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

Perhaps the next step is to have multiple addressable DNA motors bring different components together to be joined?
—James Lewis

The coming era of atomically precise manufacturing will provide digital control of the structure of matter for a very wide range of possible products and will make possible personal manufacturing of most products. Steps toward digital control of the structure of matter and personal manufacturing, although on a scale much less precise than atomic and for a much more limited range of products, are to be seen with today’s rapidly developing 3D-printing technology. Rival technologies were on display a few weeks ago in Las Vegas. From BBC News “CES 2012: 3D printer makers’ rival visions of future” by Leo Kelion:

With a whir and a click the job is done. In the space of 20 minutes a plastic bottle opener has been constructed by the Replicator – a 3D printing machine capable of making objects up to the size of a loaf of bread.

The device is made by the New York start-up Makerbot Industries and was launched this week at the Consumer Electronics Show in Las Vegas.

The newly-created bottle opener feels warm to the touch and has to be prised away from its base.

It has been created by using extrusion technology – a process in which a spindle of plastic thread is unravelled, melted and fed through a print head which draws the object layer by layer – in this case at a rate of 40mm per second. …

Objects can be created on a computer using free online software such as TinkerCAD or Google Sketchup, before being transferred to the Replicator on a SD memory card.

Alternatively other people’s designs can be downloaded from Makerbot’s community website Thingiverse. …

Take a walk to the other side of the convention centre and you will find another plastic printer maker with another new product, but a very different way of thinking.

3D Systems is a North Carolina-based veteran of the business.

“We invented 3D printers,” its Israeli-born chief executive Abe Reichental says.

“For 25 years we have taken the classic journey of taking expensive, complex technology and bringing it down in price.

“We have about 1,000 workers worldwide. We are a publicly traded company on the New York Stock Exchange. We have almost as many patents as employees.”

The firm is at CES to publicise the launch of Cube, its first consumer-focused product.

The $1,299 device is smaller than Makerbot’s but looks more user-friendly, utilising cartridges rather than spools of plastic thread.

It also boasts its own app store. The launch library includes software to customise belt buckles, a program to turn your voice into a bracelet design, and perhaps most excitingly software from developer Geomagic for Microsoft’s Kinect sensor that allows the peripheral to replicate the user’s face. …

Philippe Van Nedervelde, Foresight’s Executive Director-Europe, contributes his thoughts on the significance of current developments in 3D printers,

Check out:
-http://www.youtube.com/watch?v=jLgZL0OAJhg
-http://cubify.com/
-http://fabbaloo.com/blog/2012/1/6/secret-cubify-project-to-be-unveiled.html

The era of Personal 3D Printing for consumers [has officially started], it seems. And what with its existing track record of excellence plus the slew of key 3D printing companies it has been buying up the company 3D Systems is well poised to become the IBM, Apple, or HP of this new space. (25 years from now, someone should kick me if I do not buy any shares now.)

My sense is that this launch is a close analog to the start-of-an-era-marking launch of the first PC by IBM on August 12, 1981. In some ways, a possibly even closer analog may be the launch of the original Mac on January 24, 1984.

Very interesting times ahead!…

~ Philippe ~

Perhaps Philippe is not exaggerating the significance of this emerging personal manufacturing technology. Personal manufacturing of plastic consumer items may accelerate developing productive nanosystems to make possible personal manufacturing of complex atomically precise consumer products.
—James Lewis

Foresight’s principal focus has been the development of advanced nanotechnology for atomically precise manufacturing, but the incremental development and application of current nanotechnology is also a major interest. Meeting the challenges of incremental nanotechnology development and application includes adequately addressing any potential environmental, health, and safety issues (see Foresight’s “Nanoparticle safety” policy brief.). We therefore note with pleasure that an expert panel of the National Academy of Sciences has recommended that the potential health and environmental risks of nanomaterials should be studied further and that they will revisit the issue in 18 months, when it is to be hoped that the necessary research will be moving forward. From “With Prevalence of Nanomaterials Rising, Panel Urges Review of Risks” by Cornelia Dean:

… Nanoscale forms of substances like silver, carbon, zinc and aluminum have many useful properties. Nano zinc oxide sunscreen goes on smoothly, for example, and nano carbon is lighter and stronger than its everyday or “bulk” form. But researchers say these products and others can also be ingested, inhaled or possibly absorbed through the skin. And they can seep into the environment during manufacturing or disposal.

Nanomaterials are engineered on the scale of a billionth of a meter, perhaps one ten-thousandth the width of a human hair, or less. Not enough is known about the effects, if any, that nanomaterials have on human health and the environment, according to a report issued by the academy’s expert panel. The report says that “critical gaps” in understanding have been identified but “have not been addressed with needed research.”

And because the nanotechnology market is expanding — it represented $225 billion in product sales in 2009 and is expected to grow rapidly in the next decade — “today’s exposure scenarios may not resemble those of the future,” the report says.

The panel called for a four-part research effort focusing on identifying sources of nanomaterial releases, processes that affect exposure and hazards, nanomaterial interactions at subcellular to ecosystem-wide levels and ways to accelerate research progress. …

A free PDF of the report A Research Strategy for Environmental, Health, and Safety Aspects of Engineered Nanomaterials is available.
—James Lewis

Less than four years ago we asked here whether online gamers playing Foldit could help perfect the de novo design of proteins that do not exist in nature. Four months ago we reported that Foldit players had succeeded where scientists had failed in solving the structure of an important viral enzyme. Now Scientific American reports that Foldit players have topped scientists in redesigning a protein—the challenge we suggested less than four years ago. From “Online gamers achieve first crowd-sourced redesign of protein“:

Obsessive gamers’ hours at the computer have now topped scientists’ efforts to improve a model enzyme, in what researchers say is the first crowdsourced redesign of a protein.

The online game Foldit, developed by teams led by Zoran Popovic, director of the Center for Game Science, and biochemist David Baker, both at the University of Washington in Seattle, allows players to fiddle at folding proteins on their home computers in search of the best-scoring (lowest-energy) configurations.

The researchers have previously reported successes by Foldit players in folding proteins, but the latest work moves into the realm of protein design, a more open-ended problem. By posing a series of puzzles to Foldit players and then testing variations on the players’ best designs in the lab, researchers have created an enzyme with more than 18-fold higher activity than the original. The work was published January 22 in Nature Biotechnology [abstract].

“I worked for two years to make these enzymes better and I couldn’t do it,” says Justin Siegel, a post-doctoral researcher working in biophysics in Baker’s group. “Foldit players were able to make a large jump in structural space and I still don’t fully understand how they did it.” …

The latest effort involved an enzyme that catalyses one of a family of workhorse reactions in synthetic chemistry called Diels-Alder reactions. Members of this huge family of reactions are used throughout industry to synthesize everything from drugs to pesticides, but enzymes that catalyze Diels-Alder reactions have been elusive. In 2010, Baker and his team reported that they had designed a functional Diels–Alderase computationally from scratch [abstract], but, says Baker, “it wasn’t such a good enzyme”. The binding pocket for the pair of reactants was too open and activity was low. After their attempts to improve the enzyme plateaued, the team turned to Foldit.

In one puzzle, the researchers asked users to remodel one of four amino-acid loops on the enzyme to increase contact with the reactants. In another puzzle, players were asked for a design that would stabilize the new loop. The researchers got back nearly 70,000 designs for the first puzzle and 110,000 for the second, then synthesized a number of test enzymes based on the best designs, ultimately resulting in the final, 18-fold-more-active enzyme.…

The article was written by Jessica Marshall and reprinted in Scientific American with permission from Nature, where it was originally published as “Victory for crowdsourced biomolecule design: Players of the online game Foldit guide researchers to a better enzyme.” The article does an excellent job of describing how researchers and game players collaborated to achieve the final result. The gamers explored much more radical changes to the protein than can be done by conventional molecular biology techniques such as directed evolution, which typic[a]lly explores only single amino acid substitutions. The researchers then physically constructed and characterized the enzyme designed by the gamers.

The choice as design target of an enzyme to catalyze Diels-Alder reactions is particularly interesting from the standpoint of developing advanced nanotechnology, also referred to as molecular manufacturing. As noted in the 2010 Science paper, this reaction is a “cornerstone” in organic synthesis, and no naturally occurring enzymes are known to catalyze this reaction. As early as 1994 Markus Krummenacker proposed the use of Diels-Alder cycloaddition in a strategy to develop molecular building blocks for molecular manufacturing (“Steps towards molecular manufacturing“).

What roles crowd-sourcing, citizen science, and de novo protein design will play in the development of molecular manufacturing, or productive nanosystems, remains to be seen, but this latest result looks like an important step alog the way.
—James Lewis

Foresight Institute Co-Founder and Past President Christine Peterson was among four panelists addressing the role of technology in human existence for a Stanford University Continuing Studies series. From a report in The Stanford Daily by Marshall Watkins “Bay Area thinkers ponder ‘life’“:

Christine Peterson, co-founder and president of The Foresight Institute, a public interest group seeking to educate the community on forthcoming technological advances, emphasized the increasingly prominent role that nanotechnology has come to play.

Peterson noted that nanotechnology has the potential to create new materials and make vast advances without the side effects, such as pollution, that would currently ensue. She allowed, however, that the near-invisible and highly sensitive technology might enable intrusions on privacy.

“We need to know what data is collected,” Peterson said, “how it is used and how long it is retained. We have those rights.”

Peterson highlighted the medical benefits of nanotechnology, noting, “The ability to control atoms and molecules would mean that there really isn’t a physical illness [that] we wouldn’t be able to address.”

The report quotes the moderator of the panel, author Piero Scaruffi, as stating that the four panelists were picked because “They discussed life as in the future, rather than life as in the past.” We can certainly expect that life after advanced nanotechnology has been developed will be fundamentally different from life up until that point.

Researchers at I.B.M.’s Almaden Research Center have used a scanning tunneling microscope to assemble an array of 96 iron atoms into an antiferromagnetic structure that encodes one byte (eight bits) of information. As reported in the NY Times by John Markoff “New storage device is very small, at 12 atoms“:

SAN JOSE, Calif. — Researchers at I.B.M. have stored and retrieved digital 1s and 0s from an array of just 12 atoms, pushing the boundaries of the magnetic storage of information to the edge of what is possible.

The findings, being reported Thursday in the journal Science, could help lead to a new class of nanomaterials for a generation of memory chips and disk drives that will not only have greater capabilities than the current silicon-based computers but will consume significantly less power. And they may offer a new direction for research in quantum computing. …

The group at I.B.M.’s Almaden Research Center here, led by Andreas Heinrich, has now created the smallest possible unit of magnetic storage by painstakingly arranging two rows of six iron atoms on a surface of copper nitride. …

Although the research took place at a temperature near absolute zero, the scientists wrote that the same experiment could be done at room temperature with as few as 150 atoms. …

The remainder of the article quotes Dr. Heinrich as saying that these tiny devices built with scanning tunneling microscopes are primarily of interest as a way to explore the quantum mechanical properties of the antiferromagnetic effect in the hope of developing novel nanomaterials that might lead to quantum computers. He also noted that many research groups are exploring self-assembly methods that could lead to practical manufacturing technologies to replace current microelectronic technologies.

The potential of advanced nanotechnology is getting some attention from mainstream media. Late last year The Guardian web site posted a brief article on the prospects for nanofactories and atomically precise manufacturing, featuring quotes from Christine Peterson and Robert Freitas. From “Nanofactories – a future vision” by Penny Sarchet:

Mimicking nature is a recurring theme in nanotechnology and molecular nanotechnology, inspired by the natural nanostructures found in our own bodies, offers many exciting potential outcomes.

“Molecular nanotechnology is the expected ability to build our products with molecular-level precision, as nature can do,” says Christine Peterson, president of the Foresight Nanotech Institute in California. “It will bring unprecedented quality, energy efficiency and environmental sustainability”.

The recent development of an electron-powered molecular “nanocar”, by a team led by chemist Ben Feringa at the University of Groningen in the Netherlands, hints at the potential. Further indications that molecular nanotechnology is achievable are being found in the quest for ever-smaller computing.

Many of these efforts attempt to use nature’s own method of storing and transferring information – DNA. “DNA computing is the goal of building devices out of DNA that are able to act like computers, initially doing simple calculations but eventually doing everything that a macroscale computer can do,” says Peterson. …

One future prospect for molecular-scale nanotechnology is to build nanofactories. “The nanofactory is a proposed compact molecular manufacturing system that could build a diverse selection of large-scale, atomically precise products,” explains Robert Freitas Jr, senior research fellow at the Institute for Molecular Manufacturing, also in California. “The products of a nanofactory would be atomically precise, with every atom in exactly the right place, offering the ultimate in quality control. It could make products out of the strongest materials known to man – especially diamond, sapphire, and related ultra-strong ceramics. In manufacturing, it’s hard to do better than that.”

The first two-dimensional structure to be built atom-by-atom was made from silicon in 2003. However, Freitas says nanofactories are still a long way off. “We expect this will require a 20-year research and development effort and on the order of $1bn (£622m) in funding to achieve.” …

If anyone knows someone with a billion dollars they will not need for twenty years, ask them to contact Christine or Robert.

We received this announcement of the new M.S. in Nanomedicine program from Radiological Technologies University – VT:

Radiological Technologies University VT, located in South Bend, Indiana is pleased to announce the approval of the first Master’s of Science in Nanomedicine degree program in the country. The formal approval was granted today through the Indiana Commission for Postsecondary Proprietary Education. Nanomedicine is the medical application of Nanotechnology which focuses its work at the cellular level to do everything from repairing tissue, to cleaning arteries, to attacking cancer cells and viruses like AIDS. The RTU Nanomedicine program is the first of its kind in the country by combining Nanotechnology with an emphasis on Medical Physics. Radiological Technologies University offers degree programs ranging from a Bachelor’s degree in Medical Dosimetry to Master’s of Science degrees in Medical Dosimetry, Medical Physics, Medical Health Physics, and Nanomedicine.

Although Foresight has no information about the details of this nanomedicine program, just one item from the NCI Alliance for Nanotechnology in Cancer news archive highlights the potential of nanomedicine, specifically the application of nanoparticles to cancer therapy. From “Nanoparticles seek and destroy drug-resistant glioblastoma“:

Glioblastoma is one of the most aggressive forms of brain cancer. Rather than presenting as a well-defined tumor, glioblastoma will often infiltrate the surrounding brain tissue, making it extremely difficult to treat surgically or with chemotherapy or radiation. Likewise, several mouse models of glioblastoma have proven completely resistant to all treatment attempts.

In a new study, a team led by scientists at Sanford-Burnham Medical Research Institute (SBMRI) and the Salk Institute for Biological Studies developed a method to combine a tumor-homing peptide, a cell-killing peptide, and a nanoparticle that both enhances tumor cell death and allows the researchers to image the tumors. When used to treat mice with glioblastoma, this new nanosystem eradicated most tumors in one model and significantly delayed tumor development in another. These findings were published in the Proceedings of the National Academy of Sciences of the USA [abstract].

“This is a unique nanosystem for two reasons,” said project leader Erkki Ruoslahti of the SBMRI. “First, linking the cell-killing peptide to nanoparticles made it possible for us to deliver it specifically to tumors, virtually eliminating the killer peptide’s toxicity to normal tissues. Second, ordinarily researchers and clinicians are happy if they are able to deliver more drugs to a tumor than to normal tissues. We not only accomplished that, but were able to design our nanoparticles to deliver the killer peptide right where it acts, at the mitochondria, the cell’s energy-generating center.”

The nanosystem developed in this study is made up of three elements. First, a nanoparticle acts as the carrier framework for an imaging agent and for two peptides. One of these peptides guides the nanoparticle and its payload specifically to cancer cells and the blood vessels that feed them by binding cell surface markers that distinguish them from normal cells. This same peptide also drives the whole system inside these target cells, where the second peptide wreaks havoc on the mitochondria, triggering cellular suicide through a process known as apoptosis.

Together, these peptides and nanoparticles proved extremely effective at treating two different mouse models of glioblastoma. In the first model, treated mice survived significantly longer than untreated mice. In the second model, untreated mice survived for only eight to nine weeks. In sharp contrast, treatment with this nanosystem cured all but one of ten mice. What’s more, in addition to providing therapy, the nanoparticles could aid in diagnosing glioblastoma; they are made of iron oxide, which makes them and the tumors they target visible by magnetic resonance imaging.

In a final twist, the researchers made the whole nanosystem even more effective by administering it to the mice in conjunction with a third peptide. Ruoslahti and his team previously showed that this peptide, known as iRGD, helps co-administered drugs penetrate deeply into tumor tissue. iRGD has been shown to substantially increase treatment efficacy of various drugs against human breast, prostate, and pancreatic cancers in mice, achieving the same therapeutic effect as a normal dose with one-third as much of the drug. Here, iRGD enhanced nanoparticle penetration and therapeutic efficacy.

In this study, the researchers tested their nanoparticles on mice that developed glioblastomas with the same characteristics as observed in humans with the disease. Once the nanoparticles reached the tumors’ blood vessels, they delivered their payload directly to the cell’s power producer, the mitochondria. By destroying the blood vessels and also some surrounding tumor cells, the investigators found they were able to cure some mice and extend the lifespan of the rest.”

An important milestone in the development of nanotechnology leading to atomically precise manufacturing (molecular manufacturing) is the development of artificial molecular machines that can control molecular transformations. Two scientists from the University of Groningen, Netherlands, published a paper in Science [abstract] earlier this year demonstrating control of a chemical reaction by an artificial molecular machine. They constructed a light-driven molecular motor that catalyses different chemical reactions as the motor is stepped through its rotary cycle. The researchers’ institute has made the full text of “Dynamic Control of Chiral Space in a Catalytic Asymmetric Reaction Using a Molecular Motor” available here.

The authors constructed a rotary motor molecule in which the rotor and stator halves of the molecule rotate about an axle consisting of a carbon-carbon double bond. Rotation occurs in only one direction in a four-stage cycle driven by light absorption and by temperature change. Because the molecule is helical in shape, it is chiral, that is, it exists in two different conformations (shapes) that are mirror images of each other.

The rotor and stator halves of the molecule are each attached to a different chemical function so that when rotation about the axle brings the two functional groups spatially close to each other, they catalyze a chemical reaction. At the four different stages of the rotary cycle, the two groups are either widely separated (two trans configurations) and thus have low catalytic activity, or close to each other and therefore have high catalytic activity (the two cis configurations). In one cis configuration the active catalyst is in one chiral orientation; in the other cis configuration, the catalyst is in the opposite chiral orientation. As expected, when used to catalyze an appropriate chemical reaction that can produce either one of two chiral products, the two trans forms of the motor have low activity and they produce a mixture of the two chiral products. The two cis forms of the motor have high activity. One chiral cis form produces predominantly one chiral product; the other produces predominantly the other chiral product.

The authors conclude:

Coupling of unidirectional switching to catalytic function, as demonstrated here, may prove to be a key design tool in the construction of future catalysts that can perform multiple tasks in a sequential manner.

The molecular specificity of this initial proof-of-principle demonstration is only partial. The differences in catalytic activity and the differences in chiral ratios of the reaction products are only of the order of three- or four-fold. We can hope that continued work in this direction will lead to cleaner reaction specificities resulting from programmable control of artificial molecular machines. Eventually we hope to see arrays of programmable molecular catalysts executing complex reaction sequences, leading to productive nanosysems and atomically precise manufacturing.

A few weeks ago we noted the publication of a tutorial review that asks whether artificial molecular machines can deliver the performance that visionaries expect. Upon learning that the full text is available after a free registration, I downloaded the review to learn what the authors think about the prospects of eventually doing atomically precise manufacturing with artificial molecular machine systems.

The authors begin with the observation that, despite “remarkable progress” in synthesizing molecular switches, there have been only few and very rudimentary examples of harvesting useful work from such molecular switches. They then ask whether only incremental progress will be necessary for artificial molecular machines to achieve the levels of function so elegantly achieved by biological molecular machines, or whether some paradigm shift in thinking will be necessary (they believe the latter).

The fundamental theory of molecular machines is applied to two questions. (1) Can artificial molecular machines be developed to manipulate or chemically transform other molecular or nanoscale structures? (2) Can artificial molecular machines be assembled into integrated systems that work together to manipulate or fabricate structures at the meso- and macroscopic levels? The overall conclusion of these authors with respect to these two questions is optimistic:

Indeed, nanoscale-based machinery has been envisaged ever since the days of Feynman and today the Feynman’s Grand Prize offers a $250,000 reward to the first persons to create a nanoscale robotic arm, capable of precise positional control. While, in pursuit of this goal, the “top-down” fabrication strategies have so far failed rather dismally, we are convinced that a “bottom-up” approach, utilizing AMMs [artificial molecular machines], can deliver. Engineering a macromolecular architecture capable of robotic function will no doubt be a considerable synthetic challenge. We feel, however, that the time is ripe for such an undertaking—for instance, by combining AMMs with the DNA-origami materials, such that the former would provide the actuation within precisely folded DNA nanoscaffolds of the latter.

A major focus of this tutorial review is to describe the recently developed theoretical concepts “that distinguish simple molecular switches from fully fledged molecular machines.” Simple molecular switches differ from familiar macroscopic switches in that the switching between the states of the switch is driven by thermal noise. To advance from simple molecular switches to molecular machines, it must be possible to drive chemical reactions uphill, away from equilibrium, as do biological motor molecules. This can be accomplished by using molecular switches to alter the energy profile of the reaction by first lowering the energy of the intermediate to be less than the energy of the starting material, and then switching again to raise the energy of the intermediate above that of the product, and finally switching again to reset the system to the original energy profile. Switching makes each molecular transformation along the way spontaneous, but the end result is shifted way from the equilibrium without switching.

The authors give the example of doubly stable bistable rotaxanes—dumbbell-shaped molecules in which an electrochemical input can move reactants to different positions along the central part of the dumbbell to alter an energy profile and drive a reaction uphill. An example is given of a molecule that can be switched by an oxidation-reduction event between contracted and extended states. If such a molecule is attached to a molecular spring, then the extended form of the molecule could store energy in the spring molecule. If the architecture of the device as a whole allows the spring to be detached from the oxidation-reduction switch, then the energy stored in the spring can be harvested to do external work. Thus an oxidation-reduction switch becomes part of a simple molecular motor.

Having considered how to extract external work from externally switchable molecules, the authors consider how sufficient energy to perform macroscopic work could be harvested from mesoscopic arrays of AMMs. They note that in biological systems molecular motors are organized spatially and synchronized to act together, and consider approaches to fabricate such arrays through self-assembly. They cite metal oxide frameworks as one potentially promising type of scaffolding that might be used to array AMMs.

The brief roadmap presented in this tutorial review outlines the challenges and opportunities involved in transforming simple molecular switches into AMMs. The authors are optimistic:

On the horizon lie new types of “mechanized” enzyme-like mimicks, addressable nanomaterials, nanorobots, and possibly more into the bargain.