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Quantum Bio Working on Stability, Scalability of Single-Molecule Sequencing Technology


NEW YORK (GenomeWeb) – Backed by a recent financing, Japanese next-generation sequencing instruments firm Quantum Biosystems is continuing development of its technology with current efforts directed at improving its stability and scalability. 

Quantum Bio President and CEO Toshihiko Honkura told GenomeWeb recently that the development of its two single-molecule nanogap sequencing platforms remains in place with plans for a small-scale early-access program for specific undisclosed applications within the next two years in Japan and the US. Based on input from the EAP, the company will then launch its products in the two countries, he added. 

While it will be a few years before the technology becomes available and the firm hasn't yet fully formed its pricing strategy, Honkura said that "it is not too ambitious to set the price" at less than $10,000 for the instrument and $10 for the silicon chip. 

However, Quantum Bio remains in the early stages of developing its two platforms, both of which use a pair of nanoelectrodes separated by a sub-nanometer gap to detect tunnel current changes as single-stranded DNA or RNA translocates the gap. The intellectual property around the firm's technology was licensed from Osaka University and Nagoya University. Quantum Bio, which was founded in 2013 by Honkura and the firm's CSO, Masateru Taniguchi, has also developed its own technology for manufacturing nanosilicon devices and for getting cleaner signals and reads.

Based in Osaka, Quantum Bio recently announced that it raised Y2.4 billion ($20.1 million) in a Series B financing round, bringing total investments in the company since its founding to Y3 billion. The new funding, it said at the time, would go toward developing its two nanogap sequencing platforms.

Its main platform uses a nanowire on a piece of silicon to form the gap as a "mechanically controlled break junction," Honkura told GenomeWeb in an e-mail. Last year, Quantum Bio released data around the technology, saying it was able to generate reads of about 20 base pairs from short oligonucleotides with accuracy of better than 99 percent in non-homopolymer regions, and 90 percent in regions with homopolymers. 

Quantum Bio is "now working on improving [the] fabrication process using [an] industrial facility, and improving [the] stability of the platform," Honkura said. 

The company's second platform is based on a gating nanopore to confine the motion of translocating DNA as well as prefabricated nanogaps. The company needs to conduct more research to obtain data similar to that achieved with the original platform, however, Honkura said, adding that the company hopes to conduct a proof-of-concept study for the gating nanopore technology. 

"Our goal is to continuously improve the platform for faster, cheaper, and more reliable (accurate and robust) sequencing with longer read length, better motion control, and more scalability" by expanding the number of electrodes per chip, Honkura said in his e-mail. 

Also, as the firm continues developing its technology, it will try to integrate some of the sample preparation function into its silicon-based chip, which can separate RNA/DNA from a sample, linearize the DNA fragments, and then guide them into the gap "between a pair of electrodes in order to measure tunneling currents with single-base resolution," Honkura added. 

That is a mid- to long-term project and Honkura did not have details about how Quantum Bio plans to achieve it. "We hope that we will be able to internally develop or identify external technologies ... which [fits well] with our sillicon based chip," he said.

He said that among the technical hurdles that Quantum Bio is working to overcome is the fact that tunneling current signals are "very sensitive" to numerous factors. The company's strategy is to lower the noise and to get stable signals "from electrical and mechanical perspectives," he said. Further, it is "developing [an] efficient process to make uniform silicon chips." 

While Honkura declined to say which of the currently available or still-in-development NGS platforms Quantum Bio would directly compete against, he said that a unique aspect of his firm's technology is that it would be able to detect various kinds of DNA modifications, such as methylated C and oxidated G, based on different levels of tunneling signals without the need for lengthy sample preparation or data interpretation. Another advantage of the technology is that a quantitative analysis of RNA can be done without bias, he said. 

But while Quantum Bio expects its technology will require a relatively simple sample prep process, there may be a need for some level of quality check after extracting DNA/RNA from samples, Honkura said. 

Meanwhile, on the bioinformatics side, the firm is developing custom software and algorithms for signal identification and base calling. 

Quantum Bio plans on targeting the research community for the initial launch of its technology with the clinical space to follow. While Honkura said that the firm has not yet made any decisions on assay development for the system, he said that it is "flexible and open for discussion" with potential partners on such development. 

He also noted that the applied markets and forensics space would be a "good fit" with Quantum Bio's platform, "since the platform [would] be able to deal with a very low number of DNA copies without amplification."