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Another powerful nanoengine remembered

A nanocrystal ram is sandwiched between two MWNT lever arms. On one nanotube a metal particle serves as an atom reservoir that can source or sink atoms to or from the nanocrystal ram. The nanotube conveys the thermally excited atoms between the atom reservoir and ram. Credit: Regan et al. 2005 Nano Letters DOI: 10.1021/nl0510659

Last month we posted a report of a powerful new type of nanoengine, able to deliver a force of ~5 nN (nanonewtons). The authors noted that “The resulting nanoscale forces are several orders of magnitude larger than any produced previously.” A couple weeks later Foresight Senior Fellow—Standards David R. Forrest wrote to challenge that comparison:

Just a quick note on http://www.foresight.org/nanodot/?p=7083.

Cambridge claimed: “The forces exerted by these tiny devices are several orders of magnitude larger than those for any other previously produced device”

I don’t think that is true.

Zettl’s actuator force was 2.6 nN, vs. 5 nN for this “device.” See

http://www.imm.org/documents/IMM_Roadmap_molecular_machines.pdf Reference 8

Given the similar sizes, and noting that the gold nanoparticles ALSO require the surrounding polymer mass as part of the actuation system, I think Zettl’s device has the edge regarding smallest total mass although it’s hard to beat Cambridge’s I/O (light). Also I would note that Zettl’s actuator was positioned on a fixed CNT surface, which allowed the force to be applied at a known location; not true for the particles in suspension. To get useful work out of the device there would need to be attached substrates/levers/something. (More mass, then.)

They probably don’t know about Zettl’s work.

Prof. Zettl was the winner of the 2013 Feynman Prize for Experiment, recognizing “Prof. Zettl’s exceptional work in the fabrication of nanoscale electromechanical systems (NEMS), spanning multiple decades and including carbon nanotube-based bearings, actuators, and sensors brought to fruition with cutting-edge nanoscale engineering.” The linear nanomotor that Dr. Forrest cites above was part of those decades of exceptional work “Nanocrystal-Powered Nanomotor” BC Regan et al, Nano Lett., 2005, 5 (9), pp 1730–1733 (abstract). What will turn out to be the most useful way(s) to power nanodevices remains an open question, but we are fortunate to have options to explore.
—James Lewis, PhD

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Protein design provides a novel metabolic path for carbon fixation

Overlay of the Des1 crystal structure (blue) and the FLS model (green, with mutated residues brown) with the docked DHA product (purple). The four active site mutations (BAL vs. Des1) are shown in sticks, conserved amino acids in lines. Credit: Siegel et al. PNAS March 24, 2015

More evidence that computational protein design can create not only novel proteins but also novel functions that do not exist in nature comes from the creation of an entire novel metabolic pathway. A large collaboration involving scientists from the University of California, Davis, two research groups at the University of Washington (including the lab of David Baker, who shared the 2004 Foresight Institute Feynman Prize for theoretical work), the Fred Hutchinson Cancer Research Center, and several other institutions in California and Israel published a paper last year in PNASComputational protein design enables a novel one-carbon assimilation pathway” that describes a novel computationally designed enzyme they designate “formolase” that catalyzes the carboligation of three one-carbon formaldehyde molecules into one three-carbon dihydroxy acetone molecule. This complex project comprised many steps to create three novel enzyme functions, not previously known, in the process creating a microbial metabolic pathway that could be further optimized for enhanced production of desired products. This research demonstrates the feasibility of organizing multiple engineered enzymes into a sequence that does not exist in nature. In this particular case the goal is to address current challenges in energy storage and carbon sequestration by converting one carbon compounds, such as CO2, into multicarbon fuels and other high-value chemicals. One could also envision such systems as components along the path to productive nanosystems, leading eventually to general purpose, high throughput atomically precise manufacturing.

The authors note that the lack of one-carbon anabolic pathways in microbes suitable to address current needs in energy storage and carbon sequestration could arise from unfavorable chemical driving force at one or more pathway steps, the inherent complexity and inefficiency of the steps, or the environmental sensitivity of the steps (the ability to function efficiently under both aerobic and anaerobic conditions). Despite the lack of such a pathway in nature, they further note, the established electrochemical reduction of CO2 to formate provides an attractive starting point for a one-carbon fixation pathway. They describe in this paper the computational design of an enzyme that catalyzes the carboligation of three one-carbon formaldehyde molecules into one three-carbon molecule. The new enzyme enables the construction of the ‘formolase’ pathway, which converts formate into the centrally important metabolite dihydroxyacetone phosphate.

To find a place to start, the authors note that although there is no biochemical precedent for coupling formate molecules into a multicarbon molecule, there is a well-known organic synthesis (the formose reaction) for coupling formaldehyde into dihydroxyacetone. Although no enzyme is known to catalyze this formose reaction, the observation that thiazolium salts were known to catalyze the formose reaction provided an initial clue, pointing toward thiamine pyrophosphate-dependent enzymes. The enzyme benzaldehyde lyase (BAL) was identified as a promising starting point because it catalyzes a related coupling of two benzaldehyde molecules to form one benzoin molecule.

The authors synthesized and expressed the gene for benzaldehyde lyase, purified the protein and assayed it for formose activity. A small amount of formose activity was found—about 36,000-fold lower than for its natural reaction with benzaldehyde. They then used computational protein design to redesign the benzaldehyde binding pocket of the enzyme to increase formose activity. Four cycles of computational design and experimental evaluation totaling 121 designs led to a variant they designated Des1 with 26-fold higher activity and four amino acid substitutions. The crystal structure of Des1 showed that the computational modeling accurately predicted the structure of the active site of the protein. One additional round of computationally guided site-directed mutagenesis and two mutations found through error-prone PCR further increased Des1 activity 4-fold. Crystalizing and solving the structure of this new 7-site mutant, termed formolase, showed the overall conformation of the protein backbone and active site was similar to the Des1 intermediate step. Formolase showed a 100-fold increase in formose activity compared to the original BAL enzyme, and a 100,000-fold decrease in benzoin activity, resulting in a total specificity switch of greater than 10 million-fold.

An active formolase provides the opportunity to design a pathway to convert formate to dihydroxyacetone phosphate. However, the first step, the direct reduction of formate to formaldehyde using the metabolite NADH is an extremely unfavorable reaction. To accomplish this reaction, the authors sought to activate formate with Coenzyme A to form formyl-CoA, thus reducing the thermodynamic barrier to reducing formate to formaldehyde by NADH. No enzyme is known to catalyze this reaction, so an enzyme that catalyzes the similar reaction with acetate was cloned, expressed, and purified. Assaying for activity of this enzyme with formate as substrate revealed a clear signal.

The second step of the pathway is the reduction of formyl-CoA to formaldehyde. No enzyme is known to catalyze this step either, but enzymes are know that catalyze the reversible reduction of acetyl-CoA to acetaldehyde. The first of these enzymes tested had little activity to produce formyl-CoA, but genes for five homologous enzymes were identified, synthesize, expressed, purified and tested, and one was 100-fold more active than the first one tested. Combining the enzymes identified for the first and second steps reduced formate to formaldehyde.

Combining the above two enzymes with the de novo designed formolase and a couple of known enzymes produced a complete pathway from formate to dihydroxyacetone phosphate. Two rate-limiting steps were identified to be targeted for future enzyme engineering efforts

The formolase enzyme designed here and the two novel activities of existing enzymes identified here provide a potential route for biocatalytic conversion of one-carbon molecules into central metabolites. The authors note that this formolase pathway compares favorably with the nine known naturally occurring pathways to utilize formate or carbon dioxide. THe five steps required are fewer than all the natural pathways, it functions under fully aerobic conditions, and it has a higher chemical driving force than any of the natural pathways. THe authors discuss ways in which the pathway could be further improved, and how it could be extended to use CO2 as a sole carbon and energy source through the electrochemical reduction of CO2 to formate.

This impressive body of work provides a proof-of-principle demonstration of the ability of protein design to extend the reach of synthetic biology to address current challenges using proteins newly designed specifically for those challenges, rather than being limited to recombining natural proteins optimized by evolution for other challenges.
—James Lewis, PhD

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Simulation of quantum entanglement with subsurface dopant atoms

Atomic resolution single-hole tunnelling probes the interacting states of coupled acceptor dopants. Interference of atomic orbitals directly contained in the quasi-particle wavefunction (QPWF) allows quantifying the electron–electron correlations and the entanglement entropy. Credit: Salfi et al. and Nature Communications

Based on their success reported here four years ago of creating a working transistor from a single atom placed in a silicon crystal with atomic precision, researchers from the University of New South Wales and the University of Melbourne in Australia, and from Purdue University in the US, have created a quantum simulator with dopant atoms placed in silicon with atomic precision. A hat tip to Nanowerk for reprinting this news release from the University of New South Wales written by Deborah Smith “Atoms placed precisely in silicon can act as quantum simulator“:

Coinciding with the opening of a new quantum computing laboratory at UNSW by Prime Minister Malcolm Turnbull, UNSW researchers have made another advance towards the development of a silicon-based quantum computer.

Coinciding with the opening of a new quantum computing laboratory at UNSW by Prime Minister Malcolm Turnbull, UNSW researchers have made another advance towards the development of a silicon-based quantum computer.

In a proof-of-principle experiment, they have demonstrated that a small group of individual atoms placed very precisely in silicon can act as a quantum simulator, mimicking nature – in this case, the weird quantum interactions of electrons in materials.

“Previously this kind of exact quantum simulation could not be performed without interference from the environment, which typically destroys the quantum state,” says senior author Professor Sven Rogge, Head of the UNSW School of Physics and program manager with the ARC Centre of Excellence for Quantum Computation and Communication Technology (CQC2T).

“Our success provides a route to developing new ways to test fundamental aspects of quantum physics and to design new, exotic materials – problems that would be impossible to solve even using today’s fastest supercomputers.”

The study is published in the journal Nature Communications [“Quantum simulation of the Hubbard model with dopant atoms in silicon” OPEN ACCESS]. The lead author was UNSW’s Dr Joe Salfi and the team included CQC2T director Professor Michelle Simmons [winner of the 2015 Foresight Institute Feynman Prize, Experimental], other CQC2T researchers from UNSW and the University of Melbourne, as well as researchers from Purdue University in the US.

Two dopant atoms of boron only a few nanometres from each other in a silicon crystal were studied. They behaved like valence bonds, the “glue” that holds matter together when atoms with unpaired electrons in their outer orbitals overlap and bond.

The team’s major advance was in being able to directly measure the electron “clouds” around the atoms and the energy of the interactions of the spin, or tiny magnetic orientation, of these electrons.

They were also able to correlate the interference patterns from the electrons, due to their wave-like nature, with their entanglement, or mutual dependence on each other for their properties.

“The behaviour of the electrons in the silicon chip matched the behaviour of electrons described in one of the most important theoretical models of materials that scientists rely on, called the Hubbard model,” says Dr Salfi.

“This model describes the unusual interactions of electrons due to their wave-like properties and spins. And one of its main applications is to understand how electrons in a grid flow without resistance, even though they repel each other,” he says.

The team also made a counterintuitive find – that the entanglement of the electrons in the silicon chip increased the further they were apart.

“This demonstrates a weird behaviour that is typical of quantum systems,” says Professor Rogge.

“Our normal expectation is that increasing the distance between two objects will make them less, not more, dependent on each other.

“By making a larger set of dopant atoms in a grid in a silicon chip we could realise a vision first proposed in the 1980s by the physicist Richard Feynman of a quantum system that can simulate nature and help us understand it better,” he says.

The importance of atomic precision to the development of quantum computers is rapidly becoming apparent. Perhaps this will be the first technology in which atomic precision is vital to have a major economic impact. Extending the advance reported here, another recent paper by this same Melbourne-New South Wales-Purdue collaboration (to be the topic of another post here) has established the ability to pinpoint the precise location of individual dopant atoms as much as 5 nm deep in a silicon crystal (abstract).
—James Lewis, PhD

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Powerful nanoengine built from coated nanoparticles

Expanding polymer-coated gold nanoparticles. Credit: Yu Ji/University of Cambridge NanoPhotonics

Discussions of complex molecular machine systems or nanorobots navigating through water frequently raise the issue of whether nanoscale engines can be powerful enough. Scientists at UK’s Cavendish Laboratory have provided one response. A hat tip to KurzweilAI for showcasing this University of Cambridge news release “Little ANTs: researchers build the world’s tiniest engine“:

Researchers have built a nano-engine that could form the basis for future applications in nano-robotics, including robots small enough to enter living cells.

Researchers have developed the world’s tiniest engine – just a few billionths of a metre in size – which uses light to power itself. The nanoscale engine, developed by researchers at the University of Cambridge, could form the basis of future nano-machines that can navigate in water, sense the environment around them, or even enter living cells to fight disease.

The prototype device is made of tiny charged particles of gold, bound together with temperature-responsive polymers in the form of a gel. When the ‘nano-engine’ is heated to a certain temperature with a laser, it stores large amounts of elastic energy in a fraction of a second, as the polymer coatings expel all the water from the gel and collapse. This has the effect of forcing the gold nanoparticles to bind together into tight clusters. But when the device is cooled, the polymers take on water and expand, and the gold nanoparticles are strongly and quickly pushed apart, like a spring. The results are reported in the journal PNAS [abstract].

“It’s like an explosion,” said Dr Tao Ding from Cambridge’s Cavendish Laboratory, and the paper’s first author. “We have hundreds of gold balls flying apart in a millionth of a second when water molecules inflate the polymers around them.”

“We know that light can heat up water to power steam engines,” said study co-author Dr Ventsislav Valev, now based at the University of Bath. “But now we can use light to power a piston engine at the nanoscale.”

Nano-machines have long been a dream of scientists and public alike, but since ways to actually make them move have yet to be developed, they have remained in the realm of science fiction. The new method developed by the Cambridge researchers is incredibly simple, but can be extremely fast and exert large forces.

The forces exerted by these tiny devices are several orders of magnitude larger than those for any other previously produced device, with a force per unit weight nearly a hundred times better than any motor or muscle. According to the researchers, the devices are also bio-compatible, cost-effective to manufacture, fast to respond, and energy efficient.

Professor Jeremy Baumberg from the Cavendish Laboratory, who led the research, has named the devices ‘ANTs’, or actuating nano-transducers. “Like real ants, they produce large forces for their weight. The challenge we now face is how to control that force for nano-machinery applications.”

The research suggests how to turn Van de Waals energy – the attraction between atoms and molecules – into elastic energy of polymers and release it very quickly. “The whole process is like a nano-spring,” said Baumberg. “The smart part here is we make use of Van de Waals attraction of heavy metal particles to set the springs (polymers) and water molecules to release them, which is very reversible and reproducible.”

The team is currently working with Cambridge Enterprise, the University’s commercialisation arm, and several other companies with the aim of commercialising this technology for microfluidics bio-applications.

The authors note that various actuators used to turn energy sources into actual movement in microscopic machines all suffer from various shortcoming, especially being very slow (on the order of seconds) and only generating weak forces (on the order of piconewtons). To store large amounts of energy that can be released at greater than MHz frequencies, they turn to spherical 60-nm-diameter gold nanoparticles coated with poly(N-isopropylacrylamide (pNIPAM). This polymer undergoes a coil-to-globule transition at 32 °C, with the result that it is very hydrophilic and swells with water below that temperature, and becomes very hydrophobic and expels water above that temperature. Heating due to plasmonic resonance triggered with a laser causes the nanoparticles to collapse within a microsecond to 400-nm diameter aggregates comprising on average about 40 nanoparticles separated from each other by less than 4 nm. Cooling the solution below the transition temperature re-swells the pNIPAM, producing nanoparticles coated with a layer of pNIPAM 40 nm thick.

The authors note that these ‘ANTs’ can be repeatedly recycled between cold, isolated, inflated and hot, aggregated, deflated states. They also note that addition of salt or ethanol, or other manipulations, allows tuning the size of the clusters from 50 to 1000 nanoparticles.

The authors estimate the amount of elastic energy in the aggregated state as sufficient to drive an expansion force of ~5 nN (nanonewtons), four orders of magnitude greater than the typical Brownian forces in solution of 1 pN. They note this represents a force to unit weight ratio nearly a hundred times greater than any motor or muscle, due to very large van der Waals attractions between the gold cores in the collapsed pNIPAM state. The authors note that the next challenge for adapting this powerful reversible expansion and contraction to nanomachinery requires configurations that provide directional forces. We of course would like to see atomically precise power sources, but it will be interesting to see what can be achieved with ANTs powering MEMS, NEMS, microfluidics, and various types of nanomachinery.
—James Lewis, PhD

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Foresight Co-Founder to speak on altruism, nanotechnology

Foresight Co-Founder Christine Peterson will speak on “High-Leverage Altruism” at Effective Altruism Global 2016, August 5-7, 2016, Berkeley, California. This is the fourth annual conference of Effective Altruism, “a growing community based on using reason and evidence to improve the world as much as possible. This year, around 1000 attendees and over 50 speakers from around the world are expected to attend.” Featured topics include “CRISPR: Can and should we use it to end malaria?”, “How will philanthropy shape the development of breakthrough technologies?”, “Can we end global poverty within a generation? How?”, “Risks and benefit of advanced AI”, and “Replacing meat, reducing suffering”. EA Global 2016 is organized by the Effective Altruists of Berkeley in collaboration with the Centre for Effective Altruism. For more information on what Effective Altruism is, visit effectivealtruism.org or whatiseffectivealtruism.com.

Peterson will also speak on nanotechnology a few weeks later at the Singularity University Global Summit, August 28-30, 2016, San Francisco, California. SU Global Summit is the definitive gathering for those who understand the critical importance of exponential technologies, the impact they’ll have on the future of humanity, and the disruption these technologies will cause across all industries. Other speakers include Peter Diamandis, Ray Kurzweil, and Melanie Swan; an unconference component is included as well.

If you do attend either of these meetings, Christine asks that you stop by and say hello!
—James Lewis, PhD

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Foresight President to speak on Artificial Intelligence

The TEDxEchoPark “Paradigm Shift” event on Saturday May 14, 2016, in Los Angeles, California, will “examine the most intriguing Paradigm Shifts unraveling in every field; from artificial intelligence to education, from branding to sexuality, from food to consciousness and many more. The event examines three key drivers that are sparking this change: ideas as impetus for change, combination as impetus for change and invention or discovery as impetus for change. Common to this colorful mix of Paradigm Shifts is their promise to deliver a roadmap that is superior to its predecessor in navigating us into a better future. At TEDxEchoPark we will take this map on a tour.” Foresight President Julia Bossmann will speak on Artificial Intelligence:

Julia Bossmann
President of Foresight Institute and Founder of Synthetic to speak on AI
Julia Bossmann is the president of Foresight Institute, the leading think tank on world­changing technologies such as nanotechnology and artificial intelligence (AI). Bossmann holds a Masters degree with highest honors in brain & behavioral sciences from the University of Dusseldorf and USC. Her professional experience includes scientific research in labs in Germany and in the USA, management consulting at McKinsey & Company, R&D at Bosch Research and Technology, and entrepreneurship at Anticip8 and Synthetic. Bossmann is a GSP alumna at Singularity University and a Global Shaper at the World Economic Forum. She has spoken at the World Economic Forum’s annual meeting in Davos on the role of Artificial Intelligence in the Fourth Industrial Revolution.

Tickets are available at the event web site.
—James Lewis, PhD

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Triple helices stabilize macroscopic crystals for DNA nanotechnology

To self-assemble macroscopic, porous DNA crystals suitable for use as structural scaffolds or molecular sieves, it was first necessary to show that macroscopic crystals could be self-assembled from atomically precise DNA nanostructures, and then to show that triple helix forming oligo nucleotides could target cargo molecules to each cavity in the crystal with sub-nanometer precision. A paper published last year from Prof. Chengde Mao of Purdue University and Prof. Nadrian C Seeman of New York University, and their collaborators tackles and resolves conflicting requirements for successful self assembly. The component nanostructures must attach to each other using interactions that are weak enough that a building block in an incorrect site can detach, but strong enough that the final structure is stable. They report success using another molecule that binds to the cohesive sites and stabilizes the interactions among the subunits: “Post-Assembly Stabilization of Rationally Designed DNA Crystals” (abstract, full text behind pay wall).

Each gray rod represents a DNA duplex, and the red line represents a triplex-forming DNA strand. Credit: Zhao et al. Angewandte Chemie

The authors explain that the triangular DNA motifs that they engineered to assemble into macroscopic 3D crystals bind weakly to adjacent motifs through a pair of two-nucleotide single-stranded overhangs (sticky ends). With such weak interactions, the crystals are stable only in high salt solutions (> 1.2M (NH4)2SO4), which however, greatly limit the applications for which they can be used. Their solution is to strength the inter-triangle interactions after self-assembly by adding a triplex-forming oligonucleotide at the inter-triangle cohesion region to enhance the interactions of the tensegrity triangle subunits.

To accomplish this post self-assembly stabilization the tensegrity triangle subunit motif was modified such that the DNA duplex region that connects two adjacent triangle motifs contains only purines on one strand and only pyrimidines on the other. At an acidic pH of 5.6 this DNA duplex region can bind to a pyrimidine-only strand to form a triplex, which stabilizes the sticky-end cohesion, and thus the DNA crystal so that it is stable in low ionic strength solutions, such as 0.02M (NH4)2SO4. The authors demonstrate that without triplex formation, the crystals formed at high ionic strength (high salt) (1.7M) disintegrate when exposed to even a small decrease in ionic strength (1.2M). With the triplex, the crystals were stable at the lower ionic strength, and even at very low ionic strength (0.02M), although they too disintegrated when incubated against water without any salt. Control experiments adding single strands not capable of triplex formation instead of the triplex forming strand, or adding the triplex forming strand at pH 8.0 instead of pH 5.6, had no effect on stability of the crystals because no triplex formed.

Other experiments demonstrated that crystals stabilized by triplex formation had about 50% of the sticky end cohesions stabilized by triplex formation, so that it is not necessary to stabilize each cohesive end in the crystal to obtain stabilized DNA crystals. The authors point out that further methods of stabilization, such as using modified nucleosides to facilitate triplex formation at neutral pH, or using sequence specific protein binding to the sticky-end cohesion, could be investigated. Stabilization of crystals under more physiological conditions would permit applications with guest molecules, like enzymes or nanoparticles, that are also more active under physiological conditions.

In theory,the problem addressed by this paper could be solved by either chemical or enzymatic ligation of the cohesive ends after crystal formation, thus substituting strong covalent bonds for weak interactions; in practice, both enzymatic and chemical ligation of large DNA nanostructures have proven problematic (Nadrian C. Seeman, 2015). For the mostly biotech applications suggested by the authors, requiring macroscopic DNA crystals, the approach described here may be the best current bet. However, as a step toward productive nanosystems leading eventually to atomically precise manufacturing, smaller scaffolds containing hundreds or thousands instead of trillions of subunits might suffice. The best approach to make scaffolds in this size range may be an open question still.
—James Lewis, PhD

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DNA triplex formation decorates DNA crystals with sub-nanometer precision

Our previous post focused on the production of high quality macroscopic DNA crystals containing fairly large (on a molecular scale) cavities. This post deals with the challenge of precisely filling those cavities with guest molecules or nanoparticles. In 2014 Seeman and his collaborators reported using triplex forming oligonucleotides to programmably position guest components on the double-helical edges of the tensegrity triangles comprising the crystal: “Functionalizing Designer DNA Crystals with a Triple-Helical Veneer” [OPEN ACCESS]. Citing their earlier work reporting crystals with cavities exceeding 1000 nm3, the authors propose introducing guest molecules into these cavities by targeting a DNA sequence within the tile comprising the crystal, using triplex-forming oligonucleotides that bind in a sequence specific fashion to the major groove of the DNA double helix by forming base triplets. Because triplex formation requires a lower pH, some triplex forming oligonucleotides incorporated triplex stabilizing nucleosides in place of the usual DNA nucleosides C and T. A cyanine dye molecule was attached o he 5`-terminus of each triplex forming oligonucleotide (TFO) to facilitate characterization of the product and to serve as a test guest molecule to be incorporated into the crystal.

A) Base triplets. B) Triplex sequence. C) Cy5-labeled TFOs containing stabilizing analogues. D) Model of the TFO-bound tile. E) Functionalization of DNA crystals. Credit: Rusling et al. Angewandte Chemie

TFOs were shown to bind to the tensegrity triangle tiles as expected. Binding of the TFOs did not affect the formation of crystals from the tiles. Fluorescence of the crystals clearly showed that the dye had been incorporated. Several of the crystals were analyzed by X-ray diffraction, yielding the same results as the previous work.

The crystals produced in this study were about 100µm on a side, containing an estimated 1012 unit cells. The same TFO is targeted to each helix within the crystal, which means each guest is positioned with sub-nanometer precision. Three guest components are housed within each of the crystal’s 366 nm3 rhombohedral cavities. The authors note that each guest component is separated by ~10.5 nm along the helix axis between tiles, and by 5.8 nm through 3D space within the tile. The authors note that the diffraction resolution of these crystals is is relatively low, 0.6 nm, but that this might be improved to 0.4 nm by targeting guests to two helical turns per edge instead of three, thus producing crystals with less hollow space that therefore do not deform as easily. The authors remain focused on the goal of using these crystals as hosts to alleviate the difficulties of macromolecular crystallization for X-ray diffraction analysis.
—James Lewis, PhD

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Macroscopic DNA crystals from molecular tensegrity triangles

Schematic design, sequence, and crystal pictures. Credit: Zheng et al. and Nature.

In writing this blog I occasionally find that I missed work that is an important part of a developing story. Over the years, DNA nanotechnology has been one of the most promising paths from current nanoscience and nanotechnology to the ultimate goal of general-purpose high-throughput atomically precise manufacturing. Most of the recent progress we have reported on DNA nanotechnology has been based upon the scaffolded DNA origami technique or, to a lesser extent, the DNA bricks technique. The original introduction to DNA nanotechnology came in a 1987 paper by DNA nanotechnology pioneer Nadrian Seeman and his chemist collaborator Bruce Robinson “The design of a biochip: a self-assembling molecular-scale memory device” (full text behind a pay wall), which proposed a self-assembling DNA scaffold that could serve as a framework for a molecular wire and switch. This proposal was based on Seeman’s earlier (1985) suggestion that ligation of DNA branched junction building blocks could lead to a periodic array, analogous to the crystallization of molecular systems.

Three papers by Seeman and his collaborators published the last several years (2009, 2014, 2015) highlight progress toward Seeman’s original vision of a practical macroscopic DNA crystal array with cavities that are large on the molecular scale and could be used to precisely order molecular components in three dimensions. This post considers the earliest of these. The first step from concept to reality is explained by the title of the article “From molecular to macroscopic via the rational design of a self-assembled 3D DNA crystal“. The full text is behind a pay wall, but a free PubMed Central version is available.

The authors note that producing a macroscopic 3D periodic array of precisely arranged molecular components should be possible with appropriate branched DNA motifs with ‘sticky’ tails. “It is essential that the directions of propagation associated with the sticky ends do not share the same plane, but extend to form a 3D arrangement of matter.” Based on a ‘DNA tensegrity triangle’ motif that they had reported in 2004, they report here the construction of ~250-µm-sized DNA crystals, five orders of magnitude larger than the nanometer scale of molecular components.

The authors explain that the tensegrity triangle is motif made rigid because it is constructed from three DNA helices connected pairwise by three four-arm branched junctions to produce a stiff alternating over-and-under motif. The axes of the three helices are directed along linearly independent vectors so they are not coplanar. The design the authors chose to work with has an edge length of 21 nucleotide pairs. By extending the three helices with single-stranded ends that can be used for ligation, the helices can link to six other molecules in six different directions, producing macroscopic (> 0.25 mm) rhombohedral crystals. Iodinated heavy atom variants of the crystals were made to facilitate X-ray diffraction analysis of the crystal structure, allowing the authors to report the crystal structure to a resolution of 0.40 nm—not enough to discern atomic detail, but enough to discern DNA double helical structure. The authors report that the DNA is mostly in B form, as expected, but certain specific nucleotides in the triangle are closer to the A form. They also report that the major and minor grooves of the helix can be discerned.

The authors further report that the rhombohedral lattice yields a unit cell with a side of 6.922 nm and an angle between the edges of 101.44°, which according to the rhombohedron calculator yields a surface area of 281.773 nm2 and a volume of 308.708 nm3. The authors state that the volume of the rhombohedral cavity is ~103 nm3, and its open cross section is ~23 nm2.

The authors constructed eight other rhombohedral crystals using variations on the first triangle sequence, with edge lengths varying from 21 to 42 nucleotide pairs. These produced rhombohedral cell dimensions varying from 6.80 nm and 102.6° to 13.49 nm and 117.3°. The crystals were not as rigid and precise as the first one reported above, with structure determined to a resolution varying from 0.50 nm to 1.40 nm. The cross section of the internal cavity varied from 23 to 123 nm2, and the volume of the internal cavity varied from 101 to 1104 nm3. As expected, the resolution of the crystals decreases (that is, the length resolved increases) as the edge length increases because of stick-like lattices have more hollow space.

Having established that they can make well-ordered, macroscopic DNA crystals, the next question Seeman and his collaborators tackled, was how to address specific locations on such arrays.
—James Lewis, PhD

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Five ionized atoms provide scalable implementation of quantum computation algorithm

Researchers have designed and built a quantum computer from five atoms in an ion trap. The computer uses laser pulses to carry out Shor’s algorithm on each atom, to correctly factor the number 15. Image: Jose-Luis Olivares/MIT

Last November we cited work done at the University of New South Wales in Australia that established an architecture for a scalable atomically precise quantum computer, implemented in silicon. A collaboration from MIT and the University of Innsbruck in Austria has now put forth a similar claim, but using a very different physical implementation. A hat tip to Nanotechnology Now for reprinting this MIT news release written by Jennifer Chu “The beginning of the end for encryption schemes?“:

New quantum computer, based on five atoms, factors numbers in a scalable way.

What are the prime factors, or multipliers, for the number 15? Most grade school students know the answer — 3 and 5 — by memory. A larger number, such as 91, may take some pen and paper. An even larger number, say with 232 digits, can (and has) taken scientists two years to factor, using hundreds of classical computers operating in parallel.

Because factoring large numbers is so devilishly hard, this “factoring problem” is the basis for many encryption schemes for protecting credit cards, state secrets, and other confidential data. It’s thought that a single quantum computer may easily crack this problem, by using hundreds of atoms, essentially in parallel, to quickly factor huge numbers.

In 1994, Peter Shor, the Morss Professor of Applied Mathematics at MIT, came up with a quantum algorithm that calculates the prime factors of a large number, vastly more efficiently than a classical computer. However, the algorithm’s success depends on a computer with a large number of quantum bits. While others have attempted to implement Shor’s algorithm in various quantum systems, none have been able to do so with more than a few quantum bits, in a scalable way.

Now, in a paper published today in the journal Science [abstract], researchers from MIT and the University of Innsbruck in Austria report that they have designed and built a quantum computer from five atoms in an ion trap. The computer uses laser pulses to carry out Shor’s algorithm on each atom, to correctly factor the number 15. The system is designed in such a way that more atoms and lasers can be added to build a bigger and faster quantum computer, able to factor much larger numbers. The results, they say, represent the first scalable implementation of Shor’s algorithm.

“We show that Shor’s algorithm, the most complex quantum algorithm known to date, is realizable in a way where, yes, all you have to do is go in the lab, apply more technology, and you should be able to make a bigger quantum computer,” says Isaac Chuang, professor of physics and professor of electrical engineering and computer science at MIT. “It might still cost an enormous amount of money to build — you won’t be building a quantum computer and putting it on your desktop anytime soon — but now it’s much more an engineering effort, and not a basic physics question.”

Seeing through the quantum forest

In classical computing, numbers are represented by either 0s or 1s, and calculations are carried out according to an algorithm’s “instructions,” which manipulate these 0s and 1s to transform an input to an output. In contrast, quantum computing relies on atomic-scale units, or “qubits,” that can be simultaneously 0 and 1 — a state known as a superposition. In this state, a single qubit can essentially carry out two separate streams of calculations in parallel, making computations far more efficient than a classical computer.

In 2001, Chuang, a pioneer in the field of quantum computing, designed a quantum computer based on one molecule that could be held in superposition and manipulated with nuclear magnetic resonance to factor the number 15. The results, which were published in Nature, represented the first experimental realization of Shor’s algorithm. But the system wasn’t scalable; it became more difficult to control the system as more atoms were added.

“Once you had too many atoms, it was like a big forest — it was very hard to control one atom from the next one,” Chuang says. “The difficulty is to implement [the algorithm] in a system that’s sufficiently isolated that it can stay quantum mechanical for long enough that you can actually have a chance to do the whole algorithm.”

“Straightforwardly scalable”

Chuang and his colleagues have now come up with a new, scalable quantum system for factoring numbers efficiently. While it typically takes about 12 qubits to factor the number 15, they found a way to shave the system down to five qubits, each represented by a single atom. Each atom can be held in a superposition of two different energy states simultaneously. The researchers use laser pulses to perform “logic gates,” or components of Shor’s algorithm, on four of the five atoms. The results are then stored, forwarded, extracted, and recycled via the fifth atom, thereby carrying out Shor’s algorithm in parallel, with fewer qubits than is typically required.

The team was able to keep the quantum system stable by holding the atoms in an ion trap, where they removed an electron from each atom, thereby charging it. They then held each atom in place with an electric field.

“That way, we know exactly where that atom is in space,” Chuang explains. “Then we do that with another atom, a few microns away — [a distance] about 100th the width of a human hair. By having a number of these atoms together, they can still interact with each other, because they’re charged. That interaction lets us perform logic gates, which allow us to realize the primitives of the Shor factoring algorithm. The gates we perform can work on any of these kinds of atoms, no matter how large we make the system.”

Chuang’s team first worked out the quantum design in principle. His colleagues at the University of Innsbruck then built an experimental apparatus based on his methodology. They directed the quantum system to factor the number 15 — the smallest number that can meaningfully demonstrate Shor’s algorithm. Without any prior knowledge of the answers, the system returned the correct factors, with a confidence exceeding 99 percent.

“In future generations, we foresee it being straightforwardly scalable, once the apparatus can trap more atoms and more laser beams can control the pulses,” Chuang says. “We see no physical reason why that is not going to be in the cards.”

Mark Ritter, senior manager of physical sciences at IBM, says the group’s method of recycling qubits reduces the resources required in the system by a factor of 3 — a significant though small step towards scaling up quantum computing.

“Improving the state-of-the-art by a factor of 3 is good,” says Ritter. But truly scaling the system “requires orders of magnitude more qubits, and these qubits must be shuttled around advanced traps with many thousands of simultaneous laser control pulses.”

If the team can successfully add more quantum components to the system, Ritter says it will have accomplished a long-unrealized feat.
“Shor’s algorithm was the first non-trivial quantum algorithm showing a potential of ‘exponential’ speed-up over classical algorithms,” Ritter says. “It captured the imagination of many researchers who took notice of quantum computing because of its promise of truly remarkable algorithmic acceleration. Therefore, to implement Shor’s algorithm is comparable to the ‘Hello, World’ of classical computing.”

What will all this eventually mean for encryption schemes of the future?

“Well, one thing is that if you are a nation state, you probably don’t want to publicly store your secrets using encryption that relies on factoring as a hard-to-invert problem,” Chuang says. “Because when these quantum computers start coming out, you’ll be able to go back and unencrypt all those old secrets.”

This paper and last year’s Australian paper both claim a scalable quantum computer architecture, but the details of their respective claims are not identical. For one thing, the more recent paper is focusing on a specific quantum computing algorithm. The complete text of the more recent paper is behind a paywall. A preprint was posted on arxiv last July with the same title, but a different abstract. How different the two architectures are is a question I must leave to the experts. It is interesting to note, however, that the physical implementations of the two architectures are very different. The earlier paper implements qubits by the atomically precise placement of an array of phosphorous atoms in a silicon crystal, while the recent paper implements qubits by removing one electron from each of five calcium atoms to produce five ions held in an ion trap separated from each other by a few micrometers, and manipulated by the electric fields of laser pulses. It will be interesting to see which technologies for manipulating single atoms as qubits lead to practical, large scale quantum computers, and whether any of these paths lead to high throughput atomically precise manufacturing.
—James Lewis, PhD

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