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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 Phys.org 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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New way to couple carbon atoms yields novel molecular architectures

Posted by Jim Lewis on December 24th, 2014

Scripps Research Institute chemists have invented a practical new method for building complex molecules that uses simple, non-toxic iron-based catalysts and can be conducted in minutes open to the air even in shot glass of alcoholic spirits. The team includes (left to right) Jinghan Gui, Chung-Mao (Eddie) Pan, Phil Baran, Yuki Yabe and Julian Lo; here, Gui and Lo are holding molecular models, and Baran holds the actual iron catalysts.

One way to look at the evolution of nanotechnology toward molecular manufacturing/atomically precise manufacturing is as the extension of synthetic chemistry to making larger and more complex molecules. Accordingly, any new method for forming carbon-carbon bonds is potentially of interest to nanotechnologists, especially if it becomes possible to create molecular architectures that were previously difficult or impossible to create. A hat tip to ScienceDaily for reprinting this news release from The Scripps Research Institute “Scientists Open New Frontier of Vast Chemical ‘Space’“:

Chemists at The Scripps Research Institute (TSRI) have invented a powerful method for joining complex organic molecules that is extraordinarily robust and can be used to make pharmaceuticals, fabrics, dyes, plastics and other materials previously inaccessible to chemists.

“We are rewriting the rules for how one thinks about the reactivity of basic organic building blocks, and in doing so we’re allowing chemists to venture where none has gone before,” said Phil S. Baran, the Darlene Shiley Chair in Chemistry at TSRI, whose laboratory reports the finding on functionalized olefin cross-coupling this week in Nature [abstract].

With the new technique, scientists can join two compounds known as olefins to create a new bond between their carbon-atom backbones. Carbon-to-carbon coupling methods are central to chemistry, but until now have been plagued by certain limitations: they often fail if either of the starting compounds contains small, reactive regions known as “functional groups” attached to their main structure. They also frequently don’t work well in the presence of “heteroatoms”—non-carbon atoms such as nitrogen, oxygen and iodine—despite the importance of these types of atoms in chemical synthesis.

The new method is what chemists call “mild,” meaning that it doesn’t require the use of extreme temperatures or pressures, nor harsh chemicals. As a result, portions of the building blocks used that are particularly fragile remain unaltered by the reaction.

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Artificial enzymes created from building blocks not found in nature

Posted by Jim Lewis on December 22nd, 2014

Philipp Holliger is a Program Leader at the MRC Laboratory of Molecular Biology in Cambridge. His research spans the fields of chemical biology, synthetic biology and in vitro evolution.

Earlier this year we pointed to progress made at The Scripps Research Institute toward the long-held goal of expanding the genetic alphabet, and thus expanding the repertoire of 20 genetically encoded amino acids available for protein design and protein engineering. Further expanding the opportunities for synthetic biology to enable the development of complex molecular machines is a recent report from the British Laboratory in which the structure of DNA was discovered 61 years ago. Unlike the earlier report, which added an additional base pair to the genetic alphabet, or another recent report, in which new protein structures not found in nature were invented, the latest UK advance demonstrates that synthetic substitutes for the ribose and deoxyribose sugars found in RNA and DNA can be used to create artificial enzymes, using building blocks not found in nature. From a Medical Research Council news release “World’s first artificial enzymes created using synthetic biology“:

Medical Research Council (MRC) scientists have created the world’s first enzymes made from artificial genetic material. Their synthetic enzymes, which are made from molecules that do not occur anywhere in nature, are capable of triggering chemical reactions in the lab.

The research, published … in Nature [abstract], gives new insights into the origins of life and could provide a starting point for an entirely new generation of drugs and diagnostics.

The findings build on previous work by the team at the MRC Laboratory of Molecular Biology, which saw them create synthetic molecules called ‘XNAs’ that can store and pass on genetic information, in a similar way to DNA.

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Large, open protein cages designed and built

Posted by Jim Lewis on December 7th, 2014

A molecular cage created by designing specialized protein pieces. On the left is one copy of the designed protein molecule. The 24 copies of it on the right, each colored differently, make the molecular cage. The lavender image on the right indicates the openness of the empty space in the middle of the container and is not actually part of the molecular structure. Credit: Yen-Ting Lai, Todd Yeates

While some protein scientists make impressive progress designing novel protein folds, others combine natural protein oligomers in novel ways to make unexpected extreme structures not seen in nature. A hat tip to ScienceDaily for reprinting this University of California-Los Angeles news release “UCLA biochemists build largest synthetic molecular ‘cage’ ever“:

UCLA biochemists have created the largest-ever protein that self-assembles into a molecular “cage.” The research could lead to synthetic vaccines that protect people from the flu, HIV and other diseases.

At a size hundreds of times smaller than a human cell, it also could lead to new methods of delivering pharmaceuticals inside of cells, or to the creation of new nanoscale materials.

The protein assembly, which is shaped like a cube, was constructed from 24 copies of a protein designed in the laboratory of Todd Yeates, a UCLA professor of chemistry and biochemistry. It is porous — more so than any other protein assembly ever created — with large openings that would enable other large protein molecules to enter and exit.

The research was recently published online in the journal Nature Chemistry [abstract] ….

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Broadening the synthetic biology path to molecular nanotechnology

Posted by Jim Lewis on December 6th, 2014

A novel three-helix, hyper stable helical bundle in which five (5) distinct helix-helix interacting layers were designed. Credit: Institute for Protein Design, University of Washington

The first journal article to call for the development of molecular manufacturing (Drexler 1981, journal publication) identified the task of designing more stable proteins as a path toward more general capabilities for molecular manipulation. Proof of principle for this goal was already apparent by 1988, and we have followed progress since then (for example, here and here). A brief comment in a recent issue of Science introduces two papers that took two different routes to use rational and computational design to make new protein structures based on alpha-helical coiled coils. In the first, a collaboration headed by David Baker, co-winner of the 2004 Foresight Feynman Prize for Theory, reported the custom design of a set of hyperstable proteins with fine-tuned geometries that can be adapted for a range of applications. From “Custom design of novel alphahelical bundles“:

Researchers at the Institute for Protein Design have developed a novel computational approach for the custom design of hyper-stable alpha-helical bundles with fine-tuned geometries. The parametric design approach and experimental characterization of the resulting helical bundles is described in detail in a recent Science publication [abstract] entitled High thermodynamic stability of parametrically designed helical bundles.

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Nearly perfect carbon nanotubes key to energy-saving lights

Posted by Jim Lewis on December 2nd, 2014

Planar light source device (Left-front, Right-rear) Photo Credit-N. Shimoi/Tohoku University

Foresight’s recent Workshop on Directed/Programmable Matter for Energy focused on the potential of atomically precise materials for energy production, transport, and efficient use. A hat tip to Kurzweil Accelerating Intelligence for describing how scientists from Tohoku University in Japan had combined carbon nanotube field emitters with a solution of indium oxide and tin oxide to produce a very efficient planar light source. From an AIP Publishing news release by Zhengzheng Zhang “Beyond LEDs: Brighter, New Energy-Saving Flat Panel Lights Based on Carbon Nanotubes“:

Even as the 2014 Nobel Prize in Physics has enshrined light emitting diodes (LEDs) as the single most significant and disruptive energy-efficient lighting solution of today, scientists around the world continue unabated to search for the even-better-bulbs of tomorrow.

Enter carbon electronics.

Electronics based on carbon, especially carbon nanotubes (CNTs), are emerging as successors to silicon for making semiconductor materials, And they may enable a new generation of brighter, low-power, low-cost lighting devices that could challenge the dominance of light-emitting diodes (LEDs) in the future and help meet society’s ever-escalating demand for greener bulbs.

Scientists from Tohoku University in Japan have developed a new type of energy-efficient flat light source based on carbon nanotubes with very low power consumption of around 0.1 Watt for every hour’s operation — about a hundred times lower than that of an LED.

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Micrometer-scale structures built from DNA bricks

Posted by Jim Lewis on November 19th, 2014

Researchers have achieved 32 different-shaped crystal structures using the DNA-brick self-assembly method. Credit: Harvard's Wyss Institute

The saga of using DNA bricks to build complex 3D nanostructures continues to evolve. A hat tip to ScienceDirect for reprinting this news release from Harvard’s Wyss Institute “Crystallizing the DNA nanotechnology dream“:

DNA has garnered attention for its potential as a programmable material platform that could spawn entire new and revolutionary nanodevices in computer science, microscopy, biology, and more. Researchers have been working to master the ability to coax DNA molecules to self assemble into the precise shapes and sizes needed in order to fully realize these nanotechnology dreams.

For the last 20 years, scientists have tried to design large DNA crystals with precisely prescribed depth and complex features — a design quest just fulfilled by a team at Harvard’s Wyss Institute for Biologically Inspired Engineering. The team built 32 DNA crystals with precisely-defined depth and an assortment of sophisticated three-dimensional (3D) features, an advance reported in Nature Chemistry [abstract].

The team used their “DNA-brick self-assembly” method, which was first unveiled in a 2012 Science publication when they created more than 100 3D complex nanostructures about the size of viruses. The newly-achieved periodic crystal structures are more than 1000 times larger than those discrete DNA brick structures, sizing up closer to a speck of dust, which is actually quite large in the world of DNA nanotechnology.

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Notes for 400 hours of Richard Feynman's Hughes Lectures

Posted by Jim Lewis on November 12th, 2014

http://www.thehugheslectures.info

John Neer writes to announce that he has made available “to the public for non-commercial use” an extensive collection of notes for lectures that Richard Feynman delivered to employees of Hughes Aircraft Company from 1966 through 1971, for two hours on Monday evenings, 9 to 10 months per year. No attempt was made to record or capture Feynman’s board work for these lectures. Mr. Neer, accomplishing what would seem to have been a Herculean task, took notes as extensively as possible during Feynman’s two-hour lectures, and then spent four to six hours transcribing each lecture as soon as possible afterward. References and subsequent results from the Internet were added some time later. The lecture notes are available at http://www.thehugheslectures.info/.

These notes are for all those who want to learn more about science, math and nature as Feynman did; to learn more of how he taught and embrace his charge to pass on what we have learned.

I believe consistent with Feynman’s interest to teach as many as he could about science these notes are free and open to the public for non-commercial use.

As to Mr. Neer’s motivations for making available more than 1000 pages (about 132 MB) of notes from more than 400 hours of Feynman’s lectures on topics from cosmology to molecular biology, he writes:

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Using DNA nanotechnology to cast arbitrarily shaped nanoparticles

Posted by Jim Lewis on November 11th, 2014

By creating molds from stiff DNA, researchers were able to cast gold 'seeds' into complex metal nanoparticles. From left to right, this 3D polygonal particle was formed by designing a DNA mold, planting a gold seed, then chemically forcing the seed to expand until complete formation. Credit: Harvard's Wyss Institute

The great advantage of DNA nanotechnology is that the unique molecular recognition code of DNA bases provides a way to build complex structures with atomically precise addressability. At least as long ago as 2003 DNA nanotechnology pioneer Nadrian C. Seeman proposed using DNA nanotechnology to construct a “molecular pegboard” to organize nanoscale components into functional arrays. Initial progress toward that goal was reported in 2005 “Self-Assembling a Molecular Pegboard” [abstract; full text, courtesy of authors]. Two months ago we pointed to improvements in the scaffolded DNA origami approach that provided a “10-fold larger breadboard and 350-fold lower DNA synthesis costs”. Over the years we have cited other work in which addressable DNA scaffolds have been used to organize functional components. Such achievements have been used to precisely spatially organize small numbers of larger, atomically complex, nanoscale objects. Recently researchers have asked whether atomically precise DNA molds can be used to cast large numbers of inorganic atoms into predetermined complex (but not atomically precise) 3D nanoparticles that can be arranged in space to form larger, more complex nanoscale objects. A hat tip to ScienceDaily for reprinting this news release from the Wyss Institute for Biologically Inspired Engineering at Harvard “DNA nano-foundries cast custom-shaped metal nanoparticles“:

Researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University have unveiled a new method to form tiny 3D metal nanoparticles in prescribed shapes and dimensions using DNA, Nature’s building block, as a construction mold.

The ability to mold inorganic nanoparticles out of materials such as gold and silver in precisely designed 3D shapes is a significant breakthrough that has the potential to advance laser technology, microscopy, solar cells, electronics, environmental testing, disease detection and more.

“We built tiny foundries made of stiff DNA to fabricate metal nanoparticles in exact three–dimensional shapes that we digitally planned and designed,” said Peng Yin, senior author of the paper, Wyss Core Faculty member and Assistant Professor of Systems Biology at Harvard Medical School.

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Grant program to support nanotechnology and other infrastructure

Posted by Jim Lewis on October 25th, 2014

GENI is a fast, open, next-generation network for exploring future internets at a national scale. Credit: Nicolle Rager Fuller, National Science Foundation

Gayle Pergamit writes with news of a US National Science Foundation initiative that “addresses one of the big problems that we talked about at the [Foresight Directed/Programmable Matter for Energy Workshop]: not having enough processor power. This will be a huge boost to getting true nanotech done.” The new initiative builds upon a June 2012 Executive Order to make broadband construction faster and cheaper. From the NSF press release in June 2012:

The National Science Foundation (NSF) announced that it will serve as the lead federal agency for a White House Initiative called US Ignite, which aims to realize the potential of fast, open, next-generation networks.

US Ignite will expand on investments in the NSF-funded Global Environment for Networking Innovation (GENI) project which lays the technical groundwork for this initiative. …

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Light-driven molecular flapping emits white light

Posted by Jim Lewis on October 10th, 2014

A phosphorescent molecular butterfly that can generate dual (white) emission upon photoexcitation (credit: M. Han et al./Angewandte Chemie)

Speaking of improving energy supply and usage through improved precision in the control of matter, Kurzweil Accelerating Intelligence News reports a butterfly-shaped molecule that changes molecular structure upon photoexcitation, shortening the distance between two platinum atoms, producing both red and greenish-blue emission, resulting in white light production. From “‘Butterfly’ molecule could lead to new sensors, photoenergy conversion devices“:

A novel molecule that can take your temperature, emit white light, and convert photon energy directly to mechanical motions has been enhanced by Florida State University researchers.

Biwu Ma, associate professor in the Department of Chemical and Biomedical Engineering in the FAMU-FSU College of Engineering, created the molecular structure resembling a butterfly in a lab about a decade ago, but has continued to discover it has many other unique capabilities, described in the latest edition of the journal Angewandte Chemie [abstract].

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Foresight Directed/Programmable Matter for Energy Workshop

Posted by Jim Lewis on October 10th, 2014

Foresight has had a long-term interest in the directed evolution of nanoscale science and technology toward productive nanosystems and atomically precise manufacturing (see, for example, the 2007 Technology Roadmap for Productive Nanosystems and the 2013 conference Illuminating Atomic Precision). Foresight has also had a parallel interest in integrating incremental advances in nanotechnology to meet pressing human needs (see, for example, the Foresight Nanotechnology Challenges and the 2014 conference The Integration Conference). Bringing together these parallel interests, a recent invitation-only workshop gathered leading researchers to focus on the opportunities created to better meet human energy needs through greater control over the structure of matter. Not every useful advance in nanoscience and nanotechnology will lead to molecular/atomically precise manufacturing, and molecular/atomically precise manufacturing will not be required for every advance in nanotechnology to meet human needs, but just where do the greatest opportunities lie?
—James Lewis, PhD

Directed/Programmable Matter for Energy (DPM) Workshop

A small, highly interactive 2-1/2 day meeting focused on long-term prospects for revolutionary advances in energy storage, transmission, and generation based on improved precision in our control of matter was held September 5-7, 2014 in Palo Alto, California.

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A Breakthrough in 3D Imaging by EM Alone

Posted by Stephanie C on October 8th, 2014

Credit: Azubel-fig

The need for improved imaging and characterization on the nanoscale was emphasized in the 2007 Roadmap and again at the 2013 Foresight Conference on Atomic Precision. We noted last year a new advancement in atomic-scale resolution of 10-nm platinum particles, requiring multiple imaging techniques in combination, and recently the marked improvement in optical imaging for characterization of biological machinery at 1-nm. Now researchers at Stanford University successfully used high-resolution electron microscopy alone to characterize 1-nm gold nanoparticles (containing 68 gold atoms) – a capability new enough that x-ray scattering was used to verify the result.  This type of advancement could help remove one of the bottlenecks in progress towards nanometer-scale manufacturing.

The news release, from the Academy of Finland (the structure of the nanoparticle had been predicted by researchers at University of Jyväskylä, Finland), was reprinted at Phys.org:

Electron microscopy is similar in principle to conventional light microscopy, with the exception that the wavelength of the electron beam used for imaging is close to the spacing of atoms in solid matter, about a tenth of a nanometre, in contrast with the wavelength of visible light, which is hundreds of nanometres. A crucial aspect of the new work is the irradiation of the nanoparticle with very few electrons to avoid perturbing the structure of the nanoparticle. The success of this approach opens the way to the determination of many more nanoparticle structures and to both fundamental understanding and practical applications.

With the progress recently described in assembly-line style molecular synthesis and new NSF and DARPA funding for nanomanufacturing (see several recent posts), increased emphasis on imaging and characterization across each incremental size regime should receive more targeted attention.
-Posted by Stephanie C, Oct 2014

Tailoring the shapes of organic molecules by assembly-line synthesis

Posted by Jim Lewis on October 3rd, 2014

The image shows a hypothetical molecular assembly line where reagents are effectively added to a growing carbon chain with extraordinary high fidelity and precision. By controlling the precise orientation of the building blocks added to the carbon chain, the conformation of the molecule can be controlled so that it adopts a helical (shown) or linear shape. Credit: Amber Webster, www.amberlwebster.com

To develop a productive nanosystem for molecular manufacturing/atomically precise manufacturing it would be very useful to have a nanoscale assembly line. A month ago we posted here about a proof of principle for one such assembly line based upon biomolecules. This month Christine Peterson sends word of an assembly line for complex artificial organic molecules. An article on SingularityHUB led to this news release from the University of Bristol “Chemists create ‘assembly-line’ for organic molecules“:

Scientists at the University of Bristol have developed a process where reagents are added to a growing carbon chain with extraordinary high fidelity and precise orientation, thereby controlling the conformation of the molecule so that it adopts a helical or linear shape. The process can be likened to a molecular assembly line.

Nature has evolved highly sophisticated machinery for organic synthesis. One of the most beautiful examples is its machinery for the synthesis of polyketides, a very important class of molecules due to their broad spectrum of biological activities (for example antibiotic, antitumor, antifungal, antiparasitic).

In this process, a simple thioester (small building block) is passed from one enzyme domain to another, growing as it does so until the target molecule is formed. The process resembles a molecular assembly line.

The Bristol researchers sought to emulate nature in the construction of their own molecular assembly line through a related iterative process. But iterative processes are very challenging as each iteration must occur with >99.5 per cent efficiency, and >99.5 per cent stereocontrol otherwise mixtures would result.

In a paper published in the journal Nature today [abstract], the scientists report a reagent which reacts with their small building blocks (boronic esters) with exceptionally high fidelity and stereocontrol.

Through repeated iteration they have converted a simple building block into a complex molecule (a carbon chain with ten contiguous methyl groups) with remarkably high precision over its length, its stereochemistry and therefore its shape.

Different stereoisomers were targeted and it was found that they adopted different shapes (helical/linear) according to their stereochemistry.

This work should now enable molecules with predictable shape to be rationally designed and created which could have an impact in all areas of molecular sciences where bespoke molecules are required.

The ability demonstrated here to control the spatial configuration of the addition of each new subunit of a long molecule to achieve programmable molecular shapes is certainly a useful step toward a molecular assembly line. One interesting question is how many specially designed or specially chosen building blocks and reagents will be needed to construct a generally useful molecular assembly line.
—James Lewis, PhD

Nanomanufacturing grants available from US National Science Foundation

Posted by Jim Lewis on September 27th, 2014

US National Science Foundation

Speaking of US government programs to advance nanomanufacturing, Christine Peterson sends word of a US National Science Foundation nanomanufactring program that explicitly mentions nanorobots and other nanomachines “The NSF Nanomanufacturing Program“:

… The NSF Nanomanufacturing Program supports fundamental research in novel methods and techniques for batch and continuous processes, top-down (addition/subtraction) and bottom-up (directed self-assembly) processes leading to the formation of complex heterogeneous nanosystems. The program supports basic research in nanostructure and process design principles, integration across length-scales, and system-level integration. The Program leverages advances in the understanding of nano-scale phenomena and processes (physical, chemical, electrical, thermal, mechanical and biological), nanomaterials discovery, novel nanostructure architectures, and new nanodevice and nanosystem concepts. It seeks to address quality, efficiency, scalability, reliability, safety and affordability issues that are relevant to manufacturing. To address these issues, the Program encourages research on processes and production systems based on computation, modeling and simulation, use of process metrology, sensing, monitoring, and control, and assessment of product (nanomaterial, nanostructure, nanodevice or nanosystem) quality and performance.

The Program seeks to explore transformative approaches to nanomanufacturing, including but not limited to: micro-reactor and micro-fluidics enabled nanosynthesis, bio-inspired nanomanufacturing, manufacturing by nanomachines, additive nanomanufacturing, hierarchical nanostructure assembly, continuous high-rate nanofabrication such as roll-to-roll processing or massively-parallel large-area processing, and modular manufacturing platforms for nanosystems. The Program encourages the fabrication of nanomaterials by design, three-dimensional nanostructures, multi-layer nanodevices, and multi-material and multi-functional nanosystems. Also of interest is the manufacture of dynamic nanosystems such as nanomotors, nanorobots, and nanomachines [emphasis added], and enabling advances in transport and diffusion mechanisms at the nano-scale. …

The description of the program is broad enough to cover numerous topics relevant to both the integration of current nanomaterials and nanodevices into near-term nanofabricated products across a wide range of applications, and progress toward productive nanosystems and atomically precise manufacturing. It will be interesting to see what research actually gets funded by this program.
—James Lewis, PhD

DNA nanotechnology and the atoms to micrometer nanofabrication gap

Posted by Jim Lewis on September 26th, 2014

A PowerPoint slide shows the two technical areas DARPA’s Atoms to Product project will concentrate on. (Slide courtesy of DARPA)

A few weeks ago we posted the announcement of a new DARPA program, the Atoms To Product (A2P) project. For those who were not able to catch the webinar explaining the initiative, more information is available in an article on Fedscoop “DARPA wants help closing nanotechnology’s ‘assembly gap’:

The Pentagon’s advanced research agency wants to do something that currently cannot be done: Take things built at a really, really small level and scale them for production in really big systems.

Solving that problem will be the task of those behind the Atoms To Product (A2P) project at the Defense Advanced Research Projects Agency’s Defense Sciences Office. DARPA is soliciting proposals for how researchers can further advance and leverage nanotechnology.

Stephanie Tompkins, director of the Defense Sciences Office, said the project fits into two of the office’s main focal points: finding ways to adapt to a growing market of globally available technology and incorporating it into military systems. Currently, technology is moving too fast and the adoption costs are unsustainable for military systems. DARPA hopes the A2P project will provide a cheaper way to integrate new technology on a variety of scales. …

A2P will focus on two technical links in the scaling hierarchy: moving atomic-level tech into the micron or molecule level, then moving the micron level into the millimeter level. The atoms-to-micron level will produce what’s known as feedstock — raw materials used in product manufacturing — with that material eventually allowing scientists to move it into millimeter-sized components. …

Yesterday’s post on extensions to the scaffolded DNA origami method fall toward the far end of the TA1 step in the above slide, the atoms to micrometer step. Perhaps the real challenge remaining in this first step is not an increase in scale per se, since the 300 nm by 200 nm DNA arrays are only a factor of three from the micrometer scale, but a way to use these arrays as organizing scaffolds for methods to make an array of molecules much wider than the world of biomolecules.
—James Lewis, PhD

Scaffolded DNA origami improvements advance DNA nanotechnology

Posted by Jim Lewis on September 25th, 2014

Scaffolded DNA origami utilizes numerous chemically synthesized, short DNA strands (staple strands) to direct the folding of a larger, biologically derived strand of DNA (scaffold strand). Molecular recognition (base pairing, i.e., A binds to T and G binds to C) directs the DNA to self-assemble into a specific structure as programed by the staple strand sequences. Unique staple strands produce a molecular pegboard with single-digit nanometer site-specificity precision. The atomic force microscopy image (right) demonstrates the final origami structure. Image credit: Alexandria Marchi.

Scaffolded DNA origami provided the starting point for the modular molecular composite nanosystems approach to atomically precise productive nanosystems (see Productive Nanosystems: A Technology Roadmap PDf page x, page 51). Over the past seven years we have pointed here to numerous advances in structural DNA nanotechnology and the related underlying technologies as advances toward atomically precise manufacturing, but one limit has been the maximum size available of the conventional single stranded scaffold available from the bacteriophage M13, which limits the scale of the uniquely addressable DNA structures that can be built. A second limit has been the cost of synthesis of the DNA staple strands. Now both of those limits have been greatly extended. A hat tip to ScienceDaily for reprinting this North Carolina State University news release “Researchers Create World’s Largest DNA Origami“:

Researchers from North Carolina State University, Duke University and the University of Copenhagen have created the world’s largest DNA origami, which are nanoscale constructions with applications ranging from biomedical research to nanoelectronics.

“These origami can be customized for use in everything from studying cell behavior to creating templates for the nanofabrication of electronic components,” says Dr. Thom LaBean, an associate professor of materials science and engineering at NC State and senior author of a paper describing the work.

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