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Atomic precision in sculpting 3-D objects

ORNL researchers used a new scanning transmission electron microscopy technique to sculpt 3-D nanoscale features in a complex oxide material. (credit: Department of Energy’s Oak Ridge National Laboratory)

Atomic-level sculpting of a crystalline oxide from a metastable amorphous oxide film has been demonstrated using a scanning transmission electron microscope. A hat tip to KurzweilAI for reporting this Oak Ridge National Laboratory news release “New electron microscopy method sculpts 3-D structures at atomic level“:

Electron microscopy researchers at the Department of Energy’s Oak Ridge National Laboratory have developed a unique way to build 3-D structures with finely controlled shapes as small as one to two billionths of a meter.

The ORNL study published in the journal Small demonstrates how scanning transmission electron microscopes, normally used as imaging tools, are also capable of precision sculpting of nanometer-sized 3-D features in complex oxide materials.

By offering single atomic plane precision, the technique could find uses in fabricating structures for functional nanoscale devices such as microchips. The structures grow epitaxially, or in perfect crystalline alignment, which ensures that the same electrical and mechanical properties extend throughout the whole material.

“We can make smaller things with more precise shapes,” said ORNL’s Albina Borisevich, who led the study. “The process is also epitaxial, which gives us much more pronounced control over properties than we could accomplish with other approaches.”

ORNL scientists happened upon the method as they were imaging an imperfectly prepared strontium titanate thin film. The sample, consisting of a crystalline substrate covered by an amorphous layer of the same material, transformed as the electron beam passed through it. A team from ORNL’s Institute for Functional Imaging of Materials, which unites scientists from different disciplines, worked together to understand and exploit the discovery.

“When we exposed the amorphous layer to an electron beam, we seemed to nudge it toward adopting its preferred crystalline state,” Borisevich said. “It does that exactly where the electron beam is.”

The use of a scanning transmission electron microscope, which passes an electron beam through a bulk material, sets the approach apart from lithography techniques that only pattern or manipulate a material’s surface.

“We’re using fine control of the beam to build something inside the solid itself,” said ORNL’s Stephen Jesse. “We’re making transformations that are buried deep within the structure. It would be like tunneling inside a mountain to build a house.”

The technique offers a shortcut to researchers interested in studying how materials’ characteristics change with thickness. Instead of imaging multiple samples of varying widths, scientists could use the microscopy method to add layers to the sample and simultaneously observe what happens.

“The whole premise of nanoscience is that sometimes when you shrink a material it exhibits properties that are very different than the bulk material,” Borisevich said. “Here we can control that. If we know there is a certain dependence on size, we can determine exactly where we want to be on that curve and go there.”

Theoretical calculations on ORNL’s Titan supercomputer helped the researchers understand the process’s underlying mechanisms. The simulations showed that the observed behavior, known as a knock-on process, is consistent with the electron beam transferring energy to individual atoms in the material rather than heating an area of the material.

“With the electron beam, we are injecting energy into the system and nudging where it would otherwise go by itself, given enough time,” Borisevich said. “Thermodynamically it wants to be crystalline, but this process takes a long time at room temperature.”

The study is published as “Atomic-level sculpting of crystalline oxides: towards bulk nanofabrication with single atomic plane precision” (abstract).

Atomically precise fabrication of complex 3-D objects has been demonstrated—for certain nanostructures composed of certain materials under certain conditions. Atomic-level sculpting was accomplished using scanning transmission electron microscopy (STEM) in high-angle annular dark-field imaging (HAADF) and electron-beam sculpting. Sculpting was implemented by using the electron beam to convert a thin film of amorphous strontium titanate, covering a crystalline strontium titanate substrate, into the crystalline material, followed by removal of the remaining amorphous material. The electron beams used for sculpting were 100 to 200 keV. The crystallization rate and epitaxial growth rate were controlled by controlling electron dose and dose rate. The atomically focused electron beam induced solid phase epitaxial growth, allowing, with improved methods of beam path control, sculpting of crystalline features as small as 1-2 nm. The research paper shows the letters “ORNL” patterned on a previously amorphous region of SrTiO3 in letters 20 nm high. Since the lattice spacing of the epitaxial structure is reported as 0.39 nm, inspection of the hi-res portions of the image suggests that the precision of the sculpting is indeed close to atomically precise. The authors propose “We believe this technique can be further developed into a nanoscale complementary approach to 3D printing.”

How close does this “atomic-level sculpting” come to atomically precise manufacturing? It will be interesting to see how far the method evolves toward fabricating arbitrarily large and complex structures, but a few obvious limitations include:

  • Nanofabrication is limited to nanostructures composed of one crystalline structure.
  • Like the metal oxide used here, the substance chosen must have a metastable amorphous phase that can be nudged by an electron beam into a unique crystalline state.
  • Error rates in epitaxial growth and precision in guiding the electron beam may limit the size and complexity of the structures that can be fabricated.
  • Could this method be adapted to mechanical systems with moving parts?

Different methods of achieving, or at least approaching, atomic precision for different purposes are being reported. This top-down method joins recent bottom-up examples like synthetic molecular motors and DNA nanomachines. These methods are likely to undergo continued improvement, and perhaps be used in important near- and mid-term applications. Which, if any, will ultimately lead to general purpose high-throughput atomically precise manufacturing remains to be seen.
—James Lewis, PhD

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Generating hydrogen with single atom catalysts

Disordered graphitic carbon doped with nitrogen and augmented with cobalt atoms serves as an efficient, robust catalyst for hydrogen separation from water. The material discovered at Rice University could challenge more expensive platinum-based catalysts. (Credit: Tour Group/Rice University)

James Tour, winner of the 2008 Foresight Institute Feynman Prize in the Experimental category, and his collaborators continue to bring forward a variety of promising applications based upon graphene and other nanostructured materials. Recently we cited a nanotechnology computer memory breakthrough and before that a flexible supercapacitor from stacked nanomaterial. A hat tipp to Nanotechnology Now for reprinting this Rice University news release written by Mike Williams “Cobalt atoms on graphene a powerful combo“:

Rice University catalyst holds promise for clean, inexpensive hydrogen production

Graphene doped with nitrogen and augmented with cobalt atoms has proven to be an effective, durable catalyst for the production of hydrogen from water, according to scientists at Rice University.

The Rice lab of chemist James Tour and colleagues at the Chinese Academy of Sciences, the University of Texas at San Antonio and the University of Houston have reported the development of a robust, solid-state catalyst that shows promise to replace expensive platinum for hydrogen generation.

Catalysts can split water into its constituent hydrogen and oxygen atoms, a process required for fuel cells. The latest discovery, detailed in Nature Communications [Open Access], is a significant step toward lower-cost catalysts for energy production, according to the researchers.

“What’s unique about this paper is that we show not the use of metal particles, not the use of metal nanoparticles, but the use of atoms,&rsdquo; Tour said. “The particles doing this chemistry are as small as you can possibly get.&rsdquo;

Even particles on the nanoscale work only at the surface, he said. “There are so many atoms inside the nanoparticle that never do anything. But in our process the atoms driving catalysis have no metal atoms next to them. We’re getting away with very little cobalt to make a catalyst that nearly matches the best platinum catalysts.&rsdquo; In comparison tests, he said the new material nearly matched platinum’s efficiency to begin reacting at a low onset voltage, the amount of electricity it needs to begin separating water into hydrogen and oxygen.

The new catalyst is mixed as a solution and can be reduced to a paper-like material or used as a surface coating. Tour said single-atom catalysts have been realized in liquids, but rarely on a surface. “This way we can build electrodes out of it,&rsdquo; he said. “It should be easy to integrate into devices.&rsdquo;

The researchers discovered that heat-treating graphene oxide and small amounts of cobalt salts in a gaseous environment forced individual cobalt atoms to bind to the material.

Electron microscope images showed cobalt atoms widely dispersed throughout the samples.

They tested nitrogen-doped graphene on its own and found it lacked the ability to kick the catalytic process into gear. But adding cobalt in very small amounts significantly increased its ability to split acidic or basic water.

“This is an extremely high-performance material,&rsdquo; Tour said. He noted platinum-carbon catalysts still boast the lowest onset voltage. “No question, they’re the best. But this is very close to it and much easier to produce and hundreds of times less expensive.&rsdquo;

Atom-thick graphene is the ideal substrate, Tour said, because of its high surface area, stability in harsh operating conditions and high conductivity. Samples of the new catalyst showed a negligible decrease in activity after 10 hours of accelerated degradation studies in the lab.

As a practical development, a catalyst almost as effective as platinum but hundreds of times less expensive should have a major effect on energy markets and technology development, but the implications for catalysis might be even greater. Using appropriately structured nanomaterials to present single atom catalysts demonstrates the value of positioning single atoms for maximum efficiency. Perhaps in many cases, like this one, the right choice of nanostructured materials will provide ideal positioning, or close to it. Perhaps in other cases, atomically precise manufacturing will be necessary to optimize the positioning of single atom catalysts.
—James Lewis, PhD

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Architecture for atomically precise quantum computer in silicon

Australian researchers have figured out a way to deal with errors in quantum computers. Credit: UNSW Australia

All applications of nanotechnology will eventually benefit from the movement of current methods of nanofabrication toward atomic precision, eventually producing a general purpose method for high throughput atomically precise manufacturing. But perhaps the first and most important application in which atomically precise fabrication will make a critically important contribution is quantum computing. Back in 2012 we noted successes of Australian researchers in atomically-precise positioning of a single atom transistor and in writing of a single-atom qubit in silicon. Also in 2012 Foresight Update reported on a workshop sponsored by the Atomically Precise Manufacturing Consortium, NIST, and Zyvex Labs to discuss the fabrication of such atomically precise devices. Now Australian researchers have provided a blueprint for operational quantum computers. A hat tip to Nanotechnology-Now for reprinting this University of New South Wales news release written by Myles Gough “Researchers design architecture for a quantum computer in silicon“:

Researchers at UNSW and the University of Melbourne have designed a 3D silicon chip architecture based on single atom quantum bits, providing a blueprint to build a large-scale quantum computer.

Australian scientists have designed a 3D silicon chip architecture based on single atom quantum bits, which is compatible with atomic-scale fabrication techniques – providing a blueprint to build a large-scale quantum computer.

Scientists and engineers from the Australian Research Council Centre of Excellence for Quantum Computation and Communication Technology (CQC2T), headquartered at UNSW, are leading the world in the race to develop a scalable quantum computer in silicon – a material well-understood and favoured by the trillion-dollar computing and microelectronics industry.

Teams led by UNSW researchers have already demonstrated a unique fabrication strategy for realising atomic-scale devices and have developed the world’s most efficient quantum bits in silicon using either the electron or nuclear spins of single phosphorus atoms. Quantum bits – or qubits – are the fundamental data components of quantum computers.

One of the final hurdles to scaling up to an operational quantum computer is the architecture. Here it is necessary to figure out how to precisely control multiple qubits in parallel, across an array of many thousands of qubits, and constantly correct for ‘quantum’ errors in calculations.

Now, the CQC2T collaboration, involving theoretical and experimental researchers from the University of Melbourne and UNSW, has designed such a device. In a study published today in Science Advances [abstract, open access PDF], the CQC2T team describes a new silicon architecture, which uses atomic-scale qubits aligned to control lines – which are essentially very narrow wires – inside a 3D design.

“We have demonstrated we can build devices in silicon at the atomic-scale and have been working towards a full-scale architecture where we can perform error correction protocols – providing a practical system that can be scaled up to larger numbers of qubits,” says UNSW Scientia Professor Michelle Simmons, study co-author and Director of the CQC2T.

“The great thing about this work, and architecture, is that it gives us an endpoint. We now know exactly what we need to do in the international race to get there.”

In the team’s conceptual design, they have moved from a one-dimensional array of qubits, positioned along a single line, to a two-dimensional array, positioned on a plane that is far more tolerant to errors. This qubit layer is “sandwiched” in a three-dimensional architecture, between two layers of wires arranged in a grid.

By applying voltages to a sub-set of these wires, multiple qubits can be controlled in parallel, performing a series of operations using far fewer controls. Importantly, with their design, they can perform the 2D surface code error correction protocols in which any computational errors that creep into the calculation can be corrected faster than they occur.

“Our Australian team has developed the world’s best qubits in silicon,” says University of Melbourne Professor Lloyd Hollenberg, Deputy Director of the CQC2T who led the work with colleague Dr Charles Hill. “However, to scale up to a full operational quantum computer we need more than just many of these qubits – we need to be able to control and arrange them in such a way that we can correct errors quantum mechanically.”

“In our work, we’ve developed a blueprint that is unique to our system of qubits in silicon, for building a full-scale quantum computer.”

In their paper, the team proposes a strategy to build the device, which leverages the CQC2T’s internationally unique capability of atomic-scale device fabrication. They have also modelled the required voltages applied to the grid wires, needed to address individual qubits, and make the processor work.

“This architecture gives us the dense packing and parallel operation essential for scaling up the size of the quantum processor,” says Scientia Professor Sven Rogge, Head of the UNSW School of Physics. “Ultimately, the structure is scalable to millions of qubits, required for a full-scale quantum processor.”

In the race to build a quantum computer, atomically precise fabrication may turn out to be not merely desirable, but absolutely required. The method of atomically precise fabrication used for the first large scale quantum computers may not provide a general purpose method for high throughput atomically precise manufacturing, but establishing the importance of atomically precise fabrication may have consequences beyond even the vast consequences of the development of quantum computers.
—James Lewis, PhD

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One-directional rotation in a new artificial molecular motor

Credit: Feringa Group, University of Groningen

Biological molecular motors are amazing nanomachines that make all life possible, but even smaller artificial molecular motors based upon organic chemistry instead of biological polymers continue to become more complex and better controlled. A hat tip to Nanowerk for reprinting this news release from the University of Groningen in The Netherlands “New molecular motor mimics two wheels on an axle“:

University of Groningen scientists led by Professor of Organic Chemistry Ben Feringa have designed a new type of molecular motor. In contrast to previous designs, this molecule is symmetrical. It comprises two parts, which are connected by a central ‘axle’ and rotate in opposite directions, just like the wheels of a car. The results, which were published … in the journal Nature Chemistry [abstract], would be ideal for nano transport systems.

It may sound odd, but from the perspective of the driver, the wheels on the left and right hand side of a car turn in opposite directions. When a car drives forward, the left front wheel turns clockwise and the right front wheel anti-clockwise. This is also the basic design of a new type of molecular motor from the lab of Ben Feringa, the creator of the first light-driven molecular motor back in 1999.

‘If you want a molecular motor to be of any use, you need to be able to control the rotary motion’, says Feringa. Up to now, this was done by using what are known as chiral molecules. These consist of two mirror-image parts, like a left and right hand, which are connected at a central point. ‘These motor molecules are therefore asymmetrical, and this difference between the two halves dictates the way it turns’, Feringa explains.

In Nature Chemistry, Feringa’s group presents the first symmetrical motor molecule with controlled rotary motion. Feringa: ‘This symmetrical motor, which is light-driven just like our other molecular motors, has two rotation axles and two rotating parts.’ The axles are attached to a central part, which is also symmetrical, with the exception of one carbon atom. This atom has two different chemical groups attached to it, which force the rotating parts to turn in opposite directions, as seen from the central part.

Just like a car, this means that the two ‘wheels’ make the molecule move in one direction. ‘This discovery has fantastic implications for realizing autonomous motion on the nanoscale, such as transport over a nano road in a predetermined direction’, Feringa explains. ‘We are now working in our lab to make this type of nano transport a reality.’

The progress over the past decade with many different types of artificial molecular machines has been encouraging. This research is a good example of progress in a sustained development effort.
—James Lewis, PhD

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DNA nanomachine lights up to diagnose diseases

The light-generating DNA antibody detecting nanomachine is illustrated here in action, bound to an antibody. Credit: Marco Tripodi

As current day nanotechnology makes incremental advances in technologies that advance the goal of atomic precision in control of the structure of matter, such as DNA nanotechnology, such advances sometimes also provide opportunities to apply primitive nanomachines to current needs. A hat tip to KurzweilAI for reporting such an advance announced by the newsroom of the Université de Montréal “Detecting HIV diagnostic antibodies with DNA nanomachines“:

New research may revolutionize the slow, cumbersome and expensive process of detecting the antibodies that can help with the diagnosis of infectious and auto-immune diseases such as rheumatoid arthritis and HIV. An international team of researchers have designed and synthesized a nanometer-scale DNA “machine” whose customized modifications enable it to recognize a specific target antibody. Their new approach, which they described this month in Angewandte Chemie [abstract], promises to support the development of rapid, low-cost antibody detection at the point-of-care, eliminating the treatment initiation delays and increasing healthcare costs associated with current techniques.

The binding of the antibody to the DNA machine causes a structural change (or switch), which generates a light signal. The sensor does not need to be chemically activated and is rapid – acting within five minutes – enabling the targeted antibodies to be easily detected, even in complex clinical samples such as blood serum.

“One of the advantages of our approach is that it is highly versatile,” said Prof. Francesco Ricci, of the University of Rome, Tor Vergata, senior co-author of the study. “This DNA nanomachine can be in fact custom-modified so that it can detect a huge range of antibodies, this makes our platform adaptable for many different diseases”.

“Our modular platform provides significant advantages over existing methods for the detection of antibodies,” added Prof. Vallée-Bélisle of the University of Montreal, the other senior co-author of the paper. “It is rapid, does not require reagent chemicals, and may prove to be useful in a range of different applications such as point-of-care diagnostics and bioimaging”.

“Another nice feature of our this platform is its low-cost,” said Prof. Kevin Plaxco of the University of California, Santa Barbara. “The materials needed for one assay cost about 15 cents, making our approach very competitive in comparison with other quantitative approaches.”

“We are excited by these preliminary results, but we are looking forward to improve our sensing platform even more” said Simona Ranallo, a PhD student in the group of Prof. Ricci at the University of Rome and first-author of the paper. “For example, we could adapt our platform so that the signal of the nanoswitch may be read using a mobile phone. This will make our approach really available to anyone! We are working on this idea and we would like to start involving diagnostic companies.”

Light-emitting fluorophore (F) and quencher (green circle); appropriate target recognition elements (red hexagons). Credit: S. Ranallo et al./Angew. Chem. Int. Ed.)

The concept for this simple nanomachine is elegant enough: a light-emitting molecule is held by a weak DNA stem close to a molecule that quenches its signal. Attached near each end of the stem are two recognition elements—peptides, oligonucleotides, or other small molecules— that recognize widely separated regions on the target molecule, or on two separate target molecules. When these recognition elements bind to their targets, the weak DNA stem is broken appart, separating the quencher and fluorophore, and thus allowing the light signal to be emitted.

The success of the application will probably depend upon the sensitivity and precision of the two target recognition elements. Initial results reported in the publication indicate good sensitivity and no cross-reaction with seven target proteins representing several different types of proteins. If this application proves faster, more accurate, more convenient, and less expensive than alternative methods, it may pave the way for a wider variety of ever more sophisticated atomically precise nanomachines for diagnosis and therapy, leading eventually to complex medical nanorobots incorporating sensing, diagnosis, mobility, and therapeutic functions.
—James Lewis, PhD

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Chirality-assisted synthesis a new tool for nanotechnology

Credit: Schneebeli research group, University of Vermont.

New tools that provide chemists with greater ability to build more complex molecules are important steps on the path to atomically precise manufacturing. The newsroom of the University of Vermont reports a “fundamentally new way to control the shape of molecules.” “Scientists Build Wrench 1.7 Nanometers Wide“:

Hold up your two hands. They are identical in structure, but mirror opposites. No matter how hard you try, they can’t be superimposed onto each other. Or, as chemists would say, they have “chirality,” from the Greek word for hand. A molecule that is chiral comes in two identical, but opposite, forms–just like a left and right hand.

University of Vermont chemist Severin Schneebeli has invented a new way to use chirality to make a wrench. A nanoscale wrench. His team’s discovery allows them to precisely control nanoscale shapes and holds promise as a highly accurate and fast method of creating customized molecules.

This use of “chirality-assisted synthesis” is a fundamentally new approach to control the shape of large molecules–one of the foundational needs for making a new generation of complex synthetic materials, including polymers and medicines.

The UVM team’s results were presented online, September 9, in the top-ranked chemistry journal Angewandte Chemie [abstract].

Like Legos

Experimenting with anthracene, a substance found in coal, Schneebeli and his team assembled C-shaped strips of molecules that, because of their chirality, are able to join each other in only one direction. “They’re like Legos,” Schneebeli explains. These molecular strips form a rigid structure that’s able to hold rings of other chemicals “in a manner similar to how a five-sided bolt head fits into a pentagonal wrench,” the team writes.

The C-shaped strips can join to each other, with two bonds, in only one geometric orientation. So, unlike many chemical structures–which have the same general formula but are flexible and can twist and rotate into many different possible shapes–“this has only one shape,” Schneebeli says. “It’s like a real wrench,” he says—with an opening a hundred-thousand-times smaller than the width of human hair: 1.7 nanometers.

“It completely keeps its shape,” he explains, even in various solvents and at many different temperatures, “which makes it pre-organized to bind to other molecules in one specific way,” he says.

This wrench, the new study shows, can reliably bind to a family of well-known large molecules called “pillarene macrocycles.” These rings of pillarene have, themselves, often been used as the “host,” in chemistry-speak, to surround and modify other “guest” chemicals in their middle—and they have many possible applications from controlled drug delivery to organic light-emitting substances.

“By embracing pillarenes,” the UVM team writes, “the C-shaped strips are able to regulate the interactions of pillarene hosts with conventional guests.” In other words, the chemists can use their new wrench to remotely adjust the chemical environment inside the pillarene in the same way a mechanic can turn an exterior bolt to adjust the performance inside an engine.

The new wrench can make binding to the inside of the pillarene rings “about one hundred times stronger,” than it would be without the wrench, Schneebeli says.

Making models

Also, “because this kind of molecule is rigid, we can model it in the computer and project how it looks before we synthesize it in the lab,” says UVM theoretical chemist Jianing Li, Schneebeli’s collaborator on the research and a co-author on the new study. Which is exactly what she did, creating detailed simulations of how the wrench would work, using computer processors in the Vermont Advanced Computing Core.

“This is a revolutionary idea,” Li said, “We have 100% control of the shape, which gives great atomic economy–and lets us know what will happen before we start synthesizing in the lab.”

In the lab, post-doctoral researcher and lead author Xiaoxi Liu, undergraduate Zackariah Weinert, and other team members were guided by the computer simulations to test the actual chemistry. Using a mass spectrometer and an NMR spectrometer in the UVM chemistry department, the team was able to confirm Schneebeli’s idea.

Creative simplicity

Sir Fraser Stoddart, a world-leading chemist at Northwestern University, described the new study as, “Brilliant and elegant! Creative and simple.” And, indeed, it’s the simplicity of the approach that makes it powerful, Schneebeli says. “It’s all based on geometry that controls the symmetry of the molecules. This is the only shape it can take–which makes it very useful.”

Next, the team aims to modify the C-shaped pieces–which are tied together with two bonds formed between two nitrogens and bromines–to create other shapes. “We’re making a special kind of spiral which is going to be flexible like a real spring,” Schneebeli explains, but will hold its shape even under great stress.

“This helical shape could be super-strong and flexible. It could create new materials, perhaps for safer helmets or materials for space,” Schneebeli says. “In the big picture, this work points us toward synthetic materials with properties that, today, no material has.”

“Chirality-assisted synthesis” pioneered in this work would seem to be a very useful and powerful extension of the concept of “templated synthesis” to make mechanically interlocked molecules, pioneered by Prof. Schneebeli’s postdoctoral mentor, Prof. J. Fraser Stoddart, winner of the 2007 Foresight Institute Feynman Prize in the Experimental category for his work on molecular machines made possible by the “templated synthesis” of mechanically interlocked molecules. We can hope that “chirality-assisted synthesis” will also lead to fertile discoveries in supramolecular chemistry that will lead to molecular machine systems.
—James Lewis, PhD

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Surface assisted self-assembly of DNA origami nanostructures

Credit: Suzuki et al. Institute for Integrated Cell-Material Sciences, Kyoto University.

The frequent improvements and extensions of scaffolded DNA origami testify to the usefulness of this technology. A hat tip to KurzweilAI for reporting this advance from Kyoto University organizing DNA origami nanostructures into micrometer-scale 2D arrays “Using DNA origami to build nanodevices of the future“:

Scientists have developed a method, using a double layer of lipids, which facilitates the assembly of DNA origami units, bringing us one-step closer to organized DNA nanomachines.

Scientists have been studying ways to use synthetic DNA as a building block for smaller and faster devices. DNA has the advantage of being inherently “coded”. Each DNA strand is formed of one of four “codes” that can link to only one complementary code each, thus binding two DNA strands together. Scientists are using this inherent coding to manipulate and “fold” DNA to form “origami nanostructures”: extremely small two- and three-dimensional shapes that can then be used as construction material to build nanodevices such as nanomotors for use in targeted drug delivery inside the body.

Despite progress that has been made in this field, assembling DNA origami units into larger structures remains challenging.

A team of scientists at Kyoto University’s Institute for Integrated Cell-Material Sciences (iCeMS) has developed an approach that could bring us one step closer to the organized nanomachines of the future.

They used a double layer of lipids (fats) containing both a positive and a negative charge. DNA origami structures were weakly absorbed onto the lipid layer through an electrostatic interaction. The weak bond between the origami structures and the lipid layer allowed them to move more freely than in other approaches developed by scientists, facilitating their interaction with one another to assemble and form larger structures.

“We anticipate that our approach will further expand the potential applications of DNA origami structures and their assemblies in the fields of nanotechnology, biophysics and synthetic biology,” says chemical biologist Professor Hiroshi Sugiyama from iCeMS.

The research was published as an Open Access paper in Nature CommunicationsLipid-bilayer-assisted two-dimensional self-assembly of DNA origami nanostructures“. The authors note in their discussion that several methods exist for origami nanostructures to self-assemble into 2D lattices including blunt-end stacking and close-packing of triangles and hexagons. They also express their optimism that it will be possible to organize even dynamic systems like molecular motors and enzymatic cascase reactions on origami nanostructures, and then arrange them into more sophisticated hierarchical structures. Near-term applications in nanomaterials and other areas of nanotechnology, biophysics, and synthetic biology seem likely; whether these could eventually be extended toward high-throughput atomically precise manufacturing remains an open question.
—James Lewis, PhD

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Free online edition of The Feynman Lectures on Physics

Richard P. Feynman (1918-1988)

A core component of Foresight’s founding vision is Richard Feynman’s 1959 talk “There’s Plenty of Room at the Bottom” in which he envisioned tiny machines building complex products with atomic precision. “Put the atoms down where the chemist says, and so you make the substance,” Feynman said. Foresight annually awards the Foresight Institute Feynman Prizes: Experimental and Theory “to researchers whose recent work have most advanced the achievement of Feynman’s goal for nanotechnology: the construction of atomically-precise products through the use of molecular machine systems.” Besides sharing a Nobel Prize for Physics Richard Feynman was also well-known as an exceptionally effective teacher. A year ago we were privileged to communicate the availability, through the efforts of Mr. John Neer, of 400 hours of Richard Feynman’s Hughes Lectures. An article on The Smithsonian publicizes the free to read online edition of The Feynman Lectures on Physics, long recognized as the definitive physics textbook. Since well-understood physical law is the foundation for the expectation that High-Throughput Atomically Precise Manufacturing is feasible, a sound understanding of basic physics provides an excellent foundation for thinking about the future of technology. Now arguably the best resources toward that understanding are available online for free.
—James Lewis, PhD

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Conference video: New Methods of Exploring, Analyzing, and Predicting Molecular Interactions

Credit: Art Olson

A select set of videos from the 2013 Foresight Technical Conference: Illuminating Atomic Precision, held January 11-13, 2013 in Palo Alto, have been made available on vimeo. Videos have been posted of those presentations for which the speakers have consented. Other presentations contained confidential information and will not be posted.

The second speaker at the Computation and Molecular Nanotechnolgies session, Art Olson, presented “New Methods of Exploring, Analyzing, and Predicting Molecular Interactions” . https://vimeo.com/63008844 – video length 46:17. Prof. Olson began with three simple points on interacting with and understanding the nanoscale world: (1) human interaction—how we understand something that we can’t see directly; (2) how we integrate data from lots of different sources to form a picture of what is happening at the nanoscale; (3) how we develop software tools to move forward in these areas.

Olson recommended that we should use all of our senses as much as we can because we learn in different ways; we see in different ways; we understand in different ways. Similarly, there is no one data source that gives us a complete picture of the molecular world, so we have to synthesize across scales, and we have to synthesize across methods. With software, collaboration is important, because if we can bridge disciplines rather than reinvent what already exists, we can move a lot faster.

As a molecular biologist studying biological systems, Olson emphasized the physical continuity from atom to organism. No mysterious forces are introduced between atom and organism, but the molecular mechanisms of life introduce complexity. Physics provides the fundamental laws governing the interactions of particles at all levels, but complexity derived from combinatorics—how different atoms are combined—ensures that chemistry cannot be predicted from physics. One estimate of the number of small organic compounds that could be made from the atoms present in the human body is 1060. So chemical space is finite but huge, as is biology space. The complexity of biology space includes happenstance—it deals with how matter interacts with its environment. Since the complexity of biology is huge compared to the complexity of chemistry, we cannot predict biology from chemistry alone. We have to understand how evolution factors into this complexity, Olson explained.

Olson noted the availability of various techniques for determining the structures of life that span time and spatial scales from atoms to organisms, from x-ray crystallography and scanning probe microscopy to light microscopy. For the area in the middle—the mesoscale—no one technique can provide the picture alone. We need to synthesize from a variety of techniques.

Olson cited the memoirs of both Watson and Crick as to how important their iconic physical model of DNA was to their interpreting the x-ray fiber diffraction data that Rosalind Franklin had obtained. Olson compared this model to an analog computer—it was a framework on which to play out ideas. An interesting point is that they do not mention the model in their 1953 paper on the DNA double helix, implying to Olson that as scientists, we expound our ideas, but we do not talk about how we came to our ideas. Models can play an important part in the early stages of how we think about the molecular world.

Citing the well-known model of a kinesin molecule walking along a microtubule in a stochastic process that nevertheless moves in only one direction, Olson pointed to a paper from others describing an in vitro system comprising four types of molecules: the microtubule, kinesin, streptavidin to which multiple kinesins can be bound to make them multivalent, and a crowding agent (polyethylene glycol). The crowding agent drives these microtubules decorated with kinesins into long fibers. The fibers have a polarity according to whether the kinesins are walking up the fiber or down the fiber. For reasons not understood, the bundles elongate until, at a certain length, they buckle. With the addition of energy in the form of ATP, a large scale motion appears. Placed in a bubble large enough for the buckling to appear, a dynamic structure appears on the surface. These bubbles are about the size of cells (microscopic rather than nanoscopic) move around like cells. If these large bubbles are placed on surfaces, they tend to coordinate with each other. All of this emergent behavior arises from a system with just four molecular components, Olson emphasized. Not only is structure important, but dynamics is extremely important in understanding what is going on.

Turning next to the human-computer interface, Olson emphasized that (1) biological structures are complex, (2) spatial relationships and reasoning are difficult, (3) mouse and keyboard are limiting, and (4) images and computer graphics may not convey the whole picture. Human-computer interaction has changed dramatically with tablets, motion detectors, video everywhere, and 3D-printing (making macroscopic models because they have perceptual advantages).

Quoting artificial intelligence pioneer Marvin Minsky “If you ‘understand’ something in only one way, the you don’t ‘really’ understand it at all”, Olson described how he found that to be true with protein structure. Physical models promote perceptual integration (vision and tactile). It is also a rich cognitive substrate, like Watson and Crick’s DNA double helix model. Movement is intuitively intelligible so that instead of thinking about moving it, you can think about the implications of moving it. A physical model is also an analogical and metaphorical medium for exploration, promoting serious play as an important part of the creative process. It also promotes social cognition by sharing an object. Using a physical model of the polio virus, Prof. Olson demonstrated that it can assemble through random motion by shaking it.

Olson presented augmented reality as one way to combine the physical model with the computer model. He demonstrated a physical model representing protein folding using magnets to represent hydrogen bond donors and acceptors. the model could be physically manipulated to make alpha helices, beta sheets, etc. The physical model can act as a computer interface, manipulating the computer model by manipulating the physical model.

Next focusing on the kinds of data that are revealed by these tools, Olson showed a water color painting by his collaborator David Goodsell. These paintings changed how molecular and cell biologists see the cell by making visible the concentration, variety, and compartmentalization of proteins. The major work, Olson explained, is accumulating all the needed data—proteomics, crystal structures, etc.—to represent data that we cannot image directly.

Graham Johnson came to Olson’s lab as a graduate student to do with 3D models what Goodsell did with his water colors. This is essentially a problem of packing various shapes into a given volume. He and Ludovic Autin devised a grid-baed approach in which you take data from, for example, electron tomography, which gives you the shapes of all of the organelles, you defined the interior and exterior surfaces, you enter the data for what is inside the organelle, what is on the surface, and you use a variety of packing algorithms to generate a packing of all of the shapes into the surfaces and volumes.

Finally, Prof. Olson noted that his group were pioneers in developing molecular modeling and molecular visualization software for the past 30 years, inventing solutions for one domain. Eventually they wre overwhelmed by the advances of the entertainment industry and the gaming industry in interactions, rendering, modeling, etc. because those industries had spent billions of dollars on large packages of sophisticated software. Olson’s group wanted to take advantage of these packages, which could do, for example, fantastically fast collision detection, but could only treat molecules as dead geometry.

By happenstance, thanks to Michel Sanner recommending Python for the Olson group’s development efforts 15 years ago, all of their development has been done in Python. It turns out that all of the high-end packages developed for Hollywood, etc., have embedded Python interpreters. Therefore, the molecular modeling components from the Olson group software can be taken out, matched with a thin adapter, and plugged into any of the high-end computer graphic packages. Thus any domain-specific modeling package can be brought into Maya, or Cinema 4D, or the open source Blender. Now they have a workflow that goes from crystal structures and proteomics data all the way to the full model of, for example, an HIV virus particle or a synaptic vesicle and its associated cytoplasmic proteins. Multiple models incorporating multiple parameters can be generated automatically, and then run to see which ones give behavior compatible with observation.

Prof. Olsen made the point that it is important for scientists to communicate their results to the world. The future of science and technology lies in the hands of future scientists and technologists. To educate them, we need tools to get them excited about things they have no physical experience with. Olsen has founded a small company named Science Within Reach to provide some of these tools to high school and middle school students.
—James Lewis, PhD

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Foresight co-founder on the future of the human lifespan

Credit: The Optimized Geek and Stephan Spencer

The October 1, 2015 podcast of The Optimized Geek: Reboot Your Life, with host SEO expert, author, and professional speaker Stephan Spencer featured Foresight Co-Founder and Past President Christine Peterson: A Glimpse at the Future Lifespan of Humans (55 minutes).

Christine explained the development of nanotechnology in three stages. Currently we are moving from the first stage focus on nanomaterials, like stain-resistant pants, into the second phase, dominated by nanoscale devices. The most exciting change change will comme with the third stage, in which systems of molecular machines will operate with atomic precision.

In responding to a question from Spencer on what we might see in the next ten years, Peterson suggested that although nanotechnology in that time frame would still be mostly about nanomaterials and simple nanodevices, one of the most interesting applications would be in health, giving the example of more effective diagnosis, imaging, and treatment of cancer through the enhanced targeting specificity of nanomaterials and nanodevices.

What might advanced nanotechnology look like 30 years from now? Peterson began with the question: What limits do the laws of physics set on what we can build with systems of molecular machines able to build with atomic precision, including inside the human body? One of many applications would be correcting DNA mistakes and mutations cell by cell. Other targets could be damaged proteins and plaques from Alzheimers, etc.

With this level of technology, lifespans would not be limited by aging or traditional diseases, but only by accidents that destroyed the brain, leading to estimated lifespans on the order of 10,000 years. With technology to record the molecular structure of brain, back-up copies of individual brains could be made, eliminating even the 10,000 year limit.

Turning to the topic of the Singularity, Peterson chose to define it in terms of when artificial intelligence technologies reach the level beyond an individual human being so that trying to predict what the world looks like after that point becomes extremely difficult. While acknowledging a range of opinions on when the Singularity could occur, Peterson leaned toward it becoming a reality within our lifetimes. She encouraged the audience to check out the web site of MIRI, the Machine Intelligence Research Institute: intelligence.org/ for people working to prevent powerful non-human intelligences from posing a threat to humanity.

Continuing with potential threats of out-of-control powerful technologies, Spencer brought up the problem of “grey goo” in nanotechnology. Peterson explained how that the possible threat of nanomachinery self-replicating and devouring the environment, derived from the way biological organisms reproduced and spread in the absence of control by predators, etc., seemed a reasonable thought during the late 1970s and early 1980s, when it was first formulated, but that thinking about potential problems of advanced nanotechnology had moved on past that idea, from accidental proliferation to deliberate weaponization of molecular machinery. Such threats are similar to today’s threats from chemical and bio-weapons, so today’s efforts to control chemical and bio-weapons are useful models to control nano-weapons in the future.

Returning to medical issues, Spencer pointed to the increased prevalence of Alzheimers and autism, positing that an environmental toxin might be the cause. Peterson noted that these are complex problems with, for now, ill-defined causes, noted some progress, but does not see nanotechnology at this time playing a prominent role in treating these conditions.

What are the biggest environmental stressors, and what are some solutions to mitigate their effects? One problem noted was mold in the food supply Not only do processed foods lose nutrients, but the more the food is processed, the more likely it is to contain mold. Unless chemical tests are done on the food, there is no way to know whether processed foods contain mold. She encouraged those concerned about longevity to go to the trouble of buying raw food and processing it yourself, even growing your own garden. “Once you’ve gone to the trouble, it is really hard to go back!” (because it tastes so much better).

Peterson placed her interest in food quality as part of the “Quantified Self” movement for anyone really interested in health and longevity, and recommended the Quantified Self Conferences for those interested in ways to obtain the knowledge necessary to improve health and longevity. Spencer commented that he has also experimented with a device to monitor sleep quality. The theme of these efforts is “What gets measured, gets managed”.

Turning from “The Quantified Self” to “Biohacking”, Peterson described it as taking an engineering approach to making changes and improvements in our bodies. Approaches range from the traditional, like diet, exercise, and stress reduction, to the more exotic, like supplements to improve brain chemistry, or to improve health and longevity. Peterson cautions however, that while taking supplements is easy, figuring out which supplements to take is difficult. She considers them most useful to fix a specific problem that you’ve identified in your biochemistry, for example through a quantified self approach and ordering your own blood chemistry tests. To improve brain function, she recommended the web site examine.com, which surveys the medical and scientific literature for supplements to recommend.

Another variety of biohacking is sleep hacking. Quality of sleep is crucial because during those hours your body repairs itself. Failing to fix bad sleep accelerates aging and can cause a variety of diseases. Peterson went as far as to recommend working on your sleep if it is bad as the first place to start on a longevity program, even before taking supplements. One good place to start is blood, urine, and saliva tests for hormones. For example, many people have unhealthy cortisol levels, which can only be detected by saliva tests four times per day.

If hormone problems are responsible for poor sleep, it will be necessary to work with a physician to correct them. Finding a knowledgeable physician can be problematic. Terms used by informed physicians include “functional” or “integrative”. Another option is to ask friends in the quantified self movement, or for serious problems, she mentioned nationally known physicians, such as Terry Grossman.

Although not of immediate use for those who want to take action now to improve their health and longevity, for those who want to advance research in longevity, Peterson recommended Aubrey de Grey’s SENS Research Foundation.

For those who, due to illness or advanced age, will not be able to survive until the future when aging is cured and disease eliminated, but who would love to travel forward in time and take advantage of the technologies we will have a few decades from now, Peterson addressed the question of whether there is available today some form of suspended animation to maintain a body until it can be repaired. In the early days of “cryonics”, recently deceased bodies were placed at low (liquid nitrogen) temperatures for preservation. Later, certain chemicals were introduced as antifreeze to reduce biological damage caused by freezing. More recent technology has introduced improvements that have been tested on donated organs that are reversible; that is, a viable organ can be recovered from low temperature preservation. Arrangements can be made with cryonics organizations—the largest one is Alcor Life Extension Foundation—to implement for you the best suspended animation technology available at the time that you need it. Peterson shared that she is signed up for it because “I do not see a down side.”

Spencer brought up the topic of “Hacking your love life”. Peterson responded that she is currently working on a book tentatively titled “Finding Love in a Life Partner” (using science and technology). One of the biggest factors in longevity is personal relationships—how happy are you at home. Speaking of lessons she learned a few years go in the process of finding a new life partner, she noted that it is basically a matter of chemistry, and you are therefore triggering these chemical processes to occur. She found there are certain things that can be done that indirectly manipulate these processes in the desired direction, and other things that people do are not useful for forming tight bonds.

The final topic addressed was Ray Kurzweil’s Law of Accelerating Returns. While Kurzweil has provided examples of exponential technological progress, Peterson pointed out Peter Thiel’s observation that technological change is slowing due to regulatory issues, problems in funding science, and issues with respect to where venture capital is going. So, in thinking about the future, it is necessary to look at both sides of these issues—if we did not have to worry about regulatory barriers and could throw as much money as we wanted at science, then we could see exponential growth in a lot of areas. For areas like medicine there are huge institutional barriers to progress and even huge legal barriers. Peterson concludes she has to agree with Ray on some areas and with Peter on others.

Detailed show notes and a transcript are available.
—James Lewis, PhD

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