Oxford Nanopore unveils data from portable genome sequencer

MinION results are promising, but fall short of high expectations.

Oxford Nanopore

Oxford Nanopore's MinION sequencer can read DNA fragments up to 10 kilobases long.

A good first shot, but not a game-changer — yet. That seems to be the consensus among scientists after the first public release today of data produced by the MinION, an advanced and much-anticipated DNA sequencing device developed by Oxford Nanopore in the UK.

The MinION aims to be the first commercially available sequencer that uses nanopore technology, which has been in development for nearly two decades. The approach identifies bases of DNA by measuring the changes in electrical conductivity they generated as they pass through a biological pore. Oxford claims that its nanopore machines will be faster and cheaper than existing sequencing technologies, and will allow scientists to analyse regions of the genome that cannot be amplied.

The MinION is not yet for sale. But David Jaffe, a computational biologist at the Broad Institute in Cambridge, Massachusetts, used data produced by the device and provided by Oxford to aid in the assembly of two bacterial genomes — those of Escherichia coli and a bacterium from the genus Scardovia that is found in the human mouth. He presented his results today at the Advances in Genome Biology and Technology meeting in Marco Island, Florida.

“It’s kind of a cute device,” Jaffe says of the MinION, which is roughly the size and shape of a pack of gum. “It has pretty lights and a fan that hums pleasantly, and plugs into a USB drive.” But his technical review is mixed.

The average length of the sequences generated on the MinION was 5.4 kilobases, with some as long as 10 kilobases. That is longer than the average read delivered by the current dominant technology, sold by San Diego, California-based Illumina, which delivers fragments of DNA that are hundreds of base pairs long. But the median length of the MinION’s reads is shorter than the target that Oxford announced in 2012.

Mixed picture
Jaffe also found that the MinION appeared to have difficulty sequencing particular parts of the bacterial genomes that he studied. That is worrisome to bioinformaticians, because it is more challenging to correct for systematic sequencing errors than random ones. In Jaffe's case, the recurring errors prevented him from assembling the complete genome sequences of the two bacteria from scratch using only MinION data; instead, he used MinION sequences to supplement data generated by Illumina machines.

Yet he sounded an optimistic note about the MinION's future. Oxford has said that higher-quality DNA or different preparation methods should increase the average read length. Jaffe says that the company can work to eliminate errors, perhaps by using a mix of pores with different properties. But even now, he says, the vast majority of long MinION reads had lengthy stretches without any mistakes. The systematic errors are “a temporary feature that we hope they'll figure out how to solve.”

Other researchers will soon have a chance to form their own opinions about the new device, as Oxford today launched its early-access programme. Researchers who pay a US$1000 deposit, plus $250 for shipping costs, can receive MinIONs on which they can run their own experiments.

Isaac Ro, an analyst at the investment bank Goldman Sachs — which advised Illumina in 2012 when it fought off a takeover bid by the drug giant Roche — called Jaffe's presentation “underwhelming”. “Oxford Nanopore still appears to be in development mode and, in our view, is unlikely to threaten [Illumina’s] competitive position at this time,” he said in a research note.

But some scientists still think that the MinION has potential to shake up the sequencing industry. Geneticist Yaniv Erlich of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, says that the small, cheap and portable MinION is unlike the bulky, pricey sequencing machines that scientists are used to. If Oxford continues to improve the technology, he says, it will enable a range of applications that are not possible today, such as using sequencers in the field.

“This reminds me of the early days of Illumina, when all we could get were 36-base-pair reads, and we were all very excited about that,” Erlich says. “I think we should give [Oxford] more time.”
Nature doi:10.1038/nature.2014.14724

Related stories
Is the $1,000 genome for real?
Nanopore genome sequencer makes its debut
Personal genomes: Standard and pores

More related stories


ORIGINAL: Nature 

By Erika Check Hayden
14 February 2014 

New Device May Put DNA Testing in Doctors' Hands

A U.K.-based company, QuantuMDX, has built a working prototype of a device, shown here, that they hope will allow doctors to perform genetic tests within 15 minutes. The "x-ray" section of this image shows the nanowire biosensor chip and electronics.
Credit: QuantuMDx Group Ltd


It can take days for doctors to determine if a patient infected with malaria carries a drug-resistant version of the disease. The same is true of tuberculosis.

But a new testing device could reduce that time lag to 15 minutes, potentially helping to ensure that patients are correctly treated right away, says the company developing this device.

United Kingdom company QuantuMDX now has a working prototype for a device intended to quickly test a sample of blood, sputum (saliva mixed with mucus) or even tumor cells for genetic markers that provide information to guide a doctor's decisions on how to treat a patient. [7 Diseases You Can Learn About from a Genetic Test]


"We want to put a full diagnostic test into the palms of health professionals' hands," said Elaine Warburton, chief executive officer of QuantuMDX and the company’s cofounder.

The prototype is about the size of an iPad 5, or 6.6 by 9.4 inches (17 by 24 centimeters), but thicker. In about six months, Warburton said she anticipates the device will be reduced to about the size of an iPad mini, 5.3 by 7.9 in. (13 by 200 cm).

To use it, a doctor would put a sample from a patient into a credit-card sized, disposable cartridge and pop the cartridge into the device for analysis, she said. So far, the prototype has shown success in producing DNA test results from blood. ..

The sensor in the device is intended to detect, for example, if a person is infected by the malaria parasite, which species of parasite is responsible for the infection and whether the parasite is resistant to antimalarial medications.

Detection happens when fragments of parasite DNA from the sample bind to complementary strands, or probes, in the cartridge. These probes are associated with nanowires, thin pieces of silicon etched into a computer chip. The binding produces an electrical change in the wires, which the device interprets as a positive result.

This basic technique can be applied in many ways. QuantuMDX is developing applications that could one day provide information about tumor cells, or determine if someone has genetic variations that will affect his or her response to the blood-thinning drug warfarin. And the company has received proposals from people interested in using it in everything from veterinary work to forensics, Warburton said.

The device, currently known as Q-POC (pronounced Q-pock), is still a long way from being used in the clinic. The company still has work to do on the cartridges for use with the handheld prototype, and it needs to run clinical trials testing the device, followed by regulatory approval from bodies such as FDA, Warburton told LiveScience in an email.

Earlier this month at the Consumer Electronics Show in Las Vegas, Jonathan O'Halloran, inventor of the technology and the company's cofounder, announced plans to launch a crowdfunding campaign. The campaign is expected to begin on Feb. 12 on the site Indigogo.com, to support further development of the Q-POC. The company is also interested in suggestions for a new name and design for the device, Warburton said.

If all goes well, QuantuMDX anticipates commercially launching the device and malaria test cartridge in Africa in 2015, she said.

Follow LiveScience @livescience, Facebook & Google+. Original article on LiveScience. -

ORIGINAL: Live Science

By Wynne Parry, LiveScience Contributor

January 16, 2014

TellSpec: What's in your food?

A revolutionary hand-held device that tells you the allergens, chemicals, nutrients, calories, and ingredients in your food.

• 

  
  

• 

  
  

• 

  
  

How does it work?
TellSpec brings together laser spectroscopy, nanophotonics, and a unique mathematical algorithm in a revolutionary hand-held consumer device that can analyze the chemical composition of any food in less than 20 seconds.

The TellSpec handheld device beams a low-powered laser at the food you wish to analyze, measures the reflected light with a spectrometer, and sends the data via your smart phone, computer, or tablet to TellSpec’s servers in the cloud. Those servers use this data to deduce information about your food that is of interest to you. This information is then displayed on your computer, tablet or smart phone so you can intelligently decide if you want to buy or eat the food.

Features

Open & Accessible Our platform is available to anyone, anywhere, to raise money for anything.

Free and Immediate You can start creating your campaign right now for free. There is no application process.

Open to Any Campaign You can raise money for anything, including for-profit ventures, creative ideas or personal needs.

Global Access No matter where you live, you can start your campaign and collect money from any country in the world as long as you have a valid bank account. Back to top Start Now ▶

Powerful Tools We have the tools you need to easily create, share and manage your campaign.

Create Use our platform to customize and publish a professional online funding campaign. No tech skills needed!

Share One-click social media integration, direct email and announcement features make it easy to spread the word, raise awareness and increase funding.

Track Manage contributions with our analytics tools, and stay on top of sending off your perks with our dashboard. Track who has claimed perks and how to get in touch with contributors to ensure they receive perks on time. Back to top Start Now ▶

Global Exposure Get merit-based promotion to make people around the world aware of your campaign.

Gogofactor Exposure Indiegogo promotes campaigns based on their gogofactor. This is a unique, merit-based algorithm that tracks the level of activity of each campaign based on how much you share, update, and attract funding. Work hard on your outreach, and we'll give you a boost!

Social Media and Community Outreach Based on your gogofactor activity, you may be eligible for exposure in our social media outreach, community and content creation, and press access. This is how Indiegogo helps to generate excitement and interest in your campaign! Back to top Start Now ▶

Personalization We provide campaign options and educational support that are right for you.

Your Money, Your Choice Keep all the money you raise, even if you don't meet your goal. Or, opt for Fixed Funding and only keep your money if your campaign reaches its goal.

Customizable Template You can customize your campaign page using our step-by-step set up. Write your story, upload videos, create a gallery of images, and offer perks.

Flexible Payment Options All campaigns can offer multiple funding types to their contributors, including PayPal and major credit cards.

Ongoing Education You can learn as you go from the experts (yes, real people!). Our Customer Happiness team and our blog posts will help you along the way - and we always respond in 24 hours or less.

TellSpec's CEO and CTO show a live demo of the TellSpec's food analysis algorithm.

A message from Dr Stephen Watson, TellSpec's CTO:

A message from Isabel Hoffmann, TellSpec's CEO:


TellSpec in the News:

ORIGINAL: Indiegogo

Extracting human DNA with full genetic data in minutes

ORIGINAL: KurzweilAI
May 13, 2013

Hand-held device for extracting DNA (credit: UW/NanoFacture/KNR)

University of Washington engineers and NanoFacture, a Bellevue, Wash., company, have created a device that can extract human DNA from fluid samples in a simpler, more efficient and environmentally friendly way than conventional methods.

The device will give hospitals and research labs a much easier way to separate DNA from human fluid samples, which will help with genome sequencing, disease diagnosis and forensic investigations.

Separating DNA from bodily fluids is a cumbersome process that’s become a bottleneck as scientists make advances in genome sequencing, particularly for disease prevention and treatment. The market for DNA preparation alone is about $3 billion each year.

Conventional methods use a centrifuge to spin and separate DNA molecules or strain them from a fluid sample with a micro-filter, but these processes take 20 to 30 minutes to complete and can require excessive toxic chemicals.

A close-up view of the portable device (credit: UW/NanoFacture/KNR)

UW engineers designed microscopic probes that dip into a fluid sample – saliva, sputum or blood – and apply an electric field within the liquid. That draws particles to concentrate around the surface of the tiny probe. Larger particles hit the tip and swerve away, but DNA-sized molecules stick to the probe and are trapped on the surface. It takes two or three minutes to separate and purify DNA using this technology.

“This simple process removes all the steps of conventional methods,” said Jae-Hyun Chung, a UW associate professor of mechanical engineering who led the research.

The hand-held device can clean four separate human fluid samples at once, but the technology can be scaled up to prepare 96 samples at a time, which is standard for large-scale handling.

The tiny probes, called microtips and nanotips, were designed and built at the UW in a micro-fabrication facility where a technician can make up to 1 million tips in a year, which is key in proving that large-scale production is feasible, Chung said.

Engineers in Chung’s lab also have designed a pencil-sized device using the same probe technology that could be sent home with patients or distributed to those serving in the military overseas. Patients could swab their cheeks, collect a saliva sample, then process their DNA on the spot to send back to hospitals and labs for analysis.

This could be useful as efforts ramp up toward sequencing each person’s genome for disease prevention and treatment, Chung said.

The market for this device isn’t developed yet, but Chung’s team will be ready when it is. Meanwhile, the larger device is ready for commercialization, and its creators have started working with distributors.

A UW Center for Commercialization grant of $50,000 seeded initial research in 2008, and since then researchers have received about $2 million in funding from the National Science Foundation and the National Institutes of Health.

MinION - $900 usb-powered DNA sequencer on sale this year

ORIGINAL: GizMag

By Brian Dodson

February 19, 2012

The MinION is the size of a USB memory stick, and obtains both power and computer analysis from a normal laptop computer (Image: Oxford Nanopore)

The MinION is the size of a USB memory stick, and obtains both power and computer analysis from a normal laptop computer (Image: Oxford Nanopore)

Oxford Nanopore (ON) has been developing a disruptive nanopore-based technology for sequencing DNA, RNA, proteins, and other long-chain molecules since its birth in 2005. The company has just announced that within the next 6-9 months it will bring to market a fast, portable, and disposable protein sequencer that will democratize sequencing by eliminating large capital costs associated with equipment required to enter the field.

The MinION is the size of a USB memory stick, and obtains both power and computer analysis from a normal laptop computer. No polymerase chain reaction (PCR) or other DNA amplification technique is needed for optimum sensitivity. The MinION is capable of sequencing 100 million base pairs within its six hour working life. Samples of whole blood, plasma, and serum are accepted by the device for immediate analysis and the reagents needed for the analytic process come ready to use with each MinION.

What are nanopores?

A nanopore is an organic molecule penetrated by a very small (~1-2 nanometer) hole (Image: Oxford Nanopore)

A nanopore is an organic molecule penetrated by a very small (~1-2 nanometer) hole. These nanopores are embedded in a synthetic polymer membrane which is only two molecular layers in thickness. Initially bilayer lipid membranes, similar to those appearing throughout the body, were used, but proved far too fragile to use in a production sequencer. Development of such a thin membrane that has extremely large electrical resistance and is sufficiently rugged for use in the field was a major (and successful) ON project.

A nanopore embedded in a synthetic polymer membrane collects small molecules for identification (Image: Oxford Nanopore)

A nanopore is mounted upon such a membrane so that the hole in the nanopore forms a path from one side of the membrane to the other. The membrane is then positioned so that it divides a volume of an electrophysiological fluid in half.

This diagram shows a protein nanopore set in an electrically resistant membrane bilayer (Image: Oxford Nanopore)

The image above shows a nanopore embedded in a membrane. A voltage difference is placed between the two halves of the fluid. The fluid contains mobile ions, so an ion current then passes through the center of the nanopore. This ionic current acts to sweep nearby molecules, proteins, and even DNA or RNA into the mouth of the nanopore.

If a target molecule is drawn into or upon the nanopore, it disrupts the flow of ions in a characteristic manner which can be detected and interpreted.

Although in the image it appears that the detection current is only due to physical obstruction of the nanopore, one must remember that the chemical bonds of the nanopore and the target molecules have unique distributions of electronic charge. The target molecule will attempt to lodge in the nanopore so that the potential energy of the system is lowest. This effect, together with the possibility of modifying the structure of the nanopore to increase the difference in the ionic current for a set of target molecules implies that selectivity can be adjusted to detect small differences in molecular structure.

A wide range of molecules can be detected and identified using the nanopore ionic current measurements, ranging from small physiological or pharmaceutical molecules to proteins. However, the MinION is directed toward DNA sequencing, so the nanopore and enzymes in the electrophysiological fluid are optimized to differentiate the four amino acids (adenine, cytosine, guanine, and thymine) which encode genes in DNA. In the final result, three amino acids are read simultaneously by the nanopore, which possesses the delicacy to differentiate between the 64 possible combinations.

Strand sequencing

The MinION uses a strand sequencing technique for DNA analysis. Strand sequencing is shown in the following excellent video from Oxford Nanopore.

Nanopore DNA sequencing from Oxford Nanopore on Vimeo.

Here's a quick overview: The DNA strand is attracted to an enzyme that is part of the electrophysiological fluid. In turn, the enzyme is attracted to a nanopore, in which it lodges. The enzyme is engineered to unzip the double-helix structure of the DNA strand so that one strand is directed back into the fluid, while the other enters the nanopore for sequencing. More amazing is that the enzyme incorporates a ratcheting structure, so the single DNA strand does not pass quickly through the nanopore, but rather advances one base pair at a time. The rate at which the DNA strand passes through the nanohole is controlled by the magnitude of the unobstructed ionic current, and can be as large as 15 base pairs per second. Better accuracy is associated with slower rates.

If a target molecule is drawn into or upon the nanopore, it disrupts the flow of ions in a characteristic manner which can be detected and interpreted (Image: Oxford Nanopore)

The sensing electronics for the ionic current is fabricated on a sample chip, which comprises 512 nanopores, giving a total strand reading rate of about 7500 bases/second. The MinION has a limited operational life of about 6 hours, but in that time can read over 150 million bases.

Sample chips for the MinION incorporate 512 electrically distinct nanopores, each with its own sensing electronics (Image: Oxford Nanopore)

For comparison, the largest human chromosome, chromosome 1, contains about 250 million base pairs. Attempting to read a smaller complete chromosome (say, number 22, which has about 50 million base pairs) would require that the chromosome be split into a large number of pieces which would be analyzed concurrently, and the pieces reassembled. This is not the primary purpose of MinION, but it does provide data which would make possible such a feat.

Bringing genetic analysis out of the research lab

The MinION has successfully been used to read the genome of the lambda bacteriophage, about 48500 base pairs in length, twice in a single pass. This was accomplished by closing the end of the DNA with a hairpin closure, so that both strands in the genome would pass through the same nanopore. Reading roughly 100,000 base pairs in a single DNA capture is unheard of using more traditional sequencing techniques.

The MinION has successfully been used to read the genome of the lambda bacteriophage, about 48500 base pairs in length (Image: Oxford Nanopore)

During interviews just proceeding the product announcement at AGBT 2012, Clive Brown, the Chief Technology Officer of Oxford Nanopores, revealed that the expected $900 price tag for the MinION has a good bit of margin built in. We can thus expect prices to fall quickly as production becomes routine in its challenges.

The science and engineering research which has gone into making a device like the MinION possible is a remarkable feat for the ages. It is difficult to point to any portion of the development which was straightforward. It is to be hoped that the impact of MinION and future developments thereof is to truly begin to bring genetic analysis out of the research lab as a vital tool for physicians' office.

Source: Oxford Nanopore

About the Author

Brian Dodson

From an early age Brian wanted to become a scientist. He did, earning a Ph.D. in physics and embarking on an R&D career which has recently broken the 40th anniversary. What he didn't expect was that along the way he would become a patent agent, a gourmet cook, a biotech entrepreneur, an opera tenor and a science writer.