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What is quantum biosystems?

1)Quantum Sequencing™

Single Molecule Electronic Detection
A critical issue in medical research is the need for ultra-high-speed analysis of DNA sequences and ultra-sensitive, ultra-fast detection of viruses and allergens such as pollen. However, even leading global companies have so far been unable to develop the next-generation technology required to implement this.

The new technology we have developed—based on a gating-nanopore method, using tunneling current measurement—has the potential to change that. The U.S. National Institute of Health (NIH) has stated that our technology could lead to breakthroughs in ultra-high speed and ultra-sensitivity analysis that will never be possible using existing technologies.

Single molecule electronic detection provides the ultimate methodology for genome analysis. Our technology identifies base molecules by measuring tunnel current through nano-electrodes as DNA/RNA passes through nanogaps, and by calculating the current difference. Each chip has a nanogap through which only a single strand of DNA or RNA passes, and the device uses nanoelectrodes (one molecule-wide gap between electrodes) to measure tunnel current.

 

2)Why it’s so innovative

Bias free (PCR free)

The polymerase chain reaction (PCR) amplifies one or several copies of a piece of DNA by several orders of magnitude, to generate up to millions of copies of that DNA sequence. However, this reaction can cause mutations as the enzymes copy sequences. Current DNA sequencing technology depends on PCR, resulting in inherent accuracy issues due to PCR generated errors. Our system eliminates the need to use PCR.

High throughput

Our integrated nano-chip system can analyze multiple fragments simultaneously enabling high-throughput. Analyzing the same bases multiple times at very high speed using tunnel current reduces errors and achieves high sequencing accuracy. The extremely high throughput of our technology will enormously increase the accuracy of sequencing.

Epigenetics

Using tunnel current to identify bases also allows us to analyze base modifications such as DNA methylation, since modified and unmodified bases have different tunnel currents. The ability to do this is a crucial requirement in epigenetics, and yet current DNA sequencing methodology cannot directly identify base modifications. Our technology will make possible personal genome sequencing over the course of a person’s lifetime.

Low cost

Our technology does not require pre-treatments such as labeling, PCR, or detection with fluorescent reagents, which are widely used in current DNA sequencing. In addition, our nano chips are semiconductors that can be mass-produced at low cost. The result will be a dramatic reduction in the price of DNA sequencing, putting genetic sequencing within the reach of the individual.

3)Original Inventor – Osaka University

 

Professor Tomoji Kawai of Osaka University is Quantum Biosystems’ lead scientific advisor. He has worked toward the development of a fourth generation DNA/RNA sequencer within the Funding Program for World-Leadng Innovative R&D on Science and Technology (FIRST) project.
Unlike currently used sequencers, this fourth generation sequencer will work at the ultimate level of single molecule detection.
Last year, Professor Kawai’s project team successfully demonstrated the principle, paving the way to practical applications.
DNA sequencer researchers and engineers worldwide are closely following this project’s results.
Quantum Biosystems is a biotech start-up of Osaka University, founded with the goal of finding rapid practical applications for the FIRST project’s research findings.

4)TECHNOLOGY

The world’s first commercial quantum sequencing systems

Our sensor: a breakthrough in molecular sensing

Technology Components

We have demonstrated the direct electrical detection and sequencing of DNA and RNA for the first time. Our proprietary fabrication process creates nanoscale gaps between sensing electrodes through which strands of DNA and RNA translocate. A bias voltage applied across the gap slows the motion of the molecule and is used to measure its conductance.
The result is a clear trace, showing the translocation of single molecules, where each base produces a clear and district contribution to the signal and is easily processed into base calls.

Technology Components

On-chip sample prep

In order to provide a complete sequencing system on a chip, our devices incorporate on-chip sample preparation to denature and linearize the DNA. The molecule is first denatured by microheaters and then driven through an array of nanopillars to ensure linearization before it reaches the sensor.

On chip sample prep

Motion control

While existing sequencers work on large collections of molecules, our devices measure single molecules. This means we have to precisely control the motion of each molecule as it translocates the gap. We make use of electrophoretic flow to enable control over the motion of a single molecule.

Amplification and signal processing

Our low noise current amplification and signal processing platform amplifies the signal and processes it into base calls in real time. The digital processing core of our instruments is the open hardware Novena platform.
Amplication and signal processing

Quantum Sequencers

QS1M

Our first generation instruments are built around an MCBJ (Mechanically Controllable Break Junction). This allows us to fabricate sub-nanometer gaps in situ. An electrophoretic flow controls the motion of the DNA as it translocates the gap. While this platform is still in development, you can find some early data releases here.

QS1M

Note that multiple junctions can be integrated on a single device, scaling the technology to create a high-throughput sequencing instrument.
QS1M
Multiple junctions
QS1M
System setup

QS2G

Our second generation devices are based on prefabricated gaps and apertures, making each instrument even cheaper and smaller. The aperture confines the motion of the DNA as it translocates through the sensing electrodes propelled by electrophoretic flow.

QS2G

QS2G

5)VISION

Quantum Sequencing™: The genetic code, unlocked by physics

Mission

Our mission is to unlock the vast untapped value of genetic information through the development of innovative sequencers. This information has the power to transform biological research, improve knowledge of health and disease, and harness any genome in the challenge to address urgent global needs for food, fuel and healthcare.

At Quantum Biosystems, we are pioneering the development of innovative sequencers based on quantum mechanics. Quantum-based sequencing technologies are widely regarded as impractical, but our team at Quantum Biosystems is transforming them into a viable platform for DNA sequencing.

Our proprietary Quantum Sequencing™ technology achieves single molecule electrical DNA sequencing by integrating cutting edge silicon technology and a sophisticated electric detection system into breakthrough approaches to life sciences. This platform allows disruptively label-free, low-cost, high-throughput, and real-time analysis with no need for complex sample preparation, detection, or analysis.

Picoamperes. Nanogaps. Terabytes of Life data.

In 1958, Reona “Leo” Esaki, a Japanese physicist working for Tokyo Tsushin Kogyo (now Sony), invented a new diode based on the quantum mechanical effect known as tunneling. Leo Esaki shared the 1973 Nobel Prize in Physics for his discovery of the phenomenon of electron tunneling. His tunnel diode, also called the Esaki diode, was an innovation that would transform the history of electronics.

The tunneling effect, or quantum tunneling, is a phenomenon whereby a microscopic particle uses quantum effects to “tunnel through” a potential energy barrier. We use the dependence of current magnitude on the physical properties of an object to decrypt DNA sequence information.

To achieve single molecule sequencing, our devices travel on a data journey from pico and nano right through to the tera realm. Pico-level sensitivity is required to differentiate tunnel currents to identify bases. The controls to adjust the diameter of the nanogates through which DNA and RNA pass must have nano-level sensitivity. And the data generated by measuring tunnel current requires terabyte-level storage to enable bioinformatics analysis.

Soaring beyond physics, Quantum Sequencing™ is now poised to bring disruptive innovation to the life sciences, and extraordinary benefits to the world.

6)Japan’s Quantum Biosystems

Japan’s Quantum Biosystems has reportedly raised ¥2.4 billion ($20.5 million) in venture funding in support of its superpowerful development stage DNA sequencing machine designed to decode DNA in a couple hours for $1,000.

The funding of the potential competitor to Roche ($RHHBY) and Illumina ($ILMN) comes on top of a ¥450 million ($3.8 million) round in February 2014.

In January, Quantum released raw data access reads showing that its sequencing platform is accurate in more 99% of certain DNA regions. The company says its silicon-based platform is reagent-free. And the technology’s utility isn’t limited to just clinical purposes.

“Faster and cheaper DNA sequencing is vital to help produce the best cancer drugs for each individual,” company CEO Toshihiko Honkura told Bloomberg in a prior interview. “It would be able to sequence DNA of bacteria in soil, helping farmers identify the crop types and ways of farming best suited for each plot of the farmlands.”

Commercialization is slated to occur in 2017. Quantum plans to open a Silicon Valley office before that and conduct an IPO in the U.S. or Japan in 2018, according to Bloomberg.

Quantum’s backers include Jafco, Innovation Network Corp. of Japan, Mizuho Capital, University of Tokyo Edge Capital and Mitsubishi UFJ Capital, according to Bloomberg, which cited an unnamed source with knowledge of the company.

If successful, the company’s fourth-generation technology would epitomize the advances in genome sequencing ever since the human genome was first published. The Bloomberg article points out that the feat took 13 years and cost $3 billion.

Development and commercialization of single molecule DNA sequencer based on quantum mechanics

Quantum Biosystems is pioneering the development of innovative sequencers based on quantum mechanics. Its proprietary Quantum Sequencing[TM] technology achieves single molecule electrical DNA sequencing by integrating cutting edge silicon technology and a sophisticated electric detection system into breakthrough approaches to life sciences. This platform allows disruptively label-free, low-cost, high-throughput, and real-time analysis with no need for complex sample preparation, detection, or analysis.

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