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With $35M in Funding and First Patent, Quantapore Bets on Optical Readout for Nanopore Sequencer

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NEW YORK (GenomeWeb) – Startup Quantapore is developing a nanopore sequencer with optical readout that promises to deliver long reads and high throughput at a low cost per base and with little sample preparation.

Last week, the Menlo Park, Calif.-based company said that it raised up to $35 million from undisclosed investors in a Series B financing round. Co-founder and CEO Martin Huber told In Sequence that the firm has several million dollars of the funding at its disposal now, with a large portion contingent on milestones six and 12 months from now, and a small part to be made available later for commercialization purposes.

Huber, who holds a PhD in genetics and biochemistry from the University of Vienna in Austria and was previously at Ion Torrent, co-founded Quantapore in 2009 with Sascha Dennstedt, the firm's president. The company became operational in 2010 with $700,000 in seed financing and raised several million dollars in a Series A round from undisclosed investors in 2012.

Quantapore is currently based in a technology incubator in Menlo Park and plans to increase its headcount from a current five to about 15 by the end of this year.

Also last week, Quantapore researchers and their academic collaborators at Wake Forest University School of Medicine published an article in Nanoscale about a method for reducing the background fluorescence of silicon nitride membranes with nanopores, allowing them to detect the translocation of DNA tagged with fluorescent labels through the pores.

While the reduction in background will be important for its technology, and Quantapore has filed patents on the method, Huber said the paper does not touch on its sequencing approach, for which it has shown proof of concept and which is currently its main focus.

The approach relies on a combination of drilled solid-state nanopores, with a diameter of 5 to 7 nanometers, and biological nanopores, which helped the company solve the problem of unstable lipid bilayers that many other groups using biological pores had to grapple with.

The DNA bases are labeled in an undisclosed manner and the labels are detected as the molecule translocates through the nanopore. Not all bases are detected at the same time, so reads from several DNA molecules are combined to obtain the entire sequence. Read lengths are expected to be on the order of tens of kilobases. "We have two different approaches," Huber said, but did not elaborate. "The user can choose which type of sequencing they want to pursue."

Unlike nanopore or nanodetector systems that only label certain stretches of the DNA, such as Nabsys' platform, Quantapore labels the entire molecule without large gaps. "We might not look at all the bases at the same time but we don't hybridize [probes to] certain areas and only that's detected," Huber explained.

Last month, Quantapore obtained its first US patent, entitled "Ultrafast sequencing of biological polymers using a labeled nanopore." According to the patent, which has not yet been published in the US Patent & Trademark Office patent database, a donor label attached to a nanopore transfers energy to an acceptor label on a DNA base as the DNA translocates through the pore. The acceptor then emits a signal that can be detected optically.

The company has filed applications for six other patents that cover various aspects of its technology, two of which have published so far. One application, filed with Wake Forest collaborator and scientific advisory board member Adam Hall and entitled "Hybrid nanopore device with optical detection and methods of using same," describes a device with a protein nanopore inserted in a lipid bilayer that sits within a solid-state nanopore. This setup allows the use of Förster resonance energy transfer, or FRET, pairs to generate optical signals as labeled DNA translocates through the protein pore.

The other application, called "Apparatus and methods for performing optical nanopore detection or sequencing," mentions that the translocation rate of the DNA through the pore may be reduced by increasing the diameter of the molecule, and talks about the possibility of using an array of pores.

The main difference between Quantapore and most other nanopore sequencers is the optical readout. "That has advantages and disadvantages, no questions about that," Huber said, though he believes the pros outweigh the cons.

One advantage of optical detection over measuring the electric current through the pores, like Oxford Nanopore Technologies and others, is that the pores don't need to be insulated from each other, which he said will make it easier and less expensive to interrogate more pores in parallel. "There is a limit, it can't go indefinitely, but it's relatively easy for us to increase our throughput and still keep our cost low, so our overall cost [per base] will be lower," Huber said.

Also, Quantapore will feed the DNA through the pores faster than Oxford Nano, which uses molecular motors to slow it down. Though Quantapore will need to reduce the speed of the DNA somewhat, the translocation speed will be on the order of 800 nucleotides per second, Huber said, compared to between one and 100 bases per second, the current speed of Oxford Nano's MinIon.

Another startup, NobleGen Biosciences, has also been working on nanopore sequencing with optical detection, but its approach requires the conversion of DNA into a longer molecule where each base is replaced with an oligonucleotide, and the hybridization of labeled molecular beacons that are stripped off and detected when the DNA goes through the nanopore. NobleGen has not provided an update on its progress since 2012, but CEO Frank Feist told IS last week that the company still exists.

Unlike NobleGen, Quantapore will not convert the DNA, nor will its library preparation require clonal amplification. "The sample prep is minimal," Huber said, and should take no longer than half an hour, with five minutes of hands-on time.

Over the next year or so, Quantapore will further develop its technology. After that, it plans to test alpha versions of its systems with collaborators, followed by a commercial launch, initially as a research tool.

The system's optics will use off-the-shelf components, Huber said, and the platform will be priced similar to existing benchtop sequencers, on the order of $100,000 to $150,000, though consumables costs will be significantly lower.

While the company is focusing on building a sustainable business, it does not rule out the possibility of being acquired sometime in the future. "Looking at the sequencing market over the past five to eight years, it would be naive to say an acquisition could never happen," Huber said.

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