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Within the extensive array of instruments that Thermo Fisher Scientific offers, their Ion Torrent Next-Generation Sequencing systems remain important technologies for genomic research. Introduced in 2010 with the Ion PGM System (Personal Genome Machine), these sequencers have been continually evolving and facilitating new scientific insights.
After over a decade in the sequencing market, Jose Luis Costa, Global Director of Scientific Affairs at Thermo Fisher Scientific, maintains that Ion Torrent's sequencing systems continue to offer users multiple advantages. “The main advantage of working with Ion Torrent’s next-generation sequencing is that it's not just a sequencer; it’s an entire ecosystem of technologies that actually supports an end-to-end solution.” He underscores that this starts with the collection of biological material all the way to the data analysis and reporting. This approach simplifies and automates the process, allowing users to engage with a single vendor for all needs, including maintenance, support, and new technology acquisition.
Another important advantage that Costa emphasized is the technologies’ ability to manage challenging samples. “The technology is well-suited for more degraded samples. Even with samples that are a bit more compromised, degraded, and fragmented, this technology can provide robust results.” This is also due to some of the amplicon-based library preps offered with the sequencer.
The success rate of Ion Torrent sequencing is also one of the characteristics that Costa believes truly makes this technology stand apart from the others. He explained that when benchmarking next-generation sequencing technologies—the probability of having a successful sequencing run with valuable data—Ion Torrent sequencing is consistently high, stating that a successful run on the instrument "is usually above 94%," a figure that far outpaces the approximate success rate reported for other technologies.
Available sequencing technologies
Thermo Fisher Scientific currently offers two types of Ion Torrent sequencers. The first, the Ion Torrent Genexus Integrated Sequencer, is their all-in-one solution that streamlines the sequencing process. It automates the library prep, templating, and sequencing using one machine. Along with offering compatible analysis tools, Thermo Fisher also offers the Ion Torrent Genexus Purification System to extract and quantify the target nucleic acids. Costa implies that the Genexus System's comprehensive support for all of these essential processes provides significant benefits to their users.
This integrated system also boasts quick turnaround times. “With the Genexus System, we can reliably and robustly provide a result from DNA to report within 24 hours,” stated Costa. Traditionally with this type of technology, the sample processing, sequencing, and analysis take around three working days, but as Costa points out, collaborators and customers routinely have a turnaround time of less than 24 hours. Such speed is particularly important for their tumor profiling and liquid biopsy applications.
The alternative is the Ion GeneStudio S5 System, a more traditional option from the Ion Torrent family. This sequencer allows users to utilize all of the available Ion Torrent applications and assays and offers flexibility in throughput and runtime to match different project sizes and requirements. Like the Genexus, the Ion GeneStudio S5 System boasts fast run times and it integrates with the Ion Torrent Suite Software for a comprehensive set of analysis tools.
Semiconductor sequencing
Ion Torrent sequencers utilize semiconductor chips that detect the natural release of hydrogen ions during the DNA polymerization process. The sequencing process begins with a template preparation step where the DNA fragments to be sequenced are attached to beads, one fragment per bead. The fragments are copied and then cover the surface of each respective bead. These beads are then loaded into wells on the semiconductor chip.
Native nucleotides are added to the wells one base at a time, and each time a nucleotide is incorporated into the growing DNA chain, a hydrogen ion is released. This ion changes the pH in the well which generates a small voltage that the chip measures and records, indicating the identity of nucleotide that was added. The nucleotides are then washed away and the process is repeated with a different nucleotide. When the same type of nucleotide is added multiple times in a row, the voltage doubles, signifying that there are identical nucleotides. This process occurs across millions of wells at the same time, allowing for many different samples to be sequenced in parallel.
An advantage of this process is its use of natural nucleotides and native polymerase incorporation. This eliminates the need for fluorophores, modified bases, and laser imaging to detect nucleotide addition. As this technology bypasses fluorescence and camera scanning, it is often faster than other sequencing methods.
Common applications
Ion Torrent sequencing technology, according to Costa, excels in a variety of applications, particularly due to its ability to sequence minimal amounts of starting material. “We are the solution that has the lowest requirements for the amount of starting material.” Specifically, Thermo Fisher’s amplicon-based library preparation enables the production of sequencing reactions with as little as 1 nanogram of nucleic acids. Thermo Fisher is well established in the amplicon sequencing market with their popular Ion AmpliSeq products, which are also licensed across multiple sequencing providers. These amplicon sequencing solutions are used across a variety of research areas including disease detection, cancer studies, human identification, and custom applications.
“Our largest application area is tumor profiling,” stated Costa. “Tumor profiling is often done in tissues that are embedded in formalin-fixed paraffin-embedded, which means that these tissue biopsies tend to be quite small. So, the requirement to have a technology that can work with small samples and small amounts is a must.” FFPE processing is also notorious for causing severe degradation and fragmentation of nucleic acids. Yet, Costa asserts that the Ion Torrent is aptly equipped to handle these types of samples. “Due to our technology’s capacity to work with very degraded samples, we are a leader in the field of molecular profiling for tumor samples.”
Moreover, Ion Torrent technology has proven highly useful in oncology research involving liquid biopsy samples. Liquid biopsy involves the identification of circulating nucleic acids, often in the blood of cancer patients, which allows for an improved look into the genetics of the tumor. This method is less invasive than tissue biopsy, providing a more patient-friendly approach. The suitability of Ion Torrent technology for liquid biopsy lies in its capacity to analyze highly fragmented material. Circulating genetic material tends to be fragmented due to enzymes and endonucleases present in the bloodstream, resulting in very small DNA fragments. Ion Torrent technology can be utilized to identify these small fragments, generate amplicons from them, and sequence these fragments, which allows for a non-invasive study of tumors.
Additionally, Ion Torrent instruments commonly serve to examine peripheral blood for detecting aneuploidies and identifying genetic alterations in embryos through maternal blood analysis. This extends to pre-implantation embryo testing, facilitating the identification of embryos carrying aneuploidies to avoid their implantation.
Advances and the future
Recent advancements in Ion Torrent technologies have been marked by improvements in throughput, accuracy, and run times. One pivotal innovation has been the integration of full automation into the workflow with the Genexus System. This has expedited both the sequencing process and the time it takes to obtain actionable results.
Thermo Fisher Scientific has also been actively broadening the range of options that can be incorporated into their fully automated Genexus System platform. Initially, the platform was launched with targeted assays that were primarily relevant for solid tumors and liquid biopsies. Today, however, Thermo Fisher is expanding these offerings to facilitate more comprehensive tumor sample profiling.
This development not only enhances automation but also provides a more complete view of tumor characteristics. It enables users to explore the tumor's genetic landscape in a more detailed way, contributing to personalized treatment strategies and advancing our understanding of cancer genomics.