'Scanning tunnelling microscopy (STM) images of the quantum states of an artificial atomic defect structure in silicon. This structure was fabricated by using the STM to individually remove five hydrogen atoms from a hydrogen-terminated silicon (001) surface. The absence of the hydrogen atoms creates “dangling bond” states that interact to form extended, artificial molecular orbitals. Only the imaging bias voltage has been changed in the three images shown (from left to right, -1.4, +1.4, and +1.8 Volts).' (credit: London Centre for Nanotechnology)

We have previously speculated here whether the continued improvement of technology to place single atoms on silicon with atomic precision for the purpose of developing practical quantum computers would also lead to more general methods of atomically precise or molecular manufacturing. That speculation remains open, but we note that the field of atomically precise quantum engineering continues to advance. A hat tip to ScienceDaily for reprinting this University College London news release “Building quantum states with individual silicon atoms“:

By introducing individual silicon atom ‘defects’ using a scanning tunnelling microscope, scientists at the London Centre for Nanotechnology have coupled single atoms to form quantum states.

Published today in Nature Communications [open access paper: Quantum engineering at the silicon surface using dangling bonds], the study demonstrates the viability of engineering atomic-scale quantum states on the surface of silicon – an important step toward the fabrication of devices at the single-atom limit.

Advances in atomic physics now allow single ions to be brought together to form quantum coherent states. However, to build coupled atomic systems in large numbers, as required for applications such as quantum computing, it is highly desirable to develop the ability to construct coupled atomic systems in the solid state.

Semiconductors, such as silicon, routinely display atomic defects that have clear analogies with trapped ions. However, introducing such defects deterministically to observe the coupling between extended systems of individual defects has so far remained elusive.

Now, LCN scientists have shown that quantum states can be engineered on silicon by creating interacting single-atom defects. Each individual defect consisted of a silicon atom with a broken, or “dangling”, bond. During this study, these single-atom defects were created in pairs and extended chains, with each defect separated by just under one nanometer.

Importantly, when coupled together, these individual atomic defects produce extended quantum states resembling artificial molecular orbitals. Just as for a molecule, each structure exhibited multiple quantum states with distinct energy levels.

The visibility of these states to the scanning tunneling microscope could be tuned through the variation of two independent parameters – the voltage applied to the imaging probe and its height above the surface.

The study was led by Dr Steven Schofield, who said: “We have created precise arrays of atomic defects on a silicon surface and demonstrated that they couple to form unique and interesting quantum states.”

He added: “The next step is to replicate these results in other material systems, for example using substitutional phosphorus atoms in silicon, which holds particular interest for quantum computer fabrication.”

Ongoing research at the LCN is exploring even more complex arrangements of these defects, including the incorporation of impurity atoms within the defect structures, which is expected to alter the symmetry of the defects (similar to the role of the nitrogen atom in the nitrogen-vacancy center defect in diamond).

Will this demonstrated ability of ‘quantum engineering’ dangling silicon atom bonds lead to applications to more general atomically precise manufacturing or productive nanosystems?
—James Lewis, PhD

Credit: Zhengyi Zhao, University of Kentucky

One of nature’s many types of molecular motors combines protein and RNA subunits to force viral (in this case, bacteriophage) DNA into a protein capsid. The understanding of the molecular mechanism by which this motor works has been advanced by the discovery that it revolves the DNA around a central channel, as the Earth revolves around the sun, rather than by rotating, as the Earth does about it axis. A hat tip to ScienceDaily for pointing to this research. From a University of Kentucky news release “Guo lab discovers new class of revolution biomotor and solves mystery in viral DNA packaging:”

Scientists at the University of Kentucky have cracked a 35-year-old mystery about the workings of natural “biomotors.” These molecular machines are serving as models for development of synthetic nanomotors that will someday pump therapeutic DNA, RNA or drugs into individual diseased cells.

The report, revealing the innermost mechanisms of these motors in a bacteria-killing virus and a “new way to move DNA through cells,” is being published online today in the journal ACS Nano.

The article, “Mechanism of One-Way Traffic of Hexameric Phi29 DNA Packaging Motor with Four Electropositive Relaying Layers Facilitating Anti-Parallel Revolution,” can be downloaded with free, open access from http://pubs.acs.org/doi/abs/10.1021/nn4002775.

Peixuan Guo, director of the UK Nanobiotechnology Center, and his colleagues explain that two motors have been found in nature: A linear motor and a rotating motor. Now they report discovery of a third type, a revolving molecular motor.

Guo points out that nanomotors will open the door to practical machines and other nanotechnology devices so small that 100,000 would fit across the width of a human hair. One major natural prototype for those development efforts has been the motor that packages DNA into the shell of bacteriophage phi29, a virus that infects and kills bacteria.

Guo’s own research team wants to embed a synthetic version of that motor into nanomedical devices that are injected into the body, travel to diseased cells and pump in medication. A major barrier in doing so has been uncertainty and controversy about exactly how the phi29 motor moves. Scientists thought that it worked by rotating or spinning in the same motion as the Earth turning once every 24 hours upon its own axis.

In their ACS Nano paper, Guo — with his team, Zhengyi Zhao, Emil Khisamutdinov, and Chad Schwartz — challenge that idea. Indeed, they discovered that the phi29 motor moves DNA without any rotational motion. The motor moves DNA with a revolving in the same motion as the Earth revolving around the sun in one orbit ever 365 days. The “revolution without rotation” model could resolve a big conundrum troubling the past 35 years of painstaking investigation of the mechanism of these viral DNA packaging motors, the report states.

Near-term application of artificial molecular motors based on this work are not difficult to imagine, such as in drug delivery or gene delivery for nanomedicine. Could motors like these be useful for more complicated molecular machine systems, such as running pulleys using DNA cables to transport components in primitive molecular manufacturing systems?
—James Lewis, PhD

…
In what fields would APM cause the most pronounced economic disruption and the collapse of global supply chains to more local chains?

The digital revolution had far-reaching effects on information industries. APM-based production promises to have similarly far-reaching effects, but transposed into the world of physical products. In thinking about implications for international trade and economic organization, three aspects should be kept in mind: a shift from scarce to common raw materials, a shift from long supply chains to more direct paths from raw materials to finished products, and a shift toward flexible, localized manufacturing based on production systems with capabilities that are comparable on-demand printing. This is enough to at least suggest the scope of the changes to expect from a mature form of APM-based production — which again is a clear prospect but emphatically not around the corner.
…

-Posted by Stephanie C

Credit: Biodesign Institute

Of all of the paths toward molecular manufacturing, structural DNA nanotechnology seems to provide the most frequent and photogenic advances. By re-engineering the Holliday junction, the basic cross-over structure adapted to build complex structures from DNA, Prof. Hao Yan and his colleagues has been able to construct a variety of new wire frame and mesh structures. A hat tip to ScienceDaily for reprinting this Arizona State University news release “ASU scientists develop innovative twists to DNA nanotechnology“:

In a new discovery that represents a major step in solving a critical design challenge, Arizona State University Professor Hao Yan has led a research team to produce a wide variety of 2-D and 3-D structures that push the boundaries of the burgeoning field of DNA nanotechnology.

The field of DNA nanotechnology utilizes nature’s design rules and the chemical properties of DNA to self-assemble into an increasingly complex menagerie of molecules for biomedical and electronic applications. Some of the Yan lab’s accomplishments include building Trojan horse-like structures to improve drug delivery to cancerous cells, electrically conductive gold nanowires, single molecule sensors and programmable molecular robots.

With their bio-inspired architectural works, the group continues to explore the geometrical and physical limits of building at the molecular level.

“People in this field are very interested in making wire frame or mesh structures,” said Yan. “We needed to come up with new design principles that allow us to build with more complexity in three dimensions.”

In their latest twist to the technology, Yan’s team made new 2-D and 3-D objects that look like wire-frame art of spheres as well as molecular tweezers, scissors, a screw, hand fan, and even a spider web.

The Yan lab, which includes ASU Biodesign Institute colleagues Dongran Han, Suchetan Pal, Shuoxing Jiang, Jeanette Nangreave and assistant professor Yan Liu, published their results in the March 22 issue of Science [abstract].

The twist in their ‘bottom up,’ molecular Lego design strategy focuses on a DNA structure called a Holliday junction.

In nature, this cross-shaped, double-stacked DNA structure is like the 4-way traffic stop of genetics – where 2 separate DNA helices temporality meet to exchange genetic information. The Holliday junction is the crossroads responsible for the diversity of life on Earth, and ensures that children are given a unique shuffling of traits from a mother and father’s DNA.

In nature, the Holliday junction twists the double-stacked strands of DNA at an angle of about 60-degrees, which is perfect for swapping genes but sometimes frustrating for DNA nanotechnology scientists, because it limits the design rules of their structures.

“In principal, you can use the scaffold to connect multiple layers horizontally,” [which many research teams have utilized since the development of DNA origami by Cal Tech's Paul Rothemund in 2006]. However, when you go in the vertical direction, the polarity of DNA prevents you from making multiple layers,” said Yan. “What we needed to do is rotate the angle and force it to connect.”

Making the new structures that Yan envisioned required re-engineering the Holliday junction by flipping and rotating around the junction point about half a clock face, or 150 degrees. Such a feat has not been considered in existing designs.

“The initial idea was the hardest part,” said Yan. “Your mind doesn’t always see the possibilities so you forget about it. We had to break the conceptual barrier that this could happen.”

In the new study, by varying the length of the DNA between each Holliday junction, they could force the geometry at the Holliday junctions into an unconventional rearrangement, making the junctions more flexible to build for the first time in the vertical dimension. Yan calls the backyard barbeque grill-shaped structure a DNA Gridiron.

“We were amazed that it worked!” said Yan. “Once we saw that it actually worked, it was relatively easy to implement new designs. Now it seems easy in hindsight. If your mindset is limited by the conventional rules, it’s really hard to take the next step. Once you take that step, it becomes so obvious.”

The DNA Gridiron designs are programmed into a viral DNA, where a spaghetti-shaped single strand of DNA is spit out and folded together with the help of small ‘staple’ strands of DNA that help mold the final DNA structure. In a test tube, the mixture is heated, then rapidly cooled, and everything self-assembles and molds into the final shape once cooled. Next, using sophisticated AFM and TEM imaging technology, they are able to examine the shapes and sizes of the final products and determine that they had formed correctly.

This approach has allowed them to build multilayered, 3-D structures and curved objects for new applications.

“Most of our research team is now devoted toward finding new applications for this basic toolkit we are making,” said Yan. “There is still a long way to go and a lot of new ideas to explore. We just need to keep talking to biologists, physicists and engineers to understand and meet their needs.”

The video (computer simulation) of the sphere made from DNA, included in the news release, represents an impressive new capability. One thing I like about structural DNA nanotechnology is that every time I think they have just about exhausted the bag of tricks that DNA provides, someone proves me wrong. I look forward to seeing what else they come up with.
—James Lewis, PhD

(credit: Comp. Cog. Neurosci Lab/ Olaf Sporns, Indiana Univ.)

A proposal alluded to by President Obama in his State of the Union address to construct a dynamic “functional connectome” Brain Activity Map (BAM) would leverage current progress in neuroscience, synthetic biology, and nanotechnology to develop a map of each firing of every neuron in the human brain—a hundred billion neurons sampled on millisecond time scales. Although not the intended goal of this effort, a project on this scale, if it is funded, should also indirectly advance efforts to develop artificial intelligence and atomically precise manufacturing. In his blog, Robert L. Blum provides an excellent overview and brief introduction. From “BAM: Brain Activity Map: Every Spike from Every Neuron“:

A recent research proposal called BAM for Brain Activity Map Project generated much excitement. (The BAM proposal, published in Neuron in June 2012 is online, and an earlier draft with far greater detail is also online.)

(Addendum: 18 Feb 2013: I started drafting this story in Nov, 2012. Today it was headline news when it was made public that THIS is the very proposal that President Obama alluded to in his recent State of the Union address. See John Markoff’s NY Times piece. NIH is drafting a 3 billion dollar, 10 year proposal to fund this project. Also see this 25 Feb 2013 NY Times follow-up by Markoff.) …

The essence of the BAM proposal is to create the technology over the coming decade to be able to record every spike from every neuron in the brain of a behaving organism. While this notion seems insanely ambitious, coming from a group of top investigators, the paper deserves scrutiny. At minimum it shows what might be achieved in the future by the combination of nanotechnology and neuroscience. …

The Neuron article cited by Blum argues that in addition to breakthroughs in basic science with large medical and economic benefits, the BAM project will advance technology in terms of important general capabilities.

Many technological breakthroughs are bound to arise from the BAM Project, as it is positioned at the convergence of biotechnology and nanotechnology. These new technologies could include optical techniques to image in 3D; sensitive, miniature, and intelligent nanosystems for fundamental investigations in the life sciences, medicine, engineering, and environmental applications; capabilities for storage and manipulation of massive data sets; and development of biologically inspired, computational devices.

I think the emphasis on nanosystems of nanodevices integrated to provide complex functions is very important, even if many or most of those devices will, in the beginning, not be atomically precise. The more detailed description of the BAM proposal cited by Blum above hints at how nanoparticle-based sensors could be developed to noninvasively provide micrometer-scale spatial resolution and millisecond-scale temporal resolution to groups of millions of neurons deep inside the brain of a living, active animal (or human). The mention combining semiconductor quantum dots and nanodiamonds with organic nanostructures to functionalize them, so that they may be directed to and embedded in neural membranes to monitor synapses. In addition, nanotubes or nanowires could be developed to deliver photons to specific locations, or collect or release specific chemicals. Further, they suggest developing graphene into membrane patches for detailed monitoring of neurons. Taken together, the requirements for this ambitious project entail the need to develop a variety of nanoparticles for specific applications, and then integrating multifunctional nanoprobes, nanoparticles, and nanodevices into large functional systems, and producing such nanosystems en masse.

In his NY Times report John Markoff notes the possible effect of this project on the development of artificial intelligence: “Moreover, the project holds the potential of paving the way for advances in artificial intelligence.” Indeed, the information to be provided by BAM about how circuits of thousands or millions of neurons work should advance Ray Kurzweil’s program of reverse engineering the human brain to develop artificial general intelligence, as described in his new book How to Create a Mind: The Secret of Human Thought Revealed.

The next best thing to large program to develop molecular manufacturing is a large program aimed at other worthy and useful goals that also makes heavy use of nanotechnology and may promote some of the same or similar enabling technologies that will lead toward productive nanosystems.
—James Lewis, PhD

Harmless bacteria could be re-engineered into microscopic factories that could, in addition to more immediate applications, perhaps provide components for more general molecular manufacturing systems. (credit Imperial College, London)

Synthetic biology and molecular manufacturing/productive nanosystems have in common the effort to rationally engineer systems to make and assemble parts for complex molecular machine systems. The effort in synthetic biology to design complex biological systems in a hierarchical architecture from well-characterized molecular parts is accelerating. A hat tip to ScienceDaily for reprinting this Imperial College news release “Discovery in synthetic biology a step closer to new industrial revolution“:

Scientists report that they have developed a method that cuts down the time it takes to make new ‘parts’ for microscopic biological factories from 2 days to only 6 hours.

The scientists, from Imperial College London, say their research brings them another step closer to a new kind of industrial revolution, where parts for these biological factories could be mass-produced. These factories have a wealth of applications including better drug delivery treatments for patients, enhancements in the way that minerals are mined from deep underground and advances in the production of biofuels.

Professor Paul Freemont, Co- Director of the Centre for Synthetic Biology and Innovation at Imperial College London and principal co-investigator of the study, which is published today in the journal Nucleic Acids Research [abstract, free full text PDF], says:

“Before the industrial revolution most items were made by hand, which meant that they were slower to manufacture, more expensive to produce and limited in number. We are at a similar juncture in synthetic biology, having to test and build each part from scratch, which is a long and slow process. We demonstrate in our study a new method that could help to rapidly scale up the production and testing of biological parts.”

Parts made up of DNA are re-engineered by scientists and put into cells to make biological factories. However, a major bottleneck in synthetic biology is the lack of parts from which to build new types of factories. To build parts using the current time-consuming method, scientists have to re-engineer DNA in a cell and observe how it works. If it functions according to their specifications, then the scientists store the part specifications in a catalogue.

Now, scientists from Imperial College London have devised a much quicker method that does away with the need for them to re-engineer a cell every time they want to make a new part. The team say their work could lead to vast new libraries of off-the-shelf components that could be used to build more sophisticated biological factories.

James Chappell, co-author of the study from the Centre for Synthetic Biology and Innovation at Imperial College London, says:

“One of the major goals in synthetic biology is to find a way to industrialise our processes so that we can mass produce these biological factories much in the same way that industries such as car manufacturers mass produce vehicles in a factory line. This could unlock the potential of this field of science and enable us to develop much more sophisticated devices that could be used to improve many facets of society. Excitingly, our research takes us one step closer to this reality, providing a rapid way of developing new parts.”

When a cell is re-engineered, the re-programmed DNA in the cell encodes a message that is conveyed by molecules called messenger ribonucleic acid (mRNA) to the cell’s production factories called ribosomes. The ribosomes translate the genetic information into a command that instructs the cell to perform functions. For example, scientists can already re-engineer a cell into an infection detector factory, which produces a protein that detects chemical signals from human pathogenic bacteria and changes colour to indicate their presence.

In the study, the Imperial researchers demonstrate for the first time that the same method can be achieved in a test tube outside of a cell. This involves extracting from cells the machinery that produces mRNA and proteins and providing the energy and building blocks to help them survive in test tubes. The team then add their re-programmed DNA to the solution and observe how it functions.

The advantage of this method is that scientists can develop litres of this cell-like environment so that multiple re-programmed DNA can be tested simultaneously, which speeds up the production process of parts.

The next stage of the research is to expand the types of parts and devices that can be developed using this method. They also are aiming to develop a method using robots to speed up and make the whole process automated.

Professor Richard Kitney, co- Director of the Centre for Synthetic Biology and Innovation at Imperial College London says: “Synthetic biology is seen by the British Government as having the potential to create new industries and jobs for the benefit of the UK economy. This work is part of a wider, major research programme within the Centre to develop technology that can be used across a range of industrial applications.”

The hope driving this research is that biological parts will transform industrial sectors like drug delivery and biofuels production into molecular manufacturing processes. Whether synthetic biology can eventually be made to contribute parts for nanofactories to implement more general molecular manufacturing using stronger, more rigid parts, remains to be seen.
—James Lewis, PhD

(Credit: Miriam Wilson)

Nature has evolved a partial system of molecular manufacturing. Although not capable of making arbitrarily complex, atomically precise structures that faithfully represent the immense diversity of chemically feasible structures, biology very early on evolved a method of assembling a wide range of molecular machines by linking particular types of subunit molecules together in a defined sequence. The structure that makes the most complex biological molecular machines is the ribosome, a complex of two subunits 20 to 30 nm in diameter and comprising several dozen RNA and protein molecules, which works with hundreds of other RNA and protein molecules to link amino acids together as specified by genetic information to make specific protein molecules. Scientists in the UK have succeeded in mimicking this basic process using a simple artificial molecular machine bearing no resemblance to the ribosome and an order of magnitude smaller in linear dimension than the ribosome. A hat tip to Phys.org for reprinting this University of Manchester news release “Molecular machine could hold key to more efficient manufacturing“:

An industrial revolution on a minute scale is taking place in laboratories at The University of Manchester with the development of a highly complex machine that mimics how molecules are made in nature.

The artificial molecular machine developed by Professor David Leigh FRS and his team in the School of Chemistry is the most advanced molecular machine of its type in the world. Its development has been published in the journal Science [abstract].

Professor Leigh explains: “The development of this machine which uses molecules to make molecules in a synthetic process is similar to the robotic assembly line in car plants. Such machines could ultimately lead to the process of making molecules becoming much more efficient and cost effective. This will benefit all sorts of manufacturing areas as many manmade products begin at a molecular level. For example, we’re currently modifying our machine to make drugs such as penicillin.” …

Professor Leigh’s machine is based on the ribosome. It features a functionalized nanometre-sized ring that moves along a molecular track, picking up building blocks located on the path and connecting them together in a specific order to synthesize the desired new molecule.

First the ring is threaded onto a molecular strand using copper ions to direct the assembly process. Then a “reactive arm” is attached to the rest of the machine and it starts to operate. The ring moves up and down the strand until its path is blocked by a bulky group. The reactive arm then detaches the obstruction from the track and passes it to another site on the machine, regenerating the active site on the arm. The ring is then free to move further along the strand until its path is obstructed by the next building block. This, in turn, is removed and passed to the elongation site on the ring, thus building up a new molecular structure on the ring. Once all the building blocks are removed from the track, the ring de-threads and the synthesis is over.

Professor Leigh says the current prototype is still far from being as efficient as the ribosome: “The ribosome can put together 20 building blocks a second until up to 150 are linked. So far we have only used our machine to link together 4 blocks and it takes 12 hours to connect each block. But you can massively parallel the assembly process: We are already using a million million million (10¹⁸) of these machines working in parallel in the laboratory to build molecules.”

Professor Leigh continues: “The next step is to start using the machine to make sophisticated molecules with more building blocks. The potential is for it to be able to make molecules that have never been seen before. They’re not made in nature and can’t be made synthetically because of the processes currently used. This is a very exciting possibility for the future.”

An animation illustrating how the molecular machine works is available on YouTube. Professor Leigh was the winner of the 2007 Foresight Institute Feynman Prize in Theory for the design and synthesis of artificial molecular machines.

The small molecular machine in this work is based upon a rotaxane molecule, in which a dumbbell-shaped molecule is threaded through a macrocycle. The dumbbell is constructed from two components: a “stopper”, and a “strand”, along which the amino acids to be added are linked. A chemical moiety that will link with the stopper defines the front of the strand. The order of the amino acid subunits in the peptide molecule to be manufactured is determined by the order in which the reactive building blocks are positioned along the molecular strand, with the first one nearest the front, and the last at the opposite end of the strand. Following the practice for solid state chemical synthesis of peptides pioneered by Bruce Merrifield half a century ago, the amino groups of the amino acids are protected with a chemical group that keeps them from reacting prematurely. The third component of the rotaxane is the macrocycle, which has a site at which the reactive arm of the molecular machine will be attached.

Three amino acids are linked to the strand, separated from each other by rigid spacers: phenylalanine at the front, then leucine, then alanine. As with conventional solid state peptide synthesis, the peptide will be synthesized from the C-terminal to the N-terminal end, the opposite of direction of synthesis on the ribosome. The rotaxane is assembled in a chemical reaction catalyzed by copper ions in which the macrocycle is guided over the front of the strand as the strand is linked to the stopper. The macrocycle is held in place, at the point where the stopper and strand join, by a bulky substituent on the outside of the stopper, which forms one end of the dumbbell, and by the first amino acid (phenylalanine) on the strand, which forms the other end.

A second chemical reaction added to the macrocycle the reactive arm responsible for manufacturing the peptide. The reactive arm is a tripeptide (GlyGlyCys) attached to the macrocycle by its C-terminal cysteine residue. The thiolate group of the cysteine and the N-terminus of the tripeptide are both blocked by chemical protective groups to render them non-reactive. The machine is activated by acid-catalyzed removal of the protective groups from the thiolate, from the amino terminus of the reactive arm, and from the amino groups of the three amino acids on the strand.

The liberated thiolate is now able to attack the bond linking the C-terminus of phenylalanine to the strand (the other two amino acids on the strand are too distant to react), thus freeing phenylalanine from the strand, linking it to the N-terminus of reactive arm tripeptide, and regenerating the thiolate. The reactive arm is now longer by one amino acid at its N-terminus, and the macrocycle is now free to slide along the strand until it encounters the second amino acid. The authors explain that the glycylglycine was added to the N-terminus of the cysteine residue because the thiolate and the N-terminus of the cysteine are too close to each other for the phenylalanine released from the strand to be added to the N-terminus of the cysteine. The peptide formed is thus, from the N- toward the C-terminus, PheGlyGlyCys.

The process repeats twice more until all three amino acids have been removed from the strand and attached to the N-terminus of the peptide growing on the reactive arm. With no amino acids left on the strand, the macrocycle is free to slide off the end, bearing the newly formed hexapeptide: AlaLeuPheGlyGlyCys.

Clearly this novel artificial molecular machine was able to mimic essential features of ribosomal protein synthesis, as intended. Once the reaction was initiated, the synthesis was completed without further manipulation. As noted by the authors, major limitations include the very slow rate of synthesis, the destruction of the template after the synthesis is completed, and that the size of the peptide produced my be limited by the nature of the transition state of the machine during each cycle. Nevertheless, this work has demonstrated:

… that relatively small, highly modular, artificial molecular machines can be designed to autonomously perform iterative tasks in synthesis. The principles employed in the design and operation of 1 should be broadly applicable to other types of monomer and chemical reactions …

From the standpoint of the eventual development of molecular manufacturing, the important question will be whether or not this type of molecular machine can be extended to do more general positional control of chemical synthesis, or will it be limited to linking monomers together to form various types of folding polymers?
—James Lewis, PhD

This illustration shows the structure of the molecular motors. (Credit: Saw-Wai Hla)

An international team of scientists has taken the next step in creating nanoscale machines by designing a multi-component molecular motor that can be moved clockwise and counterclockwise.

Although researchers can rotate or switch individual molecules on and off, the new study is the first to create a stand-alone molecular motor that has multiple parts, said Saw-Wai Hla, an Ohio University professor of physics and astronomy who led the study with Christian Joachim of A*Star in Singapore and CEMES/CNRS in France and Gwenael Rapenne of CEMES/CNRS.

It’s an essential step in creating nanoscale devices—quantum machines that operate on different laws of physics than classical machines—that scientists envision could be used for everything from powering quantum computers to sweeping away blood clots in arteries.

In the study, published in Nature Nanotechnology [abstract], the scientists demonstrated that they could control the motion of the motor with energy generated by electrons from a scanning tunneling microscope tip. The motor is about 2 nanometers in length and 1 nanometer high and was constructed on a gold crystal surface. [Watch an animation of the motor at the journal's website here. Credit: F. Ample and C. Joachim. (Scroll down to "Supplementary information" for links to the two animations.)]

At a temperature of minus 315 degrees Fahrenheit, the motor could move independently through thermal excitation. When scientists cooled the sample to minus 450 degrees, the motor stopped rotating. The researchers selectively applied electron energy to different parts of the motor to prompt it to move clockwise and counterclockwise.

“If we want to build an actual device based on this motor, we would install electrodes on the surface to create an energy source,” Hla said.

To construct the molecular motor, the scientific team designed a stationary base of atoms that is connected to an upper moving part by one atom of ruthenium, which serves as the “ball bearing.” The upper piece of the motor features five arms made of iron atoms. The researchers made one arm shorter than the others to be able to track the motion of the machine. The entire device is held upright by using sulfur as an “atomic glue” to secure the motor to the gold surface, Hla explained.

The scientists now plan to use this model to build more complex machines with components that could be automated, Hla said.

One of the three corresponding authors is Christian Joachim, winner of the 2005 Foresight Nanotech Institute Feynman Prize for Theoretical work and one of three winners of the 1997 Foresight Nanotech Institute Feynman Prize for Experimental work.

The molecular motor consists of a single ruthenium atom bearing connecting a tripodal stator to a five-arm rotor. to help detect the motion of the rotor, the five arms are not all equivalent. The centner of the rotor is a cyclopentadiene, one short arms is merely a toluene, while the other four long arms each comprise a phenyl group connected to a ferrocene (two cyclopentadienyl rings sandwiching an iron atom). The ferrocene groups act as reversible electron relays. The four ferrocene end groups enable control of rotation by four nanoelectrodes. The tripodal stator comprises a boron atom connected to three indazolyl groups, each with a thioether foot that binds via a sulfur atom to the gold surface upon which the motor sits.

The motor was imaged using a scanning tunneling microscope (STM) under ultra high vacuum conditions (UHV). For some samples a large bias voltage pulse was used to remove the top (rotor) part of the motor, revealing the tripod stator positioned with each leg along a [211] surface direction of the Au(111) surface. At 80 K the image of the intact motor shows a uniform circle due to the free rotation of the rotor. At 4.6 K rotation has been stopped so that the asymmetric five-lobe structure of the rotor is visible, with four long arms and one short arm.

After positioning the tungsten STM tip above the center of the rotor and then gradually increasing the voltage, rotation was observed at 0.6 V due to inelastic electron tunneling energy transfer. Stepwise rotation was achieved at 4.6 K by placing the STM tip over the molecule at a fixed height for an excitation period of less than one second. The direction of rotation was determined by where the STM tip was placed: predominantly clockwise if electrons were passing through the truncated arm, and mostly counterclockwise if electron excitation was via a ferrocene arm. The authors point out that the tripodal stator lifts the rotor high enough about the gold surface so that the surface does not influence the rotation. They present semi-empirical and density functional theory calculations to explain the detailed rotational mechanisms of the motor. The results show that asymmetries in rotational energy potential lead to the observed rotations by selective excitation of different subunits of the motor. They believe this understanding “will further accelerate the development of complex and automated nanomachinery that can be operated on a material surface.”

The combination of a multicomponent molecular motor and detailed theoretical analysis to elucidate the mechanisms responsible for the action of the motor raises the hope that this work will indeed further accelerate development of complex automated molecular machinery.
—James Lewis, PhD

The new aperture design (left) with two layers of silver separated by another of silicon dioxide. The structure focuses light in a novel way to trap particles smaller than ever before. The focused beams are shown in the illustration on the right. Credit: Amr Saleh

To grasp and move microscopic objects, such as bacteria and the components of living cells, scientists can harness the power of concentrated light to manipulate them without ever physically touching them.

Now, doctoral student Amr Saleh and Assistant Professor Jennifer Dionne, researchers at the Stanford School of Engineering, have designed an innovative light aperture that allows them to optically trap smaller objects than ever before – potentially just a few atoms in size.

The process of optical trapping – or optical tweezing, as it is often known – involves sculpting a beam of light into a narrow point that produces a strong electromagnetic field. The beam attracts tiny objects and traps them in place, just like a pair of tweezers.

Unfortunately, there are natural limits to the technique. The process breaks down for objects significantly smaller than the wavelength of light. Therefore, optical tweezers cannot grasp super-small objects like individual proteins, which are only a couple of nanometers in diameter.

Saleh and Dionne have shown theoretically that light passed through their novel aperture would stably trap objects as small as 2 nanometers. The design was published in the journal Nano Letters [abstract], and Saleh is now building a working prototype of the microscopic device. …

Dionne says that the most promising method of moving tiny particles with light relies on plasmonics, a technology that takes advantage of the optical and electronic properties of metals. A strong conductor like silver or gold holds its electrons weakly, giving them freedom to move around near the metal’s surface.

When light waves interact with these mobile electrons, they move in what Dionne describes as “a very well-defined, intricate dance,” scattering and sculpting the light into electromagnetic waves called plasmon-polaritons. These oscillations have a very short wavelength compared to visible light, enabling them to trap small specimens more tightly.

Dionne and Saleh applied plasmonic principles to design a new aperture that focuses light more effectively. The aperture is structured much like the coaxial cables that transmit television signals, Saleh said. A nanoscale tube of silver is coated in a thin layer of silicon dioxide, and those two layers are wrapped in a second outer layer of silver. When light shines through the silicon dioxide ring, it creates plasmons at the interface where the silver and silicon dioxide meet. The plasmons travel along aperture and emerge on the other end as a powerful, concentrated beam of light.

The Stanford device is not the first plasmonic trap, but it promises to trap the smallest specimens recorded to date. Saleh and Dionne have theoretically shown that their design can trap particles as small as 2 nanometers. With further improvements, their design could even be used to optically trap molecules even smaller.

… Saleh is working on turning the design into reality. He hopes to have a prototype by early 2013.

The two obstacles to using optical tweezers to manipulate nanoscale objects are that (1) the diffraction limit to focusing light is about 200 nm, so that (2) smaller particles would require optical intensity high enough to damage the particles. This paper examines the optical force experienced by a dielectric particle interacting with the field scattered by a coaxial plasmonic aperture designed to trap particles at the surface rather than inside the aperture. By considering coaxial apertures with both straight and tapered channels, the authors’ calculations show that optical trapping of dielectric particles as small as 2 nm is possible in both water and air. Furthermore, less than 100 mW optical power would be required, overcoming the second obstacle.

How precisely should it be possible to position a 2 nm particle using the proposed coaxial aperature? Figure 7 of the paper seems to suggest to my non-expert eye that the obtainable precision would be about 8 nm in the x direction and 40 nm in the y direction. If so, achieving atomically precise positioning would require an improvement of about two orders of magnitude. The estimated current precision would, however, be close to what would be necessary to position some types of molecular building blocks.

Credit: Young-Hee Lee

… Caltech researchers, co-led by assistant professor of electrical engineering Hyuck Choo, have built a new kind of waveguide—a tunnellike device that channels light—that gets around this natural limit. The waveguide, which is described in a recent issue of the journal Nature Photonics [abstract], is made of amorphous silicon dioxide—which is similar to common glass—and is covered in a thin layer of gold. Just under two microns long, the device is a rectangular box that tapers to a point at one end.

As light is sent through the waveguide, the photons interact with electrons at the interface between the gold and the silicon dioxide. Those electrons oscillate, and the oscillations propagate along the device as waves—similarly to how vibrations of air molecules travel as sound waves. Because the electron oscillations are directly coupled with the light, they carry the same information and properties—and they therefore serve as a proxy for the light.

Instead of focusing the light alone—which is impossible due to the diffraction limit—the new device focuses these coupled electron oscillations, called surface plasmon polaritons (SPPs). The SPPs travel through the waveguide and are focused as they go through the pointy end.

Because the new device is built on a semiconductor chip with standard nanofabrication techniques, says Choo, the co-lead and the co-corresponding author of the paper, it is easy integrate with today’s technology.

The new wave guide is expected to be useful for applications in imaging, computer hard drives, and communications. As reported in the research paper, optimal tapering angles and lengths were found through computational simulations. A silicon dioxide dielectric layer measures 200 by 500 nm at the wide end and tapers down to 80 nm by 14 nm at the tip. The upper and lower surfaces were covered with a gold layer about 50 nm thick. The device was fabricated using electron beam-induced deposition, focused ion-beam milling, and electron-beam evaporation. A two-photon photoluminescence measurement shows an intensity enhancement at the tip of 400 within an area of 14 by 80 nm. Whether the efficient nanofocusing that is achieved would be useful for positioning nanostructures is not specifically addressed.

Taking together the above theoretical proposal for a nanoscale optical tweezer and the above experimental implementation of a nanoscale optical focusing device, both dependent on surface plasmon polaritons generated in metal-insulator-metal structures, it seems plausible that optical positioning to at least sub-10-nm precision may soon become possible. Would such a capability be useful for developing productive nanosystems/molecular manufacturing? Some proposals for primitive nanofactories envision building a nanofactory by manipulating molecular building blocks about 5-nm in diameter. If optical tweezers can be improved as expected, they could be really useful for making a primitive nanofactory. If the optical tweezers can be further improved to manipulate groups of a few atoms, they would be even more useful.
—James Lewis, PhD

This 3-D print shows a DNA-based structure designed to test a critical assumption -- that such objects could be realized, as designed, with subnanometer precision. This object is a relatively large, three-dimensional DNA-based structure, asymmetrical to help determine the orientation, and incorporating distinctive design motifs. Subnanometer-resolution imaging with low-temperature electron microscopy enabled researchers to map the object -- which comprises more than 460,000 atoms -- with subnanometer-scale detail. (Credit: Dietz Lab, TU Muenchen)

Before this year the best way to build complex 3D nanostructures from DNA was to use scaffolded DNA origami (see, for example, this post). Last May scientists at the Wyss Institute introduced a DNA tile method for fabricating complex DNA objects that was much faster and much less expensive, and just two weeks ago we posted news that they had extended this method to make arbitrarily complex 3D DNA nanostructures from DNA bricks. Now scientists at the Technische Universität München have published two papers documenting major enhancements to scaffolded DNA origami. From “Reality check for DNA nanotechnology“:

Two major barriers to the advancement of DNA nanotechnology beyond the research lab have been knocked down. This emerging technology employs DNA as a programmable building material for self-assembled, nanometer-scale structures. Many practical applications have been envisioned, and researchers recently demonstrated a synthetic membrane channel made from DNA. Until now, however, design processes were hobbled by a lack of structural feedback. Assembly was slow and often of poor quality. Now researchers led by Prof. Hendrik Dietz of the Technische Universitaet Muenchen (TUM) have removed these obstacles.

One barrier holding the field back was an unproven assumption. Researchers were able to design a wide variety of discrete objects and specify exactly how DNA strands should zip together and fold into the desired shapes. They could show that the resulting nanostructures closely matched the designs. Still lacking, though, was the validation of the assumed subnanometer-scale precise positional control. This has been confirmed for the first time through analysis of a test object designed specifically for the purpose. A technical breakthrough based on advances in fundamental understanding, this demonstration has provided a crucial reality check for DNA nanotechnology.

In a separate set of experiments, the researchers discovered that the time it takes to make a batch of complex DNA-based objects can be cut from a week to a matter of minutes, and that the yield can be nearly 100%. They showed for the first time that at a constant temperature, hundreds of DNA strands can fold cooperatively to form an object — correctly, as designed — within minutes. Surprisingly, they say, the process is similar to protein folding, despite significant chemical and structural differences. “Seeing this combination of rapid folding and high yield,” Dietz says, “we have a stronger sense than ever that DNA nanotechnology could lead to a new kind of manufacturing, with a commercial, even industrial future.” And there are immediate benefits, he adds: “Now we don’t have to wait a week for feedback on an experimental design, and multi-step assembly processes have suddenly become so much more practical.” …

To test the unproven assumption of subnanometer-scale precise positional control, the TUM scientists and their collaborators at MRC Laboratory of Molecular Biology in Cambridge, UK built a large asymmetrical 3D DNA nanostructure incorporating distinctive design motifs, and then characterized its structure with low-temperature electron microscopy. The research was published recently in PNAS (abstract, open access PDF). They designed a DNA nanostructure comprising 15,328 nucleotides (more than 460,000 atoms) assembled from a 7,249-nucleotide long scaffold strand of bacteriophage DNA and 163 short staple strands. The structure formed overnight in a one-pot reaction in high yield. Cryo-electron microscopy enabled a 3D reconstruction based upon tens of thousands of individual images. The resolution of the reconstructed image was sub-nanometer but not quite atomically precise, ranging from 0.97 nm in the core of the nanostructure to 1.4 nm at the periphery. Analysis of the structure determined indicates that the structural order within the nanostructure is comparable to that of natural nanomachines. Detailed comparison of the obtained structure with the designed structure showed more variation than expected in the structure of the DNA helices formed, indicating that the densely packed design led to some unusual DNA topologies. These results indicate that an interactive strategy of designing a folded DNA structure followed by 3D structural analysis will allow construction of a rich variety of precise, complex objects. The authors conclude:

By using chemical groups attached to DNA strands or even reactive motifs formed by DNA itself, this strategy offers an attractive route to achieving complex functionalities known today only from natural nanomachines.

In a second paper just published in Science [abstract], the TUM researchers tackle a major limitation of scaffolded DNA origami: week-long reaction times as the mixture of template and staple DNA strands is very slowly cooled over a very large temperature range, and poor yields. The researchers very carefully followed the rate of structure formation for three different DNA nanostructures as reaction mixes were slowly cooled over a very broad temperature range. One DNA nanostructure was a multilayer platelike structure, one a bricklike object, and a third a gearlike object. They found that the DNA nanostructures each formed at a very narrow temperature range (of about 4° C) that was different for each DNA nanostructure. In addition, the folding was complete in as little as 15 minutes. By choosing the appropriate temperature for each DNA nanostructure, the folding could be complete at constant temperature in as little as 5 minutes. Further, folding at constant temperature greatly increased the yield of correctly folded nanostructures. For several different nanostructures, the increase in yield compared to previous protocols ranged from 7-fold to 330-fold improvement. In absolute terms, the yield of properly folded nanostructres approached 100%. The authors note that several attributes of the folding they observe with their protocols resemble the folding of proteins, despite the chemical and structural differences between proteins and DNA.

From the standpoint of DNA nanotechnology as a component of the Technology Roadmap for Productive Nanosystems, the high yield of well-folded building blocks opens the door to hierarchical assembly of larger objects. It will also greatly facilitate the process of fine-tuning the design of functional molecular machine systems incorporating complex DNA nanostructures. The respective roles to be played by DNA bricks and scaffolded DNA origami, of course, remain to be seen.
—James Lewis, PhD