnology laboratory automation has many diverse applications
There are factories and production lines making a vast array of biotechnology products, from specialized chemicals and custom-synthesized nucleic acids to medical devices, but biotechnology automation also has numerous laboratory applications. The best-known examples of laboratory automation are probably thermocyclers for automating polymerase chain reaction (PCR) experiments and liquid handling robots, versatile machines that can handle processes ranging from automated pipetting to high-throughput screening (HTS) of compounds for drug discovery. But laboratory automation also extends to many other applications. For example, clinical laboratories use automated robotic systems or lab-on-a-chip systems to perform and manage in vitro diagnostic (IVD) testing such as quantitative PCR (qPCR), immunoassays, and urinalysis on blood, urine, and other patient samples for clinical diagnostics. (1) Flow cytometry systems enable rapid identification and separation of large numbers of cells based on fluorescent marker expression or cell surface marker expression. Cell culture systems, fundamental laboratory tools for biological discovery and drug screening, can also be automated including cell growth, harvesting, replating, and analysis. (2) These are just a few examples of the types of laboratory automation that contribute to biotechnology advances whether in basic research, clinical diagnostics, or corporate research laboratories.
There are many general benefits from automating individual laboratory processes or sets of processes, including (3):
- Reducing or eliminating repetitive manual work (such as sample preparation, pipetting, and data entry), which reduces experimental variability and frees highly trained scientists to focus their talents on more sophisticated work like data analysis and interpretation;
- Enabling scientists to innovate and perform more complex experiments, operations, or analyses;
- Managing samples to prevent loss or mislabeling, and managing materials to minimize waste and control costs;
- Producing more data, faster;
- Improving data quality monitoring and control;
- Promoting collaboration among teams, including globally distributed teams, and making protocols and procedures more widely; and
- Monitoring data security and regulatory compliance.
These benefits offer considerable competitive advantage for an academic research laboratory, a clinical laboratory, or a biotechnology manufacturer. Adopting laboratory automation demonstrates to customers or peers an understanding of industry directions and a commitment to staying on the cutting edge of biotechnology developments.
Laboratory automation improves experimental standardization and quality control
Standardization and reproducibility are essential to all automation applications, whether that application is assembling cars on a production line, measuring metabolite levels in blood samples, or sequencing DNA strands. Automation promotes standardization because repeatedly performing a process or set of processes the same way each time should lead to the same result. The automated process(es) can be both more efficient and more consistent—and the quality of the results can be effectively measured against an objective standard and against each other. (1)
Laboratory automation therefore provides an important means of meeting compliance and quality control requirements. Compliance with either the applicable Current Good Manufacturing Processes (CGMPs), Good Laboratory Practices (CLP), or Clinical Improvement Act (CLIA) requirements is a regulatory requirement for biotechnology laboratories manufacturing products or providing testing services. (4, 5)
Even for biotechnology laboratories that do not provide regulated products or services, quality control for experimental results is important for addressing reproducibility. Scientists across disciplines, not only in biotechnology, continue to grapple with an ongoing “reproducibility crisis.” In a Nature survey of 1,576 researchers, over 70% reported that they had failed to reproduce results from another scientist, and over 50% had failed to reproduce their own results. (6) Increased laboratory automation offers internally consistent processes—a superior alternative to the variability among experiments that is inevitably introduced by even the very best technicians.
Laboratory automation benefits next generation sequencing (NGS)
Next generation sequencing involves complex experiments that generate even more complex datasets. Researchers can examine large amounts of NGS data in detail and tease out small changes and subtle relationships. Because NGS provides the technical capacity to generate high-quality, reproducible results at larger scales for deeper, more detailed analyses it will continue to drive fundamental insights and translational innovations.
For NGS workflows, sample extraction and library preparation, liquid handling, and high-throughput sequencing are the major technical applications of automation. NGS requires many exacting steps that must be performed in the correct sequence under specific conditions, with minimal sample loss or cross-contamination.
Sample extraction and library preparation and high-throughput sequencing are key bottlenecks that automation can improve. Samples may be very precious, perhaps consisting of small amounts of tissue or nucleic acid. Even if starting sample material is abundant, sequences of interest may not be present in abundance. Moreover, quality library preparation is essential, because any errors introduced at this step will be compounded at the subsequent amplification step and incorporated into the results during the high-throughput sequencing step. Then the sequencing data must be carefully analyzed to identify any errors and determine whether they have obscured the results.
Despite the best efforts of skilled technicians, manual library preparation is a source of human-introduced variability because manual quality inevitably varies by the person and the day. Plus, an interruption or a momentary lack of concentration could result in mixing up samples or cross-contamination. In contrast, automation provides enables stronger quality control by reducing human-introduced error, contamination, and variation.
The high-throughput sequencing step is also a bottleneck because it limits the number of sequencing runs that can be performed at any one time. Manual processing also limits the scale at which samples can be processed and experiments performed because humans can only process a limited number of samples at a time. However, automation tools such as liquid handling robots can process many more samples in the same amount of time.
Advantages of Falcon and Falcon II automated NGS platforms
End-to-end automation offers the best solution for getting important NGS experiments right the first time and for doing so at a large scale. The Falcon – first generation of Novogene self developed multi-product fully automated NGS Intelligient Delivery Platform, went into production in March 2020. The recently released Falcon II platform offers the latest in automated end-to-end NGS innovation. The modular, compact (10 m2) Falcon II is Novogene’s newest innovation based on the powerful Falcon platform, which allows for efficient and flexible global localized installation and production.The first Falcon II system began operating at the Cambridge Sequencing Centre (UK) in the spring of 2022, and another has being installed and tested at the UC Davis Sequencing Center in the US, ready for commissioning. More sets are expected to be implemented at other Novogene facilities around the globe over the next few years.
As with the original Falcon platform, Falcon II takes a sample from extraction and sample quality control (QC) through library preparation, library QC and pooling, sequencing, and finally to bioinformatics analysis. Falcon II reduces manual handling up to 70% and reduces production time by up to 60%. In contrast to a partially automated workflow, it enables 7*24h uninterrupted smart operations of precise control, real-time monitoring and dynamic optimization of multi-product units, and the daily production is up to 384 samples. And like the original Falcon platform, Falcon II also reduces bottlenecks by concurrently process multiple NGS services, such as WGS, WES, and RNA-seq. Meanwhile, it maximized the reliability and stability of the whole sequencing processes, reduced manual intervention and avoided contamination to ensure the accuracy up to 99.99%.
Any interests of Novogene’s latest NGS automated intelligent delivery platform – Falcon II, please click here to get more information.
1.“Biotechnology goes automated” Healthcare industry BW. Published March 25, 2013. Accessed September 15, 2022.
2. Moore S, “Cell culture and automation: an overview” AZO Life Sciences. Published Feb. 19, 2020. Accessed September 15, 2022.
3. Holland I and Davies J, Automation in the Life Science Research Laboratory. Front Bioeng Biotechnol. 2020;8:571777.
4. “Facts about the current good manufacturing practices (CGMPs)” FDA.gov website. Published June 6, 2021. Accessed September 15, 2022.
5. Cook J, “Good laboratory practice versus CLIA” Westgard QC website. Accessed September 15, 2022.
6. Baker M, “1,500 scientists lift the lid on reproducibility”. Nature 2016;533:452-454.