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Cotranscriptional folding of single RNA strand added to nanotechnology toolkit

Posted by Jim Lewis on March 31st, 2015

Artist's impression of RNA nanostructures that can fold up while they are being synthesized by polymerase enzymes that read DNA templates. Once formed, the RNAs assemble into hexagonal lattices on the mica surface below. Credit: Cody Geary.

We have drawn attention here to RNA nanotechnology because RNA can function as a genetic material, as can DNA, so it has a molecular recognition code similar (but not identical) to that of DNA, but it can also assume a wider range of secondary structures than can DNA, and thus can also function catalytically, as do proteins. Since the replication and transmission of genetic information and the catalysis of chemical reactions are the two most basic functions of the molecular machinery of life, it is of considerable interest to explore what role RNA nanotechnology could play in developing the artificial molecular machine systems that will lead both to near term advances in various areas of nanotechnology and to the ultimate development of high-throughput atomically precise manufacturing (APM). Structural DNA nanotechnology predates RNA nanotechnology by a decade or more, and one of key developments in building more complex nanostructures and devices from DNA has been DNA origami. So, what might we expect from last summer’s introduction of RNA origami? A hat tip to ScienceDaily for reprinting this news release from Aarhus University, and for adding an extremely useful “RNA fact sheet” at the bottom of the article that summarizes the key roles of RNA and the differences in structure and function between RNA and DNA. “Scientists Fold RNA Origami From a Single Strand“:

RNA origami is a new method for organizing molecules on the nanoscale. Using just a single strand of RNA, many complicated shapes can be fabricated by this technique. Unlike existing methods for folding DNA molecules, RNA origamis are produced by enzymes and they simultaneously fold into pre-designed shapes. These features may allow designer RNA structures to be grown within living cells and used to organize cellular enzymes into biochemical factories. The method, which was developed by researchers from Aarhus University (Denmark) and California Institute of Technology (Pasadena, USA), is reported in the latest issue of Science [abstract].

Origami, the Japanese art of paper folding, derives its elegance and beauty from the manipulation of a single piece of paper to make a complex shape. The RNA origami method described in the new study likewise involves the folding of a single strand of RNA, but instead of the experimenters doing the folding, the molecules fold up on their own.

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Automated synthesis expands nanotechnology building block repertoire

Posted by Jim Lewis on March 24th, 2015

A machine in University of Illinois chemistry professor Martin Burke's lab assembles complex small molecules out of simple chemical building blocks, like a 3-D printer on the molecular level. Credit: University of Illinois. Photo by L. Brian Stauffer

High-throughput atomically precise manufacturing (APM) has been described as a manufacturing technology that could be developed over the next few decades that could radically change civilization (Radical Abundance). APM has been alternatively referred to as “molecular nanotechnology”, “molecular manufacturing” and “productive nanosystems”.

For a very limited class of objects, chemists have been doing APM for two centuries by synthesizing small to mid-size molecules to atomic precision (plus large molecules with repeating subunits, like polymers and dendrimers). In the case of molecules without repeating subunits, the limits of synthetic chemistry are reached when molecules become large enough that chemists cannot devise methods to add the next group of atoms at one specific site on the growing molecule instead of at other chemically similar sites. In proposals to develop APM, this problem will be solved by guided molecular trajectories and positionally-controlled mechanosynthesis: reactive molecular fragments will be guided by molecular machine systems to a specific position and geometric orientation with respect to the growing atomically precise work piece so that the application of mechanical force will cause the desired bond to form.

APM has also been likened to an atomic scale version of 3D-printing (also called additive manufacturing) in which a small volume element (but a couple orders of magnitude larger than molecular scale) can be added at any arbitrary position to a growing object (see, for example, Radical Abundance pp 76-77). Thus APM and 3D-printing are both manufacturing systems in which arbitrarily complex 3D objects can be manufactured from the bottom-up through the positionally controlled placement of very small elements.

In recent weeks, the blogosphere has greeted a radical advance in synthetic organic chemistry with titles like “3-D Printer for Small Molecules Opens Access to Customized Chemistry” (Phys Org), “Scientists Unveil 3D Printer for Small Molecules” (STGIST), and “This Chemistry 3D Printer Can Synthesize Molecules from Scratch”. To what extent does this huge advance in synthetic chemistry technology amount to bringing the positional control of 3D-printing to the molecular scale? How close does it get us to APM? From the University of Illinois news bureau “Molecule-making machine simplifies complex chemistry”:

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Targeted nanoparticles deliver molecules to resolve atherosclerotic inflammation

Posted by Jim Lewis on March 9th, 2015

Schematic of a targeted nanoparticle with a hydrophilic polymer shell containing targeting ligands and a hydrophobic polymer core containing therapeutic cargo. Credit: Harvard Medical School and Science Translational Medicine.

Our most recent posts (here and here) focused on increasing acceptance of the idea that the ultimate future of nanotechnology rests with high throughput atomically precise manufacturing. This one exemplifies the use of atomically precise elements from biotechnology and chemistry incorporated into non-atomically precise but increasingly sophisticated nanostructures to advance one application area—medicine. In this case the area of medical interest is the number one cause of death in the industrial world: cardiovascular disease. Foresight President Paul Melnyk forwards this link “Nanotechnology ‘could signal the future of medicine’, scientists claim“:

Microscopic drones which can seek out and repair sections of artery damage could signal the future of treatments for heart disease and strokes, scientists claim.

Successful tests of the nanodrones have been carried out in mice – and researchers hope to conduct the first human trials soon.

The tiny particles are 1,000 times smaller than the tip of a human hair, and are designed to latch on to atherosclerotic plaques – hard deposits made from accumulated fat, cholesterol and calcium that build up on the walls of arteries and are prone to rupture, producing dangerous clots.

Once they have attached, they release a drug derived from a natural protein which can repair damage in the body.

In the mice, scientists found that just five weeks of treatment resulted in significant repairs to artery damage while the plaques were shrunk and stabilised, making it less likely for fragments to break off and cause clots.…

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Atomically precise manufacturing as the future of nanotechnology

Posted by Jim Lewis on March 8th, 2015

Screenshot of DNA nanorobot designed using cadnano. Credit: Nature Nanotechnology.

Continuing the theme of our previous post, is the idea of atomically precise manufacturing as the future of nanotechnology accruing credibility in the blogosphere? Over at Gizmodo Jamie Condliffe asks “What Will the Future of Molecular Manufacturing Really Be Like?“:

Molecular machines are nano-scale assemblers that construct themselves and their surroundings into ever more complex structures. Sometimes dubbed “nanotech” in the media, these devices are promising — but also widely misunderstood. Here’s what separates the science fact from science fiction.

The concepts that underpin this form of nanotechnology have certainly had long enough to percolate through modern science. Richard Feynman first speculated about the idea of “synthesis via direct manipulation of atoms” during a talk called There’s Plenty of Room at the Bottom. Looking back, that sparked much of the subsequent thinking about treating atoms and molecules more and more like simple building blocks.

Perhaps most famously, K. Eric Drexler considered the idea of taking the bottom-up manufacturing approach to its atomic extreme in his 1986 book Engines of Creation: The Coming Era of Nanotechnology. There, he posited the idea of a nan-oscale “assembler” that could scuttle around, building copies of itself or other molecular sized objects with atomic control; one which might in turn be able to create larger and more complex structures. A kind of microscopic production line, building products from the most basic ingredients of all. Coming when it did, in the mid-eighties, it felt very much like science fiction. …

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Are nanorobots and atomically precise manufacturing becoming mainstream nanotechnology?

Posted by Jim Lewis on March 7th, 2015

Two months ago we noted renewed interest in the prospects of atomically precise manufacturing originating from outside the community of those usually interested in advanced nanotechnology. The writer we cited gave an excellent overview of the prospects based on Eric Drexler’s Radical Abundance: How a Revolution in Nanotechnology Will Change Civilization, published in 2013, and on Productive Nanosystems: A Technology Roadmap, published by Battelle Memorial Institute and the Foresight Institute in 2007. Three more articles appeared the past few weeks. Foresight President Paul Melnyk forwards this link to an article written by Giulio Prisco “Op-Ed: The nanobots are coming back“:

Nanotechnology has kept a low profile after the early hype in the 90s, but recent advances show that those nanobots might swim in our brains and build things for us sooner than we think. …

After describing how “the nanotechnology hype waves in the 90s” originated in public enthusiasm for “assemblers” described in Drexler’s Engines of Creation – The Coming Era of Nanotechnology, leading “from the Peak of Inflated Expectations to the Trough of Disillusionment”, Prisco comments on the “much less visionary and much more sedate” presentation in Radical Abundance: How a Revolution in Nanotechnology Will Change Civilization of “the mature concept of additive manufacturing at the nanoscale, or Atomically Precise Manufacturing (APM) — building precisely manufactured goods from the bottom up, one atom or molecule at the time.” Prisco subsequently makes the analogy of APM with “3D nano-printing” and concludes “APM is visionary but doable, and could be the next technology revolution — this time for real.” In support of his conclusion he cites the medical nanorobot work of Dr. Ido Bachelet of Bar-Ilan University (see “Swarms of DNA nanorobots execute complex tasks in living animal”) and the opinion of “Nicholas Negroponte, one of the founding fathers of today’s Internet” that “in 30 years nanobots will attach themselves to neurons and synapses and play an important role in our thinking and learning”.

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Small, fast, electrically-driven nanomotors

Posted by Jim Lewis on March 5th, 2015

Credit: University of Texas at Austin

In a post here a number of years ago then-Foresight President J. Storrs Hall commented on the power density that nanomotors based on advanced nanotechnology are expected to have—on the order of a megawatt in a cubic millimeter. How is current research in nanomotors progressing? Last year Phys.Org reprinted this University of Texas at Austin news release “Engineers Build World’s Smallest, Fastest Nanomotor“:

Researchers at the Cockrell School of Engineering at The University of Texas at Austin have built the smallest, fastest and longest-running tiny synthetic motor to date. The team’s nanomotor is an important step toward developing miniature machines that could one day move through the body to administer insulin for diabetics when needed, or target and treat cancer cells without harming good cells.

With the goal of powering these yet-to-be invented devices, UT Austin engineers focused on building a reliable, ultra-high-speed nanomotor that can convert electrical energy into mechanical motion on a scale 500 times smaller than a grain of salt.

Mechanical engineering assistant professor Donglei “Emma” Fan led a team of researchers in the successful design, assembly and testing of a high-performing nanomotor in a nonbiological setting. The team’s three-part nanomotor can rapidly mix and pump biochemicals and move through liquids, which is important for future applications. The team’s study was published in the April [2014] issue of Nature Communications [abstract].

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Designing mechanical functions into DNA nanotechnology

Posted by Jim Lewis on March 3rd, 2015

Extendable scissor mechanism transforms rotation about three joints into linear extension. Credit: Castro et al. Nanoscale.

Recently we pointed to work at Ohio State University that demonstrated programmed complex motions in simple molecular machines fabricated using scaffolded DNA origami. This accomplishment was the fruit of their systematic effort to implement macroscale engineering design principles in DNA molecular machinery. This past month they published a review of their approach “Mechanical design of DNA nanostructures” in the Royal Society of Chemistry journal Nanoscale. The abstract:

Structural DNA nanotechnology is a rapidly emerging field that has demonstrated great potential for applications such as single molecule sensing, drug delivery, and templating molecular components. As the applications of DNA nanotechnology expand, a consideration of their mechanical behavior is becoming essential to understand how these structures will respond to physical interactions. This review considers three major avenues of recent progress in this area: (1) measuring and designing mechanical properties of DNA nanostructures, (2) designing complex nanostructures based on imposed mechanical stresses, and (3) designing and controlling structurally dynamic nanostructures. This work has laid the foundation for mechanically active nanomachines that can generate, transmit, and respond to physical cues in molecular systems.

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Nanotechnology making 3D transistors by directed molecular self-assembly

Posted by Jim Lewis on March 1st, 2015

Schematic (public domain, from Wikipedia) of a styrene-butadiene-styrene block copolymer, one type of block copolymer. The article does not describe the components of the block copolymer used.

Three years ago Australian and American physicists created a working transistor from a single atom using a scanning tunneling microscope to precisely remove individual hydrogen atoms from the surface of a silicon crystal. Such technology provides a valuable laboratory demonstration of something close to the ultimate limits of computer technology, but a path from laboratory demonstration to economical fabrication of commercial quantities of circuit components remains a very challenging research goal. However, on a scale one or two orders of magnitude larger than atomic precision, but with the added advantage of building in three dimensions rather than being limited to a surface, physicists at IBM are developing “directed self-assembly” to use a certain type of polymer molecule to push current photolithography further into the low nanometer-scale realm. From a report in MIT Technology Review written by Katherine Bourzac “3-D Transistors Made with Molecular Self-Assembly“:

Researchers at IBM have made the first 3-D transistors using a promising new manufacturing approach

A new way of building computer chips is taking shape that involves synthesizing molecules so that they automatically assemble into complex structures—which then serve as templates for etching nanoscale circuitry into silicon. The approach could let the computer industry continue to shrink electronics beyond the resolution of existing manufacturing machinery. IBM researchers have been the first to make speedy 3-D transistors using this new method.

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Mixing two types of nanoparticle triggers structure change

Posted by Jim Lewis on February 5th, 2015

Morphological changes 62 hours after mixing homochiral cylinders of opposite configuration. Scale bars = 500 nm. (Credit: adapted from Liang Sun et al./Nature Communications)

Last month we reported research aimed at improving targeted drug delivery to specific types of cells by endowing nanorobots with the ability to compute. A recent report indicates it might be possible to achieve a subset of those goals—improving drug delivery by only having drug release happen inside cells that satisfy two target conditions—simply by mixing nanoparticles composed of polymers with opposite steric configurations. A hat tip to for reprinting this news release from the University of Warwick in the UK, written by Tom Frew “New ‘triggered-release’ mechanism could improve drug delivery“:

More efficient medical treatments could be developed thanks to a new method for triggering the rearrangement of chemical particles.

The new method, developed at the University of Warwick, uses two ‘parent’ nanoparticles that are designed to interact only when in proximity to each other and trigger the release of drug molecules contained within both.

The release of the drug molecules from the ‘parent’ nanoparticles could subsequently form a third ‘daughter’ particle, which comprises molecules from both ‘parent’ nanoparticles.

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Penta-graphene a new form of carbon for chemistry and nanotechnology

Posted by Jim Lewis on February 4th, 2015

Credit: Virginia Commonwealth University News

If nanotechnologists were to vote on their favorite atom, the winner would, I would guess, be carbon. Not only do diamond-like structures figure prominently in theoretical proposals for high throughput atomically precise manufacturing, not only does carbon bind in a wondrous variety of ways with itself and other atoms to form the molecules that underlie life and present day biomimetic nanotechnology, but a variety of allotropes of carbon exhibit a range of interesting properties that make possible a number of current day nanotechnologies. Now graphite, diamond, fullerenes, graphene, carbon nanotubes, glassy carbon, and carbon nanofoam are joined by another allotrope—penta-graphene. A hat tip to Nanotechnology Now for reprinting this Virginia Commonwealth University news release written by Brian McNeill “Penta-graphene, a new structural variant of carbon, discovered“:

The unique structure of the thin sheet of pure carbon was inspired by pentagonal tile pattern found in the streets of Cairo.

Researchers at Virginia Commonwealth University and universities in China and Japan have discovered a new structural variant of carbon called “penta-graphene” – a very thin sheet of pure carbon that has a unique structure inspired by a pentagonal pattern of tiles found paving the streets of Cairo.

The newly discovered material, called penta-graphene, is a single layer of carbon pentagons that resembles the Cairo tiling, and that appears to be dynamically, thermally and mechanically stable.

“The three last important forms of carbon that have been discovered were fullerene, the nanotube and graphene. Each one of them has unique structure. Penta-graphene will belong in that category,” said the paper’s senior author, Puru Jena, Ph.D., distinguished professor in the Department of Physics in VCU’s College of Humanities and Sciences.

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Adding layer to a piezoelectric nanostructure increases output voltage

Posted by Jim Lewis on February 3rd, 2015

Left: A conventional VING comprising a top electrode, the active ZnO element, a bottom electrode, and a substrate. Right: an insulating layer added between the active element and the bottom electrode. (Credit: adapted from Eunju Lee et al./Applied Physics Letters)

Sometimes very simple modifications of nanoscale structure can have large practical implications. Last month we noted the unexpected discovery of piezoelectricity in a molecular monolayer. The research noted today achieved a large increase in voltage output of a nanostructure several hundred nanometers thick (a vertically integrated nanogenerator, or VING) through the insertion of an insulating layer. From Kurzweil Accelerating Intelligence News “Energy-harvesting discovery generates 200 times higher voltage to power wearables, other portable devices“:

Korea Advanced Institute of Science and Technology (KAIST) researchers have discovered how to radically improve conversion of ambient energy (such as body movement) to electrical energy for powering wearable and portable devices.

As has been noted on KurzweilAI, energy-harvesting devices can convert ambient mechanical energy sources — including body movement, sound, and other forms of vibration — into electricity. The energy-harvesting devices or “nanogenerators” typically use piezoelectric materials such as zinc oxide* (ZnO) to convert mechanical energy to electricity. Uses of such devices include wearables and devices for portable communication, healthcare monitoring, environmental monitoring; and for medical implants.

The researchers explored ways to improve “vertically integrated nanogenerator” energy-harvesting chips based on ZnO. They inserted an aluminum-nitride insulating layer into a conventional energy-harvesting chip based on ZnO and found that the added layer increased the output voltage a whopping 140 to 200 times (from 7 millivolts to 1 volt, in one configuration). This increase was the result of the high dielectric constant (increasing the electric field) and large Young’s modulus (stiffness). …

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Simple nanotechnology modification of alumina surface discourages bacteria

Posted by Jim Lewis on February 2nd, 2015

Nanoporous alumina repels E. coli cells. Credit: Guoping Feng

Current nanotechnology research spans the range from steps toward molecular machine systems and nanorobots to simple nanoscale materials modifications that can have immediate and substantial practical value, such as this example that changes the electrical charge and surface energy of a metal surface. A hat to for reprinting this Cornell University news release written by Krishna Ramanujan “New tech application keeps bacteria from sticking to surfaces“:

Just as the invention of nonstick pans was a boon for chefs, a new type of nanoscale surface that bacteria can’t stick to holds promise for applications in the food processing, medical and even shipping industries.

The technology, developed collaboratively by researchers from Cornell University and Rensselaer Polytechnic Institute, uses an electrochemical process called anodization to create nanoscale pores that change the electrical charge and surface energy of a metal surface, which in turn exerts a repulsive force on bacterial cells and prevents attachment and biofilm formation. These pores can be as small as 15 nanometers; a sheet of paper is about 100,000 nanometers thick.

When the anodization process was applied to aluminum, it created a nanoporous surface called alumina, which proved effective in preventing surrogates of two well-known pathogens, Escherichia coli O157:H7 and Listeria monocytogenes, from attaching, according to a study recently published in the journal Biofouling. The study also investigates how the size of the nanopores changes the repulsive forces on bacteria.

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A tunable hinge joint for DNA nanotechnology

Posted by Jim Lewis on January 31st, 2015

Model of DNA origami compliant nanostructure. Credit: Nanoengineering and Biodesign Laboratory, The Ohio State University

Our most recent post cited research that demonstrated programmed complex motions in simple mechanisms fabricated using scaffolded DNA origami. This achievement represents initial success in what appears to be a systematic program to implement macroscale engineering design principles in molecular machinery made possible by structural DNA Nanotechnology. This approach was introduced in a 2013 paper published in ACS Nano implementing a collaboration between a DNA nanotechnology research group and a mechanical engineering and kinematics design innovation and simulation research group. From “DNA Origami Compliant Nanostructures with Tunable Mechanical Properties“:

Abstract: DNA origami enables fabrication of precise nanostructures by programming the self-assembly of DNA. While this approach has been used to make a variety of complex 2D and 3D objects, the mechanical functionality of these structures is limited due to their rigid nature. We explore the fabrication of deformable, or compliant, objects to establish a framework for mechanically functional nanostructures. This compliant design approach is used in macroscopic engineering to make devices including sensors, actuators, and robots. We build compliant nanostructures by utilizing the entropic elasticity of single-stranded DNA (ssDNA) to locally bend bundles of double-stranded DNA into bent geometries whose curvature and mechanical properties can be tuned by controlling the length of ssDNA strands. We demonstrate an ability to achieve a wide range of geometries by adjusting a few strands in the nanostructure design. We further developed a mechanical model to predict both geometry and mechanical properties of our compliant nanostructures that agrees well with experiments. Our results provide a basis for the design of mechanically functional DNA origami devices and materials.

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Structural DNA nanotechnology with programmed motions

Posted by Jim Lewis on January 28th, 2015

A machine made with DNA origami. Credit: The Ohio State University.

Progress in structural DNA nanotechnology seems to be accelerating. For example, a few weeks ago we cited work in which swarms of DNA nanorobots executed complex tasks in living animals. For the most part, this progress has centered on static structures, or on structures embodying small movements along loosely constrained paths. Now a team of researchers is beginning to use DNA nanotechnology to fabricate parts for machine designs based on the way macroscopic machines work by implementing well-defined motions. A hat tip to for reprinting this Ohio State University news release written by Pam Frost Gorder “DNA Origami Could Lead to Nano ‘Transformers’ for Biomedical Applications

Tiny hinges and pistons hint at possible complexity of future nano-robots

If the new nano-machines built at The Ohio State University look familiar, it’s because they were designed with full-size mechanical parts such as hinges and pistons in mind.

The project is the first to prove that the same basic design principles that apply to typical full-size machine parts can also be applied to DNA—and can produce complex, controllable components for future nano-robots.

In a paper published this week in the Proceedings of the National Academy of Sciences [abstract], Ohio State mechanical engineers describe how they used a combination of natural and synthetic DNA in a process called “DNA origami” to build machines that can perform tasks repeatedly.

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What sort of abundance will nanotechnology bring?

Posted by Jim Lewis on January 11th, 2015

In connection with Foresight’s mission of promoting transformative technologies, it is of interest to occasionally take note of how various commentators in other areas view the advancement of nanotechnology toward atomically precise manufacturing. Do they take this prospect seriously? Do they understand the implications? Do they view such a future fearfully or hopefully? Foresight President Paul Melnyk forwards this link to an article written by George Smith on a site devoted to gold prices, stocks, and related news. After citing Ray Kurzweil’s views on exponentially advancing technologies, Smith focuses on nanotechnology as one cogent example. From “Think small — very small — incredibly small“:

Our atomically-precise future

In this article I want to discuss nanotechnology — a term popularized by K. Eric Drexler in his 1986 book Engines of Creation: The Coming Era of Nanotechnology (online here) — and its implications for our economic lives. …

In his 2013 book Radical Abundance: How a Revolution in Nanotechnology Will Change Civilization, Drexler tells us that

Atomic precision starts with small-molecule feedstocks, atomically precise by nature and often available at a low cost per kilogram. A sequence of atomically precise processing steps then enables precise control of the structure of materials and components, yielding products with performance improved by factors that can range from ten to over one million. …

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Piezoelectric monolayer joins toolkit for nanomanipulation

Posted by Jim Lewis on January 8th, 2015

To measure in-plane piezoelectric stress, an MoS2 film was suspended on HSQ posts and clamped by two Au electrodes. When the film was indented with a scanning AFM probe, the induced stress changed the load on the cantilever, which was observed by the deflection of a laser beam. Credit: Berkeley Lab

Scanning probe microscopes provide powerful tools to image and to directly manipulate atoms and molecules on surfaces. Because piezoelectricity in bulk crystals makes scanning probe microscopes possible, the discovery of piezoelectricity in a single molecular layer of the semiconductor molybdenum disulfide (MoS2) brings a new dimension (pun intended) to the manipulation of molecules, atoms, and individual chemical bonds, as well as to other applications in which the ability to precisely sense and generate mechanical forces is key. A hat tip to KurzweilAI for reporting this news release from Berkeley Lab written by Lynn Yarris “Piezoelectricity in a 2D Semiconductor“:

A door has been opened to low-power off/on switches in micro-electro-mechanical systems (MEMS) and nanoelectronic devices, as well as ultrasensitive bio-sensors, with the first observation of piezoelectricity in a free standing two-dimensional semiconductor by a team of researchers with the U.S. Department of Energy (DOE)’s Lawrence Berkeley National Laboratory (Berkeley Lab).

Xiang Zhang, director of Berkeley Lab’s Materials Sciences Division and an international authority on nanoscale engineering, led a study in which piezoelectricity — the conversion of mechanical energy into electricity or vice versa — was demonstrated in a free standing single layer of molybdenum disulfide, a 2D semiconductor that is a potential successor to silicon for faster electronic devices in the future.

“Piezoelectricity is a well-known effect in bulk crystals, but this is the first quantitative measurement of the piezoelectric effect in a single layer of molecules that has intrinsic in-plane dipoles,” Zhang says. “The discovery of piezoelectricity at the molecular level not only is fundamentally interesting, but also could lead to tunable piezo-materials and devices for extremely small force generation and sensing.”

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Swarms of DNA nanorobots execute complex tasks in living animal

Posted by Jim Lewis on January 6th, 2015

Screenshot of DNA nanorobot designed using cadnano. Credit: Nature Nanotechnology.

Arguably the most exciting area of application for nanotechnology is medicine, especially sophisticated methods of drug delivery to increase potency and decrease adverse side effects. These span the range from current laboratory and clinical studies of incremental nanotechnology to visionary studies of complex nanomedical robots that will be feasible after the development of productive nanosystems and molecular manufacturing/high throughput atomically precise manufacturing. We frequently report here examples of promising applications of relatively simple nanoparticles, for example here, here, here, and here. However, as structural DNA nanotechnology rapidly expanded the repertoire of atomically precise nanostructures that can be fabricated, it became possible to fabricate functional DNA nanostructures incorporating logic gates to deliver and release molecular cargo for medical applications, as we reported a couple years ago (DNA nanotechnology-based nanorobot delivers cell suicide message to cancer cells). More recently, DNA nanorobots have been coated with lipid to survive immune attack inside the body. Now Christine Peterson forwards this news from Brian Wang at NextBIGfuture about another major advance in sophisticated DNA nanorobots for medical application “Ido Bachelet announces 2015 human trial of DNA nanobots to fight cancer and soon to repair spinal cords“:

At the British Friends of Bar-Ilan University’s event in Otto Uomo October 2014 Professor Ido Bachelet announced the beginning of the human treatment with nanomedicine. He indicates DNA nanobots can currently identify cells in humans with 12 different types of cancer tumors.

A human patient with late stage leukemia will be given DNA nanobot treatment. Without the DNA nanobot treatment the patient would be expected to die in the summer of 2015. Based upon animal trials they expect to remove the cancer within one month.

Within 1 or 2 years they hope to have spinal cord repair working in animals and then shortly thereafter in humans. This is working in tissue cultures.

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New software reveals more molecular machine structures

Posted by Jim Lewis on December 31st, 2014

A picture of a membrane protein called cysZ determined with Phenix software using data that could not previously be analyzed. Credit: Los Alamos National Laboratory

With the development of artificial molecular machines still at an early stage, natural biological molecular machines, mostly protein molecules, still provide most information about how molecular machines work. Crucial to extracting this information is knowledge of the 3D structures of these molecules, usually obtained by arduous analysis of X-ray diffraction of protein crystals. Scientists in the US and UK have now reported software advances that will allow many more molecular machines to be studied. A hat tip to Phys.Org for reprinting this Los Alamos National Laboratory news release “Mysteries of ‘molecular machines’ revealed“:

Phenix software uses X-ray diffraction spots to produce 3-D image

Scientists are making it easier for pharmaceutical companies and researchers to see the detailed inner workings of molecular machines.

“Inside each cell in our bodies and inside every bacterium and virus are tiny but complex protein molecules that synthesize chemicals, replicate genetic material, turn each other on and off, and transport chemicals across cell membranes,” said Tom Terwilliger, a Los Alamos National Laboratory scientist. “Understanding how all these machines work is the key to developing new therapeutics, for treating genetic disorders, and for developing new ways to make useful materials.”

To understand how a machine works you have to be able to see how it is put together and how all its parts fit together. This is where the Los Alamos scientists come in. These molecular machines are very small: a million of them placed side by side would take up less than an inch of space. Researchers can see them however, using x-rays, crystals and computers. Researchers produce billions of copies of a protein machine, dissolve them in water, and grow crystals of the protein, like growing sugar crystals except that the machines are larger than a sugar molecule.

Then they shine a beam of X-rays at a crystal and measure the brightness of each of the thousands of diffracted X-ray spots that are produced. Then researchers use the powerful Phenix software, developed by scientists at Los Alamos, Lawrence Berkeley National Laboratory, Duke and Cambridge universities, to analyze the diffraction spots and produce a three-dimensional picture of a single protein machine. This picture tells the researchers exactly how the protein machine is put together.

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Small molecule nanorobot walks through a protein nanopore

Posted by Jim Lewis on December 30th, 2014

Credit: Oxford University

Molecular robots made of DNA that walk along a molecular track made of DNA have been around for a decade, gradually becoming more sophisticated (see here and here, for example). But DNA is a large molecule. Now walking molecular robots have shrunk another order of magnitude in size with the report of a small molecule walker taking 0.6 nm steps through a protein nanopore. A hat tip to for reprinting this news release written by Pete Wilton from Oxford University’s Science Blog “”Walker’s baby steps towards molecular robots“”:

A walking molecule, so small that it cannot be observed directly with a microscope, has been recorded taking its first nanometre-sized steps.

It’s the first time that anyone has shown in real time that such a tiny object – termed a ‘small molecule walker’ – has taken a series of steps. The breakthrough, made by Oxford University chemists, is a significant milestone on the long road towards developing ‘nanorobots’.

‘In the future we can imagine tiny machines that could fetch and carry cargo the size of individual molecules, which can be used as building blocks of more complicated molecular machines; imagine tiny tweezers operating inside cells,’ said Dr Gokce Su Pulcu of Oxford University’s Department of Chemistry. ‘The ultimate goal is to use molecular walkers to form nanotransport networks,’ she says.

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Computational framework for structural DNA nanotechnology

Posted by Jim Lewis on December 27th, 2014

Top row: 3-D structural predictions generated using CanDo by Stavros Gaitanaros, a researcher in MIT's Laboratory for Computational Biology and Biophysics (LCBB), based on sequence designs provided by Fei Zhang of the Hao Yan Lab at Arizona State University. Bottom row: designs by Keyao Pan (LCBB)/Nature Communications

It seems that every month or two we write about another advance in structural DNA nanotechnology—the topic of the second (1995) Feynman Prize in Nanotechnology—most recently here, here, and here. DNA nanotechnology has remained important for a number of reasons. Among the specific recommendations of the 2007 Productive Nanosystems Technology Roadmap are (1) the development of modular molecular
composite nanosystems (MMCNs) in which “million-atom-scale DNA frameworks with dense arrays of distinct, addressable, [atomically precise] binding sites” provide scaffolds for organizing various nanoscale functional components (page x of Executive Summary of Productive Nanosystems: A Technology Roadmap PDF), and (2) “Prioritize modeling and design software as critical elements in the development and exploitation of [Atomically Precise Manufacturing], [Atomically Precise Productive Nanosystems], and spinoff [Atomically Precise Technologies] applications” (page ix of Executive Summary). An MIT news release written by Anne Trafton has announced major progress toward implementing both of these recommendations “Computer model enables design of complex DNA shapes“:

MIT biological engineers have created a new computer model that allows them to design the most complex three-dimensional DNA shapes ever produced, including rings, bowls, and geometric structures such as icosahedrons that resemble viral particles.

This design program could allow researchers to build DNA scaffolds to anchor arrays of proteins and light-sensitive molecules called chromophores that mimic the photosynthetic proteins found in plant cells, or to create new delivery vehicles for drugs or RNA therapies, says Mark Bathe, an associate professor of biological engineering.

The general idea is to spatially organize proteins, chromophores, RNAs, and nanoparticles with nanometer-scale precision using DNA. The precise nanometer-scale control that we have over 3-D architecture is what is centrally unique in this approach,” says Bathe, the senior author of a paper describing the new design approach in the Dec. 3 issue of Nature Communications [open access].

The paper’s lead authors are postdoc Keyao Pan and former MIT postdoc Do-Nyun Kim, who is now on the faculty at Seoul National University. Other authors of the paper are MIT graduate student Matthew Adendorff and Professor Hao Yan and graduate student Fei Zhang, both of Arizona State University.

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