Tag Archives: Harvard University

North Carolina universities go beyond organ-on-a-chip

The researchers in the North Carolina universities involved in this project have high hopes according to an Oct. 9, 2015 news item on Nanowerk,

A team of researchers from the University of North Carolina at Chapel Hill and NC State University has received a $5.3 million, five-year Transformative Research (R01) Award from the National Institutes of Health (NIH) to create fully functioning versions of the human gut that fit on a chip the size of a dime.

Such “organs-on-a-chip” have become vital for biomedical research, as researchers seek alternatives to animal models for drug discovery and testing. The new grant will fund a technology that represents a major step forward for the field, overcoming limitations that have mired other efforts.

The technology will use primary cells derived directly from human biopsies, which are known to provide more relevant results than the immortalized cell lines used in current approaches. In addition, the device will sculpt these cells into the sophisticated architecture of the gut, rather than the disorganized ball of cells that are created in other miniature organ systems.

“We are building a device that goes far beyond the organ-on-a-chip,” said Nancy L. Allbritton, MD, PhD, professor and chair of the UNC-NC State joint department of biomedical engineering and one of four principle investigators on the NIH grant. “We call it a ‘simulacrum,’ [emphasis mine] a term used in science fiction to describe a duplicate. The idea is to create something that is indistinguishable from your own gut.”

I’ve come across the term ‘simulacrum’ in relation to philosophy so it’s a bit of a surprise to find it in a news release about an organ-on-a-chip where it seems to have been redefined somewhat. Here’s more from the Simulacrum entry on Wikipedia (Note: Links have been removed),

A simulacrum (plural: simulacra from Latin: simulacrum, which means “likeness, similarity”), is a representation or imitation of a person or thing.[1] The word was first recorded in the English language in the late 16th century, used to describe a representation, such as a statue or a painting, especially of a god. By the late 19th century, it had gathered a secondary association of inferiority: an image without the substance or qualities of the original.[2] Philosopher Fredric Jameson offers photorealism as an example of artistic simulacrum, where a painting is sometimes created by copying a photograph that is itself a copy of the real.[3] Other art forms that play with simulacra include trompe-l’œil,[4] pop art, Italian neorealism, and French New Wave.[3]


The simulacrum has long been of interest to philosophers. In his Sophist, Plato speaks of two kinds of image making. The first is a faithful reproduction, attempted to copy precisely the original. The second is intentionally distorted in order to make the copy appear correct to viewers. He gives the example of Greek statuary, which was crafted larger on the top than on the bottom so that viewers on the ground would see it correctly. If they could view it in scale, they would realize it was malformed. This example from the visual arts serves as a metaphor for the philosophical arts and the tendency of some philosophers to distort truth so that it appears accurate unless viewed from the proper angle.[5] Nietzsche addresses the concept of simulacrum (but does not use the term) in the Twilight of the Idols, suggesting that most philosophers, by ignoring the reliable input of their senses and resorting to the constructs of language and reason, arrive at a distorted copy of reality.[6]

Postmodernist French social theorist Jean Baudrillard argues that a simulacrum is not a copy of the real, but becomes truth in its own right: the hyperreal. Where Plato saw two types of representation—faithful and intentionally distorted (simulacrum)—Baudrillard sees four: (1) basic reflection of reality; (2) perversion of reality; (3) pretence of reality (where there is no model); and (4) simulacrum, which “bears no relation to any reality whatsoever”.[7] In Baudrillard’s concept, like Nietzsche’s, simulacra are perceived as negative, but another modern philosopher who addressed the topic, Gilles Deleuze, takes a different view, seeing simulacra as the avenue by which an accepted ideal or “privileged position” could be “challenged and overturned”.[8] Deleuze defines simulacra as “those systems in which different relates to different by means of difference itself. What is essential is that we find in these systems no prior identity, no internal resemblance”.[9]

Getting back to the proposed research, an Oct. (?), 2015 University of North Carolina news release, which originated the news item, describes the proposed work in more detail,

Allbritton is an expert at microfabrication and microengineering. Also on the team are intestinal stem cell expert Scott T. Magness, associate professor of medicine, biomedical engineering, and cell and molecular physiology in the UNC School of Medicine; microbiome expert Scott Bultman, associate professor of genetics in the UNC School of Medicine; and bioinformatics expert Shawn Gomez, associate professor of biomedical engineering in UNC’s College of Arts and Sciences and NC State.

The impetus for the “organ-on-chip” movement comes largely from the failings of the pharmaceutical industry. For just a single drug to go through the discovery, testing, and approval process can take as many as 15 years and as much as $5 billion dollars. Animal models are expensive to work with and often don’t respond to drugs and diseases the same way humans do. Human cells grown in flat sheets on Petri dishes are also a poor proxy. Three-dimensional “organoids” are an improvement, but these hollow balls are made of a mishmash of cells that doesn’t accurately mimic the structure and function of the real organ.

Basically, the human gut is a 30-foot long hollow tube made up of a continuous single-layer of specialized cells. Regenerative stem cells reside deep inside millions of small pits or “crypts” along the tube, and mature differentiated cells are linked to the pits and live further out toward the surface. The gut also contains trillions of microbes, which are estimated to outnumber human cells by ten to one. These diverse microbial communities – collectively known as the microbiota – process toxins and pharmaceuticals, stimulate immunity, and even release hormones to impact behavior.

To create a dime-sized version of this complex microenvironment, the UNC-NC State team borrowed fabrication technologies from the electronics and microfluidics world. The device is composed of a polymer base containing an array of imprinted or shaped “hydrogels,” a mesh of molecules that can absorb water like a sponge. These hydrogels are specifically engineered to provide the structural support and biochemical cues for growing cells from the gut. Plugged into the device will be various kinds of plumbing that bring in chemicals, fluids, and gases to provide cues that tell the cells how and where to differentiate and grow. For example, the researchers will engineer a steep oxygen gradient into the device that will enable oxygen-loving human cells and anaerobic microbes to coexist in close proximity.

“The underlying concept – to simply grow a piece of human tissue in a dish – doesn’t seem that groundbreaking,” said Magness. “We have been doing that for a long time with cancer cells, but those efforts do not replicate human physiology. Using native stem cells from the small intestine or colon, we can now develop gut tissue layers in a dish that contains stem cells and all the differentiated cells of the gut. That is the thing stem cell biologists and engineers have been shooting for, to make real tissue behave properly in a dish to create better models for drug screening and cell-based therapies. With this work, we made a big leap toward that goal.”

Right now, the team has a working prototype that can physically and chemically guide mouse intestinal stem cells into the appropriate structure and function of the gut. For several years, Magness has been isolating and banking human stem cells from samples from patients undergoing routine colonoscopies at UNC Hospitals.

As part of the grant, he will work with the rest of the team to apply these stem cells to the new device and create “simulacra” that are representative of each patient’s individual gut. The approach will enable researchers to explore in a personalized way how both the human and microbial cells of the gut behave during healthy and diseased states.

“Having a system like this will advance microbiota research tremendously,” said Bultman. “Right now microbiota studies involve taking samples, doing sequencing, and then compiling an inventory of all the microbes in the disease cases and healthy controls. These studies just draw associations, so it is difficult to glean cause and effect. This device will enable us to probe the microbiota, and gain a better understanding of whether changes in these microbial communities are the cause or the consequence of disease.”

I wish them good luck with their work and to end on another interesting note, the concept of organs-on-a-chip won a design award. From a June 22, 2015 article by Oliver Wainwright for the Guardian (Note: Links have been removed),

Meet the Lung-on-a-chip, a simulation of the biological processes inside the human lung, developed by the Wyss Institute for Biologically Inspired Engineering at Harvard University – and now crowned Design of the Year by London’s Design Museum.

Lined with living human cells, the “organs-on-chips” mimic the tissue structures and mechanical motions of human organs, promising to accelerate drug discovery, decrease development costs and potentially usher in a future of personalised medicine.

“This is the epitome of design innovation,” says Paola Antonelli, design curator at New York’s Museum of Modern Art [MOMA], who nominated the project for the award and recently acquired organs-on-chips for MoMA’s permanent collection. “Removing some of the pitfalls of human and animal testing means, theoretically, that drug trials could be conducted faster and their viable results disseminated more quickly.”

Whodathunkit? (Tor those unfamiliar with slang written in this form: Who would have thought it?)

A fatigue-free stretchable conductor for foldable electronics

There’s been a lot of talk about foldable, stretchable, and/or bendable electronics, which is exciting in itself but I find this work on developing a fatigue-free conductor particularly intriguing. After all, who hasn’t purchased something that stretches, folds, etc. only to find that it becomes ‘fatigued’ and is now ‘stretched out’.

A Sept. 23, 2015 news item on Azonano describes the new conductors,

Researchers have discovered a new stretchable, transparent conductor that can be folded or stretched and released, resulting in a large curvature or a significant strain, at least 10,000 times without showing signs of fatigue.

This is a crucial step in creating a new generation of foldable electronics – think a flat-screen television that can be rolled up for easy portability – and implantable medical devices. The work, published Monday [Sept. 21, 2015] in the Proceedings of the National Academy of Sciences, pairs gold nanomesh with a stretchable substrate made with polydimethylsiloxane, or PDMS.

The research is the result of an international collaboration including the University of Houston (US), Harvard University (US), Methodist Research Institute (US), Zhengzhou University (China), Lawrence Berkeley National Laboratory (LBNL; US).

A Sept. 22, 2015 University of Houston news release by Jeannie Kever, which originated the news item, describes this -fatigue-free material in more detail,

The substrate is stretched before the gold nanomesh is placed on it – a process known as “prestretching” – and the material showed no sign of fatigue when cyclically stretched to a strain of more than 50 percent.

The gold nanomesh also proved conducive to cell growth, indicating it is a good material for implantable medical devices.

Fatigue is a common problem for researchers trying to develop a flexible, transparent conductor, making many materials that have good electrical conductivity, flexibility and transparency – all three are needed for foldable electronics – wear out too quickly to be practical, said Zhifeng Ren, a physicist at the University of Houston and principal investigator at the Texas Center for Superconductivity, who was the lead author for the paper.

The new material, produced by grain boundary lithography, solves that problem, he said.

In addition to Ren, other researchers on the project included Chuan Fei Guo and Ching-Wu “Paul” Chu, both from UH; Zhigang Suo, Qihan Liu and Yecheng Wang, all from Harvard University, and Guohui Wang and Zhengzheng Shi, both from the Houston Methodist Research Institute.

In materials science, “fatigue” is used to describe the structural damage to a material caused by repeated movement or pressure, known as “strain cycling.” Bend a material enough times, and it becomes damaged or breaks.    That means the materials aren’t durable enough for consumer electronics or biomedical devices.

“Metallic materials often exhibit high cycle fatigue, and fatigue has been a deadly disease for metals,” the researchers wrote.

“We weaken the constraint of the substrate by making the interface between the Au (gold) nanomesh and PDMS slippery, and expect the Au nanomesh to achieve superstretchability and high fatigue resistance,” they wrote in the paper. “Free of fatigue here means that both the structure and the resistance do not change or have little change after many strain cycles.”

As a result, they reported, “the Au nanomesh does not exhibit strain fatigue when it is stretched to 50 percent for 10,000 cycles.”

Many applications require a less dramatic stretch – and many materials break with far less stretching – so the combination of a sufficiently large range for stretching and the ability to avoid fatigue over thousands of cycles indicates a material that would remain productive over a long period of time, Ren said.

The grain boundary lithography involved a bilayer lift-off metallization process, which included an indium oxide mask layer and a silicon oxide sacrificial layer and offers good control over the dimensions of the mesh structure.

The researchers used mouse embryonic fibroblast cells to determine biocompatibility; that, along with the fact that the stretchability of gold nanomesh on a slippery substrate resembles the bioenvironment of tissue or organ surfaces, suggest the nanomesh “might be implanted in the body as a pacemaker electrode, a connection to nerve endings or the central nervous system, a beating heart, and so on,” they wrote.

Here’s a link to and citation for the paper,

Fatigue-free, superstretchable, transparent, and biocompatible metal electrodes by Chuan Fei Guo, Qihan Liu, Guohui Wang, Yecheng Wang, Zhengzheng Shi, Zhigang Suo, Ching-Wu Chu, and Zhifeng Ren. PNAS (Proceedings of the National Academy of Sciences)  doi: 10.1073/pnas.1516873112 Published online Sept. 21, 2015

This paper appears to be open access.

$81M for US National Nanotechnology Coordinated Infrastructure (NNCI)

Academics, small business, and industry researchers are the big winners in a US National Science Foundation bonanza according to a Sept. 16, 2015 news item on Nanowerk,

To advance research in nanoscale science, engineering and technology, the National Science Foundation (NSF) will provide a total of $81 million over five years to support 16 sites and a coordinating office as part of a new National Nanotechnology Coordinated Infrastructure (NNCI).

The NNCI sites will provide researchers from academia, government, and companies large and small with access to university user facilities with leading-edge fabrication and characterization tools, instrumentation, and expertise within all disciplines of nanoscale science, engineering and technology.

A Sept. 16, 2015 NSF news release provides a brief history of US nanotechnology infrastructures and describes this latest effort in slightly more detail (Note: Links have been removed),

The NNCI framework builds on the National Nanotechnology Infrastructure Network (NNIN), which enabled major discoveries, innovations, and contributions to education and commerce for more than 10 years.

“NSF’s long-standing investments in nanotechnology infrastructure have helped the research community to make great progress by making research facilities available,” said Pramod Khargonekar, assistant director for engineering. “NNCI will serve as a nationwide backbone for nanoscale research, which will lead to continuing innovations and economic and societal benefits.”

The awards are up to five years and range from $500,000 to $1.6 million each per year. Nine of the sites have at least one regional partner institution. These 16 sites are located in 15 states and involve 27 universities across the nation.

Through a fiscal year 2016 competition, one of the newly awarded sites will be chosen to coordinate the facilities. This coordinating office will enhance the sites’ impact as a national nanotechnology infrastructure and establish a web portal to link the individual facilities’ websites to provide a unified entry point to the user community of overall capabilities, tools and instrumentation. The office will also help to coordinate and disseminate best practices for national-level education and outreach programs across sites.

New NNCI awards:

Mid-Atlantic Nanotechnology Hub for Research, Education and Innovation, University of Pennsylvania with partner Community College of Philadelphia, principal investigator (PI): Mark Allen
Texas Nanofabrication Facility, University of Texas at Austin, PI: Sanjay Banerjee

Northwest Nanotechnology Infrastructure, University of Washington with partner Oregon State University, PI: Karl Bohringer

Southeastern Nanotechnology Infrastructure Corridor, Georgia Institute of Technology with partners North Carolina A&T State University and University of North Carolina-Greensboro, PI: Oliver Brand

Midwest Nano Infrastructure Corridor, University of  Minnesota Twin Cities with partner North Dakota State University, PI: Stephen Campbell

Montana Nanotechnology Facility, Montana State University with partner Carlton College, PI: David Dickensheets
Soft and Hybrid Nanotechnology Experimental Resource,

Northwestern University with partner University of Chicago, PI: Vinayak Dravid

The Virginia Tech National Center for Earth and Environmental Nanotechnology Infrastructure, Virginia Polytechnic Institute and State University, PI: Michael Hochella

North Carolina Research Triangle Nanotechnology Network, North Carolina State University with partners Duke University and University of North Carolina-Chapel Hill, PI: Jacob Jones

San Diego Nanotechnology Infrastructure, University of California, San Diego, PI: Yu-Hwa Lo

Stanford Site, Stanford University, PI: Kathryn Moler

Cornell Nanoscale Science and Technology Facility, Cornell University, PI: Daniel Ralph

Nebraska Nanoscale Facility, University of Nebraska-Lincoln, PI: David Sellmyer

Nanotechnology Collaborative Infrastructure Southwest, Arizona State University with partners Maricopa County Community College District and Science Foundation Arizona, PI: Trevor Thornton

The Kentucky Multi-scale Manufacturing and Nano Integration Node, University of Louisville with partner University of Kentucky, PI: Kevin Walsh

The Center for Nanoscale Systems at Harvard University, Harvard University, PI: Robert Westervelt

The universities are trumpeting this latest nanotechnology funding,

NSF-funded network set to help businesses, educators pursue nanotechnology innovation (North Carolina State University, Duke University, and University of North Carolina at Chapel Hill)

Nanotech expertise earns Virginia Tech a spot in National Science Foundation network

ASU [Arizona State University] chosen to lead national nanotechnology site

UChicago, Northwestern awarded $5 million nanotechnology infrastructure grant

That is a lot of excitement.

Nanoscale imaging of a mouse brain

Researchers have developed a new brain imaging tool they would like to use as a founding element for a national brain observatory. From a July 30, 2015 news item on Azonano,

A new imaging tool developed by Boston scientists could do for the brain what the telescope did for space exploration.

In the first demonstration of how the technology works, published July 30 in the journal Cell, the researchers look inside the brain of an adult mouse at a scale previously unachievable, generating images at a nanoscale resolution. The inventors’ long-term goal is to make the resource available to the scientific community in the form of a national brain observatory.

A July 30, 2015 Cell Press news release on EurekAlert, which originated the news item, expands on the theme,

“I’m a strong believer in bottom up-science, which is a way of saying that I would prefer to generate a hypothesis from the data and test it,” says senior study author Jeff Lichtman, of Harvard University. “For people who are imagers, being able to see all of these details is wonderful and we’re getting an opportunity to peer into something that has remained somewhat intractable for so long. It’s about time we did this, and it is what people should be doing about things we don’t understand.”

The researchers have begun the process of mining their imaging data by looking first at an area of the brain that receives sensory information from mouse whiskers, which help the animals orient themselves and are even more sensitive than human fingertips. The scientists used a program called VAST, developed by co-author Daniel Berger of Harvard and the Massachusetts Institute of Technology, to assign different colors and piece apart each individual “object” (e.g., neuron, glial cell, blood vessel cell, etc.).

“The complexity of the brain is much more than what we had ever imagined,” says study first author Narayanan “Bobby” Kasthuri, of the Boston University School of Medicine. “We had this clean idea of how there’s a really nice order to how neurons connect with each other, but if you actually look at the material it’s not like that. The connections are so messy that it’s hard to imagine a plan to it, but we checked and there’s clearly a pattern that cannot be explained by randomness.”

The researchers see great potential in the tool’s ability to answer questions about what a neurological disorder actually looks like in the brain, as well as what makes the human brain different from other animals and different between individuals. Who we become is very much a product of the connections our neurons make in response to various life experiences. To be able to compare the physical neuron-to-neuron connections in an infant, a mathematical genius, and someone with schizophrenia would be a leap in our understanding of how our brains shape who we are (or vice versa).

The cost and data storage demands for this type of research are still high, but the researchers expect expenses to drop over time (as has been the case with genome sequencing). To facilitate data sharing, the scientists are now partnering with Argonne National Laboratory with the hopes of creating a national brain laboratory that neuroscientists around the world can access within the next few years.

“It’s bittersweet that there are many scientists who think this is a total waste of time as well as a big investment in money and effort that could be better spent answering questions that are more proximal,” Lichtman says. “As long as data is showing you things that are unexpected, then you’re definitely doing the right thing. And we are certainly far from being out of the surprise element. There’s never a time when we look at this data that we don’t see something that we’ve never seen before.”

Here’s a link to and a citation for the paper,

Saturated Reconstruction of a Volume of Neocortex by Narayanan Kasthuri, Kenneth Jeffrey Hayworth, Daniel Raimund Berger, Richard Lee Schalek, José Angel Conchello, Seymour Knowles-Barley, Dongil Lee, Amelio Vázquez-Reina, Verena Kaynig, Thouis Raymond Jones, Mike Roberts, Josh Lyskowski Morgan, Juan Carlos Tapia, H. Sebastian Seung, William Gray Roncal, Joshua Tzvi Vogelstein, Randal Burns, Daniel Lewis Sussman, Carey Eldin Priebe, Hanspeter Pfister, Jeff William Lichtman. Cell Volume 162, Issue 3, p648–661, 30 July 2015 DOI: http://dx.doi.org/10.1016/j.cell.2015.06.054

This appears to be an open access paper.

SINGLE (3D Structure Identification of Nanoparticles by Graphene Liquid Cell Electron Microscopy) and the 3D structures of two individual platinum nanoparticles in solution

It seems to me there’s been an explosion of new imaging techniques lately. This one from the Lawrence Berkelely National Laboratory is all about imaging colloidal nanoparticles (nanoparticles in solution), from a July 20, 2015 news item on Azonano,

Just as proteins are one of the basic building blocks of biology, nanoparticles can serve as the basic building blocks for next generation materials. In keeping with this parallel between biology and nanotechnology, a proven technique for determining the three dimensional structures of individual proteins has been adapted to determine the 3D structures of individual nanoparticles in solution.

A multi-institutional team of researchers led by the U.S. Department of Energy (DOE)’s Lawrence Berkeley National Laboratory (Berkeley Lab), has developed a new technique called “SINGLE” that provides the first atomic-scale images of colloidal nanoparticles. SINGLE, which stands for 3D Structure Identification of Nanoparticles by Graphene Liquid Cell Electron Microscopy, has been used to separately reconstruct the 3D structures of two individual platinum nanoparticles in solution.

A July 16, 2015 Berkeley Lab news release, which originated the news item, reveals more details about the reason for the research and the research itself,

“Understanding structural details of colloidal nanoparticles is required to bridge our knowledge about their synthesis, growth mechanisms, and physical properties to facilitate their application to renewable energy, catalysis and a great many other fields,” says Berkeley Lab director and renowned nanoscience authority Paul Alivisatos, who led this research. “Whereas most structural studies of colloidal nanoparticles are performed in a vacuum after crystal growth is complete, our SINGLE method allows us to determine their 3D structure in a solution, an important step to improving the design of nanoparticles for catalysis and energy research applications.”

Alivisatos, who also holds the Samsung Distinguished Chair in Nanoscience and Nanotechnology at the University of California Berkeley, and directs the Kavli Energy NanoScience Institute at Berkeley (Kavli ENSI), is the corresponding author of a paper detailing this research in the journal Science. The paper is titled “3D Structure of Individual Nanocrystals in Solution by Electron Microscopy.” The lead co-authors are Jungwon Park of Harvard University, Hans Elmlund of Australia’s Monash University, and Peter Ercius of Berkeley Lab. Other co-authors are Jong Min Yuk, David Limmer, Qian Chen, Kwanpyo Kim, Sang Hoon Han, David Weitz and Alex Zettl.

Colloidal nanoparticles are clusters of hundreds to thousands of atoms suspended in a solution whose collective chemical and physical properties are determined by the size and shape of the individual nanoparticles. Imaging techniques that are routinely used to analyze the 3D structure of individual crystals in a material can’t be applied to suspended nanomaterials because individual particles in a solution are not static. The functionality of proteins are also determined by their size and shape, and scientists who wanted to image 3D protein structures faced a similar problem. The protein imaging problem was solved by a technique called “single-particle cryo-electron microscopy,” in which tens of thousands of 2D transmission electron microscope (TEM) images of identical copies of an individual protein or protein complex frozen in random orientations are recorded then computationally combined into high-resolution 3D reconstructions. Alivisatos and his colleagues utilized this concept to create their SINGLE technique.

“In materials science, we cannot assume the nanoparticles in a solution are all identical so we needed to develop a hybrid approach for reconstructing the 3D structures of individual nanoparticles,” says co-lead author of the Science paper Peter Ercius, a staff scientist with the National Center for Electron Microscopy (NCEM) at the Molecular Foundry, a DOE Office of Science User Facility.

“SINGLE represents a combination of three technological advancements from TEM imaging in biological and materials science,” Ercius says. “These three advancements are the development of a graphene liquid cell that allows TEM imaging of nanoparticles rotating freely in solution, direct electron detectors that can produce movies with millisecond frame-to-frame time resolution of the rotating nanocrystals, and a theory for ab initio single particle 3D reconstruction.”

The graphene liquid cell (GLC) that helped make this study possible was also developed at Berkeley Lab under the leadership of Alivisatos and co-author Zettl, a physicist who also holds joint appointments with Berkeley Lab, UC Berkeley and Kavli ENSI. TEM imaging uses a beam of electrons rather than light for illumination and magnification but can only be used in a high vacuum because molecules in the air disrupt the electron beam. Since liquids evaporate in high vacuum, samples in solutions must be hermetically sealed in special solid containers – called cells – with a very thin viewing window before being imaged with TEM. In the past, liquid cells featured silicon-based viewing windows whose thickness limited resolution and perturbed the natural state of the sample materials. The GLC developed at Berkeley lab features a viewing window made from a graphene sheet that is only a single atom thick.

“The GLC provides us with an ultra-thin covering of our nanoparticles while maintaining liquid conditions in the TEM vacuum,” Ercius says. “Since the graphene surface of the GLC is inert, it does not adsorb or otherwise perturb the natural state of our nanoparticles.”

Working at NCEM’s TEAM I, the world’s most powerful electron microscope, Ercius, Alivisatos and their colleagues were able to image in situ the translational and rotational motions of individual nanoparticles of platinum that were less than two nanometers in diameter. Platinum nanoparticles were chosen because of their high electron scattering strength and because their detailed atomic structure is important for catalysis.

“Our earlier GLC studies of platinum nanocrystals showed that they grow by aggregation, resulting in complex structures that are not possible to determine by any previously developed method,” Ercius says. “Since SINGLE derives its 3D structures from images of individual nanoparticles rotating freely in solution, it enables the analysis of heterogeneous populations of potentially unordered nanoparticles that are synthesized in solution, thereby providing a means to understand the structure and stability of defects at the nanoscale.”

The next step for SINGLE is to recover a full 3D atomic resolution density map of colloidal nanoparticles using a more advanced camera installed on TEAM I that can provide 400 frames-per-second and better image quality.

“We plan to image defects in nanoparticles made from different materials, core shell particles, and also alloys made of two different atomic species,” Ercius says. [emphasis mine]

“Two different atomic species?”, they really are pushing that biology analogy.

Here’s a link to and a citation for the paper,

3D structure of individual nanocrystals in solution by electron microscopy by Jungwon Park, Hans Elmlund, Peter Ercius, Jong Min Yuk, David T. Limme, Qian Chen, Kwanpyo Kim, Sang Hoon Han, David A. Weitz, A. Zettl, A. Paul Alivisatos. Science 17 July 2015: Vol. 349 no. 6245 pp. 290-295 DOI: 10.1126/science.aab1343

This paper is behind a paywall.

Injectable electronics

Having taught a course on bioelectronics for Simon Fraser University’s (Vancouver, Canada) Continuing Studies Program, this  latest work from Harvard University (US) caught my attention. A Harvard research team has developed a technique which could allow doctors to inject us with electronics, should we need them. From a June 8, 2015 news item on phys.org,

It’s a notion that might be pulled from the pages of science-fiction novel – electronic devices that can be injected directly into the brain, or other body parts, and treat everything from neurodegenerative disorders to paralysis.

It sounds unlikely, until you visit Charles Lieber’s lab.

A team of international researchers, led by Lieber, the Mark Hyman, Jr. Professor of Chemistry, an international team of researchers developed a method for fabricating nano-scale electronic scaffolds that can be injected via syringe. Once connected to electronic devices, the scaffolds can be used to monitor neural activity, stimulate tissues and even promote regenerations of neurons. …

Here’s an image provided by the researchers,

Bright-field image showing the mesh electronics being injected through sub-100 micrometer inner diameter glass needle into aqueous solution. mage courtesy of Lieber Research Group, Harvard University

Bright-field image showing the mesh electronics being injected through sub-100 micrometer inner diameter glass needle into aqueous solution. mage courtesy of Lieber Research Group, Harvard University

A June 8, 2015 Harvard University new release by Peter Reuell (also on EurekAlert), which originated the news item, describes the work in more detail,

“I do feel that this has the potential to be revolutionary,” Lieber said. “This opens up a completely new frontier where we can explore the interface between electronic structures and biology. For the past thirty years, people have made incremental improvements in micro-fabrication techniques that have allowed us to make rigid probes smaller and smaller, but no one has addressed this issue – the electronics/cellular interface – at the level at which biology works.”

The idea of merging the biological with the electronic is not a new one for Lieber.

In an earlier study, scientists in Lieber’s lab demonstrated that the scaffolds could be used to create “cyborg” tissue – when cardiac or nerve cells were grown with embedded scaffolds. [emphasis mine] Researchers were then able to use the devices to record electrical signals generated by the tissues, and to measure changes in those signals as they administered cardio- or neuro-stimulating drugs.

“We were able to demonstrate that we could make this scaffold and culture cells within it, but we didn’t really have an idea how to insert that into pre-existing tissue,” Lieber said. “But if you want to study the brain or develop the tools to explore the brain-machine interface, you need to stick something into the body. When releasing the electronics scaffold completely from the fabrication substrate, we noticed that it was almost invisible and very flexible like a polymer and could literally be sucked into a glass needle or pipette. From there, we simply asked, would it be possible to deliver the mesh electronics by syringe needle injection, a process common to delivery of many species in biology and medicine – you could go to the doctor and you inject this and you’re wired up.'”

Though not the first attempts at implanting electronics into the brain – deep brain stimulation has been used to treat a variety of disorders for decades – the nano-fabricated scaffolds operate on a completely different scale.

“Existing techniques are crude relative to the way the brain is wired,” Lieber explained. “Whether it’s a silicon probe or flexible polymers…they cause inflammation in the tissue that requires periodically changing the position or the stimulation. But with our injectable electronics, it’s as if it’s not there at all. They are one million times more flexible than any state-of-the-art flexible electronics and have subcellular feature sizes. They’re what I call “neuro-philic” – they actually like to interact with neurons..”

Despite their enormous potential, the fabrication of the injectable scaffolds is surprisingly easy.

“That’s the beauty of this – it’s compatible with conventional manufacturing techniques,” Lieber said.

The process is similar to that used to etch microchips, and begins with a dissolvable layer deposited on a substrate. To create the scaffold, researchers lay out a mesh of nanowires sandwiched in layers of organic polymer. The first layer is then dissolved, leaving the flexible mesh, which can be drawn into a syringe needle and administered like any other injection.

After injection, the input/output of the mesh can be connected to standard measurement electronics so that the integrated devices can be addressed and used to stimulate or record neural activity.

“These type of things have never been done before, from both a fundamental neuroscience and medical perspective,” Lieber said. “It’s really exciting – there are a lot of potential applications.”

Going forward, Lieber said, researchers hope to better understand how the brain and other tissues react to the injectable electronics over longer periods.

Lieber’s earlier work on “cyborg tissue” was briefly mentioned here in a Feb. 20, 2014 posting.

Getting back to the most recent work, here’s a link to and a citation for the paper,

Syringe-injectable electronics by Jia Liu, Tian-Ming Fu, Zengguang Cheng, Guosong Hong, Tao Zhou, Lihua Jin, Madhavi Duvvuri, Zhe Jiang, Peter Kruskal, Chong Xie, Zhigang Suo, Ying Fang, & Charles M. Lieber. Nature Nanotechnology (2015) doi:10.1038/nnano.2015.115 Published online 08 June 2015

This paper is behind a paywall but there is a free preview via ReadCube Access.

One final note, the researchers have tested the injectable electronics (or mesh electronics) in vivo (live animals).

Animal-based (some of it ‘fishy’) sunscreen from Oregon State University

In the Northern Hemisphere countries it’s time to consider one’s sunscreen options.While this Oregon State University into animal-based sunscreens is intriguing,  market-ready options likely won’t be available for quite some time. (There is a second piece of related research, more ‘fishy’ in nature [pun], featured later in this post.) From a May 12, 2015 Oregon State University news release,

Researchers have discovered why many animal species can spend their whole lives outdoors with no apparent concern about high levels of solar exposure: they make their own sunscreen.

The findings, published today in the journal eLife by scientists from Oregon State University, found that many fish, amphibians, reptiles, and birds can naturally produce a compound called gadusol, which among other biologic activities provides protection from the ultraviolet, or sun-burning component of sunlight.

The researchers also believe that this ability may have been obtained through some prehistoric, natural genetic engineering.

Here’s an amusing image to illustrate the researchers’ point,

Gadusol is the gene found in some animals which gives natural sun protection. Courtesy: Oregon State University

Gadusol is the gene found in some animals which gives natural sun protection.
Courtesy: Oregon State University

The news release goes on to describe gadusol and its believed evolutionary pathway,

The gene that provides the capability to produce gadusol is remarkably similar to one found in algae, which may have transferred it to vertebrate animals – and because it’s so valuable, it’s been retained and passed along for hundreds of millions of years of animal evolution.

“Humans and mammals don’t have the ability to make this compound, but we’ve found that many other animal species do,” said Taifo Mahmud, a professor in the OSU College of Pharmacy, and lead author on the research.

The genetic pathway that allows gadusol production is found in animals ranging from rainbow trout to the American alligator, green sea turtle and a farmyard chicken.

“The ability to make gadusol, which was first discovered in fish eggs, clearly has some evolutionary value to be found in so many species,” Mahmud said. “We know it provides UV-B protection, it makes a pretty good sunscreen. But there may also be roles it plays as an antioxidant, in stress response, embryonic development and other functions.”

In their study, the OSU researchers also found a way to naturally produce gadusol in high volumes using yeast. With continued research, it may be possible to develop gadusol as an ingredient for different types of sunscreen products, cosmetics or pharmaceutical products for humans.

A conceptual possibility, Mahmud said, is that ingestion of gadusol could provide humans a systemic sunscreen, as opposed to a cream or compound that has to be rubbed onto the skin.

The existence of gadusol had been known of in some bacteria, algae and other life forms, but it was believed that vertebrate animals could only obtain it from their diet. The ability to directly synthesize what is essentially a sunscreen may play an important role in animal evolution, and more work is needed to understand the importance of this compound in animal physiology and ecology, the researchers said.

Here’s a link to and a citation for the paper,

De novo synthesis of a sunscreen compound in vertebrates by Andrew R Osborn, Khaled H Almabruk, Garrett Holzwarth, Shumpei Asamizu, Jane LaDu, Kelsey M Kean, P Andrew Karplus, Robert L Tanguay, Alan T Bakalinsky, and Taifo Mahmud. eLife 2015;4:e05919 DOI: http://dx.doi.org/10.7554/eLife.05919 Published May 12, 2015

This is an open access paper.

The second piece of related research, also published yesterday on May 12, 2015, comes from a pair of scientists at Harvard University. From a May 12, 2015  eLife news release on EurekAlert,

Scientists from Oregon State University [two authors are listed for the ‘zebrafish’ paper and both are from Harvard University] have discovered that fish can produce their own sunscreen. They have copied the method used by fish for potential use in humans.

In the study published in the journal eLife, scientists found that zebrafish are able to produce a chemical called gadusol that protects against UV radiation. They successfully reproduced the method that zebrafish use by expressing the relevant genes in yeast. The findings open the door to large-scale production of gadusol for sunscreen and as an antioxidant in pharmaceuticals.

Gadusol was originally identified in cod roe and has since been discovered in the eyes of the mantis shrimp, sea urchin eggs, sponges, and in the dormant eggs and newly hatched larvae of brine shrimps. It was previously thought that fish can only acquire the chemical through their diet or through a symbiotic relationship with bacteria.

Marine organisms in the upper ocean and on reefs are subject to intense and often unrelenting sunlight. Gadusol and related compounds are of great scientific interest for their ability to protect against DNA damage from UV rays. There is evidence that amphibians, reptiles, and birds can also produce gadusol, while the genetic machinery is lacking in humans and other mammals.

The team were investigating compounds similar to gadusol that are used to treat diabetes and fungal infections. It was believed that the biosynthetic enzyme common to all of them, EEVS, was only present in bacteria. The scientists were surprised to discover that fish and other vertebrates contain similar genes to those that code for EEVS.

Curious about their function in animals, they expressed the zebrafish gene in E. coli and analysis suggested that fish combine EEVS with another protein, whose production may be induced by light, to produce gadusol. To check that this combination is really sufficient, the scientists transferred the genes to yeast and set them to work to see what they would create. This confirmed the production of gadusol. Its successful production in yeast provides a viable route to commercialisation.

As well as providing UV protection, gadusol may also play a role in stress responses, in embryonic development, and as an antioxidant.

Here’s a link to and a citation for the second paper from this loosely affiliated team of Oregon State University and Harvard University researchers,

Biochemistry: Shedding light on sunscreen biosynthesis in zebrafish by Carolyn A Brotherton and Emily P Balskus. eLife 2015;4:e07961 DOI: http://dx.doi.org/10.7554/eLife.07961 Published May 12, 2015

This paper, too, is open access.

One final bit and this is about the journal, eLife, from their news release on EurekAlert,

About eLife

eLife is a unique collaboration between the funders and practitioners of research to improve the way important research is selected, presented, and shared. eLife publishes outstanding works across the life sciences and biomedicine — from basic biological research to applied, translational, and clinical studies. eLife is supported by the Howard Hughes Medical Institute, the Max Planck Society, and the Wellcome Trust. Learn more at elifesciences.org.

It seems this journal is a joint, US (Howard Hughes Medical Institute), German (Max Planck Society), UK (Wellcome Trust) effort.

Disinfectants without chemicals for the food industry

Michael Berger in his March 16, 2015 Nanowerk Spotlight article profiles some very interesting research into replacing chemicals with water nanostructures,

The burden of foodborne diseases worldwide is huge, with serious economic and public health consequences. The CDC [US Centers for Disease Control] estimates that each year in the USA approximately 48 million people get sick, 128,000 get hospitalized and 3,000 die from the consumption of food contaminated with pathogenic microorganisms. The food industry is in search of effective intervention methods that can be applied from ‘farm to fork’ to ensure the safety of the food chain and be consumer and environment friendly at the same time.

In the food industry, chemicals are routinely used to clean and disinfect product contact surfaces as well as the outer surface of the food itself. These chemicals provide a necessary and required step to ensure that the foods produced and consumed are as free as possible from microorganisms that can cause foodborne illness.

Food activists are concerned that some of the chemicals used by the food industry for disinfection can cause health issues for consumers. A prime example is the current discussion in Europe about ‘American chlorine chicken’. …

Berger goes on to highlight the research being conducted at the Harvard T. Chan School of Public Health (Harvard University). The team announced a new technique called Engineered Water Nanostructures (EWNS), which is generated by electrospraying water. The team published this paper in 2014,

A chemical free, nanotechnology-based method for airborne bacterial inactivation using engineered water nanostructures by Georgios Pyrgiotakis, James McDevitt, Andre Bordini, Edgar Diaz, Ramon Molina, Christa Watson, Glen Deloid, Steve Lenard, Natalie Fix, Yosuke Mizuyama, Toshiyuki Yamauchi, Joseph Brain and Philip Demokritou. Environ. Sci.: Nano, 2014,1, 15-26 DOI: 10.1039/C3EN00007A

First published online 28 Nov 2013

This paper is open access.

More recently, the team has proved the efficacy of this technique on stainless steel surfaces and tomatoes. A Feb. 25, 2015 Harvard T. Chan School of Public Health news release provides information about the costs of foodborne diseases and goes on to describe the technique and the latest experiments,

The burden of foodborne diseases worldwide is huge, with serious economic and public health consequences. The U.S. Department of Agriculture’s (USDA’s) Economic Research Service reported in 2014 that foodborne illnesses are costing the economy more than $15.6 billion and about 53,245 Americans visit the hospital annually due to foodborne illnesses. The food industry is in search of effective intervention methods that can be applied form “farm to fork” to ensure the safety of the food chain and be consumer and environment friendly at the same time.

Researchers at the Center for Nanotechnology and Nanotoxicology of the Harvard T. Chan School of Public Health are currently exploring the effectiveness of a nanotechnology based, chemical free, intervention method for the inactivation of foodborne and spoilage microorganisms on fresh produce and on food production surfaces. This method utilizes Engineered Water Nanostructures (EWNS) generated by electrospraying of water. EWNS possess unique properties; they are 25 nm in diameter, remain airborne in indoor conditions for hours, contain Reactive Oxygen Species (ROS), have very strong surface charge (on average 10e/structure) and have the ability to interact and inactivate pathogens by destroying their membrane.

In a study funded by the USDA and just published this week in the premier Environmental Science and Technology journal, the efficacy of these tiny water nanodroplets, in inactivating representative foodborne pathogens such as Escherichia coli, Salmonella enterica and Listeria innocua, on stainless steel surfaces and on tomatoes, was assessed showing significant log reductions in inactivation of select food pathogens. These promising results could open up the gateway for further exploration into the dynamics of this method in the battle against foodborne disease. More importantly this novel, chemical-free, cost effective and environmentally friendly intervention method holds great potential for development and application in the food industry, as a ‘green’ alternative to existing inactivation methods.

Here’s a link to and a citation for the latest paper,

Inactivation of Foodborne Microorganisms Using Engineered Water Nanostructures (EWNS) by Georgios Pyrgiotakis, Archana Vasanthakumar, Ya Gao, Mary Eleftheriadou, Eduardo Toledo, Alice DeAraujo, James McDevitt, Taewon Han, Gediminas Mainelis, Ralph Mitchell, and Philip Demokritou. Environ. Sci. Technol., Article ASAP DOI: 10.1021/es505868a Publication Date (Web): February 19, 2015

Copyright © 2015 American Chemical Society

This paper is behind a paywall. The researchers have made this image illustrating a ‘water shell’s’ effect on a bacterium located on a tomato,

Courtesy: Researchers and the American Chemical Society

Courtesy: Researchers and the American Chemical Society

I’m not sure how chemical companies are going to feel but this is very exciting news. Still, one has to wonder just how much water this technique would require for full scale adoption and would it be reusable?

Blue-striped limpets and their nanophotonic features

This is a structural colour story limpets and the Massachusetts Institute of Technology (MIT) and Harvard University. For the impatient here’s a video summary of the work courtesy of the researchers,

A Feb. 26, 2015 news item on ScienceDaily reiterates the details for those who like to read their science,

The blue-rayed limpet is a tiny mollusk that lives in kelp beds along the coasts of Norway, Iceland, the United Kingdom, Portugal, and the Canary Islands. These diminutive organisms — as small as a fingernail — might escape notice entirely, if not for a very conspicuous feature: bright blue dotted lines that run in parallel along the length of their translucent shells. Depending on the angle at which light hits, a limpet’s shell can flash brilliantly even in murky water.

Now scientists at MIT and Harvard University have identified two optical structures within the limpet’s shell that give its blue-striped appearance. The structures are configured to reflect blue light while absorbing all other wavelengths of incoming light. The researchers speculate that such patterning may have evolved to protect the limpet, as the blue lines resemble the color displays on the shells of more poisonous soft-bodied snails.

A Feb. 26, 2015 MIT news release (also on EurekAlert), which originated the news item, explains why this discovery is special,

The findings, reported this week in the journal Nature Communications, represent the first evidence of an organism using mineralized structural components to produce optical displays. While birds, butterflies, and beetles can display brilliant blues, among other colors, they do so with organic structures, such as feathers, scales, and plates. The limpet, by contrast, produces its blue stripes through an interplay of inorganic, mineral structures, arranged in such a way as to reflect only blue light.

The researchers say such natural optical structures may serve as a design guide for engineering color-selective, controllable, transparent displays that require no internal light source and could be incorporated into windows and glasses.

“Let’s imagine a window surface in a car where you obviously want to see the outside world as you’re driving, but where you also can overlay the real world with an augmented reality that could involve projecting a map and other useful information on the world that exists on the other side of the windshield,” says co-author Mathias Kolle, an assistant professor of mechanical engineering at MIT. “We believe that the limpet’s approach to displaying color patterns in a translucent shell could serve as a starting point for developing such displays.”

The news release then reveals how this research came about,

Kolle, whose research is focused on engineering bioinspired, optical materials — including color-changing, deformable fibers — started looking into the optical features of the limpet when his brother Stefan, a marine biologist now working at Harvard, brought Kolle a few of the organisms in a small container. Stefan Kolle was struck by the mollusk’s brilliant patterning, and recruited his brother, along with several others, to delve deeper into the limpet shell’s optical properties.

To do this, the team of researchers — which also included Ling Li and Christine Ortiz at MIT and James Weaver and Joanna Aizenberg at Harvard — performed a detailed structural and optical analysis of the limpet shells. They observed that the blue stripes first appear in juveniles, resembling dashed lines. The stripes grow more continuous as a limpet matures, and their shade varies from individual to individual, ranging from deep blue to turquoise.

The researchers scanned the surface of a limpet’s shell using scanning electron microscopy, and found no structural differences in areas with and without the stripes — an observation that led them to think that perhaps the stripes arose from features embedded deeper in the shell.

To get a picture of what lay beneath, the researchers used a combination of high-resolution 2-D and 3-D structural analysis to reveal the 3-D nanoarchitecture of the photonic structures embedded in the limpets’ translucent shells.

What they found was revealing: In the regions with blue stripes, the shells’ top and bottom layers were relatively uniform, with dense stacks of calcium carbonate platelets and thin organic layers, similar to the shell structure of other mollusks. However, about 30 microns beneath the shell surface the researchers noted a stark difference. In these regions, the researchers found that the regular plates of calcium carbonate morphed into two distinct structural features: a multilayered structure with regular spacing between calcium carbonate layers resembling a zigzag pattern, and beneath this, a layer of randomly dispersed, spherical particles.

The researchers measured the dimensions of the zigzagging plates, and found the spacing between them was much wider than the more uniform plates running through the shell’s unstriped sections. They then examined the potential optical roles of both the multilayer zigzagging structure and the spherical particles.

Kolle and his colleagues used optical microscopy, spectroscopy, and diffraction microscopy to quantify the blue stripe’s light-reflection properties. They then measured the zigzagging structures and their angle with respect to the shell surface, and determined that this structure is optimized to reflect blue and green light.

The researchers also determined that the disordered arrangement of spherical particles beneath the zigzag structures serves to absorb transmitted light that otherwise could de-saturate the reflected blue color.

From these results, Kolle and his team deduced that the zigzag pattern acts as a filter, reflecting only blue light. As the rest of the incoming light passes through the shell, the underlying particles absorb this light — an effect that makes a shell’s stripes appear even more brilliantly blue.

And, for those who can never get enough detail, the news release provides a bit more than the video,

The team then sought to tackle a follow-up question: What purpose do the blue stripes serve? The limpets live either concealed at the base of kelp plants, or further up in the fronds, where they are visually exposed. Those at the base grow a thicker shell with almost no stripes, while their blue-striped counterparts live higher on the plant.

Limpets generally don’t have well-developed eyes, so the researchers reasoned that the blue stripes must not serve as a communication tool, attracting one organism to another. Rather, they think that the limpet’s stripes may be a defensive mechanism: The mollusk sits largely exposed on a frond, so a plausible defense against predators may be to appear either invisible or unappetizing. The researchers determined that the latter is more likely the case, as the limpet’s blue stripes resemble the patterning of poisonous marine snails that also happen to inhabit similar kelp beds.

Kolle says the group’s work has revealed an interesting insight into the limpet’s optical properties, which may be exploited to engineer advanced transparent optical displays. The limpet, he points out, has evolved a microstructure in its shell to satisfy an optical purpose without overly compromising the shell’s mechanical integrity. Materials scientists and engineers could take inspiration from this natural balancing act.

“It’s all about multifunctional materials in nature: Every organism — no matter if it has a shell, or skin, or feathers — interacts in various ways with the environment, and the materials with which it interfaces to the outside world frequently have to fulfill multiple functions simultaneously,” Kolle says. “[Engineers] are more and more focusing on not only optimizing just one single property in a material or device, like a brighter screen or higher pixel density, but rather on satisfying several … design and performance criteria simultaneously. We can gain inspiration and insight from nature.”

Peter Vukusic, an associate professor of physics at the University of Exeter in the United Kingdom, says the researchers “have done an exquisite job” in uncovering the optical mechanism behind the limpet’s conspicuous appearance.

“By using multiple and complementary analysis techniques they have elucidated, in glorious detail, the many structural and physiological factors that have given rise to the optical signature of this highly evolved system,” says Vukusic, who was not involved in the study. “The animal’s complex morphology is highly interesting for photonics scientists and technologists interested in manipulating light and creating specialized appearances.”

Here’s a link to and a citation for the paper,

A highly conspicuous mineralized composite photonic architecture in the translucent shell of the blue-rayed limpet by Ling Li, Stefan Kolle, James C. Weaver, Christine Ortiz, Joanna Aizenberg & Mathias Kolle. Nature Communications 6, Article number: 6322 doi:10.1038/ncomms7322 Published 26 February 2015

This article is open access.

Getting up to the size of a dust speck, the first ‘large’ self-assembling DNA crystals

An Oct. 19, 2014 news item on ScienceDaily describes the latest developments in ‘DNA nanotechnology’ research at the Wyss Institute for Biologically Inspired Engineering at Harvard University,

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.

It seems a bit of a misleading for the Wyss Institute to state the ‘team built’ the DNA crystals as they are self-assembling according to this Oct. 19, 2014 Wyss Institute news release (also on EurekAlert), which originated the news item,

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.

“We are very pleased that our DNA brick approach has solved this challenge,” said senior author and Wyss Institute Core Faculty member Peng Yin, Ph.D., who is also an Associate Professor of Systems Biology at Harvard Medical School, “and we were actually surprised by how well it works.”

The news release goes on to describe some of the issues with other self-assembly methods along with more details about the ‘DNA brick’ approach,

Scientists have struggled to crystallize complex 3D DNA nanostructures using more conventional self-assembly methods. The risk of error tends to increase with the complexity of the structural repeating units and the size of the DNA crystal to be assembled.

The DNA brick method uses short, synthetic strands of DNA that work like interlocking Lego® bricks to build complex structures. Structures are first designed using a computer model of a molecular cube, which becomes a master canvas. Each brick is added or removed independently from the 3D master canvas to arrive at the desired shape – and then the design is put into action: the DNA strands that would match up to achieve the desired structure are mixed together and self assemble to achieve the designed crystal structures.

“Therein lies the key distinguishing feature of our design strategy—its modularity,” said co-lead author Yonggang Ke, Ph.D., formerly a Wyss Institute Postdoctoral Fellow and now an assistant professor at the Georgia Institute of Technology and Emory University. “The ability to simply add or remove pieces from the master canvas makes it easy to create virtually any design.”

The modularity also makes it relatively easy to precisely define the crystal depth. “This is the first time anyone has demonstrated the ability to rationally design crystal depth with nanometer precision, up to 80 nm in this study,” Ke said. In contrast, previous two-dimensional DNA lattices are typically single-layer structures with only 2 nm depth.

“DNA crystals are attractive for nanotechnology applications because they are comprised of repeating structural units that provide an ideal template for scalable design features”, said co-lead author graduate student Luvena Ong.

Furthermore, as part of this study the team demonstrated the ability to position gold nanoparticles into prescribed 2D architectures less than two nanometers apart from each other along the crystal structure – a critical feature for future quantum devices and a significant technical advance for their scalable production, said co-lead author Wei Sun, Ph.D., Wyss Institute Postdoctoral Fellow.

“My preconceived notions of the limitations of DNA have been consistently shattered by our new advances in DNA nanotechnology,” said William Shih, Ph.D., who is co-author of the study and a Wyss Institute Founding Core Faculty member, as well as Associate Professor in the Department of Biological Chemistry and Molecular Pharmacology at Harvard Medical School and the Department of Cancer Biology at the Dana-Farber Cancer Institute. “DNA nanotechnology now makes it possible for us to assemble, in a programmable way, prescribed structures rivaling the complexity of many molecular machines we see in Nature.”

“Peng’s team is using the DNA-brick self-assembly method to build the foundation for the new landscape of DNA nanotechnology at an impressive pace,” said Wyss Institute Founding Director Don Ingber, M.D., Ph.D. “What have been mere visions of how the DNA molecule could be used to advance everything from the semiconductor industry to biophysics are fast becoming realities.”

Here’s a link to and a citation for the latest paper,

DNA brick crystals with prescribed depths by Yonggang Ke, Luvena L. Ong, Wei Sun, Jie Song, Mingdong Dong, William M. Shih, & Peng Yin. Nature Chemistry (2014) doi:10.1038/nchem.2083 Published online 19 October 2014

This paper is behind a paywall.