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Oxford Nanopore Technologies Launches Smaller PromethIon Sequencer


BALTIMORE – Accompanied by a stadium rock product animation video, Oxford Nanopore Technologies on Monday formally rolled out its PromethIon 2 Solo (P2 Solo) sequencer, moving the platform from developer release to early-access phase.

Comparing P2 Solo’s size to "one printed volume of 'The Lord of the Rings' trilogy," Oxford Nanopore claimed that the palm-sized, high-yield sequencing unit can deliver "comprehensive DNA analysis for anyone, anywhere." At full capacity, the company said, P2 Solo allows researchers to generate as many as 380 human genomes a year in their own lab while capturing other genomic features such as single nucleotide polymorphisms (SNPs), structural variants, and methylation.

"[F]rom our experience in the market, we have seen a huge desire to access the high-yield nanopore sequencing that is done on [PromethIon flow cells], at a level that is vastly more accessible to scientists," an Oxford Nanopore spokesperson wrote in an email. "The PromethIon 2 device was conceived as an extension to the existing PromethIon family to meet that need."

The concepts of P2 Solo and its sibling model, PromethIon 2 (P2), were both first unveiled during Oxford Nanopore’s annual user meeting in London last year. Both instruments are designed to accommodate up to two PromethIon flow cells and generate the same amount of sequencing data.

However, P2 Solo, as a modular sequencing unit, works principally similar to a MinIon — it requires a host platform, which the company said could be a GridIon or a laptop, that is capable of operating the sequencer and carrying out basecalling. In comparison, P2, which is equipped with a computer, a GPU for basecalling, and a touch screen for control, can carry out sequencing alone.

As such, while P2 Solo "provides a lower cost barrier to entry for accessing high-yield nanopore sequencing," the spokesperson said, P2 offers researchers "a straightforward, streamlined solution" at a higher cost. According to Oxford Nanopore’s website, the list price for a P2 Solo starter pack, which includes the sequencer, flow cells, and other consumables, is $10,455; and the list price for a P2 starter pack is $59,995.

Although P2 Solo uses the same flow cells and "has the same capabilities" as the higher-throughput PromethIon 24 and 48 devices, the electronics of P2 Solo were designed for miniaturization and incorporated other design improvements, according to the spokesperson. One such improvement, she said, is that P2 Solo moved away from the PCIe connector previously used on the P24 and P48 to the standard USB-C connector, enabling the sequencer to be compatible with a GridIon or modern IT setups. 

When it comes to the new platform’s performance, the company claimed that customers in the developer program, which took off this spring and included researchers with a range of biological applications, have been achieving "anticipated accuracies" with the newest Q20+ chemistry. In a statement, Oxford Nanopore said using the latest R10.4.1 flow cell and the Q20+ chemistry, P2 Solo delivered sequencing data with modal raw-read simplex accuracies of 99.6 percent (Q24) and single-molecule duplex accuracies of 99.92 percent (Q31).

Beyond that, the firm did not share data on the platform’s accuracy, and it did not directly address a question regarding some researchers’ concerns about the technology’s accuracy on indels and homopolymers. According to the spokesperson, although P2 Solo was designed to run Oxford Nanopore’s latest Q20+ sequencing chemistry, the platform maintains back compatibility with earlier chemistries.

As for sequencing cost, Oxford Nanopore said with its "box is free" model, customers can complete "comprehensive" human genomes in their own lab for less than $1,000 with the P2 series, at one to two human genomes per flow cell.

In terms of other applications, the company said the data yield of the PromethIon flow cell allows researchers to carry out sequencing on large genomes as well as to conduct transcriptomic studies such as single-cell sequencing with full-length transcripts. Additionally, the company said it hopes P2 Solo will lead current GridIon users to the higher-yield PromethIon flow cells and support core labs to expand "at hugely reduced capital expenditures compared to other sequencing platforms."

In that regard, P2 Solo appears to have some researchers excited.

Rasmus Wollenberg, chief technology officer of DNASense, a Danish DNA sequencing company, said in an email that his company, an early adopter of P2 Solo, has been using the platform mainly for metagenomic sequencing since this summer.

"The P2 Solo is a flexible solution that [enables] small-scale in-house handling of DNA from input-limited metagenome samples or samples requiring more data than a single MinIon flow cell can provide," he said. "Excluding a few bad runs, so far, we are routinely generating more than 120 GB of data, which is very promising considering that we have been running early-access flow cells on an early-access device," he noted.

In addition, Wollenberg said P2 Solo can be a more cost-effective platform for the company because sequencing on a single PromethIon flow cell reduces the DNA input requirement and sequencing costs versus multiple MinIon flow cells. "For us, this is very ideal, as we can have samples associated with very low DNA extraction yield, when splitting the DNA onto five MinIon flow cells would not be feasible," he added.

Commenting on the new platform’s performance, Wollenberg said that using the latest R10.4.1 chemistry, the P2 Solo in his team's hands has achieved Q19 to Q20 modal accuracies for metagenomes and Q20+ for pure fungal culture genomes.

Despite the new instrument’s promises, he also pointed out some of its current pitfalls. "It should be noted that we did experience a few initial software glitches, including pores suddenly dropping to zero, needing to restart runs, [being] unable to basecall, which were frustrating," he said. However, Wollenberg added that Oxford Nanopore "has been relatively fast with the updates," and his team is overall "very pleased" with P2 Solo and Oxford Nanopore’s technical support.

Still, "basecalling and IT infrastructure will be a challenge for most people as massive amounts of data need to be basecalled using high-end GPUs," he said. "[P2 Solo] was intended to be paired with their GridIon. That said, [using] super-accurate basecalling algorithm via the GridIon is not able to keep up with the rate of raw data generation."

To circumvent the problem, Wollenberg said his lab is currently basecalling P2 Solo data on its own server, and he is hoping Oxford Nanopore’s upcoming basecaller, Dorado, will eventually solve this problem.

Scott Tighe, technical director of the University of Vermont’s Advanced Genomics Lab, shared similar hopes. His lab recently ordered a P2 Solo but is still waiting for the instrument to arrive. We are "excited to attach it to our GridIon and start large, multiplexed experiments," he said, adding that with about 10 times the data output of a standard GridIon flow cell, P2 Solo "will be perfect" for his team to sequence human genomes and carry out high-density multiplexing genomic studies.

At least for some researchers, P2 Solo appears to be a replacement for the MinIon without significantly more investment. That said, it is unclear how P2 Solo will impact the market share of Oxford Nanopore’s existing products.

"Basically, the P2 Solo is a replacement for the MinIons we are using in the lab," said Christopher Vollmers, a biomolecular engineering professor at the University of California, Santa Cruz, whose lab just received the instrument. "Altogether, we can generate more data for less money without having to outsource experiments. We are really excited about this machine."

According to Vollmers, his lab already has a computer that could run the P2 Solo. Therefore, the upgrade is "basically free, considering the value of flow cells and reagents that are included with the purchase," he said.

"In terms of flow cell cost, PromethIon flow cells and MinIon flow cells can be fairly close in price depending on the volume of flow cells you buy, but PromethIon flow cells generate about four to five times the amount of data," he added.

Oxford Nanopore said the difference in data output between a MinIon and a PromethIon flow cell is still "significantly different," and the company believes MinIon "will always be useful" for sequencing smaller genomes or for more targeted sequencing studies.

The company did not disclose how many researchers have participated in P2 Solo’s development phase or how many customers have signed up to become early customers so far. "We always receive a high amount of interest from end users to be the first to try our newest products, and PromethIon 2 devices were no exception to this," the spokesperson said.

In terms of customer base, she said the company is seeing "interest from users with GridIon devices who want to further increase their nanopore sequencing capabilities, and from customers who have been regularly running on MinIon who wish to access higher yields in a similar affordable, accessible device."

Oxford Nanopore did not release a clear timeline of when the P2 series instruments will be fully released after the early-access phase. For now, the company’s website indicates that new orders for P2 Solo are targeted to ship before the end of this year while P2 is available for pre-order and will be available for shipment in the coming months.