285-micron racecar (credit: Vienna University of Technology) For those interested in atomically precise manufacturing, 3D-printing is an interesting microscale technology for making centimeter-scale objects. We commented on this technology a few months ago with the introduction of two competing technologies for printing complex digitally-designed plastic consumer items. Foresight Senior Associate Charles Vollum sends word of the extension of 3D-printing to nanoscale (approximately 100 nm) resolution. In addition, the new procedure is much faster and enables true 3D fabrication, without requiring layer-by-layer fabrication. A hat tip to KurzweilAI for describing this Vienna University of Technology news release “ 3D-printer with nano-precision “: Printing three dimensional objects with incredibly fine details is now possible using “two-photon lithography”. With this technology, tiny structures on a nanometer scale can be fabricated. Researchers at the Vienna University of Technology (TU Vienna) have now made a major breakthrough in speeding up this printing technique: The high-precision-3D-printer at TU Vienna is orders of magnitude faster than similar devices (see video). This opens up completely new areas of application, such as in medicine. The video shows the 3d-printing process in real time. Due to the very fast guiding of the laser beam, 100 layers, consisting of approximately 200 single lines each, are produced in four minutes. Setting a New World Record The 3D printer uses a liquid resin, which is hardened at precisely the correct spots by a focused laser beam. The focal point of the laser beam is guided through the resin by movable mirrors and leaves behind a polymerized line of solid polymer, just a few hundred nanometers wide. This high resolution enables the creation of intricately structured sculptures as tiny as a grain of sand. “Until now, this technique used to be quite slow”, says Professor J
Posts Tagged ‘NANOTECH’
Fast nanoscale 3D-printing (link to video)
Posted in Nanotechnology 
Tags: charles-vollum, dramatically, laser, Mems, NANOTECH, Printing, Professor, Technology, Video, vienna, world-record 
Comments OffNanoparticles reduce tumors in clinical trial
An artist’s rendering of BIND-014. Image credit: Digizyme, Inc. We have often reported here that targeted nanoparticles to treat cancer have shown great promise in animal studies. An MIT news release written by Anne Trafton now informs us that “ Targeted nanoparticles show success in clinical trials “: Targeted therapeutic nanoparticles that accumulate in tumors while bypassing healthy cells have shown promising results in an ongoing clinical trial, according to a new paper. The nanoparticles feature a homing molecule that allows them to specifically attack cancer cells, and are the first such targeted particles to enter human clinical studies. Originally developed by researchers at MIT and Brigham and Women’s Hospital in Boston, the particles are designed to carry the chemotherapy drug docetaxel, used to treat lung, prostate and breast cancers, among others. In the study, which appears April 4 in the journal Science Translational Medicine [ abstract ], the researchers demonstrate the particles’ ability to target a receptor found on cancer cells and accumulate at tumor sites. The particles were also shown to be safe and effective: Many of the patients’ tumors shrank as a result of the treatment, even when they received lower doses than those usually administered. “The initial clinical results of tumor regression even at low doses of the drug validates our preclinical findings that actively targeted nanoparticles preferentially accumulate in tumors,” says Robert Langer, the David H. Koch Institute Professor in MIT’s Department of Chemical Engineering and a senior author of the paper. “Previous attempts to develop targeted nanoparticles have not successfully translated into human clinical studies because of the inherent difficulty of designing and scaling up a particle capable of targeting tumors, evading the immune system and releasing drugs in a controlled way.” The Phase I clinical trial was performed by researchers at BIND Biosciences, a company cofounded by Langer and Omid Farokhzad in 2007. “This study demonstrates for the first time that it is possible to generate medicines with both targeted and programmable properties that can concentrate the therapeutic effect directly at the site of disease, potentially revolutionizing how complex diseases such as cancer are treated,” says Farokhzad, director of the Laboratory of Nanomedicine and Biomaterials at Brigham and Women’s Hospital, associate professor of anesthesia at Harvard Medical School and a senior author of the paper. … The news release goes on to detail several features of these nanoparticles that may be useful in evaluating other types of nanoparticles that are currently at earlier stages of development and have only been tested in animal models. First of all, nanoparticles of many different compositions have been developed, from gold to DNA. These, called AccurinsTM , use clinically validated biocompatible polymers and incorporate a “stealth” layer to avoid removal by the immune system. As explained in the news release: One of the challenges in developing effective drug-delivery nanoparticles, Langer says, is designing them so they can perform two critical functions: evading the body’s normal immune response and reaching their intended targets. “You need exactly the right combination of these properties, because if they don’t have the right concentration of targeting molecules, they won’t get to the cells you want, and if they don’t have the right stealth properties, they’ll get taken up by macrophages,” says Langer, also a member of the David H. Koch Institute for Integrative Cancer Research at MIT. The BIND-014 nanoparticles have three components: one that carries the drug, one that targets PSMA, and one that helps evade macrophages and other immune-system cells. A few years ago, Langer and Farokhzad developed a way to manipulate these properties very precisely, creating large collections of diverse particles that could then be tested for the ideal composition. “They systematically made a set of materials that varied in the properties they thought would matter, and developed a way to screen them. That’s not been done in this kind of setting before,” says Mark Saltzman, a professor of biomedical engineering at Yale University who was not involved in this study. “They’ve taken the concept from the lab into clinical trials, which is quite impressive.” The systematic way in which these researchers addressed multiple variables and issues gives us some indication of what will be required to move nanoparticles and other nanotherapeutics from laboratory studies into clinical trials. —James Lewis, PhD
Posted in Nanotechnology Tags: boston, dna, future medicine, harvard-medical, Laboratory, Nanobiotechnology, nanobusiness, NANOTECH, Particles Comments OffGold nanostars shuttled to cancer cell nucleus to release drug
One of the most promising current applications of nanotechnology to medicine is the use of nanoparticles to specifically target drug therapy to cancer cells. A variety of different types of nanoparticles using different drug delivery strategies are being investigated, including one type using biopolymers that we described here last week. Another report shows that a very different type of nanoparticle, composed of gold, works by delivering a drug directly to the nucleus of cancer cells. A hat tip to ScienceDaily for reprinting this news release from Northwestern University written by Megan Fellman “ Tiny hitchhikers attack cancer cells: Gold nanostars first to deliver drug directly to cancer cell nucleus “: Nanotechnology offers powerful new possibilities for targeted cancer therapies, but the design challenges are many. Northwestern University scientists now are the first to develop a simple but specialized nanoparticle that can deliver a drug directly to a cancer cell’s nucleus — an important feature for effective treatment. They also are the first to directly image at nanoscale dimensions how nanoparticles interact with a cancer cell’s nucleus. “Our drug-loaded gold nanostars are tiny hitchhikers,” said Teri W. Odom, who led the study of human cervical and ovarian cancer cells. “They are attracted to a protein on the cancer cell’s surface that conveniently shuttles the nanostars to the cell’s nucleus. Then, on the nucleus’ doorstep, the nanostars release the drug, which continues into the nucleus to do its work.” … Using electron microscopy, Odom and her team found their drug-loaded nanoparticles dramatically change the shape of the cancer cell nucleus. What begins as a nice, smooth ellipsoid becomes an uneven shape with deep folds. They also discovered that this change in shape after drug release was connected to cells dying and the cell population becoming less viable — both positive outcomes when dealing with cancer cells. The results are published in the journal ACS Nano [ abstract ]. Since this initial research, the researchers have gone on to study effects of the drug-loaded gold nanostars on 12 other human cancer cell lines. The effect was much the same. “All cancer cells seem to respond similarly,” Odom said. “This suggests that the shuttling capabilities of the nucleolin protein for functionalized nanoparticles could be a general strategy for nuclear-targeted drug delivery.” The nanoparticle is simple and cleverly designed. It is made of gold and shaped much like a star, with five to 10 points. (A nanostar is approximately 25 nanometers wide.) The large surface area allows the researchers to load a high concentration of drug molecules onto the nanostar. Less drug would be needed than current therapeutic approaches using free molecules because the drug is stabilized on the surface of the nanoparticle. The drug used in the study is a single-stranded DNA aptamer called AS1411. Approximately 1,000 of these strands are attached to each nanostar’s surface. The DNA aptamer serves two functions: it is attracted to and binds to nucleolin, a protein overexpressed in cancer cells and found on the cell surface (as well as within the cell). And when released from the nanostar, the DNA aptamer also acts as the drug itself. Bound to the nucleolin, the drug-loaded gold nanostars take advantage of the protein’s role as a shuttle within the cell and hitchhike their way to the cell nucleus. The researchers then direct ultrafast pulses of light — similar to that used in LASIK surgery — at the cells. The pulsed light cleaves the bond attachments between the gold surface and the thiolated DNA aptamers, which then can enter the nucleus. In addition to allowing a large amount of drug to be loaded, the nanostar’s shape also helps concentrate the light at the points, facilitating drug release in those areas. Drug release from nanoparticles is a difficult problem, Odom said, but with the gold nanostars the release occurs easily. That the gold nanostar can deliver the drug without needing to pass through the nuclear membrane means the nanoparticle is not required to be a certain size, offering design flexibility. Also, the nanostars are made using a biocompatible synthesis, which is unusual for nanoparticles. Odom envisions the drug-delivery method, once optimized, could be particularly useful in cases where tumors are fairly close to the skin’s surface, such as skin and some breast cancers. (The light source would be external to the body.) Surgeons removing cancerous tumors also might find the gold nanostars useful for eradicating any stray cancer cells in surrounding tissue. A particular advantage of these nanostars is that the plasmonic electrons produced on the surface of the nanostars by the laser solves the problem of how to efficiently discharge the drug target from the nanoparticle vehicle. —James Lewis, PhD
Posted in Nanotechnology Tags: Bionanotechnology, dna, health & longevity, Journal, Light, Nano, Nanomedicine, Nanoparticle, NANOTECH, nucleolin, Surface Comments OffNanotechnology-based sensor does rapid reads of single DNA molecule
Photo and description courtesy of University of Washington “The various levels of electrical signal from the sequence of a DNA strand pulled through a nanopore reader (top) corresponds to specific DNA nucleotides, thymine, adenine, cytosine and guanine (bottom).” We recently noted the contribution of nanotechnology-based DNA sequencing methods to research and to the emerging field of personalized medicine. Another major step along this path was taken more recently by combining a mutated protein pore with a DNA polymerase molecular motor. A hat tip to ScienceDaily for reprinting this University of Washington news release written by Vince Stricherz “ Tiny reader makes fast, cheap DNA sequencing feasible “: Researchers have devised a nanoscale sensor to electronically read the sequence of a single DNA molecule, a technique that is fast and inexpensive and could make DNA sequencing widely available. The technique could lead to affordable personalized medicine, potentially revealing predispositions for afflictions such as cancer, diabetes or addiction. “There is a clear path to a workable, easily produced sequencing platform,” said Jens Gundlach, a University of Washington physics professor who leads the research team. “We augmented a protein nanopore we developed for this purpose with a molecular motor that moves a DNA strand through the pore a nucleotide at a time.” The researchers previously reported creating the nanopore by genetically engineering a protein pore from a mycobacterium. The nanopore, from Mycobacterium smegmatis porin A, has an opening 1 billionth of a meter in size, just large enough for a single DNA strand to pass through. To make it work as a reader, the nanopore was placed in a membrane surrounded by potassium-chloride solution, with a small voltage applied to create an ion current flowing through the nanopore. The electrical signature changes depending on the type of nucleotide traveling through the nanopore. Each type of DNA nucleotide – cytosine, guanine, adenine and thymine – produces a distinctive signature. The researchers attached a molecular motor, taken from an enzyme associated with replication of a virus, to pull the DNA strand through the nanopore reader. The motor was first used in a similar effort by researchers at the University of California, Santa Cruz, but they used a different pore that could not distinguish the different nucleotide types. Gundlach is the corresponding author of a paper published online March 25 by Nature Biotechnology [ abstract ] that reports a successful demonstration of the new technique using six different strands of DNA. The results corresponded to the already known DNA sequence of the strands, which had readable regions 42 to 53 nucleotides long. “The motor pulls the strand through the pore at a manageable speed of tens of milliseconds per nucleotide, which is slow enough to be able to read the current signal,” Gundlach said. Gundlach said the nanopore technique also can be used to identify how DNA is modified in a given individual. Such modifications, referred to as epigenetic DNA modifications, take place as chemical reactions within cells and are underlying causes of various conditions. “Epigenetic modifications are rather important for things like cancer,” he said. Being able to provide DNA sequencing that can identify epigenetic changes “is one of the charms of the nanopore sequencing method.” The ability to identify epigenetic modifications (mostly methylations of specific nucleotides) is indeed a plus, although we can hope that with further development the technology will be able to read DNA sequences far longer than 42 to 53 nucleotides. Because repeating sequences are prevalent in the human genome, the ability to do long reads is very important. —James Lewis, PhD
Posted in Nanotechnology Tags: dna, easily-produced, molecular-motor, nanopore, NANOTECH, pore, Research, Science, sequence, University, vince-stricherz Comments OffAdding to the toolbox for making complex molecular machines
As synthetic biology seeks to build ever more complex biological machines, the possibility of a bridge from biological to artificial molecular machine systems grows less far-fetched. Recent advances in yeast molecular biology are leading to the ability to make more complex molecular machines in yeast, substantially augmenting the synthetic biology toolkit. A hat tip to ScienceDaily for reprinting this AlphaGalileo news release from Imperial College London: “ Scientists develop tools to make more complex biological machines from yeast “: Scientists are one step closer to making more complex microscopic biological machines, following improvements in the way that they can “re-wire” DNA in yeast, according to research published today in the journal PLoS ONE [ open access article ]. The researchers, from Imperial College London, have demonstrated a way of creating a new type of biological “wire”, using proteins that interact with DNA and behave like wires in electronic circuitry. The scientists say the advantage of their new biological wire is that it can be re-engineered over and over again to create potentially billions of connections between DNA components. Previously, scientists have had a limited number of “wires” available with which to link DNA components in biological machines, restricting the complexity that could be achieved. The team has also developed more of the fundamental DNA components, called “promoters”, which are needed for re-programming yeast to perform different tasks. Scientists currently have a very limited catalogue of components from which to engineer biological machines. By enlarging the components pool and making it freely available to the scientific community via rapid Open Access publication, the team in today’s study aims to spur on development in the field of synthetic biology. Future applications of this work could include tiny yeast-based machines that can be dropped into water supplies to detect contaminants, and yeast that records environmental conditions during the manufacture of biofuels to determine if improvements can be made to the production process. Dr Tom Ellis, senior author of the paper from the Centre for Synthetic Biology and Innovation and the Department of Bioengineering at Imperial College London, says: “From viticulture to making bread, humans have been working with yeast for thousands of years to enhance society. Excitingly, our work is taking us closer to developing more complex biological machines with yeast. These tiny biological machines could help to improve things such as pollution monitoring and cleaner fuels, which could make a difference in all our lives.” Dr Benjamin Blount, first author of the paper from the Centre for Synthetic Biology and Innovation and the Department of Bioengineering at Imperial College London, says: “Our new approach to re-wiring yeast opens the door to an exciting array of more complex biological devices, including cells engineered to carry out tasks similar to computers.” In the study, the Imperial researchers modified a protein-based technology called TAL Effectors, which produce TALOR proteins, with similar qualities to wires in electronic devices. These TALORS can be easily re-engineered, which means that they can connect with many DNA-based components without causing a short circuit in the device. The team says their research now provides biological engineers working in yeast with a valuable new toolbox. Professor Richard Kitney, Co-Director of the Centre for Synthetic Biology and Innovation at the College, adds: “The work by Dr Ellis and the team at the Centre really takes us closer to developing much more complex biological machines with yeast, which may help to usher in a new age where biological machines could help to improve our health, the way we work, play and live.” Professor Paul Freemont, Co-Director of the Centre for Synthetic Biology and Innovation at the College, concludes: “One of the core aims of the Centre is to provide tools and resources to the wider scientific community by sharing our research. Dr Ellis’s team has now begun to assemble characterised biological parts for yeast that will be available to researchers both in academia and industry.” Promoters are DNA sequences that signal transcription of a gene to make a messenger RNA molecule that is then translated to make the protein product encoded by the gene. By systematically mutagenizing the core sequence of one promoter, the researchers created a library of 36 promoters that could be independently regulated. They also created a library of proteins to specifically turn off individual variant promoters. They thus designed a complex network of gene regulation that can be used for arbitrary engineering purposes rather than those networks that have evolved to fit the yeast’s own metabolic needs. One wonderful aspect of this work is that, not only are the results published in an open access journal rather than sequestered behind a pay wall, but the biological “parts” created are available to other biological engineers to elaborate the toolbox that is available to synthetic biology and, perhaps eventually, for a folded polymer path toward productive nanosystems. IMHO, this collaborative “Open Source-like” approach being pursued in synthetic biology provides an admirable paradigm for the development of advanced nanotechnology. —James Lewis, PhD
Posted in Nanotechnology Tags: College, dna, imperial-college, Innovation, Journal, molecular manufacturing, molecular nanotechnology, NANOTECH, Nanotechnology, open source, Research, Science, Study, synthetic Comments OffAtomically-precise positioning of a single atom transistor-VIDEO
A team led by Michelle Y. Simmons, who spoke on “Atomic-scale device fabrication in silicon” at the 2007 Productive Nanosystems: Launching the Technology Roadmap conference, which introduced the Technology Roadmap for Productive Nanosystems , has succeeded in the atomically precise placement of a transistor consisting of a single atom of phosphorous between source and drain electrodes and gate electrodes all made from phosphorous wires only a few atoms wide. A YouTube video illustrating this working transistor of a single atom of phosphorous placed with atomic precision on a silicon crystal includes an STM image that shows the single phosphorous atom placed several tens of rows of silicon atoms from source and drain electrodes of phosphorous that appear to be about 10 rows of atoms wide. To manufacture the phosphorous transistor and electrodes, a scanning tunneling microscope was used to remove precisely determined hydrogen atoms from the passivating layer covering a silicon crystal to form a mask that was then used to apply phosphorous atoms to the vacancies created. An overlay of silicon atoms then preserved these phosphorous nanostructures. The accomplishment is described in a NY Times article by John Markoff, which describes both the place of this work in the progression of Moore’s Law and its potential for a new generation of quantum computers: “ Physicists Create a Working Transistor From a Single Atom “: Australian and American physicists have built a working transistor from a single phosphorus atom embedded in a silicon crystal. The group of physicists, based at the University of New South Wales and Purdue University, said they had laid the groundwork for a futuristic quantum computer that might one day function in a nanoscale world and would be orders of magnitude smaller and quicker than today’s silicon-based machines. … “Their approach is extremely powerful,” said Andreas Heinrich, an I.B.M. physicist. “This is at least a 10-year effort to make very tiny electrical wires and combine them with the placement of a phosphorous atom exactly where they want them.” He said the research was a significant step toward making a functioning quantum computing system. However, whether quantum computing will ever be harnessed for useful tasks remains uncertain, and the researchers also noted that their work demonstrated the fundamental limits that today’s computers would be able to shrink to. “It shows that Moore’s Law can be scaled toward atomic scales in silicon,” said Gerhard Klimeck, professor of electrical and computer engineering at Purdue, referring to the rate at which computing gets faster and cheaper. “The technologies for classical computing can survive to the atomic scale.” The results were published in Nature Nanotechnology [ abstract ]. At least for the moment (February 19, 2012), the full text is available without charge. Also available in the same issue is a commentary by Gabriel P. Lansbergen “ Nanoelectronics: Transistors arrive at the atomic limit “, which gives additional background and details on this accomplishment. … Single-atom transistors represent the ultimate limit in solid-state device miniaturization, but they are also interesting for another reason. Deterministically positioned single-dopant atoms in silicon, electrically addressable by metallic leads, are at the heart of a number of promising proposals for quantum-information-processing devices3. The long coherence and relaxation times associated with single dopants make them very attractive candidates for quantum-device architectures. The atom-by-atom fabrication technique developed by Simmons and co-workers therefore fulfills a long-standing need for a method that is capable of atomic-scale device fabrication in silicon. And although the technique is not directly applicable on an industrial scale, it does bring the development of truly atomistic electronics — and the possibilities they offer — into the experimental realm. This latest accomplishment from Prof. Simmons and her collaborators follows swiftly on their recent demonstration published just last month in Science [ abstract ], that Ohms law holds for nanowire only four phosphorous atoms wide. From the Purdue University news service “ Down to the wire for silicon: Researchers create a wire 4 atoms wide, 1 atom tall “: The smallest wires ever developed in silicon – just one atom tall and four atoms wide – have been shown by a team of researchers from the University of New South Wales, Melbourne University and Purdue University to have the same current-carrying capability as copper wires. Experiments and atom-by-atom supercomputer models of the wires have found that the wires maintain a low capacity for resistance despite being more than 20 times thinner than conventional copper wires in microprocessors. The discovery, which was published in this week’s journal Science, has several implications, including: For engineers it could provide a roadmap to future nanoscale computational devices where atomic sizes are at the end of Moore’s law. The theory shows that a single dense row of phosphorus atoms embedded in silicon will be the ultimate limit of downscaling. For computer scientists, it places donor-atom based silicon quantum computing closer to realization. And for physicists, the results show that Ohm’s Law, which demonstrates the relationship between electrical current, resistance and voltage, continues to apply all the way down to an atomic-scale wire. … Although the path from this laboratory demonstration to a practical technology is not yet clear, as emphasized above by the researchers themselves and commentators, the progress at Zyvex Labs (and elsewhere) that we cited in Oct. 2010 in this basic technology of using an STM for atomically precise lithography holds hope that a convergence of manufacturing technology and demonstrated prototypes will not be too distant. —James Lewis
Posted in Nanotechnology Tags: collaborators, gerhard-klimeck, molecular manufacturing, NANOTECH, Nanotechnology, Possibilities, productive nanosystems, Purdue, Research, Science, south-wales, Technology, University, Work Comments OffNanotechnology, DNA sequencing, and personalized medicine
Credit: Lab of Jene Golovchenko, Harvard University Artist’s conception of a nanopore drilled into a layer of graphene to speed up DNA sequencing. One of the greatest promises of near-term nanotechnoloogy is cheaper DNA sequencing to speed the development of personalized medicine. There are not only genetic differences between different patients, but also genetic differences between, for example, different cancers of the same organ diagnosed in different patients, or even from different locations in the same patient, that can greatly affect the success of a therapy. Nanopore sensors are among the promising new third-generation DNA sequencing technologies being developed to make inexpensive whole genome sequencing a reality. A review of the potential of this emerging nanotechnology was published recently in Nature Nanotechnology [ abstract ]. The full text of the review “ Nanopore sensors for nucleic acid analysis ” has been made available by the authors for down-loading. Nanopores and other third generation sequencing technologies sequence single molecules of DNA in real time. Single molecules of DNA are pulled through a nanopore of some type and changes in the ionic current, dependent on whether an A, G, C, or T nucleotide is passing through the pore, are recorded. The review discusses the different types of nanopore that have been tried, both biological and solid-state, and the challenges encountered, such as reducing the speed at which the DNA molecule transits the nanopore, and improving sensitivity. Research done by scientists at Harvard and MIT and published in Nature [ abstract , free authors' manuscript deposited in PubMedCentral] showed that a graphene sheet one or two atomic layers thick could form an electrode separating two liquid reservoirs so that current from ions passing through a nanopore in the graphene sheet could be measured, and the current blockade seen when DNA molecules passed through the pore indicated it should be possible to resolve individual nucleotides with an insulating membrane this thin. From a Harvard Gazette article by Michael Rutter “ Graphene may help speed up DNA sequencing “: … By drilling a tiny pore just a few nanometers in diameter, called a nanopore, in the graphene membrane, the researchers were able to measure exchange of ions through the pore and demonstrate that a long DNA molecule can be pulled through the graphene nanopore just as a thread is pulled through the eye of a needle. “By measuring the flow of ions passing through a nanopore drilled in graphene we have demonstrated that the thickness of graphene immersed in liquid is less then 1 nm thick, or many times thinner than the very thin membrane which separates a single animal or human cell from its surrounding environment,” says lead author Slaven Garaj, a physics research associate at Harvard. “This makes graphene the thinnest membrane able to separate two liquid compartments from each other. The thickness of the membrane was determined by its interaction with water molecules and ions.” … “Although the membrane prevents ions and water from flowing through it, the graphene membrane can attract different ions and other chemicals to its two atomically close surfaces. This affects graphene’s electrical conductivity and could be used for chemical sensing,” says co-author Jene Golovchenko, the Rumford Professor of Physics and Gordon McKay Professor of Applied Physics at Harvard, whose pioneering work started the field of artificial nanopores in solid-state membranes. “I believe the atomic thickness of the graphene makes it a novel electrical device that will offer new insights into the physics of surface processes and lead to a wide range of practical application, including chemical sensing and detection of single molecules.” … When the researchers added long DNA chains in the liquid, they were electrically pulled one by one through the graphene nanopore. As the DNA molecule threaded the nanopore, it blocked the flow of ions, resulting in a characteristic electrical signal that reflects the size and conformation of the DNA molecule. … As a DNA chain passes through the nanopore, the nucleobases, which are the letters of the genetic code, can be identified. But a nanopore in graphene is the first nanopore short enough to distinguish between two closely neighboring nucleobases.… More recently another group at Harvard has integrated nanowire field-effect transistors with a solid-state nanopore to achieve rapid, sensitive detection of the very small currents created as DNA molecules zip through the nanopore. From a Harvard Gazette story by Peter Reuell “ Reading life’s building blocks “: Scientists are one step closer to a revolution in DNA sequencing, following the development in a Harvard lab of a tiny device designed to read the minute electrical changes produced when DNA strands are passed through tiny holes — called nanopores — in an electrically charged membrane. As described in Nature Nanotechnology [ abstract , free full text provided by authors] on Dec. 11, a research team led by Charles Lieber, the Mark Hyman Jr. Professor of Chemistry [and also winner of the 2001 Feynman Prize in Nanotechnology-Experimental ], have succeeded for the first time in creating an integrated nanopore detector, a development that opens the door to the creation of devices that could use arrays of millions of the microscopic holes to sequence DNA quickly and cheaply. First described more than 15 years ago, nanopore sequencing measures subtle electrical current changes produced as the four base molecules that make up DNA pass through the pore. By reading those changes, researchers can effectively sequence DNA. But reading those subtle changes in current is far from easy. A series of challenges — from how to record the tiny changes in current to how to scale up the sequencing process — meant the process has never been possible on a large scale. Lieber and his team, however, believe they have found a unified solution to most of those problems. “Until we developed our detector, there was no way to locally measure the changes in current,” Lieber said. “Our method is ideal because it is extremely localized. We can use all the existing work that has been done on nanopores, but with a local detector we’re one step closer to completely revolutionizing sequencing.” The detector developed by Lieber and his team grew out of earlier work on nanowires. Using the ultra-thin wires as a nanoscale transistor, they are able to measure the changes in current more locally and accurately than ever before. “The nanowire transistor measures the electrical potential change at the pore and effectively amplifies the signal,” Lieber said. “In addition to a larger signal, that allows us to read things much more quickly. That’s important because DNA is so large [that] the throughput for any sequencing method needs to be high. In principle, this detector can work at gigahertz frequencies.” The highly localized measurement also opens the door to parallel sequencing, which uses arrays of millions of pores to speed the sequencing process dramatically. In addition to the potential for greatly improving the speed of sequencing, the new detector holds the promise of dramatically reducing the cost of DNA sequencing, said Ping Xie, an associate of the Department of Chemistry and Chemical Biology and co-author of the paper describing the research. … “Right now, we are limited in our ability to perform DNA sequencing,” Xie said. “Current sequencing technology is where computers were in the ’50s and ’60s. It requires a lot of equipment and is very expensive. But just 50 years later, computers are everywhere, even in greeting cards. Our detector opens the door to doing a blood draw and immediately knowing what a patient is infected with, and very quickly making treatment decisions.” Rapid, inexpensive DNA sequencing and other nanotechnology-based innovations in drug-delivery and tissue regeneration may transform health care in the coming decade. —James Lewis
Posted in Nanotechnology Tags: dna, future medicine, harvard, health & longevity, NANOTECH, Nanotechnology, Professor, Research, REVIEW Comments OffDNA nanotechnology-based nanorobot delivers cell suicide message to cancer cells
Image courtesy of the Wyss Institute “ The nanosized robot was created in the form of an open barrel whose two halves are connected by a hinge. The DNA barrel, which acts as a container, is held shut by special DNA latches that can recognize and seek out combinations of cell-surface proteins, including disease markers. This image was created by Campbell Strong, Shawn Douglas, and Gaël McGill using Molecular Maya and cadnano. “ DNA nanotechnology is not only a very promising path toward productive nanosystems and atomically precise manufacturing, but also a path to increasingly sophisticated DNA molecular machines for near-term drug delivery applications in nanomedicine. A recent advance comprises an autonomous DNA nanorobot incorporating a DNA origami chasis and DNA aptamer locks functioning as logical AND gates that are unlocked after the aptamers bind a protein target on the target cell, allowing the nanorobot to discharge its therapeutic cargo. A hat tip to KurzweilAI.net for reprinting this Harvard Gazette news release written by Twig Mowatt “ Sending DNA robot to do the job: Technology has potential to seek out cancer cells, cause them to self-destruct “: Researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University have developed a robotic device made from DNA that could potentially seek out specific cell targets within a complex mixture of cell types and deliver important molecular instructions, such as telling cancer cells to self-destruct. Inspired by the mechanics of the body’s own immune system, the technology might one day be used to program immune responses to treat various diseases. The research findings appear today in Science ["A Logic-Gated Nanorobot for Targeted Transport of Molecular Payloads" abstract ; full text available for fair use on Church lab web site]. Using the DNA origami method, in which complex 3-D shapes and objects are constructed by folding strands of DNA, Shawn Douglas, a Wyss Technology Development Fellow, and Ido Bachelet, a former Wyss postdoctoral fellow who is now an assistant professor in the Faculty of Life Sciences and the Nano-Center at Bar-Ilan University in Israel, created a nanosized robot in the form of an open barrel whose two halves are connected by a hinge. The DNA barrel, which acts as a container, is held shut by special DNA latches that can recognize and seek out combinations of cell-surface proteins, including disease markers. When the latches find their targets, they reconfigure, causing the two halves of the barrel to swing open and expose its contents, or payload. The container can hold various types of payloads, including specific molecules with encoded instructions that can interact with specific cell surface signaling receptors. Douglas and Bachelet used this system to deliver instructions, which were encoded in antibody fragments, to two different types of cancer cells — leukemia and lymphoma. In each case, the message to the cell was to activate its “suicide switch” — a standard feature that allows aging or abnormal cells to be eliminated. And because leukemia and lymphoma cells speak different languages, the messages were written in different antibody combinations. … “We can finally integrate sensing and logical computing functions via complex, yet predictable, nanostructures — some of the first hybrids of structural DNA, antibodies, aptamers, and metal atomic clusters — aimed at useful, very specific targeting of human cancers and T-cells,” said George Church, a Wyss core faculty member and professor of genetics at Harvard Medical School, who is principal investigator on the project. … A key feature of this work is that the DNA aptamer changes structure upon binding its target so it releases its hold on the complementary part of the DNA latch. Since two DNA latches hold the nanorobot in a closed configuration, the latches can be programmed to both respond to the same cell surface target, or to each respond to a different target so that both targets would need to be on the cell to activate the nanorobot to open and allow the payload molecules to bind their targets. This logical AND function allows for much greater specificity in recognizing target cells. As the authors conclude, “These findings demonstrate that the robots can induce a variety of tunable changes in cell behavior.” Conceivably a similar mechanism could be used in an atomically precise manufacturing operation in which DNA nanorobots could add a payload molecule to a workpiece depending on whether both of two specific molecular signals on the workpiece were present. —James Lewis
Posted in Nanotechnology Tags: Bionanotechnology, dna, Faculty, future medicine, harvard-medical, Israel, molecular nanotechnology, Nano, Nanobiotechnology, Nanomedicine, NANOTECH, Nanotechnology, Project, Research, targets Comments OffDNA motor navigates network of DNA tracks
The structural DNA path toward productive nanosystems has achieved another step forward with the demonstration that a DNA origami scaffolding can be used to program a DNA motor to navigate a network of tracks. A hat tip to PhysOrg.com for reprinting this news release from Kyoto University “ DNA Motor Programmed to Navigate a Network of Tracks “: Kyoto, Japan — Expanding on previous work with engines traveling on straight tracks, a team of researchers at Kyoto University and the University of Oxford have successfully used DNA building blocks to construct a motor capable of navigating a programmable network of tracks with multiple switches. The findings, published in the January 22 online edition of the journal Nature Nanotechnology [ abstract ], are expected to lead to further developments in the field of nanoengineering. The research utilizes the technology of DNA origami, where strands of DNA molecules are sequenced in a way that will cause them to self-assemble into desired 2D and even 3D structures. In this latest effort, the scientists built a network of tracks and switches atop DNA origami tiles, which made it possible for motor molecules to travel along these rail systems. “We have demonstrated that it is not only possible to build nanoscale devices that function autonomously,” explained Dr. Masayuki Endo of Kyoto University’s Institute for Integrated Cell-Material Sciences (iCeMS), “but that we can cause such devices to produce predictable outputs based on different, controllable starting conditions.” The team, including lead author Dr. Shelley Wickham at Oxford, expects that the work may lead to the development of even more complex systems, such as programmable molecular assembly lines and sophisticated sensors. “We are really still at an early stage in designing DNA origami-based engineering systems,” elaborated iCeMS Prof. Hiroshi Sugiyama. “The promise is great, but at the same time there are still many technical hurdles to overcome in order to improve the quality of the output. This is just the beginning for this new and exciting field.” Courtesy Sugiyama Lab, Kyoto University iCeMS A depiction of a DNA origami tile with a built-in network of tracks. The DNA engine or motor, in red, can be programmed to navigate a series of junctions to reach one of four desired end points. Perhaps the next step is to have multiple addressable DNA motors bring different components together to be joined? —James Lewis
Posted in Nanotechnology Tags: Bionanotechnology, Development, engine-or-motor, Japan, kyoto, molecular manufacturing, Nanobiotechnology, NANOTECH, News, productive nanosystems, prof-hiroshi, roadmaps, Scientists, University, Work Comments OffGraphene heterostructures may lead to graphene-based computer chips
Tunnelling transistor Tunnelling transistor based on vertical graphene heterostructures. Tunnelling current between two graphene layers can be controlled by gating. Credit: University of Manchester . L. Britnell et al. Science DOI: 10.1126/science.1218461 Combining atomically thin graphene with layers of atomically thin insulators appears to open the door to using graphene in computer chips. A hat tip to KurzweilAI.net for reprinting this University of Manchester news release “ Graphene electronics moves into a third dimension “: Wonder material graphene has been touted as the next silicon, with one major problem—it is too conductive to be used in computer chips. Now scientists from The University of Manchester have given its prospects a new lifeline. In a paper published this week in Science [ abstract ], a Manchester team lead by Nobel laureates Professor Andre Geim and Professor Konstantin Novoselov has literally opened a third dimension in graphene research. Their research shows a transistor that may prove the missing link for graphene to become the next silicon. Graphene—one atomic plane of carbon—is a remarkable material with endless unique properties, from electronic to chemical and from optical to mechanical. One of many potential applications of graphene is its use as the basic material for computer chips instead of silicon. This potential has alerted the attention of major chip manufactures, including IBM, Samsung, Texas Instruments and Intel. Individual transistors with very high frequencies (up to 300 GHz) have already been demonstrated by several groups worldwide. Unfortunately, those transistors cannot be packed densely in a computer chip because they leak too much current, even in the most insulating state of graphene. This electric current would cause chips to melt within a fraction of a second. … The University of Manchester scientists now suggest using graphene not laterally (in plane)—as all the previous studies did—but in the vertical direction. They used graphene as an electrode from which electrons tunnelled through a dielectric into another metal. This is called a tunnelling diode. Then they exploited a truly unique feature of graphene—that an external voltage can strongly change the energy of tunnelling electrons. As a result they got a new type of a device—vertical field-effect tunnelling transistor in which graphene is a critical ingredient. Dr Leonid Ponomarenko, who spearheaded the experimental effort, said: “We have proved a conceptually new approach to graphene electronics. Our transistors already work pretty well. I believe they can be improved much further, scaled down to nanometre sizes and work at sub-THz frequencies.” … The Manchester team made the transistors by combining graphene together with atomic planes of boron nitride and molybdenum disulfide. The transistors were assembled layer by layer in a desired sequence, like a layer cake but on an atomic scale. Such layer-cake superstructures do not exist in nature. It is an entirely new concept introduced in the report by the Manchester researchers. The atomic-scale assembly offers many new degrees of functionality, without some of which the tunnelling transistor would be impossible. “The demonstrated transistor is important but the concept of atomic layer assembly is probably even more important,” explains Professor Geim. Professor Novoselov added: “Tunnelling transistor is just one example of the inexhaustible collection of layered structures and novel devices which can now be created by such assembly. “It really offers endless opportunities both for fundamental physics and for applications. Other possible examples include light emission diodes, photovoltaic devices, and so on.” Graphene is one area of nanotechnology that is generating both increased scientific rewards and increased application potential as work continues. It provides an example of the opportunities that can be opened by an apparently serendipitous discovery. It is also an indication of the rich rewards that are to be found from approaching atomic precision in the control of the structure of matter. —James Lewis
Posted in Nanotechnology Tags: atomically-thin, attention, experimental, inexhaustible, molecular nanotechnology, Nano, NANOTECH, Professor, professor-andre, Research, Texas, Transistors, Tunnelling Comments Off