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Scientists Trumpet Advanced DNA Robots


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#1 Reno

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Posted 12 May 2010 - 06:15 PM


For the first time, microscopic robots made from DNA molecules can walk, follow instructions and work together to assemble simple products in an atomic-scale assembly line, mimicking the machinery of living cells, two independent research teams announced Wednesday.

These experimental devices, described in the journal Nature, are advances in DNA nanotechnology, in which bioengineers are using the molecules of the genetic code as nuts, bolts, girders and other building materials, on a scale measured in billionths of a meter. The effort, which combines synthetic chemistry, enzymology, structural nanotechnology and computer science, takes advantage of the unique physical properties of DNA molecules to assemble shapes according to predictable chemical rules.

Until now, such experiments had yielded molecular novelties, from smiley faces so small that a billion can fit in a teaspoon to molecule-size boxes with lids can be opened, closed and locked with a DNA key.

These new construction projects, however, bring researchers a step closer to a time when, at least in theory, scientists might be able to build test-tube factories that churn out self-assembling computers, rare chemical compounds or autonomous medical robots able to cruise the human bloodstream.

In one, a pioneering research group based at New York University built the prototype of a molecular factory in which mobile DNA robots assembled gold particles in eight different ways, in response to chemical commands. The second team, led by a biochemist at Columbia University, programmed a DNA robot that could start, stop, turn and move without human intervention.

"Here we can see some glimmers of things to come," said Harvard University biophysicist William Shih, who was not involved in the projects. "This is exciting."

Both research groups tinkered with creations called DNA walkers—mobile DNA molecules, about 100,000 times smaller than the diameter of a human hair, that have three or more legs made of a string of genetic enzymes. Each leg moves forward based on its chemical attraction to sequences of biochemicals laid down, like stepping stones, in front of it.

These robots are so small that the researchers program their actions by encoding commands in the world around them. They follow chemical cues programmed into the ground on which they walk.

In the first project, a team of scientists led by biochemist Milan Stojanovic at Columbia built a molecular robot that moved on its own along a track of chemical instructions—the DNA equivalent of the punched paper tape used to control automated machine tools.

Once programmed, it required no further human intervention, the researchers reported. It could turn, move in a straight line or follow a complex a curve and then stop, all essentially on its own initiative. They documented its progress with an atomic force microscope as it strode along a path 100 nanometers long, about 30 times further than earlier DNA walkers could manage.

"In the future, this could be used as a molecular machine that could bind to a cell surface, maybe carry a cargo and release something," said biochemist Hao Yan at the Biodesign Institute at Arizona State University, one of 12 researchers at four universities involved in the project.

At New York University, scientists led by chemist Nadrian Seeman took that idea a step further. They combined a programmable DNA track and a squad of mobile robotic walkers with a set of independently controlled molecular forklifts that can deliver parts on command. The result was a functioning nano-factory, the researchers reported.

"An industrial assembly line includes a factory, workers and a conveyor system," said Dr. Seeman. "We have emulated each of those features using DNA components."

By triggering different DNA sequences, the researchers could order up to eight different combinations in their experimental product line.

"It is very significant," said Caltech bioengineer Paul Rothemund, who was not involved in either project. "This is the kind of thing that happens in living cells all the time."

Biochemist Lloyd Smith at the University of Wisconsin in Madison cautioned that it may be a decade or more before DNA nanotechnology leads to any useful applications. "This is a field to watch," Dr. Smith said. "But this is still fundamental research to find out what ability mankind has to make molecules that can do its bidding."


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#2 Reno

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Posted 12 May 2010 - 06:17 PM

Teams of automated programmable molecular robots working together on nanoscale assembly lines is one step closer, say scientists in the US.

A collaboration between four US institutions has developed a 'molecular spider' whose direction and motion can be controlled to make it travel along a particular path,1 while a separate team led by Ned Seeman at New York University has developed a nanoscale assembly line that can be programmed to 'manufacture' eight different products.2

Milan Stojanovic and colleagues from Columbia University and collaborators at Arizona State University, the University of Michigan and the California Institute of Technology developed their DNA walker - a spider-shaped molecule made of DNA - to move along a fixed track on a surface. 'We don't use a remote control or anything like that so essentially we wind it up, release it and away it goes,' says Stojanovic.

The walker is made up of an inert body and four single strands of DNA. Three of the strands act as legs and include DNAzymes - DNA molecules that catalyse a chemical reaction - while the fourth strand anchors the walker in position at the beginning of the path until it is ready to move. The path surface is programmed to initiate the 'walking' process and is made of folded DNA strands designed to complement the DNA in the legs of the walker.

DNA walking down a track
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DNA walker moves along a fixed track on a surface

© Nature

The legs form duplexes - double stranded links - to the complementary strands in the surface. One of the duplexes is cleaved and the leg explores the surrounding surface forming another duplex at another position. If the leg binds to a position already visited, its stay there is brief as it 'remembers' the process; for new positions, the cleavage takes longer. By repeating this process the walker moves along the surface independently. At the end of the track the walker binds to uncleavable DNA strands and stops.

Seeman comments that Stojanovic's team has developed 'a really great autonomous system that will walk on one trajectory over a path'. 'They have made far more steps than we made in the past, but this is only in one direction,' he adds.

Stojanovic explains that the next step will be to introduce more than one walker molecule and programme the behaviour of the spider so that it chooses between two paths. 'The wildest dream might be to have a swarm of robots that repair torn ligaments,' he adds.

Seeman and his team took their research in a different direction, developing a system in which a DNA walker travels along a path with three DNA 'modules' at fixed intervals in an assembly line arrangement. The modules hold a cargo of gold nanoparticles and are individually programmed to either donate or keep their cargo, so as the DNA walker passes by it can be loaded with cargo resulting in eight possible end products.

'I think of these DNA walkers as being similar to a chassis of a car rolling down the assembly line and we are adding components to it,' says Seeman.

DNA assembly line
Nanoscale assembly line inspired by assembly lines in a factory

The DNA walkers in Seeman's system differ from Stojanovic's by having essentially seven 'limbs'. Four DNA strands are used as feet while the other three are used to carry the cargo donated by the DNA modules, which are anchored to a DNA origami tile that acts as the DNA walker's track. In addition, the walker is moved, not by DNAzymes in the DNA leg strands, but by externally controlled 'fuel' strands that are added to displace the feet, so they move to other positions. In this way, Seeman can control the binding and releasing of the feet and have greater control over the end products.

'The next step is to improve the system so that we can have these assembly lines churning out products and make the assembly lines longer, providing more complex products,' says Seeman.

Stojanovic described Seeman's nanoscale assembly line as a masterful example of non-autonomous robotics. He describes Seeman as 'like a micro-surgeon that slowly organises materials on this scale by adding DNA strands and taking them away. It's just beautiful work'.


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#3 Reno

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Posted 12 May 2010 - 06:18 PM

The latest installment in DNA nanotechnology has arrived: A molecular nanorobot dubbed a "spider" and labeled with green dyes traverses a substrate track built upon a DNA origami scaffold. It journeys towards its red-labeled goal by cleaving the visited substrates, thus exhibiting the characteristics of an autonomously moving, behavior-based robot at the molecular scale. Credit: Courtesy of Paul Michelotti

A team of scientists from Columbia University, Arizona State University, the University of Michigan, and the California Institute of Technology (Caltech) have programmed an autonomous molecular "robot" made out of DNA to start, move, turn, and stop while following a DNA track.

The development could ultimately lead to molecular systems that might one day be used for medical therapeutic devices and molecular-scale reconfigurable robots—robots made of many simple units that can reposition or even rebuild themselves to accomplish different tasks.

A paper describing the work appears in the current issue of the journal Nature.

The traditional view of a robot is that it is "a machine that senses its environment, makes a decision, and then does something—it acts," says Erik Winfree, associate professor of computer science, computation and neural systems, and bioengineering at Caltech.

Milan N. Stojanovic, a faculty member in the Division of Experimental Therapeutics at Columbia University, led the project and teamed up with Winfree and Hao Yan, professor of chemistry and biochemistry at Arizona State University and an expert in DNA nanotechnology, and with Nils G. Walter, professor of chemistry and director of the Single Molecule Analysis in Real-Time (SMART) Center at the University of Michigan in Ann Arbor, for what became a modern-day self-assembly of like-minded scientists with the complementary areas of expertise needed to tackle a tough problem.

Shrinking robots down to the molecular scale would provide, for molecular processes, the same kinds of benefits that classical robotics and automation provide at the macroscopic scale. Molecular robots, in theory, could be programmed to sense their environment (say, the presence of disease markers on a cell), make a decision (that the cell is cancerous and needs to be neutralized), and act on that decision (deliver a cargo of cancer-killing drugs).

Or, like the robots in a modern-day factory, they could be programmed to assemble complex molecular products. The power of robotics lies in the fact that once programmed, the robots can carry out their tasks autonomously, without further human intervention.

With that promise, however, comes a practical problem: how do you program a molecule to perform complex behaviors?

"In normal robotics, the robot itself contains the knowledge about the commands, but with individual molecules, you can't store that amount of information, so the idea instead is to store information on the commands on the outside," says Walter. And you do that, says Stojanovic, "by imbuing the molecule's environment with informational cues."

"We were able to create such a programmed or 'prescribed' environment using DNA origami," explains Yan. DNA origami, an invention by Caltech Senior Research Associate Paul W. K. Rothemund, is a type of self-assembled structure made from DNA that can be programmed to form nearly limitless shapes and patterns (such as smiley faces or maps of the Western Hemisphere or even electrical diagrams). Exploiting the sequence-recognition properties of DNA base pairing, DNA origami are created from a long single strand of DNA and a mixture of different short synthetic DNA strands that bind to and "staple" the long DNA into the desired shape. The origami used in the Nature study was a rectangle that was 2 nanometers (nm) thick and roughly 100 nm on each side.

The researchers constructed a trail of molecular "bread crumbs" on the DNA origami track by stringing additional single-stranded DNA molecules, or oligonucleotides, off the ends of the staples. These represent the cues that tell the molecular robots what to do—start, walk, turn left, turn right, or stop, for example—akin to the commands given to traditional robots.

The molecular robot the researchers chose to use—dubbed a "spider"—was invented by Stojanovic several years ago, at which time it was shown to be capable of extended, but undirected, random walks on two-dimensional surfaces, eating through a field of bread crumbs.

To build the 4-nm-diameter molecular robot, the researchers started with a common protein called streptavidin, which has four symmetrically placed binding pockets for a chemical moiety called biotin. Each robot leg is a short biotin-labeled strand of DNA, "so this way we can bind up to four legs to the body of our robot," Walter says. "It's a four-legged spider," quips Stojanovic. Three of the legs are made of enzymatic DNA, which is DNA that binds to and cuts a particular sequence of DNA. The spider also is outfitted with a "start strand"—the fourth leg—that tethers the spider to the start site (one particular oligonucleotide on the DNA origami track). "After the robot is released from its start site by a trigger strand, it follows the track by binding to and then cutting the DNA strands extending off of the staple strands on the molecular track," Stojanovic explains.

"Once it cleaves," adds Yan, "the product will dissociate, and the leg will start searching for the next substrate." In this way, the spider is guided down the path laid out by the researchers. Finally, explains Yan, "the robot stops when it encounters a patch of DNA that it can bind to but that it cannot cut," which acts as a sort of flypaper.

Although other DNA walkers have been developed before, they've never ventured farther than about three steps. "This one," says Yan, "can walk up to about 100 nanometers. That's roughly 50 steps."

"This in itself wasn't a surprise," adds Winfree, "since Milan's original work suggested that spiders can take hundreds if not thousands of processive steps. What's exciting here is that not only can we directly confirm the spiders' multistep movement, but we can direct the spiders to follow a specific path, and they do it all by themselves—autonomously."

In fact, using atomic force microscopy and single-molecule fluorescence microscopy, the researchers were able to watch directly spiders crawling over the origami, showing that they were able to guide their molecular robots to follow four different paths.

"Monitoring this at a single molecule level is very challenging," says Walter. "This is why we have an interdisciplinary, multi-institute operation. We have people constructing the spider, characterizing the basic spider. We have the capability to assemble the track, and analyze the system with single-molecule imaging. That's the technical challenge." The scientific challenges for the future, Yan says, "are how to make the spider walk faster and how to make it more programmable, so it can follow many commands on the track and make more decisions, implementing logical behavior."

"In the current system," says Stojanovic, "interactions are restricted to the walker and the environment. Our next step is to add a second walker, so the walkers can communicate with each other directly and via the environment. The spiders will work together to accomplish a goal." Adds Winfree, "The key is how to learn to program higher-level behaviors through lower-level interactions."

Such collaboration ultimately could be the basis for developing molecular-scale reconfigurable robots—complicated machines that are made of many simple units that can reorganize themselves into any shape—to accomplish different tasks, or fix themselves if they break. For example, it may be possible to use the robots for medical applications. "The idea is to have molecular robots build a structure or repair damaged tissues," says Stojanovic.

"You could imagine the spider carrying a drug and bonding to a two-dimensional surface like a cell membrane, finding the receptors and, depending on the local environment," adds Yan, "triggering the activation of this drug."

Such applications, while intriguing, are decades or more away. "This may be 100 years in the future," Stojanovic says. "We're so far from that right now."

"But," Walter adds, "just as researchers self-assemble today to solve a tough problem, molecular nanorobots may do so in the future."


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#4 ken_akiba

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Posted 16 May 2010 - 04:54 AM

Not to belittle this amazing achievement, nowadays I begin to think that this approach, that nanobot with "moving" body parts like arms and legs may fix and mend us from inside, may face a dead end. Let's say a nanobot can scrape off arterial palque. This requires nanobot to identify fat deposited in artery, fine, it will be achievable but how would the bot distinguish it from other fats that should be there. Blood vessels leak all the time and some bots may "leak out" and start scrapping brain tissue. Nanobots, as small it is, does not enjoy the luxury of Mars Rover i.e. cannot have an "antenna" to accept command from the master computer outside of the human body let alone a powerful cpu of its own. Once injected, we have no choice but to let nanobots be atonomous and I just do not see how we would program all the intelligence that is required to perform even simplestest tasks, in that small body.

Edited by ken_akiba, 16 May 2010 - 05:13 AM.


#5 Reno

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Posted 16 May 2010 - 08:57 AM

Not to belittle this amazing achievement, nowadays I begin to think that this approach, that nanobot with "moving" body parts like arms and legs may fix and mend us from inside, may face a dead end. Let's say a nanobot can scrape off arterial palque. This requires nanobot to identify fat deposited in artery, fine, it will be achievable but how would the bot distinguish it from other fats that should be there. Blood vessels leak all the time and some bots may "leak out" and start scrapping brain tissue. Nanobots, as small it is, does not enjoy the luxury of Mars Rover i.e. cannot have an "antenna" to accept command from the master computer outside of the human body let alone a powerful cpu of its own. Once injected, we have no choice but to let nanobots be atonomous and I just do not see how we would program all the intelligence that is required to perform even simplestest tasks, in that small body.


In most fiction i've read there is always some small system maintained by a larger system. That would be a grouping of a type of nanomachine with a certain function, say removing a particular fat molecule, controlled by a local node whose function was assigned by a larger node and so on.

I'm not saying life will follow fiction, but that's just what i've always envisioned molecular nanotechnology looking like. The truth is the future will probably be more complicated and look far stranger than most of us can imagine.

#6 valkyrie_ice

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Posted 16 May 2010 - 09:31 PM

Not to belittle this amazing achievement, nowadays I begin to think that this approach, that nanobot with "moving" body parts like arms and legs may fix and mend us from inside, may face a dead end. Let's say a nanobot can scrape off arterial palque. This requires nanobot to identify fat deposited in artery, fine, it will be achievable but how would the bot distinguish it from other fats that should be there. Blood vessels leak all the time and some bots may "leak out" and start scrapping brain tissue. Nanobots, as small it is, does not enjoy the luxury of Mars Rover i.e. cannot have an "antenna" to accept command from the master computer outside of the human body let alone a powerful cpu of its own. Once injected, we have no choice but to let nanobots be atonomous and I just do not see how we would program all the intelligence that is required to perform even simplestest tasks, in that small body.


Actually that's not quite true. I've read a couple of plans for control systems using ultrasound/.

#7 ken_akiba

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Posted 17 May 2010 - 11:55 AM

Interesting :-) Would I find it in your thread?

#8 valkyrie_ice

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Posted 17 May 2010 - 04:57 PM

Interesting :-) Would I find it in your thread?

Not sure if I listed it there or not but this is from : http://www.futurist....f-small-things/


One of the most anticipated uses of nanotechnology is the creation of medical nanobots, made up of a few molecules and controlled by a nanocomputer or ultrasound. These nanobots will be used to manipulate other molecules, destroying cholesterol molecules in arties, destroying cancer cells or constructing nerve tissue atom by atom in order to end paralysis.




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