Tag Archives: Germany

Nanotechnology research protocols for Environment, Health and Safety Studies in US and a nanomedicine characterization laboratory in the European Union

I have two items relating to nanotechnology and the development of protocols. The first item concerns the launch of a new web portal by the US National Institute of Standards and Technology.

US National Institute of Standards and Technology (NIST)

From a July 1, 2015 news item on Azonano,

As engineered nanomaterials increasingly find their way into commercial products, researchers who study the potential environmental or health impacts of those materials face a growing challenge to accurately measure and characterize them. These challenges affect measurements of basic chemical and physical properties as well as toxicology assessments.

To help nano-EHS (Environment, Health and Safety)researchers navigate the often complex measurement issues, the National Institute of Standards and Technology (NIST) has launched a new website devoted to NIST-developed (or co-developed) and validated laboratory protocols for nano-EHS studies.

A July 1, 2015 NIST news release on EurekAlert, which originated the news item, offers more details about the information available through the web portal,

In common lab parlance, a “protocol” is a specific step-by-step procedure used to carry out a measurement or related activity, including all the chemicals and equipment required. Any peer-reviewed journal article reporting an experimental result has a “methods” section where the authors document their measurement protocol, but those descriptions are necessarily brief and condensed, and may lack validation of any sort. By comparison, on NIST’s new Protocols for Nano-EHS website the protocols are extraordinarily detailed. For ease of citation, they’re published individually–each with its own unique digital object identifier (DOI).

The protocols detail not only what you should do, but why and what could go wrong. The specificity is important, according to program director Debra Kaiser, because of the inherent difficulty of making reliable measurements of such small materials. “Often, if you do something seemingly trivial–use a different size pipette, for example–you get a different result. Our goal is to help people get data they can reproduce, data they can trust.”

A typical caution, for example, notes that if you’re using an instrument that measures the size of nanoparticles in a solution by how they scatter light, it’s important also to measure the transmission spectrum of the particles if they’re colored, because if they happen to absorb light strongly at the same frequency as your instrument, the result may be biased.

“These measurements are difficult because of the small size involved,” explains Kaiser. “Very few new instruments have been developed for this. People are adapting existing instruments and methods for the job, but often those instruments are being operated close to their limits and the methods were developed for chemicals or bulk materials and not for nanomaterials.”

“For example, NIST offers a reference material for measuring the size of gold nanoparticles in solution, and we report six different sizes depending on the instrument you use. We do it that way because different instruments sense different aspects of a nanoparticle’s dimensions. An electron microscope is telling you something different than a dynamic light scattering instrument, and the researcher needs to understand that.”

The nano-EHS protocols offered by the NIST site, Kaiser says, could form the basis for consensus-based, formal test methods such as those published by ASTM and ISO.

NIST’s nano-EHS protocol site currently lists 12 different protocols in three categories: sample preparation, physico-chemical measurements and toxicological measurements. More protocols will be added as they are validated and documented. Suggestions for additional protocols are welcome at nanoprotocols@nist.gov.

The next item concerns European nanomedicine.

CEA-LETI and Europe’s first nanomedicine characterization laboratory

A July 1, 2015 news item on Nanotechnology Now describes the partnership which has led to launch of the new laboratory,

CEA-Leti today announced the launch of the European Nano-Characterisation Laboratory (EU-NCL) funded by the European Union’s Horizon 2020 research and innovation programm[1]e. Its main objective is to reach a level of international excellence in nanomedicine characterisation for medical indications like cancer, diabetes, inflammatory diseases or infections, and make it accessible to all organisations developing candidate nanomedicines prior to their submission to regulatory agencies to get the approval for clinical trials and, later, marketing authorization.

“As reported in the ETPN White Paper[2], there is a lack of infrastructure to support nanotechnology-based innovation in healthcare,” said Patrick Boisseau, head of business development in nanomedicine at CEA-Leti and chairman of the European Technology Platform Nanomedicine (ETPN). “Nanocharacterisation is the first bottleneck encountered by companies developing nanotherapeutics. The EU-NCL project is of most importance for the nanomedicine community, as it will contribute to the competiveness of nanomedicine products and tools and facilitate regulation in Europe.”

EU-NCL is partnered with the sole international reference facility, the Nanotechnology Characterization Lab of the National Cancer Institute in the U.S. (US-NCL)[3], to get faster international harmonization of analytical protocols.

“We are excited to be part of this cooperative arrangement between Europe and the U.S.,” said Scott E. McNeil, director of U.S. NCL. “We hope this collaboration will help standardize regulatory requirements for clinical evaluation and marketing of nanomedicines internationally. This venture holds great promise for using nanotechnologies to overcome cancer and other major diseases around the world.”

A July 2, 2015 EMPA (Swiss Federal Laboratories for Materials Science and Technology) news release on EurekAlert provides more detail about the laboratory and the partnerships,

The «European Nanomedicine Characterization Laboratory» (EU-NCL), which was launched on 1 June 2015, has a clear-cut goal: to help bring more nanomedicine candidates into the clinic and on the market, for the benefit of patients and the European pharmaceutical industry. To achieve this, EU-NCL is partnered with the sole international reference facility, the «Nanotechnology Characterization Laboratory» (US-NCL) of the US-National Cancer Institute, to get faster international harmonization of analytical protocols. EU-NCL is also closely connected to national medicine agencies and the European Medicines Agency to continuously adapt its analytical services to requests of regulators. EU-NCL is designed, organized and operated according to the highest EU regulatory and quality standards. «We are excited to be part of this cooperative project between Europe and the U.S.,» says Scott E. McNeil, director of US-NCL. «We hope this collaboration will help standardize regulatory requirements for clinical evaluation and marketing of nanomedicines internationally. This venture holds great promise for using nanotechnologies to overcome cancer and other major diseases around the world.»

Nine partners from eight countries

EU-NCL, which is funded by the EU for a four-year period with nearly 5 million Euros, brings together nine partners from eight countries: CEA-Tech in Leti and Liten, France, the coordinator of the project; the Joint Research Centre of the European Commission in Ispra, Italy; European Research Services GmbH in Münster Germany; Leidos Biomedical Research, Inc. in Frederick, USA; Trinity College in Dublin, Ireland; SINTEF in Oslo, Norway; the University of Liverpool in the UK; Empa, the Swiss Federal Laboratories for Materials Science and Technology in St. Gallen, Switzerland; Westfälische Wilhelms-Universität (WWU) and Gesellschaft für Bioanalytik, both in Münster, Germany. Together, the partnering institutions will provide a trans-disciplinary testing infrastructure covering a comprehensive set of preclinical characterization assays (physical, chemical, in vitro and in vivo biological testing), which will allow researchers to fully comprehend the biodistribution, metabolism, pharmacokinetics, safety profiles and immunological effects of their medicinal nano-products. The project will also foster the use and deployment of standard operating procedures (SOPs), benchmark materials and quality management for the preclinical characterization of medicinal nano-products. Yet another objective is to promote intersectoral and interdisciplinary communication among key drivers of innovation, especially between developers and regulatory agencies.

The goal: to bring safe and efficient nano-therapeutics faster to the patient

Within EU-NCL, six analytical facilities will offer transnational access to their existing analytical services for public and private developers, and will also develop new or improved analytical assays to keep EU-NCL at the cutting edge of nanomedicine characterization. A complementary set of networking activities will enable EU-NCL to deliver to European academic or industrial scientists the high-quality analytical services they require for accelerating the industrial development of their candidate nanomedicines. The Empa team of Peter Wick at the «Particles-Biology Interactions» lab will be in charge of the quality management of all analytical methods, a key task to guarantee the best possible reproducibility and comparability of the data between the various analytical labs within the consortium. «EU-NCL supports our research activities in developing innovative and safe nanomaterials for healthcare within an international network, which will actively shape future standards in nanomedicine and strengthen Empa as an enabler to facilitate the transfer of novel nanomedicines from bench to bedside», says Wick.

You can find more information about the laboratory on the Horizon 2020 (a European Union science funding programme) project page for the EU-NCL laboratory. For anyone curious about CEA-Leti, it’s a double-layered organization. CEA is France’s Commission on Atomic Energy and Alternative Energy (Commissariat à l’énergie atomique et aux énergies alternatives); you can go here to their French language site (there is an English language clickable option on the page). Leti is one of the CEA’s institutes and is known as either Leti or CEA-Leti. I have no idea what Leti stands for. Here’s the Leti website (this is the English language version).

Japanese researchers note the emergence of the ‘Devil’s staircase’

I wanted to know why it’s called the ‘Devil’s staircase’ and this is what I found. According to Wikipedia there are several of them,

I gather the scientists are referring to the Cantor function (mathematics), Note: Links have been removed,

In mathematics, the Cantor function is an example of a function that is continuous, but not absolutely continuous. It is also referred to as the Cantor ternary function, the Lebesgue function, Lebesgue’s singular function, the Cantor-Vitali function, the Devil’s staircase,[1] the Cantor staircase function,[2] and the Cantor-Lebesgue function.[3]

Here’s a diagram illustrating the Cantor function (from the Wikipedia entry),

CC BY-SA 3.0 File:CantorEscalier.svg Uploaded by Theon Created: January 24, 2009

CC BY-SA 3.0
Uploaded by Theon
Created: January 24, 2009

As for this latest ‘Devil’s staircase’, a June 17, 2015 news item on Nanowerk announces the research (Note: A link has been removed),

Researchers at the University of Tokyo have revealed a novel magnetic structure named the “Devil’s staircase” in cobalt oxides using soft X-rays (“Observation of a Devil’s Staircase in the Novel Spin-Valve System SrCo6O11“). This is an important result since the researchers succeeded in determining the detailed magnetic structure of a very small single crystal invisible to the human eye.

A June 17, 2015 University of Tokyo press release, which originated the news item on Nanowerk, describes why this research is now possible and the impact it could have,

Recent remarkable progress in resonant soft x-ray diffraction performed in synchrotron facilities has made it possible to determine spin ordering (magnetic structure) in small-volume samples including thin films and nanostructures, and thus is expected to lead not only to advances in materials science but also application to spintronics, a technology which is expected to form the basis of future electronic devices. Cobalt oxide is known as one material that is suitable for spintronics applications, but its magnetic structure was not fully understood.

The research group of Associate Professor Hiroki Wada at the University of Tokyo Institute for Solid State Physics, together with the researchers at Kyoto University and in Germany, performed a resonant soft X-ray diffraction study of cobalt (Co) oxides in the synchrotron facility BESSY II in Germany. They observed all the spin orderings which are theoretically possible and determined how these orderings change with the application of magnetic fields. The plateau-like behavior of magnetic structure as a function of magnetic field is called the “Devil’s staircase,” and is the first such discovery in spin systems in 3D transition metal oxides including cobalt, iron, manganese.

By further resonant soft X-ray diffraction studies, one can expect to find similar “Devil’s staircase” behavior in other materials. By increasing the spatial resolution of microscopic observation of the “Devil’s staircase” may lead to the development of novel types of spintronics materials.

Here’s an example of the ‘cobalt’ Devil’s staircase,

The magnetic structure that gives rise to the Devil's Staircase Magnetization (vertical axis) of cobalt oxide shows plateau like behaviors as a function of the externally-applied magnetic field (horizontal axis). The researchers succeeded in determining the magnetic structures which create such plateaus. Red and blue arrows indicate spin direction. © 2015 Hiroki Wadati.

The magnetic structure that gives rise to the Devil’s Staircase
Magnetization (vertical axis) of cobalt oxide shows plateau like behaviors as a function of the externally-applied magnetic field (horizontal axis). The researchers succeeded in determining the magnetic structures which create such plateaus. Red and blue arrows indicate spin direction.
© 2015 Hiroki Wadati.

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

Observation of a Devil’s Staircase in the Novel Spin-Valve System SrCo6O11 by T. Matsuda, S. Partzsch, T. Tsuyama, E. Schierle, E. Weschke, J. Geck, T. Saito, S. Ishiwata, Y. Tokura, and H. Wadati. Phys. Rev. Lett. 114, 236403 – Published 11 June 2015 (paper: Vol. 114, Iss. 23 — 12 June 2015)  DOI: 10.1103/PhysRevLett.114.236403

This paper is behind a paywall.

Discovering why your teeth aren’t perfectly crack-resistant

This helps make your teeth crack-resistant?

Caption: Illustration shows complex biostructure of dentin: the dental tubuli (yellow hollow cylinders, diameters appr. 1 micrometer) are surrounded by layers of mineralized collagen fibers (brown rods). The tiny mineral nanoparticles are embedded in the mesh of collagen fibers and not visible here. Credit: JB Forien @Charité

Caption: Illustration shows complex biostructure of dentin: the dental tubuli (yellow hollow cylinders, diameters appr. 1 micrometer) are surrounded by layers of mineralized collagen fibers (brown rods). The tiny mineral nanoparticles are embedded in the mesh of collagen fibers and not visible here. Credit: JB Forien @Charité

A June 10, 2015 Helmholtz Zentrum Berlin (HZB) press release (also on EurekAlert) explains how the illustration above relates to the research,

Human teeth have to serve for a lifetime, despite being subjected to huge forces. But the high failure resistance of dentin in teeth is not fully understood. An interdisciplinary team led by scientists of Charite Universitaetsmedizin Berlin has now analyzed the complex structure of dentin. At the synchrotron sources BESSY II at HZB, Berlin, Germany, and the European Synchrotron Radiation Facility ESRF, Grenoble, France, they could reveal that the mineral particles are precompressed.

The internal stress works against crack propagation and increases resistance of the biostructure.

Engineers use internal stresses to strengthen materials for specific technical purposes. Now it seems that evolution has long ‘known’ about this trick, and has put it to use in our natural teeth. Unlike bones, which are made partly of living cells, human teeth are not able to repair damage. Their bulk is made of dentin, a bonelike material consisting of mineral nanoparticles. These mineral nanoparticles are embedded in collagen protein fibres, with which they are tightly connected. In every tooth, such fibers can be found, and they lie in layers, making teeth tough and damage resistant. Still, it was not well understood, how crack propagation in teeth can be stopped.

The press release goes on to describe the new research and the teams which investigated the role of the mineral nanoparticles with regard to compression and cracking,

Now researchers from Charite Julius-Wolff-Institute, Berlin have been working with partners from Materials Engineering Department of Technische Universitaets Berlin, MPI of Colloids and Interfaces, Potsdam and Technion – Israel Institute of Technology, Haifa, to examine these biostructures more closely. They performed Micro-beam in-situ stress experiments in the mySpot BESSY facility of HZB, Berlin, Germany and analyzed the local orientation of the mineral nanoparticles using the nano-imaging facility of the European Synchrotron Radiation Facility (ESRF) in Grenoble, France.

When the tiny collagen fibers shrink, the attached mineral particles become increasingly compressed, the science team found out. “Our group was able to use changes in humidity to demonstrate how stress appears in the mineral in the collagen fibers, Dr. Paul Zaslansky from Julius Wolff-Institute of Charite Berlin explains. “The compressed state helps to prevents cracks from developing and we found that compression takes place in such a way that cracks cannot easily reach the tooth inner parts, which could damage the sensitive pulp. In this manner, compression stress helps to prevent cracks from rushing through the tooth.

The scientists also examined what happens if the tight mineral-protein link is destroyed by heating: In that case, dentin in teeth becomes much weaker. We therefore believe that the balance of stresses between the particles and the protein is important for the extended survival of teeth in the mouth, Charite scientist Jean-Baptiste Forien says. Their results may explain why artificial tooth replacements usually do not work as well as healthy teeth do: they are simply too passive, lacking the mechanisms found in the natural tooth structures, and consequently fillings cannot sustain the stresses in the mouth as well as teeth do. “Our results might inspire the development of tougher ceramic structures for tooth repair or replacement, Zaslansky hopes.

Experiments took place as part of the DFG project “Biomimetic Materials Research: Functionality by Hierarchical Structuring of Materials (SPP1420).

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

Compressive Residual Strains in Mineral Nanoparticles as a Possible Origin of Enhanced Crack Resistance in Human Tooth Dentin by Jean-Baptiste Forien, Claudia Fleck, Peter Cloetens, Georg Duda, Peter Fratzl, Emil Zolotoyabko, and Paul Zaslansky. Nano Lett., 2015, 15 (6), pp 3729–3734 DOI: 10.1021/acs.nanolett.5b00143 Publication Date (Web): May 26, 2015

Copyright © 2015 American Chemical Society

This paper is behind a paywall.

Observing photo exposure one nanoscale grain at a time

A June 9, 2015 news item on Nanotechnology Now highlights research into a common phenomenon, photographic exposure,

Photoinduced chemical reactions are responsible for many fundamental processes and technologies, from energy conversion in nature to micro fabrication by photo-lithography. One process that is known from everyday’s life and can be observed by the naked eye, is the exposure of photographic film. At DESY’s [Deutsches Elektronen-Synchrotron] X-ray light source PETRA III, scientists have now monitored the chemical processes during a photographic exposure at the level of individual nanoscale grains in real-time. The advanced experimental method enables the investigation of a broad variety of chemical and physical processes in materials with millisecond temporal resolution, ranging from phase transitions to crystal growth. The research team lead by Prof. Jianwei (John) Miao from the University of California in Los Angeles and Prof. Tim Salditt from the University of Göttingen report their technique and observations in the journal Nature Materials.

A June 9, 2015 DESY press release (also on EurekAlert), which originated the news item, provides more detail about the research,

The researchers investigated a photographic paper (Kodak linagraph paper Type 2167 or “yellow burn paper”) that is often used to determine the position of the beam at X-ray experiments. “The photographic paper we looked at is not specially designed for X-rays. It works by changing its colour on exposure to light or X-rays,” explains DESY physicist Dr. Michael Sprung, head of the PETRA III beamline P10 where the experiments took place.

The X-rays were not only used to expose the photographic paper, but also to analyse changes of its inner composition at the same time. The paper carries a photosensitive film of a few micrometre thickness, consisting of tiny silver bromide grains dispersed in a gelatine matrix, and with an average size of about 700 nanometres. A nanometre is a millionth of a millimetre. When X-rays impinge onto such a crystalline grain, they are diffracted in a characteristic way, forming a unique pattern on the detector that reveals properties like crystal lattice spacing, chemical composition and orientation. “We could observe individual silver bromide grains within the ‘burn’ paper since the X-ray beam had a size of only 270 by 370 nanometres – smaller than the average grain,” says Salditt, who is a partner of DESY in the construction and operation of the GINIX (Göttingen Instrument for Nano-Imaging with X-Rays) at beamline P10.

The X-ray exposure starts the photolysis from silver bromide to produce silver. An absorbed X-ray photon can create many photolytic silver atoms, which grow and agglomerate at the surface and inside the silver bromide grain. The scientists observed how the silver bromide grains were strained, began to turn in the gelatine matrix and broke up into smaller crystallites as well as the growth of pure silver nano grains. The exceptionally bright beam of PETRA III together with a high-speed detector enabled the ‘filming’ of the process with up to five milliseconds temporal resolution. “We observed, for the first time, grain rotation and lattice deformation during photoinduced chemical reactions,” emphasises Miao. “We were actually surprised how fast some of these single grains rotate,” adds Sprung. “Some spin almost one time every two seconds.”

“As advanced synchrotron light sources are currently under rapid development in the US, Europe and Asia,” the authors anticipate that “in situ X-ray nanodiffraction, which enables to measure atomic resolution diffraction patterns with several millisecond temporal resolution, can be broadly applied to investigate phase transitions, chemical reactions, crystal growth, grain boundary dynamics, lattice expansion, and contraction in materials science, nanoscience, physics, and chemistry.”

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

Grain rotation and lattice deformation during photoinduced chemical reactions revealed by in situ X-ray nanodiffraction by Zhifeng Huang, Matthias Bartels, Rui Xu, Markus Osterhoff, Sebastian Kalbfleisch, Michael Sprung, Akihiro Suzuki, Yukio Takahashi, Thomas N. Blanton, Tim Salditt, & Jianwei Miao. Nature Materials (2015) doi:10.1038/nmat4311 Published online 08 June 2015

This paper is behind a paywall.

Synthesizing spider silk

Most of the research on spider silk and spider webs that’s featured here is usually from the Massachusetts Institute of Technology (MIT) and, more specifically, from professor Markus J. Buehler. This May 28, 2015 news item on ScienceDaily, which heralds the development of synthetic spider silk, is no exception,

After years of research decoding the complex structure and production of spider silk, researchers have now succeeded in producing samples of this exceptionally strong and resilient material in the laboratory. The new development could lead to a variety of biomedical materials — from sutures to scaffolding for organ replacements — made from synthesized silk with properties specifically tuned for their intended uses.

The findings are published this week in the journal Nature Communications by MIT professor of civil and environmental engineering (CEE) Markus Buehler, postdocs Shangchao Lin and Seunghwa Ryu, and others at MIT, Tufts University, Boston University, and in Germany, Italy, and the U.K.

The research, which involved a combination of simulations and experiments, paves the way for “creating new fibers with improved characteristics” beyond those of natural silk, says Buehler, who is also the department head in CEE. The work, he says, should make it possible to design fibers with specific characteristics of strength, elasticity, and toughness.

The new synthetic fibers’ proteins — the basic building blocks of the material — were created by genetically modifying bacteria to make the proteins normally produced by spiders. These proteins were then extruded through microfluidic channels designed to mimic the effect of an organ, called a spinneret, that spiders use to produce natural silk fibers.

A May 28, 2015 MIT news release (also on EurekAlert), which originated the news item, describes the work in more detail,

While spider silk has long been recognized as among the strongest known materials, spiders cannot practically be bred to produce harvestable fibers — so this new approach to producing a synthetic, yet spider-like, silk could make such strong and flexible fibers available for biomedical applications. By their nature, spider silks are fully biocompatible and can be used in the body without risk of adverse reactions; they are ultimately simply absorbed by the body.

The researchers’ “spinning” process, in which the constituent proteins dissolved in water are extruded through a tiny opening at a controlled rate, causes the molecules to line up in a way that produces strong fibers. The molecules themselves are a mixture of hydrophobic and hydrophilic compounds, blended so as to naturally align to form fibers much stronger than their constituent parts. “When you spin it, you create very strong bonds in one direction,” Buehler says.

The team found that getting the blend of proteins right was crucial. “We found out that when there was a high proportion of hydrophobic proteins, it would not spin any fibers, it would just make an ugly mass,” says Ryu, who worked on the project as a postdoc at MIT and is now an assistant professor at the Korea Advanced Institute of Science and Technology. “We had to find the right mix” in order to produce strong fibers, he says.

The researchers made use of computational modelling to speed up the process of synthesizing proteins for synthetic spider silk, from the news release,

This project represents the first use of simulations to understand silk production at the molecular level. “Simulation is critical,” Buehler explains: Actually synthesizing a protein can take several months; if that protein doesn’t turn out to have exactly the right properties, the process would have to start all over.

Using simulations makes it possible to “scan through a large range of proteins until we see changes in the fiber stiffness,” and then home in on those compounds, says Lin, who worked on the project as a postdoc at MIT and is now an assistant professor at Florida State University.

Controlling the properties directly could ultimately make it possible to create fibers that are even stronger than natural ones, because engineers can choose characteristics for a particular use. For example, while spiders may need elasticity so their webs can capture insects without breaking, those designing fibers for use as surgical sutures would need more strength and less stretchiness. “Silk doesn’t give us that choice,” Buehler says.

The processing of the material can be done at room temperature using water-based solutions, so scaling up manufacturing should be relatively easy, team members say. So far, the fibers they have made in the lab are not as strong as natural spider silk, but now that the basic process has been established, it should be possible to fine-tune the materials and improve its strength, they say.

“Our goal is to improve the strength, elasticity, and toughness of artificially spun fibers by borrowing bright ideas from nature,” Lin says. This study could inspire the development of new synthetic fibers — or any materials requiring enhanced properties, such as in electrical and thermal transport, in a certain direction.

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

Predictive modelling-based design and experiments for synthesis and spinning of bioinspired silk fibres by Shangchao Lin, Seunghwa Ryu, Olena Tokareva, Greta Gronau, Matthew M. Jacobsen, Wenwen Huang, Daniel J. Rizzo, David Li, Cristian Staii, Nicola M. Pugno, Joyce Y. Wong, David L. Kaplan, & Markus J. Buehler. Nature Communications 6, Article number: 6892 doi:10.1038/ncomms7892 Published 28 May 2015

This paper is behind a paywall.

My two most recent (before this one) postings about Buehler’s work are an August 5, 2014 piece about structural failures and a June 4, 2014 piece about spiderwebs and music.

Finally, I recognized one of the authors, Nicola Pugno from Italy. He’s been mentioned here more than once in regard to his biomimicry work which has often been focused on geckos and their adhesive qualities as per this April 3, 2014 post announcing his book ‘An Experimental Study on Adhesive or Anti-Adhesive, Bio-Inspired Experimental Nanomaterials‘ (co-authored with Emiliano Lepore).

McGill University researchers put the squeeze Tomonaga-Luttinger theory in quantum mechanics

McGill University (Montréal, Québec, Canada) researchers testing the Tomonaga-Luttinger theory had international help according to a May 15, 2015 news item on ScienceDaily,

We all know intuitively that normal liquids flow more quickly as the channel containing them tightens. Think of a river flowing through narrow rapids.

But what if a pipe were so amazingly tiny that only a few atoms of superfluid helium could squeeze through its opening at once? According to a longstanding quantum-mechanics model, the superfluid helium would behave differently from a normal liquid: far from speeding up, it would actually slow down.

For more than 70 years, scientists have been studying the flow of helium through ever smaller pipes. But only recently has nanotechnology made it possible to reach the scale required to test the theoretical model, known as the Tomonaga-Luttinger theory (after the scientists who developed it).

Now, a team of McGill University researchers, with collaborators at the University of Vermont and at Leipzig University in Germany, has succeeded in conducting experiments with the smallest channel yet – less than 30 atoms wide. In results published online today in Science Advances, the researchers report that the flow of superfluid helium through this miniature faucet does, indeed, appear to slow down.

A May 15, 2015 University of McGill news release (also on EurekAlert), which originated the news item, expands on the theme and notes this is one step on the road to proving the theory,

“Our results suggest that a quantum faucet does show a fundamentally different behaviour,” says McGill physics professor Guillaume Gervais, who led the project. “We don’t have the smoking gun yet. But we think this a great step toward proving experimentally the Tomonaga-Luttinger theory in a real liquid.”

The zone where physics changes

Insights from the research could someday contribute to novel technologies, such as nano-sensors with applications in GPS systems. But for now, Gervais says, the results are significant simply because “we’re pushing the limit of understanding things on the nanoscale. We’re approaching the grey zone where all physics changes.”

Prof. Adrian Del Maestro from the University of Vermont has been employing high-performance computer simulations to understand just how small the faucet has to be before this new physics emerges. “The ability to study a quantum liquid at such diminutive length scales in the laboratory is extremely exciting as it allows us to extend our fundamental understanding of how atoms cooperate to form the superfluid state of matter,” he says. “The superfluid slowdown we observe signals that this cooperation is starting to break down as the width of the pipe narrows to the nanoscale” and edges closer to the exotic one-dimensional limit envisioned in the Tomonaga-Luttinger theory.

Building what is probably the world’s smallest faucet has been no simple task. Gervais hatched the idea during a five-minute conversation over coffee with a world-leading theoretical physicist. That was eight years ago. But getting the nano-plumbing to work took “at least 100 trials – maybe 200,” says Gervais, who is a fellow of the Canadian Institute for Advanced Research.

A beam of electrons as drill bit

Using a beam of electrons as a kind of drill bit, the team made holes as small as seven nanometers wide in a piece of silicon nitride, a tough material used in applications such as automotive diesel engines and high-performance ball bearings. By cooling the apparatus to very low temperatures, placing superfluid helium on one side of the pore and applying a vacuum to the other, the researchers were able to observe the flow of the superfluid through the channel. Varying the size of the channel, they found that the maximum speed of the flow slowed as the radius of the pore decreased.

The experiments take advantage of a unique characteristic of superfluids. Unlike ordinary liquids – water or maple syrup, for example – superfluids can flow without any viscosity. As a result, they can course through extremely narrow channels; and once in motion, they don’t need any pressure to keep going. Helium is the only element in nature known to become a superfluid; it does so when cooled to an extremely low temperature.

An inadvertent breakthrough

For years, however, the researchers were frustrated by a technical glitch: the tiny pore in the silicon nitride material kept getting clogged by contaminants. Then one day, while Gervais was away at a conference abroad, a new student in his lab inadvertently deviated from the team’s operating procedure and left a valve open in the apparatus. “It turned out that this open valve kept the hole open,” Gervais says. “It was the key to getting the experiment to work. Scientific breakthroughs don’t always happen by design!”

Prof. Bernd Rosenow, a quantum physicist at Leipzig University’s Institute for Theoretical Physics, also contributed to the study.

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

Critical flow and dissipation in a quasi–one-dimensional superfluid by Pierre-François Duc, Michel Savard, Matei Petrescu, Bernd Rosenow, Adrian Del Maestro, Guillaume Gervais. Science Advances 15 May 2015: Vol. 1 no. 4 e1400222 DOI: 10.1126/sciadv.1400222

This is an open access paper.

I sing the body cyber: two projects funded by the US National Science Foundation

Points to anyone who recognized the reference to Walt Whitman’s poem, “I sing the body electric,” from his classic collection, Leaves of Grass (1867 edition; h/t Wikipedia entry). I wonder if the cyber physical systems (CPS) work being funded by the US National Science Foundation (NSF) in the US will occasion poetry too.

More practically, a May 15, 2015 news item on Nanowerk, describes two cyber physical systems (CPS) research projects newly funded by the NSF,

Today [May 12, 2015] the National Science Foundation (NSF) announced two, five-year, center-scale awards totaling $8.75 million to advance the state-of-the-art in medical and cyber-physical systems (CPS).

One project will develop “Cyberheart”–a platform for virtual, patient-specific human heart models and associated device therapies that can be used to improve and accelerate medical-device development and testing. The other project will combine teams of microrobots with synthetic cells to perform functions that may one day lead to tissue and organ re-generation.

CPS are engineered systems that are built from, and depend upon, the seamless integration of computation and physical components. Often called the “Internet of Things,” CPS enable capabilities that go beyond the embedded systems of today.

“NSF has been a leader in supporting research in cyber-physical systems, which has provided a foundation for putting the ‘smart’ in health, transportation, energy and infrastructure systems,” said Jim Kurose, head of Computer & Information Science & Engineering at NSF. “We look forward to the results of these two new awards, which paint a new and compelling vision for what’s possible for smart health.”

Cyber-physical systems have the potential to benefit many sectors of our society, including healthcare. While advances in sensors and wearable devices have the capacity to improve aspects of medical care, from disease prevention to emergency response, and synthetic biology and robotics hold the promise of regenerating and maintaining the body in radical new ways, little is known about how advances in CPS can integrate these technologies to improve health outcomes.

These new NSF-funded projects will investigate two very different ways that CPS can be used in the biological and medical realms.

A May 12, 2015 NSF news release (also on EurekAlert), which originated the news item, describes the two CPS projects,

Bio-CPS for engineering living cells

A team of leading computer scientists, roboticists and biologists from Boston University, the University of Pennsylvania and MIT have come together to develop a system that combines the capabilities of nano-scale robots with specially designed synthetic organisms. Together, they believe this hybrid “bio-CPS” will be capable of performing heretofore impossible functions, from microscopic assembly to cell sensing within the body.

“We bring together synthetic biology and micron-scale robotics to engineer the emergence of desired behaviors in populations of bacterial and mammalian cells,” said Calin Belta, a professor of mechanical engineering, systems engineering and bioinformatics at Boston University and principal investigator on the project. “This project will impact several application areas ranging from tissue engineering to drug development.”

The project builds on previous research by each team member in diverse disciplines and early proof-of-concept designs of bio-CPS. According to the team, the research is also driven by recent advances in the emerging field of synthetic biology, in particular the ability to rapidly incorporate new capabilities into simple cells. Researchers so far have not been able to control and coordinate the behavior of synthetic cells in isolation, but the introduction of microrobots that can be externally controlled may be transformative.

In this new project, the team will focus on bio-CPS with the ability to sense, transport and work together. As a demonstration of their idea, they will develop teams of synthetic cell/microrobot hybrids capable of constructing a complex, fabric-like surface.

Vijay Kumar (University of Pennsylvania), Ron Weiss (MIT), and Douglas Densmore (BU) are co-investigators of the project.

Medical-CPS and the ‘Cyberheart’

CPS such as wearable sensors and implantable devices are already being used to assess health, improve quality of life, provide cost-effective care and potentially speed up disease diagnosis and prevention. [emphasis mine]

Extending these efforts, researchers from seven leading universities and centers are working together to develop far more realistic cardiac and device models than currently exist. This so-called “Cyberheart” platform can be used to test and validate medical devices faster and at a far lower cost than existing methods. CyberHeart also can be used to design safe, patient-specific device therapies, thereby lowering the risk to the patient.

“Innovative ‘virtual’ design methodologies for implantable cardiac medical devices will speed device development and yield safer, more effective devices and device-based therapies, than is currently possible,” said Scott Smolka, a professor of computer science at Stony Brook University and one of the principal investigators on the award.

The group’s approach combines patient-specific computational models of heart dynamics with advanced mathematical techniques for analyzing how these models interact with medical devices. The analytical techniques can be used to detect potential flaws in device behavior early on during the device-design phase, before animal and human trials begin. They also can be used in a clinical setting to optimize device settings on a patient-by-patient basis before devices are implanted.

“We believe that our coordinated, multi-disciplinary approach, which balances theoretical, experimental and practical concerns, will yield transformational results in medical-device design and foundations of cyber-physical system verification,” Smolka said.

The team will develop virtual device models which can be coupled together with virtual heart models to realize a full virtual development platform that can be subjected to computational analysis and simulation techniques. Moreover, they are working with experimentalists who will study the behavior of virtual and actual devices on animals’ hearts.

Co-investigators on the project include Edmund Clarke (Carnegie Mellon University), Elizabeth Cherry (Rochester Institute of Technology), W. Rance Cleaveland (University of Maryland), Flavio Fenton (Georgia Tech), Rahul Mangharam (University of Pennsylvania), Arnab Ray (Fraunhofer Center for Experimental Software Engineering [Germany]) and James Glimm and Radu Grosu (Stony Brook University). Richard A. Gray of the U.S. Food and Drug Administration is another key contributor.

It is fascinating to observe how terminology is shifting from pacemakers and deep brain stimulators as implants to “CPS such as wearable sensors and implantable devices … .” A new category has been created, CPS, which conjoins medical devices with other sensing devices such as wearable fitness monitors found in the consumer market. I imagine it’s an attempt to quell fears about injecting strange things into or adding strange things to your body—microrobots and nanorobots partially derived from synthetic biology research which are “… capable of performing heretofore impossible functions, from microscopic assembly to cell sensing within the body.” They’ve also sneaked in a reference to synthetic biology, an area of research where some concerns have been expressed, from my March 19, 2013 post about a poll and synthetic biology concerns,

In our latest survey, conducted in January 2013, three-fourths of respondents say they have heard little or nothing about synthetic biology, a level consistent with that measured in 2010. While initial impressions about the science are largely undefined, these feelings do not necessarily become more positive as respondents learn more. The public has mixed reactions to specific synthetic biology applications, and almost one-third of respondents favor a ban “on synthetic biology research until we better understand its implications and risks,” while 61 percent think the science should move forward.

I imagine that for scientists, 61% in favour of more research is not particularly comforting given how easily and quickly public opinion can shift.

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.

Wound healing is nature’s way of zipping up your skin

Scientists have been able to observe the healing process at the molecular scale—in fruit flies. From an April 21, 2015 news item on ScienceDaily,

Scientists from the Goethe University (GU) Frankfurt, the European Molecular Biology Laboratory (EMBL) Heidelberg and the University of Zurich explain skin fusion at a molecular level and pinpoint the specific molecules that do the job in their latest publication in the journal Nature Cell Biology.

An April 21, 2015 Goethe University Frankfurt press release on EurekAlert, which originated the news item, describes similarities between humans and fruit flies allowing scientists to infer the wound healing process for human skin,

In order to prevent death by bleeding or infection, every wound (skin opening) must close at some point. The events leading to skin closure had been unclear for many years. Mikhail Eltsov (GU) and colleagues used fruit fly embryos as a model system to understand this process. Similarly to humans, fruit fly embryos at some point in their development have a large opening in the skin on their back that must fuse. This process is called zipping, because two sides of the skin are fastened in a way that resembles a zipper that joins two sides of a jacket.

The scientists have used a top-of-the-range electron microscope to study exactly how this zipping of the skin works. “Our electron microscope allows us to distinguish the molecular components in the cell that act like small machines to fuse the skin. When we look at it from a distance, it appears as if skin cells simply fuse to each other, but if we zoom in, it becomes clear that membranes, molecular machines, and other cellular components are involved”, explains Eltsov.

“In order to visualize this orchestra of healing, a very high-resolution picture of the process is needed. For this purpose we have recorded an enormous amount of data that surpasses all previous studies of this kind”, says Mikhail Eltsov.

As a first step, as the scientists discovered, cells find their opposing partner by “sniffing” each other out. As a next step, they develop adherens junctions which act like a molecular Velcro. This way they become strongly attached to their opposing partner cell. The biggest revelation of this study was that small tubes in the cell, called microtubules, attach to this molecular Velcro and then deploy a self-catastrophe, which results in the skin being pulled towards the opening, as if one pulls a blanket over.

Damian Brunner who led the team at the University of Zurich has performed many genetic manipulations to identify the correct components. The scientists were astonished to find that microtubules involved in cell-division are the primary scaffold used for zipping, indicating a mechanism conserved during evolution.

“What was also amazing was the tremendous plasticity of the membranes in this process which managed to close the skin opening in a very short space of time. When five to ten cells have found their respective neighbors, the skin already appears normal”, says Achilleas Frangakis from the Goethe University Frankfurt, who led the study.

The scientists hope that their results will open new avenues into the understanding of epithelial plasticity and wound healing. They are also investigating the detailed structural organization of the adherens junctions, work for which they were awarded a starting grant from European Research Council (ERC).

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

Quantitative analysis of cytoskeletal reorganization during epithelial tissue sealing by large-volume electron tomography by Mikhail Eltsov, Nadia Dubé, Zhou Yu, Laurynas Pasakarnis, Uta Haselmann-Weiss, Damian Brunner, & Achilleas S. Frangakis. Nature Cell Biology (2015) doi:10.1038/ncb3159 Published online 20 April 2015

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

The researchers have provided an image illustrating ‘wound zipping’.

Caption: This is a perspective view of the zipping area with 17 skin cells. Credit: GU

Caption: This is a perspective view of the zipping area with 17 skin cells.
Credit: GU

Stress makes quantum dots ‘breathe’

A March 19, 2015 news item on ScienceDaily describes some new research on quantum dots,

Researchers at the Department of Energy’s SLAC National Accelerator Laboratory watched nanoscale semiconductor crystals expand and shrink in response to powerful pulses of laser light. This ultrafast “breathing” provides new insight about how such tiny structures change shape as they start to melt — information that can help guide researchers in tailoring their use for a range of applications.

In the experiment using SLAC’s Linac Coherent Light Source (LCLS) X-ray laser, a DOE Office of Science User Facility, researchers first exposed the nanocrystals to a burst of laser light, followed closely by an ultrabright X-ray pulse that recorded the resulting structural changes in atomic-scale detail at the onset of melting.

“This is the first time we could measure the details of how these ultrasmall materials react when strained to their limits,” said Aaron Lindenberg, an assistant professor at SLAC and Stanford who led the experiment. The results were published March 12 [2015] in Nature Communications.

A March 18, 2015 SLAC news release, which originated the news item, provides a general description of quantum dots,

The crystals studied at SLAC are known as “quantum dots” because they display unique traits at the nanoscale that defy the classical physics governing their properties at larger scales. The crystals can be tuned by changing their size and shape to emit specific colors of light, for example.

So scientists have worked to incorporate them in solar panels to make them more efficient and in computer displays to improve resolution while consuming less battery power. These materials have also been studied for potential use in batteries and fuel cells and for targeted drug delivery.

Scientists have also discovered that these and other nanomaterials, which may contain just tens or hundreds of atoms, can be far more damage-resistant than larger bits of the same materials because they exhibit a more perfect crystal structure at the tiniest scales. This property could prove useful in battery components, for example, as smaller particles may be able to withstand more charging cycles than larger ones before degrading.

The news release then goes on to describe the latest research showing the dots ‘breathe’ (Note: A link has been removed),

In the LCLS experiment, researchers studied spheres and nanowires made of cadmium sulfide and cadmium selenide that were just 3 to 5 nanometers, or billionths of a meter, across. The nanowires were up to 25 nanometers long. By comparison, amino acids – the building blocks of proteins – are about 1 nanometer in length, and individual atoms are measured in tenths of nanometers.

By examining the nanocrystals from many different angles with X-ray pulses, researchers reconstructed how they change shape when hit with an optical laser pulse. They were surprised to see the spheres and nanowires expand in width by about 1 percent and then quickly contract within femtoseconds, or quadrillionths of a second. They also found that the nanowires don’t expand in length, and showed that the way the crystals respond to strain was coupled to how their structure melts.

In an earlier, separate study, another team of researchers had used LCLS to explore the response of larger gold particles on longer timescales.

“In the future, we want to extend these experiments to more complex and technologically relevant nanostructures, and also to enable X-ray exploration of nanoscale devices while they are operating,” Lindenberg said. “Knowing how materials change under strain can be used together with simulations to design new materials with novel properties.”

Participating researchers were from SLAC, Stanford and two of their joint institutes, the Stanford Institute for Materials and Energy Sciences (SIMES) and Stanford PULSE Institute; University of California, Berkeley; University of Duisburg-Essen in Germany; and Argonne National Laboratory. The work was supported by the DOE Office of Science and the German Research Council.

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

Visualization of nanocrystal breathing modes at extreme strains by Erzsi Szilagyi, Joshua S. Wittenberg, Timothy A. Miller, Katie Lutker, Florian Quirin, Henrik Lemke, Diling Zhu, Matthieu Chollet, Joseph Robinson, Haidan Wen, Klaus Sokolowski-Tinten, & Aaron M. Lindenberg. Nature Communications 6, Article number: 6577 doi:10.1038/ncomms7577 Published 12 March 2015

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