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ASU Spinout INanoBio Aims to Develop Nanopore Transistor

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Arizona State University spinout INanoBio is developing a field-effect nanopore transistor for DNA sequencing and analyte sensing applications.

The company is based in Tempe, Ariz., was founded in 2007, and currently has eight employees. It is licensing technology from Arizona State University related to the nanopore sensor it is developing. It also has multiple patent applications for techniques related to sequencing unmodified DNA, Founder and CEO Bharath Takulapalli told In Sequence.

The company is currently in discussions with life sciences and pharmaceutical companies about forming strategic partnerships, aims to have a preliminary publication on its technology in the next several months, and is in the process of raising funds.

Takulapalli said that INanoBio is aiming to develop a sequencing device that will essentially combine nanopore technology with silicon transistor chip technology. "It's called a field effect nanopore transistor, because we are building a transistor around a nanopore," he said.

A key feature that will set it apart from other nanopore sequencing technologies is that DNA will not need to be slowed down as it translocates through the pore.

Most nanopore sequencing technologies use ion current blockages as a signal for identifying the bases trapped in the nanopore as DNA passes through. However, to use this technique, DNA must be slowed down as it passes through the pore.

While researchers have developed techniques to do this, including the "ratcheting" technique being commercialized by Oxford Nanopore Technologies where an enzyme slows down movement through the pore, INanoBio is working on an approach that will not require the DNA to be slowed down.

"We're trying to develop a sensor where you do not need to slow down the DNA," Takulapalli said. Instead, the nanopore acts as a high-frequency field-effect transistor.

The sensor is based on technology that Takulapalli published on in 2010 in the journal ACS Nano. In the study, he described a sensor that used unique capacitive charge-coupling mechanisms to exponentially increase the signal elicited from the analyte. In the study, the sensing technology was applied to nanowires, but now the company is working to develop a nanopore sequencing device that uses the same principles.

In the device, the field effect transistor surrounds the nanopore in all three dimensions, so that the DNA can be detected as it passes through by measuring the electric current signal inside the transistor, Takulapalli said. As DNA passes through, the electrostatic interactions modulate the current inside the field effect transistor device, he explained.

The transistor the firm is developing will operate at a frequency of 100 megahertz or higher, Takulapalli said, which will enable the detection of bases at a rate of about one million bases per second — fast enough to detect DNA translocation at its natural speed.

Ultimately, INanoBio is aiming for a low-cost, rapid device that would cost several thousand dollars with chips starting at around $50. Each chip would hold thousands of nanopores and Takulapalli anticipates that a 10,000-nanopore transistor chip could sequence a whole human genome at 10x coverage, while a 100,000-nanopore transistor chip could sequence a genome at 50x coverage.

He said that the device would be able to sequence 1 megabase-sized DNA fragments with no amplification needed. Data will be read as an electronic signal through the transistor.

The company is currently working on building a prototype device, which it expects to be ready by the end of the year.

While INanoBio is developing its own sequencing device based on this technology, Takulapalli said that he is also open to working or partnering with sequencing companies to integrate INanoBio's nanopore transistor detection method with alternative platforms.

Partnering with established sequencing companies could help INanoBio enter a highly competitive market. Already, Takulapalli said the company has had discussions with two sequencing companies.

Additionally, INanoBio's sensor concept could be adapted to tag sequencing approaches.

Genia's so-called NanoTag technology, for instance, uses a polymerase coupled to a protein nanopore to incorporate tagged nucleotides into a DNA template such that each nucleotide carries a tag of a different size.

Rather than then identifying the tags via ionic current blockage, INanoBio's field effect nanopore transistor could theoretically distinguish each of the tags, Takulapalli said

Regardless of how INanoBio first commercializes its technology, the startup will be entering a highly competitive market. Aside from the established players, such as Illumina and Life Technologies, a number of other startups also plan to hit the market with their own devices soon.

Oxford Nanopore Technologies recently began an early access program for its MinIon system. David Jaffe from the Broad Institute presented the first data from the system at the Advances in Genome Technology and Biology meeting in Marco Island, Fla., last month. Earlier this month, the company's Chief Technology Officer Clive Brown presented additional details of the MinIon technology at the Plant Genomics Congress in Kuala Lumpur, Malaysia.

Last year, Genia said it planned to launch its instrument in late 2014.

Takulapalli said the next steps for INanoBio are to secure investors and financing, finish building the prototype, and to demonstrate data.

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