Tag Archives: University of Zurich

Gilding medieaval statues with nanoscale gold sheets

The altar examined is thought to have been made around 1420 in Southern Germany and for a long time stood in a mountain chapel on Alp Leiggern in the Swiss canton of Valais. Today it is on display at the Swiss National Museum (Landesmuseum Zürich). (Photo: Swiss National Museum, Landesmuseum Zürich) [ddownloaded from https://www.psi.ch/en/media/our-research/nanomaterial-from-the-middle-ages]

As amazing as the altar appears, it was hiding some even more amazing secrets. From an October 10, 2022 Paul Scherrer Institute (PSI) press release (also on EurekAlert but published October 11, 2022) by Barbara Vonarburg,

To gild sculptures in the late Middle Ages, artists often applied ultra-thin gold foil supported by a silver base layer. For the first time, scientists at the Paul Scherrer Institute [PSI] have managed to produce nanoscale 3D images of this material, known as Zwischgold. The pictures show this was a highly sophisticated mediaeval production technique and demonstrate why restoring such precious gilded artefacts is so difficult.

The samples examined at the Swiss Light Source SLS using one of the most advanced microscopy methods were unusual even for the highly experienced PSI team: minute samples of materials taken from an altar and wooden statues originating from the fifteenth century. The altar is thought to have been made around 1420 in Southern Germany and stood for a long time in a mountain chapel on Alp Leiggern in the Swiss canton of Valais. Today it is on display at the Swiss National Museum (Landesmuseum Zürich). In the middle you can see Mary cradling Baby Jesus. The material sample was taken from a fold in the Virgin Mary’s robe. The tiny samples from the other two mediaeval structures were supplied by Basel Historical Museum.

The material was used to gild the sacred figures. It is not actually gold leaf, but a special double-sided foil of gold and silver where the gold can be ultra-thin because it is supported by the silver base. This material, known as Zwischgold (part-gold) was significantly cheaper than using pure gold leaf. “Although Zwischgold was frequently used in the Middle Ages, very little was known about this material up to now,” says PSI physicist Benjamin Watts: “So we wanted to investigate the samples using 3D technology which can visualise extremely fine details.” Although other microscopy techniques had been used previously to examine Zwischgold, they only provided a 2D cross-section through the material. In other words, it was only possible to view the surface of the cut segment, rather than looking inside the material.  The scientists were also worried that cutting through it may have changed the structure of the sample. The advanced microscopy imaging method used today, ptychographic tomography, provides a 3D image of Zwischgold’s exact composition for the first time.

X-rays generate a diffraction pattern

The PSI scientists conducted their research using X-rays produced by the Swiss Light Source SLS. These produce tomographs displaying details in the nanoscale range – millionths of a millimetre, in other words. “Ptychography is a fairly sophisticated method, as there is no objective lens that forms an image directly on the detector,” Watts explains. Ptychography actually produces a diffraction pattern of the illuminated area, in other words an image with points of differing intensity. By manipulating the sample in a precisely defined manner, it is possible to generate hundreds of overlapping diffraction patterns. “We can then combine these diffraction patterns like a sort of giant Sudoku puzzle and work out what the original image looked like,” says the physicist. A set of ptychographic images taken from different directions can be combined to create a 3D tomogram.

The advantage of this method is its extremely high resolution. “We knew the thickness of the Zwischgold sample taken from Mary was of the order of hundreds of nanometres,” Watts explains. “So we had to be able to reveal even tinier details.” The scientists achieved this using ptychographic tomography, as they report in their latest article in the journal Nanoscale. “The 3D images clearly show how thinly and evenly the gold layer is over the silver base layer,” says Qing Wu, lead author of the publication. The art historian and conservation scientist completed her PhD at the University of Zurich, in collaboration with PSI and the Swiss National Museum. “Many people had assumed that technology in the Middle Ages was not particularly advanced,” Wu comments. “On the contrary: this was not the Dark Ages, but a period when metallurgy and gilding techniques were incredibly well developed.”

Secret recipe revealed

Unfortunately there are no records of how Zwischgold was produced at the time. “We reckon the artisans kept their recipe secret,” says Wu. Based on nanoscale images and documents from later epochs, however, the art historian now knows the method used in the 15th century: first the gold and the silver were hammered separately to produce thin foils, whereby the gold film had to be much thinner than the silver. Then the two metal foils were worked on together. Wu describes the process: “This required special beating tools and pouches with various inserts made of different materials into which the foils were inserted,” Wu explains. This was a fairly complicated procedure that required highly skilled specialists.

“Our investigations of Zwischgold samples showed the average thickness of the gold layer to be around 30 nanometres, while gold leaf produced in the same period and region was approximately 140 nanometres thick,” Wu explains. “This method saved on gold, which was much more expensive”. At the same time, there was also a very strict hierarchy of materials: gold leaf was used to make the halo of one figure, for example, while Zwischgold was used for the robe. Because this material has less of a sheen, the artists often used it to colour the hair or beards of their statues. “It is incredible how someone with only hand tools was able to craft such nanoscale material,” Watts says. Mediaeval artisans also benefited from a unique property of gold and silver crystals when pressed together: their morphology is preserved across the entire metal film. “A lucky coincidence of nature that ensures this technique works,” says the physicist.

Golden surface turns black

The 3D images do bring to light one drawback of using Zwischgold, however: the silver can push through the gold layer and cover it. The silver moves surprisingly quickly – even at room temperature. Within days, a thin silver coating covers the gold completely. At the surface the silver comes into contact with water and sulphur in the air, and corrodes. “This makes the gold surface of the Zwischgold turn black over time,” Watts explains. “The only thing you can do about this is to seal the surface with a varnish so the sulphur does not attack the silver and form silver sulphide.” The artisans using Zwischgold were aware of this problem from the start. They used resin, glue or other organic substances as a varnish. “But over hundreds of years this protective layer has decomposed, allowing corrosion to continue,” Wu explains.

The corrosion also encourages more and more silver to migrate to the surface, creating a gap below the Zwischgold. “We were surprised how clearly this gap under the metal layer could be seen,” says Watts. Especially in the sample taken from Mary’s robe, the Zwischgold had clearly come away from the base layer. “This gap can cause mechanical instability, and we expect that in some cases it is only the protective coating over the Zwischgold that is holding the metal foil in place,” Wu warns. This is a massive problem for the restoration of historical artefacts, as the silver sulphide has become embedded in the varnish layer or even further down. “If we remove the unsightly products of corrosion, the varnish layer will also fall away and we will lose everything,” says Wu. She hopes it will be possible in future to develop a special material that can be used to fill the gap and keep the Zwischgold attached. “Using ptychographic tomography, we could check how well such a consolidation material would perform its task,” says the art historian.

About PSI

The Paul Scherrer Institute PSI develops, builds and operates large, complex research facilities and makes them available to the national and international research community. The institute’s own key research priorities are in the fields of matter and materials, energy and environment and human health. PSI is committed to the training of future generations. Therefore about one quarter of our staff are post-docs, post-graduates or apprentices. Altogether PSI employs 2100 people, thus being the largest research institute in Switzerland. The annual budget amounts to approximately CHF 400 million. PSI is part of the ETH Domain, with the other members being the two Swiss Federal Institutes of Technology, ETH Zurich and EPFL Lausanne, as well as Eawag (Swiss Federal Institute of Aquatic Science and Technology), Empa (Swiss Federal Laboratories for Materials Science and Technology) and WSL (Swiss Federal Institute for Forest, Snow and Landscape Research). Insight into the exciting research of the PSI with changing focal points is provided 3 times a year in the publication 5232 – The Magazine of the Paul Scherrer Institute.

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

A modern look at a medieval bilayer metal leaf: nanotomography of Zwischgold by
Qing Wu, Karolina Soppa, Elisabeth Müller, Julian Müller, Michal Odstrcil, Esther Hsiao Rho Tsai, Andreas Späth, Mirko Holler, Manuel Guizar-Sicairos, Benjamin Butz, Rainer H. Fink, and Benjamin Watts. Nanoscale DOI: https://doi.org/10.1039/D2NR03367D First published: 10 Oct 2022

This paper is open access.

Swiss researchers, memristors, perovskite crystals, and neuromorphic (brainlike) computing

A May 18, 2022 news item on Nanowerk highlights research into making memristors more ‘flexible’, (Note: There’s an almost identical May 18, 2022 news item on ScienceDaily but the issuing agency is listed as ETH Zurich rather than Empa as listed on Nanowerk),

Compared with computers, the human brain is incredibly energy-efficient. Scientists are therefore drawing on how the brain and its interconnected neurons function for inspiration in designing innovative computing technologies. They foresee that these brain-inspired computing systems, will be more energy-efficient than conventional ones, as well as better at performing machine-learning tasks.

Much like neurons, which are responsible for both data storage and data processing in the brain, scientists want to combine storage and processing in a single type of electronic component, known as a memristor. Their hope is that this will help to achieve greater efficiency because moving data between the processor and the storage, as conventional computers do, is the main reason for the high energy consumption in machine-learning applications.

Researchers at ETH Zurich, Empa and the University of Zurich have now developed an innovative concept for a memristor that can be used in a far wider range of applications than existing memristors.

“There are different operation modes for memristors, and it is advantageous to be able to use all these modes depending on an artificial neural network’s architecture,” explains ETH Zurich postdoc Rohit John. “But previous conventional memristors had to be configured for one of these modes in advance.”

The new memristors can now easily switch between two operation modes while in use: a mode in which the signal grows weaker over time and dies (volatile mode), and one in which the signal remains constant (non-volatile mode).

Once you get past the first two paragraphs in the Nanowerk news item, you find the ETH Zurich and Empa May 18, 2022 press releases by Fabio Begamin, in both cases, are identical (ETH is listed as the authoring agency on EurekAlert), (Note: A link has been removed in the following),

Just like in the brain

“These two operation modes are also found in the human brain,” John says. On the one hand, stimuli at the synapses are transmitted from neuron to neuron with biochemical neurotransmitters. These stimuli start out strong and then gradually become weaker. On the other hand, new synaptic connections to other neurons form in the brain while we learn. These connections are longer-​lasting.

John, who is a postdoc in the group headed by ETH Professor Maksym Kovalenko, was awarded an ETH fellowship for outstanding postdoctoral researchers in 2020. John conducted this research together with Yiğit Demirağ, a doctoral student in Professor Giacomo Indiveri’s group at the Institute for Neuroinformatics of the University of Zurich and ETH Zurich.

Semiconductor known from solar cells

The memristors the researchers have developed are made of halide perovskite nanocrystals, a semiconductor material known primarily from its use in photovoltaic cells. “The ‘nerve conduction’ in these new memristors is mediated by temporarily or permanently stringing together silver ions from an electrode to form a nanofilament penetrating the perovskite structure through which current can flow,” explains Kovalenko.

This process can be regulated to make the silver-​ion filament either thin, so that it gradually breaks back down into individual silver ions (volatile mode), or thick and permanent (non-​volatile mode). This is controlled by the intensity of the current conducted on the memristor: applying a weak current activates the volatile mode, while a strong current activates the non-​volatile mode.

New toolkit for neuroinformaticians

“To our knowledge, this is the first memristor that can be reliably switched between volatile and non-​volatile modes on demand,” Demirağ says. This means that in the future, computer chips can be manufactured with memristors that enable both modes. This is a significance advance because it is usually not possible to combine several different types of memristors on one chip.

Within the scope of the study, which they published in the journal Nature Communications, the researchers tested 25 of these new memristors and carried out 20,000 measurements with them. In this way, they were able to simulate a computational problem on a complex network. The problem involved classifying a number of different neuron spikes as one of four predefined patterns.

Before these memristors can be used in computer technology, they will need to undergo further optimisation.  However, such components are also important for research in neuroinformatics, as Indiveri points out: “These components come closer to real neurons than previous ones. As a result, they help researchers to better test hypotheses in neuroinformatics and hopefully gain a better understanding of the computing principles of real neuronal circuits in humans and animals.”

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

Reconfigurable halide perovskite nanocrystal memristors for neuromorphic computing by Rohit Abraham John, Yiğit Demirağ, Yevhen Shynkarenko, Yuliia Berezovska, Natacha Ohannessian, Melika Payvand, Peng Zeng, Maryna I. Bodnarchuk, Frank Krumeich, Gökhan Kara, Ivan Shorubalko, Manu V. Nair, Graham A. Cooke, Thomas Lippert, Giacomo Indiveri & Maksym V. Kovalenko. Nature Communications volume 13, Article number: 2074 (2022) DOI: https://doi.org/10.1038/s41467-022-29727-1 Published: 19 April 2022

This paper is open access.

Connecting biological and artificial neurons (in UK, Switzerland, & Italy) over the web

Caption: The virtual lab connecting Southampton, Zurich and Padova. Credit: University of Southampton

A February 26, 2020 University of Southampton press release (also on EurekAlert) describes this work,

Research on novel nanoelectronics devices led by the University of Southampton enabled brain neurons and artificial neurons to communicate with each other. This study has for the first time shown how three key emerging technologies can work together: brain-computer interfaces, artificial neural networks and advanced memory technologies (also known as memristors). The discovery opens the door to further significant developments in neural and artificial intelligence research.

Brain functions are made possible by circuits of spiking neurons, connected together by microscopic, but highly complex links called ‘synapses’. In this new study, published in the scientific journal Nature Scientific Reports, the scientists created a hybrid neural network where biological and artificial neurons in different parts of the world were able to communicate with each other over the internet through a hub of artificial synapses made using cutting-edge nanotechnology. This is the first time the three components have come together in a unified network.

During the study, researchers based at the University of Padova in Italy cultivated rat neurons in their laboratory, whilst partners from the University of Zurich and ETH Zurich created artificial neurons on Silicon microchips. The virtual laboratory was brought together via an elaborate setup controlling nanoelectronic synapses developed at the University of Southampton. These synaptic devices are known as memristors.

The Southampton based researchers captured spiking events being sent over the internet from the biological neurons in Italy and then distributed them to the memristive synapses. Responses were then sent onward to the artificial neurons in Zurich also in the form of spiking activity. The process simultaneously works in reverse too; from Zurich to Padova. Thus, artificial and biological neurons were able to communicate bidirectionally and in real time.

Themis Prodromakis, Professor of Nanotechnology and Director of the Centre for Electronics Frontiers at the University of Southampton said “One of the biggest challenges in conducting research of this kind and at this level has been integrating such distinct cutting edge technologies and specialist expertise that are not typically found under one roof. By creating a virtual lab we have been able to achieve this.”

The researchers now anticipate that their approach will ignite interest from a range of scientific disciplines and accelerate the pace of innovation and scientific advancement in the field of neural interfaces research. In particular, the ability to seamlessly connect disparate technologies across the globe is a step towards the democratisation of these technologies, removing a significant barrier to collaboration.

Professor Prodromakis added “We are very excited with this new development. On one side it sets the basis for a novel scenario that was never encountered during natural evolution, where biological and artificial neurons are linked together and communicate across global networks; laying the foundations for the Internet of Neuro-electronics. On the other hand, it brings new prospects to neuroprosthetic technologies, paving the way towards research into replacing dysfunctional parts of the brain with AI [artificial intelligence] chips.”

I’m fascinated by this work and after taking a look at the paper, I have to say, the paper is surprisingly accessible. In other words, I think I get the general picture. For example (from the Introduction to the paper; citation and link follow further down),

… To emulate plasticity, the memristor MR1 is operated as a two-terminal device through a control system that receives pre- and post-synaptic depolarisations from one silicon neuron (ANpre) and one biological neuron (BN), respectively. …

If I understand this properly, they’ve integrated a biological neuron and an artificial neuron in a single system across three countries.

For those who care to venture forth, here’s a link and a citation for the paper,

Memristive synapses connect brain and silicon spiking neurons by Alexantrou Serb, Andrea Corna, Richard George, Ali Khiat, Federico Rocchi, Marco Reato, Marta Maschietto, Christian Mayr, Giacomo Indiveri, Stefano Vassanelli & Themistoklis Prodromakis. Scientific Reports volume 10, Article number: 2590 (2020) DOI: https://doi.org/10.1038/s41598-020-58831-9 Published 25 February 2020

The paper is open access.

Hallucinogenic molecules and the brain

Psychedelic drugs seems to be enjoying a ‘moment’. After decades of being vilified and  declared illegal (in many jurisdictions), psychedelic (or hallucinogenic) drugs are once again being tested for use in therapy. A Sept. 1, 2017 article by Diana Kwon for The Scientist describes some of the latest research (I’ve excerpted the section on molecules; Note: Links have been removed),

Mind-bending molecules

© SEAN MCCABE

All the classic psychedelic drugs—psilocybin, LSD, and N,N-dimethyltryptamine (DMT), the active component in ayahuasca—activate serotonin 2A (5-HT2A) receptors, which are distributed throughout the brain. In all likelihood, this receptor plays a key role in the drugs’ effects. Krähenmann [Rainer Krähenmann, a psychiatrist and researcher at the University of Zurich]] and his colleagues in Zurich have discovered that ketanserin, a 5-HT2A receptor antagonist, blocks LSD’s hallucinogenic properties and prevents individuals from entering a dreamlike state or attributing personal relevance to the experience.12,13

Other research groups have found that, in rodent brains, 2,5-dimethoxy-4-iodoamphetamine (DOI), a highly potent and selective 5-HT2A receptor agonist, can modify the expression of brain-derived neurotrophic factor (BDNF)—a protein that, among other things, regulates neuronal survival, differentiation, and synaptic plasticity. This has led some scientists to hypothesize that, through this pathway, psychedelics may enhance neuroplasticity, the ability to form new neuronal connections in the brain.14 “We’re still working on that and trying to figure out what is so special about the receptor and where it is involved,” says Katrin Preller, a postdoc studying psychedelics at the University of Zurich. “But it seems like this combination of serotonin 2A receptors and BDNF leads to a kind of different organizational state in the brain that leads to what people experience under the influence of psychedelics.”

This serotonin receptor isn’t limited to the central nervous system. Work by Charles Nichols, a pharmacology professor at Louisiana State University, has revealed that 5-HT2A receptor agonists can reduce inflammation throughout the body. Nichols and his former postdoc Bangning Yu stumbled upon this discovery by accident, while testing the effects of DOI on smooth muscle cells from rat aortas. When they added this drug to the rodent cells in culture, it blocked the effects of tumor necrosis factor-alpha (TNF-α), a key inflammatory cytokine.

“It was completely unexpected,” Nichols recalls. The effects were so bewildering, he says, that they repeated the experiment twice to convince themselves that the results were correct. Before publishing the findings in 2008,15 they tested a few other 5-HT2A receptor agonists, including LSD, and found consistent anti-inflammatory effects, though none of the drugs’ effects were as strong as DOI’s. “Most of the psychedelics I have tested are about as potent as a corticosteroid at their target, but there’s something very unique about DOI that makes it much more potent,” Nichols says. “That’s one of the mysteries I’m trying to solve.”

After seeing the effect these drugs could have in cells, Nichols and his team moved on to whole animals. When they treated mouse models of system-wide inflammation with DOI, they found potent anti-inflammatory effects throughout the rodents’ bodies, with the strongest effects in the small intestine and a section of the main cardiac artery known as the aortic arch.16 “I think that’s really when it felt that we were onto something big, when we saw it in the whole animal,” Nichols says.

The group is now focused on testing DOI as a potential therapeutic for inflammatory diseases. In a 2015 study, they reported that DOI could block the development of asthma in a mouse model of the condition,17 and last December, the team received a patent to use DOI for four indications: asthma, Crohn’s disease, rheumatoid arthritis, and irritable bowel syndrome. They are now working to move the treatment into clinical trials. The benefit of using DOI for these conditions, Nichols says, is that because of its potency, only small amounts will be required—far below the amounts required to produce hallucinogenic effects.

In addition to opening the door to a new class of diseases that could benefit from psychedelics-inspired therapy, Nichols’s work suggests “that there may be some enduring changes that are mediated through anti-inflammatory effects,” Griffiths [Roland Griffiths, a psychiatry professor at Johns Hopkins University] says. Recent studies suggest that inflammation may play a role in a number of psychological disorders, including depression18 and addiction.19

“If somebody has neuroinflammation and that’s causing depression, and something like psilocybin makes it better through the subjective experience but the brain is still inflamed, it’s going to fall back into the depressed rut,” Nichols says. But if psilocybin is also treating the inflammation, he adds, “it won’t have that rut to fall back into.”

If it turns out that psychedelics do have anti-inflammatory effects in the brain, the drugs’ therapeutic uses could be even broader than scientists now envision. “In terms of neurodegenerative disease, every one of these disorders is mediated by inflammatory cytokines,” says Juan Sanchez-Ramos, a neuroscientist at the University of South Florida who in 2013 reported that small doses of psilocybin could promote neurogenesis in the mouse hippocampus.20 “That’s why I think, with Alzheimer’s, for example, if you attenuate the inflammation, it could help slow the progression of the disease.”

For anyone who was never exposed to the anti-hallucinogenic drug campaigns, this turn of events is mindboggling. There was a great deal of concern especially with LSD in the 1960s and it was not entirely unfounded. In my own family, a distant cousin, while under the influence of the drug, jumped off a building believing he could fly.  So, Kwon’s story opening with a story about someone being treated successfully for depression with a psychedelic drug was surprising to me . Why these drugs are being used successfully for psychiatric conditions when so much damage was apparently done under the influence in decades past may have something to do with taking the drugs in a controlled environment and, possibly, smaller dosages.

A nano fabrication technique used to create next generation heart valve

I am going to have take the researchers’ word that these somehow lead to healthy heart valve tissue,

In rotary jet spinning technology, a rotating nozzle extrudes a solution of extracellular matrix (ECM) into nanofibers that wrap themselves around heart valve-shaped mandrels. By using a series of mandrels with different sizes, the manufacturing process becomes fully scalable and is able to provide JetValves for all age groups and heart sizes. Credit: Wyss Institute at Harvard University

From a May 18, 2017 news item on ScienceDaily,

The human heart beats approximately 35 million times every year, effectively pumping blood into the circulation via four different heart valves. Unfortunately, in over four million people each year, these delicate tissues malfunction due to birth defects, age-related deteriorations, and infections, causing cardiac valve disease.

Today, clinicians use either artificial prostheses or fixed animal and cadaver-sourced tissues to replace defective valves. While these prostheses can restore the function of the heart for a while, they are associated with adverse comorbidity and wear down and need to be replaced during invasive and expensive surgeries. Moreover, in children, implanted heart valve prostheses need to be replaced even more often as they cannot grow with the child.

A team lead by Kevin Kit Parker, Ph.D. at Harvard University’s Wyss Institute for Biologically Inspired Engineering recently developed a nanofiber fabrication technique to rapidly manufacture heart valves with regenerative and growth potential. In a paper published in Biomaterials, Andrew Capulli, Ph.D. and colleagues fabricated a valve-shaped nanofiber network that mimics the mechanical and chemical properties of the native valve extracellular matrix (ECM). To achieve this, the team used the Parker lab’s proprietary rotary jet spinning technology — in which a rotating nozzle extrudes an ECM solution into nanofibers that wrap themselves around heart valve-shaped mandrels. “Our setup is like a very fast cotton candy machine that can spin a range of synthetic and natural occurring materials. In this study, we used a combination of synthetic polymers and ECM proteins to fabricate biocompatible JetValves that are hemodynamically competent upon implantation and support cell migration and re-population in vitro. Importantly, we can make human-sized JetValves in minutes — much faster than possible for other regenerative prostheses,” said Parker.

A May 18,2017 Wyss Institute for Biologically Inspired Engineering news release (also on EurekAlert), which originated the news item, expands on the theme of Jetvalves,

To further develop and test the clinical potential of JetValves, Parker’s team collaborated with the translational team of Simon P. Hoerstrup, M.D., Ph.D., at the University of Zurich in Switzerland, which is a partner institution with the Wyss Institute. As a leader in regenerative heart prostheses, Hoerstrup and his team in Zurich have previously developed regenerative, tissue-engineered heart valves to replace mechanical and fixed-tissue heart valves. In Hoerstrup’s approach, human cells directly deposit a regenerative layer of complex ECM on biodegradable scaffolds shaped as heart valves and vessels. The living cells are then eliminated from the scaffolds resulting in an “off-the-shelf” human matrix-based prostheses ready for implantation.

In the paper, the cross-disciplinary team successfully implanted JetValves in sheep using a minimally invasive technique and demonstrated that the valves functioned properly in the circulation and regenerated new tissue. “In our previous studies, the cell-derived ECM-coated scaffolds could recruit cells from the receiving animal’s heart and support cell proliferation, matrix remodeling, tissue regeneration, and even animal growth. While these valves are safe and effective, their manufacturing remains complex and expensive as human cells must be cultured for a long time under heavily regulated conditions. The JetValve’s much faster manufacturing process can be a game-changer in this respect. If we can replicate these results in humans, this technology could have invaluable benefits in minimizing the number of pediatric re-operations,” said Hoerstrup.

In support of these translational efforts, the Wyss Institute for Biologically Inspired Engineering and the University of Zurich announced today a cross-institutional team effort to generate a functional heart valve replacement with the capacity for repair, regeneration, and growth. The team is also working towards a GMP-grade version of their customizable, scalable, and cost-effective manufacturing process that would enable deployment to a large patient population. In addition, the new heart valve would be compatible with minimally invasive procedures to serve both pediatric and adult patients.

The project will be led jointly by Parker and Hoerstrup. Parker is a Core Faculty member of the Wyss Institute and the Tarr Family Professor of Bioengineering and Applied Physics at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS). Hoerstrup is Chair and Director of the University of Zurich’s Institute for Regenerative Medicine (IREM), Co-Director of the recently founded Wyss Translational Center Zurich and a Wyss Institute Associate Faculty member.

Since JetValves can be manufactured in all desired shapes and sizes, and take seconds to minutes to produce, the team’s goal is to provide customized, ready-to-use, regenerative heart valves much faster and at much lower cost than currently possible.

“Achieving the goal of minimally invasive, low-cost regenerating heart valves could have tremendous impact on patients’ lives across age-, social- and geographical boundaries. Once again, our collaborative team structure that combines unique and leading expertise in bioengineering, regenerative medicine, surgical innovation and business development across the Wyss Institute and our partner institutions, makes it possible for us to advance technology development in ways not possible in a conventional academic laboratory,” said Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at HMS and the Vascular Biology Program at Boston Children’s Hospital, as well as Professor of Bioengineering at SEAS.

This scanning electron microscopy image shows how extracellular matrix (ECM) nanofibers generated with JetValve technology are arranged in parallel networks with physical properties comparable to those found in native heart tissue. Credit: Wyss Institute at Harvard University

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

JetValve: Rapid manufacturing of biohybrid scaffolds for biomimetic heart valve replacement by Andrew K. Capulli, Maximillian Y. Emmert, Francesco S. Pasqualini, b, Debora Kehl, Etem Caliskan, Johan U. Lind, Sean P. Sheehy, Sung Jin Park, Seungkuk Ahn, Benedikt Webe, Josue A. Goss. Biomaterials Volume 133, July 2017, Pages 229–241  https://doi.org/10.1016/j.biomaterials.2017.04.033

This paper is behind a paywall.

New model to track flow of nanomaterials through our air, earth, and water

Just how many tons of nanoparticles are making their way through the environment? Scientists at the Swiss Federal Laboratories for Materials Science and Technology (Empa) have devised a new model which could help answer that question. From a May 12, 2016 news item on phys.org,

Carbon nanotubes remain attached to materials for years while titanium dioxide and nanozinc are rapidly washed out of cosmetics and accumulate in the ground. Within the National Research Program “Opportunities and Risks of Nanomaterials” (NRP 64) a team led by Empa scientist Bernd Nowack has developed a new model to track the flow of the most important nanomaterials in the environment.

A May 12, 2016 Empa press release by Michael Hagmann, which also originated the news item, provides more detail such as an estimated tonnage for titanium dioxide nanoparticles produced annually in Europe,

How many man-made nanoparticles make their way into the air, earth or water? In order to assess these amounts, a group of researchers led by Bernd Nowack from Empa, the Swiss Federal Laboratories for Materials Science and Technology, has developed a computer model as part of the National Research Program “Opportunities and Risks of Nanomaterials” (NRP 64). “Our estimates offer the best available data at present about the environmental accumulation of nanosilver, nanozinc, nano-tinanium dioxide and carbon nanotubes”, says Nowack.

In contrast to the static calculations hitherto in use, their new, dynamic model does not just take into account the significant growth in the production and use of nanomaterials, but also makes provision for the fact that different nanomaterials are used in different applications. For example, nanozinc and nano-titanium dioxide are found primarily in cosmetics. Roughly half of these nanoparticles find their way into our waste water within the space of a year, and from there they enter into sewage sludge. Carbon nanotubes, however, are integrated into composite materials and are bound in products such as which are immobilized and are thus found for example in tennis racquets and bicycle frames. It can take over ten years before they are released, when these products end up in waste incineration or are recycled.

39,000 metric tons of nanoparticles

The researchers involved in this study come from Empa, ETH Zurich and the University of Zurich. They use an estimated annual production of nano-titanium dioxide across Europe of 39,000 metric tons – considerably more than the total for all other nanomaterials. Their model calculates how much of this enters the atmosphere, surface waters, sediments and the earth, and accumulates there. In the EU, the use of sewage sludge as fertilizer (a practice forbidden in Switzerland) means that nano-titanium dioxide today reaches an average concentration of 61 micrograms per kilo in affected soils.

Knowing the degree of accumulation in the environment is only the first step in the risk assessment of nanomaterials, however. Now this data has to be compared with results of eco-toxicological tests and the statutory thresholds, says Nowack. A risk assessment has not been carried out with his new model so far. Earlier work with data from a static model showed, however, that the concentrations determined for all four nanomaterials investigated are not expected to have any impact on the environment.

But in the case of nanozinc at least, its concentration in the environment is approaching the critical level. This is why this particular nanomaterial has to be given priority in future eco-toxicological studies – even though nanozinc is produced in smaller quantities than nano-titanium dioxide. Furthermore, eco-toxicological tests have until now been carried out primarily with freshwater organisms. The researchers conclude that additional investigations using soil-dwelling organisms are a priority.

Here are links to and citations for papers featuring the work,

Dynamic Probabilistic Modeling of Environmental Emissions of Engineered Nanomaterials by Tian Yin Sun†, Nikolaus A. Bornhöft, Konrad Hungerbühler, and Bernd Nowack. Environ. Sci. Technol., 2016, 50 (9), pp 4701–4711 DOI: 10.1021/acs.est.5b05828 Publication Date (Web): April 04, 2016

Copyright © 2016 American Chemical Society

Probabilistic environmental risk assessment of five nanomaterials (nano-TiO2, nano-Ag, nano-ZnO, CNT, and fullerenes) by Claudia Coll, Dominic Notter, Fadri Gottschalk, Tianyin Sun, Claudia Som, & Bernd Nowack. Nanotoxicology Volume 10, Issue 4, 2016 pages 436-444 DOI: 10.3109/17435390.2015.1073812 Published online: 10 Nov 2015

The first paper, which is listed in Environmental Science & Technology, appears to be open access while the second paper is behind a paywall.

Saharan silver ants: the nano of it all (science and technology)

Researchers at Columbia University (US) are on quite a publishing binge lately. The latest is a biomimicry story where researchers (from Columbia amongst other universities and including Brookhaven National Laboratory, which has issued its own news release) have taken a very close look at Saharan silver ants to determine how they stay cool in one of the hottest climates in the world. From a June 18, 2015 Columbia University news release (also on EurekAlert), Note: Links have been removed,

Nanfang Yu, assistant professor of applied physics at Columbia Engineering, and colleagues from the University of Zürich and the University of Washington, have discovered two key strategies that enable Saharan silver ants to stay cool in one of the hottest terrestrial environments on Earth. Yu’s team is the first to demonstrate that the ants use a coat of uniquely shaped hairs to control electromagnetic waves over an extremely broad range from the solar spectrum (visible and near-infrared) to the thermal radiation spectrum (mid-infrared), and that different physical mechanisms are used in different spectral bands to realize the same biological function of reducing body temperature. Their research, “Saharan silver ants keep cool by combining enhanced optical reflection and radiative heat dissipation,” is published June 18 [2015] in Science magazine.

The Columbia University news release expands on the theme,

“This is a telling example of how evolution has triggered the adaptation of physical attributes to accomplish a physiological task and ensure survival, in this case to prevent Saharan silver ants from getting overheated,” Yu says. “While there have been many studies of the physical optics of living systems in the ultraviolet and visible range of the spectrum, our understanding of the role of infrared light in their lives is much less advanced. Our study shows that light invisible to the human eye does not necessarily mean that it does not play a crucial role for living organisms.”

The project was initially triggered by wondering whether the ants’ conspicuous silvery coats were important in keeping them cool in blistering heat. Yu’s team found that the answer to this question was much broader once they realized the important role of infrared light. Their discovery that there is a biological solution to a thermoregulatory problem could lead to the development of novel flat optical components that exhibit optimal cooling properties.

“Such biologically inspired cooling surfaces will have high reflectivity in the solar spectrum and high radiative efficiency in the thermal radiation spectrum,” Yu explains. “So this may generate useful applications such as a cooling surface for vehicles, buildings, instruments, and even clothing.”

Saharan silver ants (Cataglyphis bombycina) forage in the Saharan Desert in the full midday sun when surface temperatures reach up to 70°C (158°F), and they must keep their body temperature below their critical thermal maximum of 53.6°C (128.48°F) most of the time. In their wide-ranging foraging journeys, the ants search for corpses of insects and other arthropods that have succumbed to the thermally harsh desert conditions, which they are able to endure more successfully. Being most active during the hottest moment of the day also allows these ants to avoid predatory desert lizards. Researchers have long wondered how these tiny insects (about 10 mm, or 3/8” long) can survive under such thermally extreme and stressful conditions.

Using electron microscopy and ion beam milling, Yu’s group discovered that the ants are covered on the top and sides of their bodies with a coating of uniquely shaped hairs with triangular cross-sections that keep them cool in two ways. These hairs are highly reflective under the visible and near-infrared light, i.e., in the region of maximal solar radiation (the ants run at a speed of up to 0.7 meters per second and look like droplets of mercury on the desert surface). The hairs are also highly emissive in the mid-infrared portion of the electromagnetic spectrum, where they serve as an antireflection layer that enhances the ants’ ability to offload excess heat via thermal radiation, which is emitted from the hot body of the ants to the cold sky. This passive cooling effect works under the full sun whenever the insects are exposed to the clear sky.

“To appreciate the effect of thermal radiation, think of the chilly feeling when you get out of bed in the morning,” says Yu. “Half of the energy loss at that moment is due to thermal radiation since your skin temperature is temporarily much higher than that of the surrounding environment.”

The researchers found that the enhanced reflectivity in the solar spectrum and enhanced thermal radiative efficiency have comparable contributions to reducing the body temperature of silver ants by 5 to 10 degrees compared to if the ants were without the hair cover. “The fact that these silver ants can manipulate electromagnetic waves over such a broad range of spectrum shows us just how complex the function of these seemingly simple biological organs of an insect can be,” observes Norman Nan Shi, lead author of the study and PhD student who works with Yu at Columbia Engineering.

Yu and Shi collaborated on the project with Rüdiger Wehner, professor at the Brain Research Institute, University of Zürich, Switzerland, and Gary Bernard, electrical engineering professor at the University of Washington, Seattle, who are renowned experts in the study of insect physiology and ecology. The Columbia Engineering team designed and conducted all experimental work, including optical and infrared microscopy and spectroscopy experiments, thermodynamic experiments, and computer simulation and modeling. They are currently working on adapting the engineering lessons learned from the study of Saharan silver ants to create flat optical components, or “metasurfaces,” that consist of a planar array of nanophotonic elements and provide designer optical and thermal radiative properties.

Yu and his team plan next to extend their research to other animals and organisms living in extreme environments, trying to learn the strategies these creatures have developed to cope with harsh environmental conditions.

“Animals have evolved diverse strategies to perceive and utilize electromagnetic waves: deep sea fish have eyes that enable them to maneuver and prey in dark waters, butterflies create colors from nanostructures in their wings, honey bees can see and respond to ultraviolet signals, and fireflies use flash communication systems,” Yu adds. “Organs evolved for perceiving or controlling electromagnetic waves often surpass analogous man-made devices in both sophistication and efficiency. Understanding and harnessing natural design concepts deepens our knowledge of complex biological systems and inspires ideas for creating novel technologies.”

Next, there’s the perspective provided by Brookhaven National Laboratory in a June 18, 2015 news item on Nanowerk (Note: It is very similar to the Columbia University news release but it takes a turn towards the technical challenges as you’ll see if you keep reading),

The paper, published by Columbia Engineering researchers and collaborators—including researchers from the U.S. Department of Energy’s (DOE) Brookhaven National Laboratory—describes how the nanoscale structure of the hairs helps increase the reflectivity of the ant’s body in both visible and near-infrared wavelengths, allowing the insects to deflect solar radiation their bodies would otherwise absorb. The hairs also enhance emissivity in the mid-infrared spectrum, allowing heat to dissipate efficiently from the hot body of the ants to the cool, clear sky.

A June 18, 2015 BNL news release by Alasdair Wilkins, which originated the Nanowerk news item, describes the collaboration between the researchers and the special adjustments made to the equipment in service of this project (Note: A link has been removed),

In a typical experiment involving biological material such as nanoscale hairs, it would usually be sufficient to use an electron microscope to create an image of the surface of the specimen. This research, however, required Yu’s group to look inside the ant hairs and produce a cross-section of the structure’s interior. The relatively weak beam of electrons from a standard electron microscope would not be able to penetrate the surface of the sample.

The CFN’s dual beam system solves the problem by combining the imaging of an electron microscope with a much more powerful beam of gallium ions.  With 31 protons and 38 neutrons, each gallium ion is about 125,000 times more massive than an electron, and massive enough to create dents in the nanoscale structure – like throwing a stone against a wall. The researchers used these powerful beams to drill precise cuts into the hairs, revealing the crucial information hidden beneath the surface. Indeed, this particular application, in which the system was used to investigate a biological problem, was new for the team at CFN.

“Conventionally, this tool is used to produce cross-sections of microelectronic circuits,” said Camino. “The focused ion beam is like an etching tool. You can think of it like a milling tool in a machine shop, but at the nanoscale. It can remove material at specific places because you can see these locations with the SEM. So locally you remove material and you look at the under layers, because the cuts give you access to the cross section of whatever you want to look at.”

The ant hair research challenged the CFN team to come up with novel solutions to investigate the internal structures without damaging the more delicate biological samples.

“These hairs are very soft compared to, say, semiconductors or crystalline materials. And there’s a lot of local heat that can damage biological samples. So the parameters have to be carefully tuned not to do much damage to it,” he said. “We had to adapt our technique to find the right conditions.”

Another challenge lay in dealing with the so-called charging effect. When the dual beam system is trained on a non-conducting material, electrons can build up at the point where the beams hit the specimen, distorting the resulting image. The team at CFN was able to solve this problem by placing thin layers of gold over the biological material, making the sample just conductive enough to avoid the charging effect.

Revealing Reflectivity

While Camino’s team focused on helping Yu’s group investigate the structure of the ant hairs, Matthew Sfeir’s work with high-brightness Fourier transform optical spectroscopy helped to reveal how the reflectivity of the hairs helped Saharan silver ants regulate temperature. Sfeir’s spectrometer revealed precisely how much those biological structures reflect light across multiple wavelengths, including both visible and near-infrared light.

“It’s a multiplexed measurement,” Sfeir said, explaining his team’s spectrometer. “Instead of tuning through this wavelength and this wavelength, that wavelength, you do them all in one swoop to get all the spectral information in one shot. It gives you very fast measurements and very good resolution spectrally. Then we optimize it for very small samples. It’s a rather unique capability of CFN.”

Sfeir’s spectroscopy work draws on knowledge gained from his work at another key Brookhaven facility: the original National Synchrotron Light Source, where he did much of his postdoc work. His experience was particularly useful in analyzing the reflectivity of the biological structures across many different wavelengths of the electromagnetic spectrum.

“This technique was developed from my experience working with the infrared synchrotron beamlines,” said Sfeir. “Synchrotron beamlines are optimized for exactly this kind of thing. I thought, ‘Hey, wouldn’t it be great if we could develop a similar measurement for the type of solar devices we make at CFN?’ So we built a bench-top version to use here.”

Fascinating, non? At last, here’s a link to and a citation for the paper,

Keeping cool: Enhanced optical reflection and heat dissipation in silver ants by Norman Nan Shi, Cheng-Chia Tsai, Fernando Camino, Gary D. Bernard, Nanfang Yu, and Rüdiger Wehner. Science DOI: 10.1126/science.aab3564 Published online June 18, 2015

This paper is behind a paywall.

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