Graphene could accelerate genomics

Oct 28, 2008
DNA moving through a graphene nanogap

Artist's impression of a DNA molecule (helix) moving through a tiny slit in a graphene sheet (shown in blue). (Courtesy: Henk Postma)

The “wonder material” graphene could soon be used to analyse DNA at a record-breaking pace. That’s the claim of a physicist in the US who has proposed a new way of reading the sequence of chemical bases in a DNA strand by sending the molecule through a tiny slit in a graphene sheet.

While the technique has yet to be verified experimentally, if successful it could be eligible for the $10 million X Prize for Genomics, which has set the challenge of developing a new rapid and low-cost sequencing technology.

The genetic profile — or “genome” — of an organism is determined by recording the full sequence of acid base pairs that make up its DNA. In 2003, the Human Genome Project made history by determining the entire human genetic code — 3 billion DNA base pairs that took 13 years to analyse using a technique that has changed very little since the late 1970s.

This “shotgun” approach first isolates a DNA strand and forces it to copy itself millions of times over in a chemical reaction. These are then “blasted” into tiny fragments because current techniques for sequence reading can detectors can only analyse very short sections of DNA. Finally, a supercomputer matches up overlapping base patterns to piece together the full genome.

No processing required

Now, Henk Postma at California State University Northridge has proposed a way of sequencing an entire DNA strand without the need for blasting or computer processing (arXiv:0810.3035v1 ).

Rapid Sequencing of Individual DNA Molecules in Graphene Nanogaps
http://arxiv.org/PS_cache/arxiv/pdf/0810/0810.3035v1.pdf

The technique involves cutting a very narrow slit or “nanogap” along the length of a piece of graphene — an extremely strong sheet of carbon just one atom thick. A voltage is applied perpendicular to the graphene’s surface, which causes the DNA strand to pass slowly through the slit one base at a time.

A second voltage is applied across slit and electrons are able to “tunnel” across the nanogap via the base that happens to be passing through the slit. There are four different types of base in a DNA molecule, and each should support a different tunnelling current — allowing the base type to be identified.

While the idea of sequencing DNA by sending it through a tiny gap is not new, previous schemes had relied on using separate materials for the membrane and electrodes — and aligning the two materials has proved to be a considerable challenge. Postma’s design gets around this problem by having the graphene function as both membrane and electrode.

Postma believes that detector could be made from a graphene sheet sandwiched between glass plates that are held together by van der Waals forces.

Technology should be possible

According to Changgu Lee, a mechanical engineer at Colombia University, some of the technology to realize Postma’s design may be available already. “Creating the nanogaps in graphene was demonstrated this year using both STM [scanning tunnelling microscopy] and catalytic cutting with metal particles”, he said.

Postma told physicsworld.com that traditional sequencing techniques are limited to determining about 800 base pairs per recording. By contrast, he estimates his design could yield 100,000 bases per recording, and if run continuously it would read the whole human genome in two and a half hours. He also believes that his technique could lead to sequencing devices that are smaller and cheaper than existing systems.

If successful, Postma's system could be a contender for the X Prize for Genomics, which aims to award $10m to the inventor of a device that can sequence 100 human genomes within 10 days or less,to a specified accuracy and costing no more than $10,000 per genome.

Postma said he is continuing to develop his design, but added: “I published the paper to get feedback from the scientific community, in the open, because I believe that will lead to the best possible technology.”

And it seems DNA experts are ready for a new technology. Geoffrey Baldwin, a molecular biologist from Imperial College in the UK said “to truly develop health care we need the profile of 100s of genomes not just the few we have at the moment”. He added “there is now a great opportunity for a new technique to become the standard in base sequencing”.

About the author

James Dacey is a science journalist based in the UK

Source

Strikes me as a DNA computer in the making.

Electroporation device and injection apparatus

United States Patent Application	20080234655
Kind Code	A1
Mathiesen; Iacob ; et al.	September 25, 2008

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Electroporation device and injection apparatus

Abstract

An apparatus is provided for injecting a fluid into body tissue, the apparatus comprising: a hollow needle; and fluid delivery means, wherein the apparatus is adapted to actuate the fluid delivery means in use so as to automatically inject fluid into body tissue during insertion of the needle into the said body tissue.

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Inventors:	Mathiesen; Iacob; (Oslo, NO) ; Tjelle; Torunn; (Oslo, NO) ; Rekdahl; Knut Arvid Sorensen; (Tarnasen, NO) ; David-Andersen; Bjorn; (Oslo, NO)
Assignee Name and Adress:	INOVIO AS San Diego CA

Claims

1. Apparatus for injecting a fluid into body tissue, the apparatus comprising: a hollow needle; and fluid delivery means, wherein the apparatus is adapted to actuate the fluid delivery means in use so as to concurrently inject fluid into body tissue during insertion of the needle into the said body tissue.

2. Apparatus as claimed in claim 1 adapted to automatically inject fluid into body tissue during insertion.

14. A method of injecting a fluid into body tissue, the method comprising: injecting the fluid into the body tissue through a hollow needle while the said needle is being inserted into the said body tissue.

[0007]From a first aspect, the present invention provides an apparatus for injecting a fluid into body tissue, the apparatus comprising: a hollow needle; and fluid delivery means, wherein the apparatus is adapted to actuate the fluid delivery means in use so as to concurrently (preferably automatically) inject fluid into body tissue during insertion of the needle into the said body tissue. This has the advantage that the ability to inject the fluid gradually while the needle is being inserted leads to a more even distribution of the fluid through the body tissue. It is also believed that the pain experienced during injection is reduced due to the distribution of the volume of fluid being injected over a larger area.

Source

See also - WO/2004/004825
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A DNA-based vaccine shows promise against avian flu

Posted: September 30, 2008

Though it has fallen from the headlines, a global pandemic caused by bird flu still has the United States’ Centers for Disease Control and Prevention on high alert. Yet, to date, the only vaccines that have proven even semi-effective are produced in chicken eggs, take five to six months to prepare and act against a single variant of the H5N1 virus, which mutates incredibly quickly. Now, new research by scientists in New York and Taiwan has led to a vaccine with the potential to stop most strains of H5N1 flu viruses in their tracks. David D. Ho, Rockefeller’s Irene Diamond Professor and scientific director of the Aaron Diamond AIDS Research Center, together with his colleagues at Taiwan’s Academia Sinica, has built a vaccine that stimulates immunity to a broad range of H5N1 viruses in mice by using DNA rather than dead virus particles grown in eggs. Such a vaccine, which consists of plasmid DNA that’s been genetically modified to elicit specific immune responses, is much easier to rapidly modify and produce — critical advantages when racing to prevent an epidemic. Ho and his collaborators first had to address virus specificity: Because H5N1 viruses are incredibly diverse, and mutate fast, the researchers created a consensus sequence that incorporated all of the conserved parts of the gene encoding the virus’s outer protein. Then they had to figure out how to deliver it. This is where DNA vaccines often fail. They aren’t very good at making sure the DNA gets where it needs to go. To solve this problem, Ho and his colleagues turned to electroporation, a technique that is just beginning to gain traction in the vaccine world and that, according to preliminary studies, helps increase uptake of the vaccine. By combining their consensus-sequence vaccine with a small electric stimulus, the researchers found that their mouse subjects responded with an incredibly broad immune reaction. “The immune responses directed to our DNA vaccine seem to be very broad,” Ho says. “It could be that the vaccine in its current form could protect against most of the H5N1 viruses out there.” And even if it can’t, he notes, if a different strain of H5N1 begins to circulate, it should only take a few days to obtain its genetic sequence and adapt the existing vaccine to fight it. A version of the consensus vaccine is already being produced, Ho says, so that it can move into human clinical trials as quickly as possible. And a separate electroporation study is under way at The Rockefeller University Hospital, this one examining the effectiveness of electroporation combined with a DNA vaccine against HIV. Proceedings of the National Academy of Sciences 105(36): 13538–13543 (September 9, 2008) Contact: Zach Veilleux 212-327-8982 newswire@rockefeller.edu

Source
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Making GNA for nanotechnology

In the rapid and fast-growing world of nanotechnology, researchers are continually on the lookout for new building blocks to push innovation and discovery to scales much smaller than the tiniest speck of dust.

In the Biodesign Institute at Arizona State University, researchers are using DNA to make intricate nano-sized objects. Working at this scale holds great potential for advancing medical and electronic applications. DNA, often thought of as the molecule of life, is an ideal building block for nanotechnology because they self-assemble, snapping together into shapes based on natural chemical rules of attraction. This is a major advantage for Biodesign researchers like Hao Yan, who rely on the unique chemical and physical properties of DNA to make their complex nanostructures.

While scientists are fully exploring the promise of DNA nanotechnology, Biodesign Institute colleague John Chaput is working to give researchers brand new materials to aid their designs. In an article recently published in the Journal of the American Chemical Society, Chaput and his research team have made the first self-assembled nanostructures composed entirely of glycerol nucleic acid (GNA)-a synthetic analog of DNA.

"Everyone in DNA nanotechnology is essentially limited by what they can buy off the shelf," said Chaput, who is also an ASU assistant professor in the Department of Chemistry and Biochemistry. "We wanted to build synthetic molecules that assembled like DNA, but had additional properties not found in natural DNA."

The DNA helix is made up of just three simple parts: a sugar and a phosphate molecule that form the backbone of the DNA ladder, and one of four nitrogenous bases that make up the rungs. The nitrogenous base pairing rules in the DNA chemical alphabet fold DNA into a variety of useful shapes for nanotechnology, given that "A" can only form a zipper-like chemical bond with "T" and "G" only pair with "C."

In the case of GNA, the sugar is the only difference with DNA. The five carbon sugar commonly found in DNA, called deoxyribose, is substituted by glycerol, which contains just three carbon atoms.

Chaput has had a long-standing interest in tinkering with chemical building blocks used to make molecules like proteins and nucleic acids that do not exist in nature. When it came time to synthesize the first self-assembled GNA nanostructures, Chaput had to go back to basics. "The idea behind the research was what to start with a simple DNA nanostructure that we could just mimic."

The first self-assembled DNA nanostructure was made by Ned Seeman's lab at Columbia University in 1998, the very same laboratory where ASU professor Hao Yan received his Ph.D. Chaput's team, which includes graduate students Richard Zhang and Elizabeth McCullum were not only able to duplicate these structures, but, unique to GNA, found they could make mirror image nanostructures.

In nature, many molecules important to life like DNA and proteins have evolved to exist only as right-handed. The GNA structures, unlike DNA, turned out to be 'enantiomeric' molecules, which in chemical terms means both left and right-handed.

The only chemical difference between DNA and a synthetic cousin, GNA, is in the sugar molecule. GNA uses a three-carbon sugar called glycerol rather than the five-carbon deoxyribose used in DNA. The sugar provides the chemical backbone for nucleic acid polymers, anchoring a phosphate molecule and nitrogenous base (B). Credit: Biodesign Institute at Arizona State University

"Making GNA is not tricky, it's just three steps, and with three carbon atoms, only one stereo center," said Chaput. "It allows us to make these right and left-handed biomolecules. People have actually made left-handed DNA, but it is a synthetic nightmare. To use it for DNA nanotechnology could never work. It's too high of a cost to make, so one could never get enough material."

The ability to make mirror image structures opens up new possibilities for making nanostructures. The research team also found a number of physical and chemical properties that were unique to GNA, including having a higher tolerance to heat than DNA nanostructures. Now, with a new material in hand, which Chaput dubs 'unnatural nucleic acid nanostructures,' the group hopes to explore the limits on the topology and types of structure they can make.

"We think we can take this as a basic building block and begin to build more elaborate structures in 2-D and see them in atomic force microscopy images," said Chaput. "I think it will be interesting to see where it will all go. Researchers come up with all of these clever designs now."

Source

IBM experimenting with DNA to build chips

The research uses DNA molecules to arrange carbon nanotubes into a grid that might function as a data storage device or to perform calculations.

By Michael Kanellos
Staff Writer, CNET News.com

Published: February 20, 2008, 4:00 AM PST

Will the building block of life become the building block of the semiconductor industry? It's possible.

Scientists at IBM are conducting research into arranging carbon nanotubes--strands of carbon atoms that can conduct electricity--into arrays with DNA molecules. Once the nanotube array is meticulously constructed, the laboratory-generated DNA molecules could be removed, leaving an orderly grid of nanotubes. The nanotube grid, conceivably, could function as a data storage device or perform calculations.

"These are DNA nanostructures that are self-assembled into discrete shapes. Our goal is to use these structures as bread boards on which to assemble carbon nanotubes, silicon nanowires, quantum dots," said Greg Wallraff, an IBM scientist and a lithography and materials expert working on the project. "What we are really making are tiny DNA circuit boards that will be used to assemble other components."

The work, which builds on the groundbreaking research on "DNA origami" conducted by California Institute of Technology's Paul Rothemund, is only in the preliminary stages. Nonetheless, a growing number of researchers believe that designer DNA could become the vehicle for turning the long-touted dream of "self-assembly" into reality.

Chips made on these procedures could also be quite small. Potentially, DNA could address, or recognize, features as small as two nanometers. Cutting-edge chips today have features that average 45 nanometers. (A nanometer is a billionth of a meter.)

"What we are really making are tiny DNA circuit boards that will be used to assemble other components."

--Greg Wallraff, IBM scientist

"There is nothing else out there that we can do that with," said Jennifer Cha, an IBM biochemist working on getting the biological and nonbiological molecules to interact.

Right now, products get manufactured in a top-down approach with machinery and equipment manipulating raw materials. In self-assembly, the intrinsic chemical and physical properties of molecules, along with environmental factors, coax the raw materials into complex structures. It works with snowflakes, after all.

Getting the raw materials to behave in a precise, orderly manner, however, remains a challenge, which is where DNA comes in. DNA consists of specific chemical bases (guanine, cytosine) that bind and react in somewhat predictable ways with each other.

"The sequence (of base pairs in DNA) is well known," said Cha. "Most people are acknowledging that DNA and these biological scaffolds are actually quite useful to at least pattern very small systems."

How it works
In creating chip arrays, DNA assembly might work as follows: scientists would first create scaffolds of designer DNA manipulated into specific shapes. Rothemund has made DNA structures in the shapes of circles, stars, and happy faces.

A pattern would then be etched into a photo-resistant surface with e-beam lithography and the combination of several interacting thin films. A solution of the designer DNA would then be poured on the patterned surface and the DNA would space themselves out according to the patterns on the substrate and the chemical/physical forces between the molecules.

The nanotubes would then be poured in. Interactions between the nanotubes and the DNA would occur until they formed the desired pattern. Single strand DNA, along with origami, could be used in concert.

Another key part in the system revolves around peptides that can bind to the DNA and a nonbiologically inspired molecule like a nanotube.

"Building a DNA scaffold is not trivial because you need the biological system to recognize something that doesn't exist at all in biology," said Cha. "We can also use these biomechanical scaffolds to position inorganic nanomaterials. Potentially, we could also use these biomechanical systems to synthesize inorganic materials."

Although it's early, progress is occurring. Researchers have published papers on how DNA can coil around nanotubes and disperse them in water. Papers detailing how DNA can arrange nanotubes will come soon. Future experiments will need to be conducted into aligning nanotubes into arrays. Other researchers in this field include Nadrian Seeman at New York University and Thom LaBean at Duke University.

IBM will also examine ways of employing DNA to sort nanotubes, said Cha. Not all nanotubes are equal. The arrangement and relative position of carbon atoms in a nanotube, called chirality, can change the properties of a nanotube. Some nanotubes can't conduct electricity, for instance, even though they were made with others that do conduct electrons. Separating good from bad nanotubes currently requires applying an electric field, soaking them in solutions, or selecting by hand.

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If DNA manufacturing can become a reality, worries about the pace of progress in the computing world slowing down because of the difficulties involved in following Moore's Law would likely fade, at least for a while. Chipmakers shrink the size of the features of their chips every two years. While this improves the performance, producing smaller circuits has strained the financial and technical resources of the industry. The limits of lithography (used to "draw" circuits) have prompted many, including Intel co-founder Gordon Moore, to predict that the pace of progress would slow down.

With DNA, chipmakers could phase out multibillion fabrication facilities stocked with lithography systems, which cost tens of millions of dollars, and the other "top-down" style equipment.

Potentially, DNA techniques could allow manufacturers to produce features that are smaller than patterns that could be achieved even with the most advanced lithography systems, predicted Wallraff. E-beam lithography, which is extremely difficult to use in mass manufacturing, goes down to 10 nanometers.

"Of course, the devil is in the details," said Wallraff. "These are self-assembly procedures and error rates--missing features could be the downfall."

http://www.news.com/IBM-experimenting-with-DNA-to-build-chips/2100-1008_3-6231183.html

Applied Nanotech Inc - ANI - enters the DNA scaffolding self-assembly picture

Biophysicist / Biochemist

Applied Nanotech, Inc., (Austin TX) is looking for a Biophysicist / Biochemist to help start a project in DNA electronics, sensors or similar applications. This could include using DNA scaffolding for self-assembly of devices or systems. Will require building a team, which may include collaborative efforts with university or other organizations or companies. Require writing proposals to help acquire funding support.

Education: PhD or equivalent required. Candidate should demonstrate good verbal and written command of the English language. US citizen or Green Card desired. Please send resumes to Jsoptick@appliednanotech.net

http://www.nano-proprietary.com/ANI/EmploymentANI.asp

The next frontier for information processing may lie at the interface of nanoelectronics and biotechnology.

DNA scaffolding
Special report: Minnesota's Digital Dynasty

An interdisciplinary team led by electrical and computer engineering professor Richard Kiehl is exploring the use of DNA as a programmable scaffolding for the self-assembly of nanoscale electronic components. As a model for fabricating and designing semiconductor devices and circuits, DNA offers two key advantages: size scale and programmability.

Most industry experts believe that within the next 10 to 15 years the ability to scale down conventional technologies will reach its limit. At that point, the operating principles of conventional devices—and the techniques used to fabricate them—will break down. The basic elements of the DNA molecule are at just the right scale, says Kiehl.

Self-assembly uses bio-recognition, a natural process in which one molecule is attracted to and binds with another to form small structures. In the case of DNA, the attraction can be programmed so that the molecules will spontaneously assemble in solution to achieve a desired result.

“It's possible to synthesize small versions of DNA molecules in the laboratory and program in whatever code you want,” says Kiehl. “And because the two strands of DNA have complementary codes that match up, you can design one strand of DNA in a certain way so it will match another strand and assemble a nanoscale structure this way."

The matched segments form a scaffolding on which nanoparticles are affixed at highly selective attachment points. It's an approach that offers the programmability and precision needed for assembling electronic circuitry on the nanoscale.

“We have to make a real paradigm shift,” Kiehl says. “Not only do we have to keep improving performance, but we also must look at the kinds of devices we can make at those scales and how we want to use them to process information."

To that end, the researchers are turning to the human brain for inspiration. They envision devices whose electrical characteristics resemble those of neuron-like electrical waveforms in the brain. Like certain regions of the brain, the devices would process information based on pattern recognition rather than on individual bits of information. It's a more sophisticated level of information processing than can be achieved using conventional computers.

Kiehl predicts there will be a wide range of applications for this technology, including signal processing, communications systems, and computer systems. “The higher end of this [work] will be things that computers can't do very well today because the operations they use are too restrictive. One is the ability to recognize a pattern, such as identifying a letter as being an 'A' or a 'B', or being able to identify a face.

“It won't be just making things faster and faster in the conventional way,” he says. “It will really be opening up new ways to process information in machines."

http://www.it.umn.edu/news/inventing/2000_Fall/nano_dnascaffold.html

3/26/2007 7:10:17 AM
US Department of Defense grant gives $6M to team of 9 scholars for the study of quantum electronic arrays

The U.S. Department of Defense (DoD) has awarded a team of nine scholars from six universities a grant of $6 million over five years to exploit precise biological assembly techniques for the study of quantum physics in nanoparticle arrays. This research will produce a fundamental understanding of quantum electronic systems that could impact future electronics.

Leading the effort is electrical and computer engineering professor Richard Kiehl of the University of Minnesota, who has wide experience in investigating the potential of novel fabrication techniques, physical structures and architectures for electronics. Kiehl has brought together a multidisciplinary team to develop biological strategies combining DNA, proteins and peptides with chemical synthesis techniques to construct arrays of nanoparticles and to systematically characterize the resulting quantum electronic systems.

Interactions between precisely arranged nanoparticles could lead to exotic quantum physics, as well as to new mechanisms for computing, signal processing and sensing. But even basic studies of such nanoparticle arrays have been hampered by the need to fabricate test structures with extreme control and precision. "By exploiting biology to precisely control size, spacing and composition in the arrays, we will be able to examine electronic, magnetic and optical interactions at much smaller scales than before," said Kiehl. "Our project blends some really fascinating science at the edges of biology, chemistry, materials science and physics. And, I'm excited about the chance to impact how electronic circuits could be engineered in the future."

The team members are UCLA professors Yu Huang (materials science), Kang Wang (electrical engineering) and Todd Yeates (biochemistry); New York University professors Andrew Kent (physics) and Nadrian Seeman (chemistry); University of Texas at Austin professor Allan MacDonald (physics); University of Pennsylvania professor Christopher Murray (chemistry & materials science); and Columbia University professor Colin Nuckolls (chemistry).

Kiehl and Seeman have previously collaborated in the first demonstrations of metallic nanoparticle self-assembly by DNA scaffolding, which will be central to this project. Seeman will exploit DNA nanotechnology to construct 2-D and 3-D scaffolding, while Huang and Yeates will use peptides and proteins to make nanoparticle clusters for assembly onto the scaffolding. Murray and Nuckolls will synthesize metallic and magnetic nanoparticles with organic shells that will self-assemble onto the scaffolding and control the interparticle coupling. Kent, Kiehl and Wang will carry out experiments to characterize the electronic, magnetic and optical properties of the arrays. MacDonald will provide theoretical guidance for the studies and analysis of the experimental results.

The award was made by the Army Research Office (Marc Ulrich, research topic chief) and is one of 36 recently made under the highly competitive DoD Multidisciplinary University Research Initiative (MURI).

http://nanotechwire.com/news.asp?nid=4466&ntid=&pg=51

Re Seeman - NANS - his company was ~$1 then - it is now a shell and sits at $0.012
http://finance.yahoo.com/q?s=NANS.OB

NANS Annual Report - 8-Jan-2008

ITEM 6. MANAGEMENT'S DISCUSSION AND ANALYSIS OR PLAN OF OPERATION

The following information should be read in conjunction with the consolidated financial statements and notes thereto appearing elsewhere in this Form 10-KSB. We have determined on December 1, 2007 to cease operations immediately and, at the request of our principal creditor appointed a director designated by such creditor to our Board of Directors. Immediately following such appointment, our existing directors resigned effective immediately and terminated their association with us. Accordingly, such creditor may be deemed to control us at the date of the filing of this Report. As a result of our cessation of operations and the termination of the License Agreement, we became a "blank check" or "shell company" whose sole purpose at this time is to locate and consummate a merger or acquisition with a private entity.
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Certainly not greatly encouraging! Looks like the future is in the hands of the DOD grants and perhaps ANI - who knows!! I'm looking forward to my first DNA scaffold assembled....whatever - TV? ;-)