Tag Archives: ETH Zurich

Graphene can be used in quantum components

A November 3, 2022 news item on phys.org provides a brief history of graphene before announcing the latest work from ETH Zurich,

Less than 20 years ago, Konstantin Novoselov and Andre Geim first created two-dimensional crystals consisting of just one layer of carbon atoms. Known as graphene, this material has had quite a career since then.
Due to its exceptional strength, graphene is used today to reinforce products such as tennis rackets, car tires or aircraft wings. But it is also an interesting subject for fundamental research, as physicists keep discovering new, astonishing phenomena that have not been observed in other materials.
The right twist
Bilayer graphene crystals, in which the two atomic layers are slightly rotated relative to each other, are particularly interesting for researchers. About one year ago, a team of researchers led by Klaus Ensslin and Thomas Ihn at ETH Zurich’s Laboratory for Solid State Physics was able to demonstrate that twisted graphene could be used to create Josephson junctions, the fundamental building blocks of superconducting devices.
Based on this work, researchers were now able to produce the first superconducting quantum interference device, or SQUID, from twisted graphene for the purpose of demonstrating the interference of superconducting quasiparticles. Conventional SQUIDs are already being used, for instance in medicine, geology and archaeology. Their sensitive sensors are capable of measuring even the smallest changes in magnetic fields. However, SQUIDs work only in conjunction with superconducting materials, so they require cooling with liquid helium or nitrogen when in operation.
In quantum technology, SQUIDs can host quantum bits (qubits); that is, as elements for carrying out quantum operations. “SQUIDs are to superconductivity what transistors are to semiconductor technology—the fundamental building blocks for more complex circuits,” Ensslin explains.
…

A November 3, 2022 ETH Zurich news release by Felix Würsten, which originated the news item, delves further into the work,

The spectrum is widening
The graphene SQUIDs created by doctoral student Elías Portolés are not more sensitive than their conventional counterparts made from aluminium and also have to be cooled down to temperatures lower than 2 degrees above absolute zero. “So it’s not a breakthrough for SQUID technology as such,” Ensslin says. However, it does broaden graphene’s application spectrum significantly. “Five years ago, we were already able to show that graphene could be used to build single-electron transistors. Now we’ve added superconductivity,” Ensslin says.
What is remarkable is that the graphene’s behaviour can be controlled in a targeted manner by biasing an electrode. Depending on the voltage applied, the material can be insulating, conducting or superconducting. “The rich spectrum of opportunities offered by solid-state physics is at our disposal,” Ensslin says.
Also interesting is that the two fundamental building blocks of a semiconductor (transistor) and a superconductor (SQUID) can now be combined in a single material. This makes it possible to build novel control operations. “Normally, the transistor is made from silicon and the SQUID from aluminium,” Ensslin says. “These are different materials requiring different processing technologies.”
An extremely challenging production process
Superconductivity in graphene was discovered by an MIT [Massachusetts Institute of Technology] research group five years ago, yet there are only a dozen or so experimental groups worldwide that look at this phenomenon. Even fewer are capable of converting superconducting graphene into a functioning component.
The challenge is that scientists have to carry out several delicate work steps one after the other: First, they have to align the graphene sheets at the exact right angle relative to each other. The next steps then include connecting electrodes and etching holes. If the graphene were to be heated up, as happens often during cleanroom processing, the two layers re-align the twist angle vanishes. “The entire standard semiconductor technology has to be readjusted, making this an extremely challenging job,” Portolés says.
The vision of hybrid systems
Ensslin is thinking one step ahead. Quite a variety of different qubit technologies are currently being assessed, each with its own advantages and disadvantages. For the most part, this is being done by various research groups within the National Center of Competence in Quantum Science and Technology (QSIT). If scientists succeed in coupling two of these systems using graphene, it might be possible to combine their benefits as well. “The result would be two different quantum systems on the same crystal,” Ensslin says.
This would also generate new possibilities for research on superconductivity. “With these components, we might be better able to understand how superconductivity in graphene comes about in the first place,” he adds. “All we know today is that there are different phases of superconductivity in this material, but we do not yet have a theoretical model to explain them.”

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

A tunable monolithic SQUID in twisted bilayer graphene by Elías Portolés, Shuichi Iwakiri, Giulia Zheng, Peter Rickhaus, Takashi Taniguchi, Kenji Watanabe, Thomas Ihn, Klaus Ensslin & Folkert K. de Vries. Nature Nanotechnology volume 17, pages 1159–1164 (2022) Issue Date: November 2022 DOI: https://doi.org/10.1038/s41565-022-01222-0 Published online: 24 October 2022

This paper is behind a paywall.

Exotic magnetism: a quantum simulation from D-Wave Sytems

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Vancouver (Canada) area company, D-Wave Systems is trumpeting itself (with good reason) again. This 2021 ‘milestone’ achievement builds on work from 2018 (see my August 23, 2018 posting for the earlier work). For me, the big excitement was finding the best explanation for quantum annealing and D-Wave’s quantum computers that I’ve seen yet (that explanation and a link to more is at the end of this posting).

A February 18, 2021 news item on phys.org announces the latest achievement,

D-Wave Systems Inc. today [February 18, 2021] published a milestone study in collaboration with scientists at Google, demonstrating a computational performance advantage, increasing with both simulation size and problem hardness, to over 3 million times that of corresponding classical methods. Notably, this work was achieved on a practical application with real-world implications, simulating the topological phenomena behind the 2016 Nobel Prize in Physics. This performance advantage, exhibited in a complex quantum simulation of materials, is a meaningful step in the journey toward applications advantage in quantum computing.
…

A February 18, 2021 D-Wave Systems press release (also on EurekAlert), which originated the news item, describes the work in more detail,

The work by scientists at D-Wave and Google also demonstrates that quantum effects can be harnessed to provide a computational advantage in D-Wave processors, at problem scale that requires thousands of qubits. Recent experiments performed on multiple D-Wave processors represent by far the largest quantum simulations carried out by existing quantum computers to date.
The paper, entitled “Scaling advantage over path-integral Monte Carlo in quantum simulation of geometrically frustrated magnets”, was published in the journal Nature Communications (DOI 10.1038/s41467-021-20901-5, February 18, 2021). D-Wave researchers programmed the D-Wave 2000Q™ system to model a two-dimensional frustrated quantum magnet using artificial spins. The behavior of the magnet was described by the Nobel-prize winning work of theoretical physicists Vadim Berezinskii, J. Michael Kosterlitz and David Thouless. They predicted a new state of matter in the 1970s characterized by nontrivial topological properties. This new research is a continuation of previous breakthrough work published by D-Wave’s team in a 2018 Nature paper entitled “Observation of topological phenomena in a programmable lattice of 1,800 qubits” (Vol. 560, Issue 7719, August 22, 2018). In this latest paper, researchers from D-Wave, alongside contributors from Google, utilize D-Wave’s lower noise processor to achieve superior performance and glean insights into the dynamics of the processor never observed before.
“This work is the clearest evidence yet that quantum effects provide a computational advantage in D-Wave processors,” said Dr. Andrew King, principal investigator for this work at D-Wave. “Tying the magnet up into a topological knot and watching it escape has given us the first detailed look at dynamics that are normally too fast to observe. What we see is a huge benefit in absolute terms, with the scaling advantage in temperature and size that we would hope for. This simulation is a real problem that scientists have already attacked using the algorithms we compared against, marking a significant milestone and an important foundation for future development. This wouldn’t have been possible today without D-Wave’s lower noise processor.”
“The search for quantum advantage in computations is becoming increasingly lively because there are special problems where genuine progress is being made. These problems may appear somewhat contrived even to physicists, but in this paper from a collaboration between D-Wave Systems, Google, and Simon Fraser University [SFU], it appears that there is an advantage for quantum annealing using a special purpose processor over classical simulations for the more ‘practical’ problem of finding the equilibrium state of a particular quantum magnet,” said Prof. Dr. Gabriel Aeppli, professor of physics at ETH Zürich and EPF Lausanne, and head of the Photon Science Division of the Paul Scherrer Institute. “This comes as a surprise given the belief of many that quantum annealing has no intrinsic advantage over path integral Monte Carlo programs implemented on classical processors.”
“Nascent quantum technologies mature into practical tools only when they leave classical counterparts in the dust in solving real-world problems,” said Hidetoshi Nishimori, Professor, Institute of Innovative Research, Tokyo Institute of Technology. “A key step in this direction has been achieved in this paper by providing clear evidence of a scaling advantage of the quantum annealer over an impregnable classical computing competitor in simulating dynamical properties of a complex material. I send sincere applause to the team.”
“Successfully demonstrating such complex phenomena is, on its own, further proof of the programmability and flexibility of D-Wave’s quantum computer,” said D-Wave CEO Alan Baratz. “But perhaps even more important is the fact that this was not demonstrated on a synthetic or ‘trick’ problem. This was achieved on a real problem in physics against an industry-standard tool for simulation–a demonstration of the practical value of the D-Wave processor. We must always be doing two things: furthering the science and increasing the performance of our systems and technologies to help customers develop applications with real-world business value. This kind of scientific breakthrough from our team is in line with that mission and speaks to the emerging value that it’s possible to derive from quantum computing today.”
The scientific achievements presented in Nature Communications further underpin D-Wave’s ongoing work with world-class customers to develop over 250 early quantum computing applications, with a number piloting in production applications, in diverse industries such as manufacturing, logistics, pharmaceutical, life sciences, retail and financial services. In September 2020, D-Wave brought its next-generation Advantage™ quantum system to market via the Leap™ quantum cloud service. The system includes more than 5,000 qubits and 15-way qubit connectivity, as well as an expanded hybrid solver service capable of running business problems with up to one million variables. The combination of Advantage’s computing power and scale with the hybrid solver service gives businesses the ability to run performant, real-world quantum applications for the first time.

That last paragraph seems more sales pitch than research oriented. It’s not unexpected in a company’s press release but I was surprised that the editors at EurekAlert didn’t remove it.

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

Scaling advantage over path-integral Monte Carlo in quantum simulation of geometrically frustrated magnets by Andrew D. King, Jack Raymond, Trevor Lanting, Sergei V. Isakov, Masoud Mohseni, Gabriel Poulin-Lamarre, Sara Ejtemaee, William Bernoudy, Isil Ozfidan, Anatoly Yu. Smirnov, Mauricio Reis, Fabio Altomare, Michael Babcock, Catia Baron, Andrew J. Berkley, Kelly Boothby, Paul I. Bunyk, Holly Christiani, Colin Enderud, Bram Evert, Richard Harris, Emile Hoskinson, Shuiyuan Huang, Kais Jooya, Ali Khodabandelou, Nicolas Ladizinsky, Ryan Li, P. Aaron Lott, Allison J. R. MacDonald, Danica Marsden, Gaelen Marsden, Teresa Medina, Reza Molavi, Richard Neufeld, Mana Norouzpour, Travis Oh, Igor Pavlov, Ilya Perminov, Thomas Prescott, Chris Rich, Yuki Sato, Benjamin Sheldan, George Sterling, Loren J. Swenson, Nicholas Tsai, Mark H. Volkmann, Jed D. Whittaker, Warren Wilkinson, Jason Yao, Hartmut Neven, Jeremy P. Hilton, Eric Ladizinsky, Mark W. Johnson, Mohammad H. Amin. Nature Communications volume 12, Article number: 1113 (2021) DOI: https://doi.org/10.1038/s41467-021-20901-5 Published: 18 February 2021

This paper is open access.

Quantum annealing and more

Dr. Andrew King, one of the D-Wave researchers, has written a February 18, 2021 article on Medium explaining some of the work. I’ve excerpted one of King’s points,

…
Insight #1: We observed what actually goes on under the hood in the processor for the first time
Quantum annealing — the approach adopted by D-Wave from the beginning — involves setting up a simple but purely quantum initial state, and gradually reducing the “quantumness” until the system is purely classical. This takes on the order of a microsecond. If you do it right, the classical system represents a hard (NP-complete) computational problem, and the state has evolved to an optimal, or at least near-optimal, solution to that problem.
What happens at the beginning and end of the computation are about as simple as quantum computing gets. But the action in the middle is hard to get a handle on, both theoretically and experimentally. That’s one reason these experiments are so important: they provide high-fidelity measurements of the physical processes at the core of quantum annealing. Our 2018 Nature article introduced the same simulation, but without measuring computation time. To benchmark the experiment this time around, we needed lower-noise hardware (in this case, we used the D-Wave 2000Q lower noise quantum computer), and we needed, strangely, to slow the simulation down. Since the quantum simulation happens so fast, we actually had to make things harder. And we had to find a way to slow down both quantum and classical simulation in an equitable way. The solution? Topological obstruction.
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If you have time and the inclination, I encourage you to read King’s piece.

Graphene and its magnetism

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I have two news bits about graphene and magnetism. If I understood what I was reading, one is more focused on applications and the other is focused on further establishing the field of valleytronics.

University of Cambridge and superconductivity

A February 8, 2021 news item on Nanowerk announces ‘magnetic work’ from the University of Cambridge (Note: A link has been removed),

The researchers, led by the University of Cambridge, were able to control the conductivity and magnetism of iron thiophosphate (FePS3), a two-dimensional material which undergoes a transition from an insulator to a metal when compressed. This class of magnetic materials offers new routes to understanding the physics of new magnetic states and superconductivity.
Using new high-pressure techniques, the researchers have shown what happens to magnetic graphene during the transition from insulator to conductor and into its unconventional metallic state, realised only under ultra-high pressure conditions. When the material becomes metallic, it remains magnetic, which is contrary to previous results and provides clues as to how the electrical conduction in the metallic phase works. The newly discovered high-pressure magnetic phase likely forms a precursor to superconductivity so understanding its mechanisms is vital.
Their results, published in the journal Physical Review X, also suggest a way that new materials could be engineered to have combined conduction and magnetic properties, which could be useful in the development of new technologies such as spintronics, which could transform the way in which computers process information.
…

A February 8, 2021 University of Cambridge press release (also on EurekAlert), which originated the news item, delves into the topic,

Properties of matter can alter dramatically with changing dimensionality. For example, graphene, carbon nanotubes, graphite and diamond are all made of carbon atoms, but have very different properties due to their different structure and dimensionality.
“But imagine if you were also able to change all of these properties by adding magnetism,” said first author Dr Matthew Coak, who is jointly based at Cambridge’s Cavendish Laboratory and the University of Warwick. “A material which could be mechanically flexible and form a new kind of circuit to store information and perform computation. This is why these materials are so interesting, and because they drastically change their properties when put under pressure so we can control their behaviour.”
In a previous study by Sebastian Haines of Cambridge’s Cavendish Laboratory and the Department of Earth Sciences, researchers established that the material becomes a metal at high pressure, and outlined how the crystal structure and arrangement of atoms in the layers of this 2D material change through the transition.
“The missing piece has remained however, the magnetism,” said Coak. “With no experimental techniques able to probe the signatures of magnetism in this material at pressures this high, our international team had to develop and test our own new techniques to make it possible.”
The researchers used new techniques to measure the magnetic structure up to record-breaking high pressures, using specially designed diamond anvils and neutrons to act as the probe of magnetism. They were then able to follow the evolution of the magnetism into the metallic state.
“To our surprise, we found that the magnetism survives and is in some ways strengthened,” co-author Dr Siddharth Saxena, group leader at the Cavendish Laboratory. “This is unexpected, as the newly-freely-roaming electrons in a newly conducting material can no longer be locked to their parent iron atoms, generating magnetic moments there – unless the conduction is coming from an unexpected source.”
In their previous paper, the researchers showed these electrons were ‘frozen’ in a sense. But when they made them flow or move, they started interacting more and more. The magnetism survives, but gets modified into new forms, giving rise to new quantum properties in a new type of magnetic metal.
How a material behaves, whether conductor or insulator, is mostly based on how the electrons, or charge, move around. However, the ‘spin’ of the electrons has been shown to be the source of magnetism. Spin makes electrons behave a bit like tiny bar magnets and point a certain way. Magnetism from the arrangement of electron spins is used in most memory devices: harnessing and controlling it is important for developing new technologies such as spintronics, which could transform the way in which computers process information.
“The combination of the two, the charge and the spin, is key to how this material behaves,” said co-author Dr David Jarvis from the Institut Laue-Langevin, France, who carried out this work as the basis of his PhD studies at the Cavendish Laboratory. “Finding this sort of quantum multi-functionality is another leap forward in the study of these materials.”
“We don’t know exactly what’s happening at the quantum level, but at the same time, we can manipulate it,” said Saxena. “It’s like those famous ‘unknown unknowns’: we’ve opened up a new door to properties of quantum information, but we don’t yet know what those properties might be.”
There are more potential chemical compounds to synthesise than could ever be fully explored and characterised. But by carefully selecting and tuning materials with special properties, it is possible to show the way towards the creation of compounds and systems, but without having to apply huge amounts of pressure.
Additionally, gaining fundamental understanding of phenomena such as low-dimensional magnetism and superconductivity allows researchers to make the next leaps in materials science and engineering, with particular potential in energy efficiency, generation and storage.
As for the case of magnetic graphene, the researchers next plan to continue the search for superconductivity within this unique material. “Now that we have some idea what happens to this material at high pressure, we can make some predictions about what might happen if we try to tune its properties through adding free electrons by compressing it further,” said Coak.
“The thing we’re chasing is superconductivity,” said Saxena. “If we can find a type of superconductivity that’s related to magnetism in a two-dimensional material, it could give us a shot at solving a problem that’s gone back decades.”

The citation and link to the paper are at the end of this blog posting.

Aalto University’s valleytronics

Further north in Finland, researchers at Aalto University make some advances applicable to the field of valleytronics, from a February 5, 2021 Aalto University press release (also on EurekAltert but published February 8, 2021),

Electrons in materials have a property known as ‘spin’, which is responsible for a variety of properties, the most well-known of which is magnetism. Permanent magnets, like the ones used for refrigerator doors, have all the spins in their electrons aligned in the same direction. Scientists refer to this behaviour as ferromagnetism, and the research field of trying to manipulate spin as spintronics.
Down in the quantum world, spins can arrange in more exotic ways, giving rise to frustrated states and entangled magnets. Interestingly, a property similar to spin, known as “the valley,” appears in graphene materials. This unique feature has given rise to the field of valleytronics, which aims to exploit the valley property for emergent physics and information processing, very much like spintronics relies on pure spin physics.
‘Valleytronics would potentially allow encoding information in the quantum valley degree of freedom, similar to how electronics do it with charge and spintronics with the spin.’ Explains Professor Jose Lado, from Aalto’s Department of applied physics, and one of the authors of the work. ‘What’s more, valleytronic devices would offer a dramatic increase in the processing speeds in comparison with electronics, and with much higher stability towards magnetic field noise in comparison with spintronic devices.’
Structures made of rotated, ultra-thin materials provide a rich solid-state platform for designing novel devices. In particular, slightly twisted graphene layers have recently been shown to have exciting unconventional properties, that can ultimately lead to a new family of materials for quantum technologies. These unconventional states which are already being explored depend on electrical charge or spin. The open question is if the valley can also lead to its own family of exciting states.
Making materials for valleytronics
For this goal, it turns out that conventional ferromagnets play a vital role, pushing graphene to the realms of valley physics. In a recent work, Ph.D. student Tobias Wolf, together with Profs. Oded Zilberberg and Gianni Blatter at ETH Zurich, and Prof. Jose Lado at Aalto University, showed a new direction for correlated physics in magnetic van der Waals materials.
The team showed that sandwiching two slightly rotated layers of graphene between a ferromagnetic insulator provides a unique setting for new electronic states. The combination of ferromagnets, graphene’s twist engineering, and relativistic effects force the “valley” property to dominate the electrons behaviour in the material. In particular, the researchers showed how these valley-only states can be tuned electrically, providing a materials platform in which valley-only states can be generated. Building on top of the recent breakthrough in spintronics and van der Waals materials, valley physics in magnetic twisted van der Waals multilayers opens the door to the new realm of correlated twisted valleytronics.
‘Demonstrating these states represents the starting point towards new exotic entangled valley states.’ Said Professor Lado, ‘Ultimately, engineering these valley states can allow realizing quantum entangled valley liquids and fractional quantum valley Hall states. These two exotic states of matter have not been found in nature yet, and would open exciting possibilities towards a potentially new graphene-based platform for topological quantum computing.’

Citations and links

Here’s a link to and a citation for the University of Cambridge research,

Emergent Magnetic Phases in Pressure-Tuned van der Waals Antiferromagnet FePS3 by Matthew J. Coak, David M. Jarvis, Hayrullo Hamidov, Andrew R. Wildes, Joseph A. M. Paddison, Cheng Liu, Charles R. S. Haines, Ngoc T. Dang, Sergey E. Kichanov, Boris N. Savenko, Sungmin Lee, Marie Kratochvílová, Stefan Klotz, Thomas C. Hansen, Denis P. Kozlenko, Je-Geun Park, and Siddharth S. Saxena. Phys. Rev. X 11, 011024 DOI: https://doi.org/10.1103/PhysRevX.11.011024 Published 5 February 2021

This article appears to be open access.

Here’s a link to and a citation for the Aalto University research,

Spontaneous Valley Spirals in Magnetically Encapsulated Twisted Bilayer Graphene by Tobias M. R. Wolf, Oded Zilberberg, Gianni Blatter, and Jose L. Lado. Phys. Rev. Lett. 126, 056803 DOI: https://doi.org/10.1103/PhysRevLett.126.056803 Published 4 February 2021

This paper is behind a paywall.

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

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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 (AN_pre) 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.

Detecting off-target effects of CRISPR gene-editing

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In amidst all the hyperbole about CRISPR (clustered regularly interspaced short palindromic repeats), the gene editing technology, you will sometimes find a mild cautionary note. It seems that CRISPR is not as precise as you might think.

Some months ago there was a story about research into detecting possible unanticipated (off target) effects from using CRISPR, from an April 19, 2019 news item on ScienceDaily,

Since the CRISPR genome editing technology was invented in 2012, it has shown great promise to treat a number of intractable diseases. However, scientists have struggled to identify potential off-target effects in therapeutically relevant cell types, which remains the main barrier to moving therapies to the clinic. Now, a group of scientists at the Gladstone Institutes and the Innovative Genomics Institute (IGI), with collaborators at AstraZeneca, have developed a reliable method to do just that.
…

An April 19, 2019 Gladstone Institutes press release by Julie Langelier, which originated the press release, provides details,

CRISPR edits a person’s genome by cutting the DNA at a specific location. The challenge is to ensure the tool doesn’t also make cuts elsewhere along the DNA—damage referred to as “off-target effects,” which could have unforeseen consequences.
In a study published in the journal Science, the two first authors, Beeke Wienert and Stacia Wyman, found a new way to approach the problem.
“When CRISPR makes a cut, the DNA is broken,” says Wienert, PhD, who began the work in Jacob E. Corn’s IGI laboratory and who is now a postdoctoral scholar in Bruce R. Conklin’s laboratory at Gladstone. “So, in order to survive, the cell recruits many different DNA repair factors to that particular site in the genome to fix the break and join the cut ends back together. We thought that if we could find the locations of these DNA repair factors, we could identify the sites that have been cut by CRISPR.”
To test their idea, the researchers studied a panel of different DNA repair factors. They found that one of them, called MRE11, is one of the first responders to the site of the cut. Using MRE11, the scientists developed a new technique, named DISCOVER-Seq, that can identify the exact sites in the genome where a cut has been made by CRISPR.
“The human genome is extremely large—if you printed the entire DNA sequence, you would end up with a novel as tall as a 16-story building,” explains Conklin, MD, senior investigator at Gladstone and deputy director at IGI. “When we want to cut DNA with CRISPR, it’s like we’re trying to remove one specific word on a particular page in that novel.”
“You can think of the DNA repair factors as different types of bookmarks added to the book,” Conklin adds. “While some may bookmark an entire chapter, MRE11 is a bookmark that drills down to the exact letter than has been changed.”
Different methods currently exist to detect CRISPR off-target effects. However, they come with limitations that range from producing false-positive results to killing the cells they’re examining. In addition, the most common method used to date is currently limited to cultured cells in the laboratory, excluding its use in patient-derived stem cells or animal tissue.
“Because our method relies on the cell’s natural repair process to identify cuts, it has proven to be much less invasive and much more reliable,” says Corn, PhD, who now runs a laboratory at ETH Zurich. “We were able to test our new DISCOVER-Seq method in induced pluripotent stem cells, patient cells, and mice, and our findings indicate that this method could potentially be used in any system, rather than just in the lab.”
The DISCOVER-Seq method, by being applied to new cell types and systems, has also revealed new insights into the mechanisms used by CRISPR to edit the genome, which will lead to a better understanding of the biology of how this tool works.
“The new method greatly simplifies the process of identifying off-target effects while also increasing the accuracy of the results,” says Conklin, who is also a professor of medical genetics and molecular pharmacology at UC San Francisco (UCSF). “This could allow us to better predict how genome editing would work in a clinical setting. As a result, it represents an essential step in improving pre-clinical studies and bringing CRISPR-based therapies closer to the patients in need.”
###
About the Study
The paper “Unbiased detection of CRISPR off-targets in vivo 1 using DISCOVER-Seq” was published by the journal Science on April 19, 2019. Gladstone’s Hannah L. Watry and Luke M. Judge (who is also at UCSF) contributed to this study. Other authors also include Christopher D. Richardson, Jonathan T. Vu, and Katelynn R. Kazane from IGI, Charles D. Yeh from ETH Zurich, as well as Pinar Akcakaya, Michelle J. Porritt, and Michaela Morlock from AstraZeneca.
The work was supported by Gladstone, the National Institutes of Health (grants EY028249 and HL13535801), the Li Ka Shing Foundation, the Heritage Medical Research Institute, the Fanconi Anemia Research Foundation, a Sir Keith Murdoch Fellowship from the American Australian Association, and an Early Career Fellowship from the National Health and Medical Research Council.

About the Gladstone Institute
To ensure our work does the greatest good, the Gladstone Institutes focuses on conditions with profound medical, economic, and social impact—unsolved diseases. Gladstone is an independent, nonprofit life science research organization that uses visionary science and technology to overcome disease. It has an academic affiliation with the University of California, San Francisco.

Before getting to the link and citation that I usually offer you might find this July 17, 2018 posting, The CRISPR ((clustered regularly interspaced short palindromic repeats)-CAS9 gene-editing technique may cause new genetic damage kerfuffle of interest. I wonder if this latest news affected the CRISPR market as the did the news in 2018.

In addition to the link in the press release, I am including a link and a citation for the study,

Unbiased detection of CRISPR off-targets in vivo using DISCOVER-Seq by Beeke Wienert, Stacia K. Wyman, Christopher D. Richardson, Charles D. Yeh, Pinar Akcakaya, Michelle J. Porritt, Michaela Morlock, Jonathan T. Vu, Katelynn R. Kazane, Hannah L. Watry, Luke M. Judge, Bruce R. Conklin, Marcello Maresca, Jacob E. Corn. Science 19 Apr 2019: Vol. 364, Issue 6437, pp. 286-289 DOI: 10.1126/science.aav9023

This paper is behind a paywall.

Money

Over the last 10 or more years, I have, on occasion made a point, of finding out about the funding for various non-profit agencies and projects. I find that sort of thing interesting and have hoped that my readers might feel the same way.

It seems that my readers and I might not be the only ones to care about the source of funding. Joi Ito who held appointments with Harvard University and the Massachusetts Institute of Technology (MIT) resigned from his various appointments on Sept. 7, 2019 after news of major donations from Jeffrey Epstein (a disgraced financier and sex offender) to MIT were revealed. From the Joi Ito’s entry on Wikipedia (Note: Links have been removed),

Joichi “Joi” Ito (伊藤穰一 Itō Jōichi, born June 19, 1966) is a Japanese activist, entrepreneur and venture capitalist. He is the former director of the MIT Media Lab, and a former professor of the practice of media arts and sciences at MIT. He is a former visiting professor of practice at the Harvard Law School.[1][2]
Ito has received recognition for his role as an entrepreneur focused on Internet and technology companies and has founded, among other companies, PSINet Japan, Digital Garage and Infoseek Japan. Ito is a strategic advisor to Sony Corporation[3] and general partner of Neoteny Labs.[4] Ito writes a monthly column in the Ideas section of Wired.[5]
Ito resigned from his roles at MIT, Harvard, the John D. and Catherine T. MacArthur Foundation, the Knight Foundation, PureTech Health and The New York Times Company on September 7, 2019, following allegations of financial ties to sex offender and financier Jeffrey Epstein.[2][6][7]
…

Many, many institutions have accepted funds from sketchy characters and orgnaizations. It’s not new to academia, the sciences, or the arts. For a contemporary view of how some of this works, take a look at Anand Giridharadas’s 2018 book, Winners Take All. From the webepage for the book,

WINNERS TAKE ALL
The Elite Charade of Changing the World

An insider’s groundbreaking investigation of how the global elite’s efforts to “change the world” preserve the status quo and obscure their role in causing the problems they later seek to solve.

Former New York Times columnist Anand Giridharadas takes us into the inner sanctums of a new gilded age, where the rich and powerful fight for equality and justice any way they can–except ways that threaten the social order and their position atop it. We see how they rebrand themselves as saviors of the poor; how they lavishly reward “thought leaders” who redefine “change” in winner-friendly ways; and how they constantly seek to do more good, but never less harm. We hear the limousine confessions of a celebrated foundation boss; witness an American president hem and haw about his plutocratic benefactors; and attend a cruise-ship conference where entrepreneurs celebrate their own self-interested magnanimity.
…

I don’t recall any mention of Epstein in Giridharadas’s book but he did have this to say on Twitter about Epstein,

Anand Giridharadas‏Verified account @AnandWrites

Everything that made Epstein’s life possible remains in place after his arrest: the Caribbean tax havens, the hidden real-estate deals, the buying of politicians, the nonprofits that sell reputational glow, the editors who cover for people of their class.
7:34 PM – 8 Jul 2019

it can’t be easy to withstand the temptation to take the money and hope that the misdoings have been exaggerated or that they have stopped. I imagine Ito and others are under constant pressure to get funds.

AstraZeneca

One of the partners in this research about CRISPR, AstraZeneca, is a pharmaceutical company. In fact, it’s one of the largest in the world (from the AstraZeneca Wikipedia entry; Note: Links have been removed),

AstraZeneca plc[4] is a British-Swedish multinational pharmaceutical and biopharmaceutical company. In 2013, it moved its headquarters to Cambridge, UK, and concentrated its R&D in three sites: Cambridge; Gaithersburg, Maryland, USA (location of MedImmune) for work on biopharmaceuticals; and Mölndal (near Gothenburg) in Sweden, for research on traditional chemical drugs.[5] AstraZeneca has a portfolio of products for major disease areas including cancer, cardiovascular, gastrointestinal, infection, neuroscience, respiratory and inflammation.[6]
The company was founded in 1999 through the merger of the Swedish Astra AB and the British Zeneca Group[7][8] (itself formed by the demerger of the pharmaceutical operations of Imperial Chemical Industries in 1993). Since the merger it has been among the world’s largest pharmaceutical companies and has made numerous corporate acquisitions, including Cambridge Antibody Technology (in 2006), MedImmune (in 2007), Spirogen (in 2013) and Definiens (by MedImmune in 2014).
…
Controversies
Seroquel
In April 2010 AstraZeneca settled a qui tam lawsuit brought by Stefan P. Kruszewski for $520 million to settle allegations that the company defrauded Medicare, Medicaid, and other government-funded health care programs in connection with its marketing and promotional practices for the blockbuster atypical antipsychotic, Seroquel.[76]
In March 2011, AstraZeneca settled a lawsuit in the United States totalling $68.5 million to be divided up to 38 states.[77]
Nexium
The company’s most commercially successful medication is esomeprazole (Nexium). The primary uses are treatment of gastroesophageal reflux disease, treatment and maintenance of erosive esophagitis, treatment of duodenal ulcers caused by Helicobacter pylori, prevention of gastric ulcers in those on chronic NSAID therapy, and treatment of gastrointestinal ulcers associated with Crohn’s disease. When it is manufactured the result is a mixture of two mirror-imaged molecules, R and S. Two years before the omeprazole patent expired, AstraZeneca patented S-omeprazole in pure form, pointing out that since some people metabolise R-omeprazole slowly, pure S-omeprazole treatment would give higher dose efficiency and less variation between individuals.[78] In March 2001, the company began to market Nexium, as it would a brand new drug.[79]
…
In 2007, Marcia Angell, former editor-in-chief of the New England Journal of Medicine and a lecturer in social medicine at the Harvard Medical School, said in Stern, a German-language weekly newsmagazine, that AstraZeneca’s scientists had misrepresented their research on the drug’s efficiency, saying “Instead of using presumably comparable doses [of each drug], the company’s scientists used Nexium in higher dosages. They compared 20 and 40 mg Nexium with 20 mg Prilosec. With the cards having been marked in that way, Nexium looked like an improvement – which however was only small and shown in only two of the three studies.”[83]
Bildman fraud, and faithless servant clawback
…
Study
In 2004, University of Minnesota research participant Dan Markingson committed suicide while enrolled in an industry-sponsored pharmaceutical trial comparing three FDA-approved atypical antipsychotics: Seroquel (quetiapine), Zyprexa (olanzapine), and Risperdal (risperidone). University of Minnesota Professor of Bioethics Carl Elliott noted that Markingson was enrolled in the study against the wishes of his mother, Mary Weiss, and that he was forced to choose between enrolling in the study or being involuntarily committed to a state mental institution.[89] Further investigation revealed financial ties to AstraZeneca by Markingson’s psychiatrist, Stephen C. Olson, oversights and biases in AstraZeneca’s trial design, and the inadequacy of university Institutional Review Board (IRB) protections for research subjects.[90][unreliable source?] A 2005 FDA investigation cleared the university. Nonetheless, controversy around the case has continued. A Mother Jones article[89] resulted in a group of university faculty members sending a public letter to the university Board of Regents urging an external investigation into Markingson’s death.[91]
…

Is it ok to take money and/or other goods and services from them?

Innovative Genomics Institute (IGI)

Also mentioned as a partner in the research, is the Innovative Genomics Institute (IGI). Here’s more from the company’s Overview webpage (Note: Links have been removed),,

The IGI began in 2014 through the Li Ka Shing Center for Genetic Engineering, which was created thanks to a generous donation from the Li Ka Shing Foundation. [emphasis mine] The Innovative Genomics Initiative formed as a partnership between the University of California, Berkeley and the University of California, San Francisco. Combining the fundamental research expertise and the biomedical talent at UCB and UCSF, the Innovative Genomics Initiative focused on unraveling the mechanisms underlying CRISPR-based genome editing and applying this technology to improve human health. Early achievements include improving the efficiency of gene replacement and foundational work toward a treatment for sickle cell disease.
In late 2015, generous philanthropic donations enabled a bolder vision and broader mission for the IGI. With this expansion came a significant enhancement of the organization, and in January 2017, the IGI officially re-launched as the Innovative Genomics Institute.
…

As it turns out, there is a Li Ka-shing and he has a bit of a history with Vancouver (Canada). First, here’s more about him from the Li Ka-shing Wikipedia entry,(Note: Links have been removed),

Sir Li Ka-shing GBM KBE JP[4] (born 13 June 1928)[5][6] is a Hong Kong business magnate, investor, and philanthropist. As of June 2019, Li is the 30th richest person in the world, with an estimated net wealth of US$29.4 billion.[3] He is the senior advisor for CK Hutchison Holdings,[7] after he retired from the Chairman of the Board in May 2018;[8] through it, he is the world’s leading port investor, developer, and operator of the largest health and beauty retailer in Asia and Europe.[9]
…
Besides business through his flagship companies Cheung Kong Property Holdings and CK Hutchison Holdings Limited, Li Ka-shing has also personally invested extensively in real estate in Singapore and Canada. He was the single largest shareholder of Canadian Imperial Bank of Commerce (CIBC), the fifth largest bank in Canada, until the sale of his share in 2005 (with all proceedings donated, see below). He is also the majority shareholder of a major energy company, Husky Energy, based in Alberta, Canada.[48]
In January 2005, Li announced plans to sell his $1.2 billion CAD stake in the Canadian Imperial Bank of Commerce, with all proceeds going to private charitable foundations established by Li, including the Li Ka Shing Foundation in Hong Kong and the Li Ka Shing (Canada) Foundation based in Toronto, Ontario.[49]
…
His son Victor Li was kidnapped in 1996 on his way home after work by gangster “Big Spender” Cheung Tze-keung. Li Ka-shing paid a ransom of HK$1 billion, directly to Cheung who had come to his house.^[53] A report was never filed with Hong Kong police. Instead the case was pursued by Mainland authorities, leading to Cheung’s execution in 1998, an outcome not possible under Hong Kong law. Rumours circulated of a deal between Li and the Mainland.^[53] In interviews, when this rumor was brought up, Li brushed it off and dismissed it completely.
…

Li Ka-shing was well known here in Vancouver due to his purchase of a significant chunk of land in the city. This January 9, 2015 article by Glen Korstrum for Business in Vancouver notes some rather interesting news and contextualizes with Li’s Vancouver history,

Hong Kong billionaire Li Ka-shing is restructuring his empire and shifting his base to the Cayman Islands and away from the Chinese special administrative region.
His January 9 [2015] announcement came the same day that Forbes ranked him as Hong Kong’s richest man for the 17th consecutive year, with a total wealth of US$33.5 billion.
Li is best known in Vancouver for buying an 82.5-hectare parcel of land around False Creek for $328 million in 1988 along with partners, who included fellow Hong Kong tycoons, Lee Shau Kee and Cheng Yu Tung.
The group formed Concord Pacific, which redeveloped the site that had been home to Vancouver’s 1986 world’s fair, Expo ’86.

Li cashed out of Concord Pacific in the late 1990s and, in 2007, invested in Deltaport through his Hutchison Port Holdings.
Li’s biggest Canadian holding is his controlling stake in Husky Energy. …

Intriguing, yes? It also makes the prospect of deciding whose money you’re going to accept a bit more complicated than it might seem.

Gladstone Institutes

In what seems to be a decided contrast to the previous two partners, here’s more from the Gladstone Institutes, About Us, History webpage,

Born in London in 1910, J. David Gladstone was orphaned as a boy and came to North America at age 10. He began a career in real estate in Southern California at age 28, eventually making his fortune as the first developer to create the region’s enclosed shopping malls (such as the Northridge Fashion Center mall). His accidental death in 1971 left an estate valued at about $8 million to support medical students interested in research.
It soon became clear to the three trustees administering Mr. Gladstone’s trust that his legacy could support a far more substantial philanthropic enterprise. In 1979, they launched The J. David Gladstone Institutes under the leadership of Robert W. Mahley, MD, PhD, a leading cardiovascular scientist who at the time was working at the National Institutes of Health.
…
In 2010, after three decades of leading Gladstone, Dr. Mahley stepped down in order to return to more active research. That same year, R. Sanders “Sandy” Williams, MD, left Duke University, where he had been Dean of the School of Medicine—as well as Senior Vice Chancellor and Senior Advisor for International Strategy—to become Gladstone’s new president. The following year, the S.D. Bechtel, Jr. Foundation [emphasis mine] helped launch the Center for Comprehensive Alzheimer’s Disease Research with a generous $6M lead gift, while the Roddenberry Foundation [emphasis mine] gave $5 million to launch the Roddenberry Center for Stem Cell Biology and Medicine. Also in 2011, the independent and philanthropic Gladstone Foundation formed with the mission of expanding the financial resources available to drive’s Gladstone’s mission.
…

The S. D. Bechtel jr. mentioned is associated with Bechtel, an international engineering firm. I did not find any scandals or controversies in the Bechtel Wikipedia entry. That seemed improbable so I did a little digging and found a January 30, 2015 (?) article by Matthew Brunwasser for foreignpolicy.com (Note: A link has been removed),

Steamrolled; A special investigation into the diplomacy of doing business abroad.
One of Europe’s poorest countries wanted a road, so U.S. mega-contractor Bechtel sold it a $1.3 billion highway, with the backing of a powerful American ambassador. Funny thing is, the highway is barely being used—and the ambassador is now working for Bechtel.
…
Bechtel, the largest contractor by revenue in the United States and the third-largest internationally, according to an annual list compiled by the Engineering News-Record, has in recent years constructed expensive highways in Kosovo, Croatia, Romania, and Albania. A six-month investigation by the Investigative Reporting Program at the University of California at Berkeley Graduate School of Journalism has found that these highways were boondoggles for the countries in which they were constructed, and that members of governments and international institutions often saw problems coming before Bechtel (along with its Turkish joint venture partner, Enka) even began work on the roads.
…

My other source is a May 8, 1988 article by Walter Russell Mead for the Los Angeles Time,s

From San Francisco to Saudi Arabia, the Bechtel Group Inc. has left its mark around the world. Yet the privately owned Bechtel Group is one of the country’s most mysterious operations–or was, until the publication of Laton McCartney’s critical and controversial “Friends in High Places.”
Those who believe that “Dynasty” and “Falcon Crest” describe life at the top of America’s corporate pyramids will find a picture here that makes the most far-fetched TV plots look dull. One Bechtel executive was torn to pieces by an angry mob; another, kidnaped, survived two days in the trunk of a Mercedes that had been driven over the edge of a cliff but caught on an obstacle half way down. Wheeling and dealing from Beirut to the Bohemian Grove, Bechtel executives fought off Arab and Jewish nationalists, angry senators, bitter business rivals, and furious consumer groups to build the world’s largest construction and engineering firm.
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Poor Bechtel sometimes seems damned if it does and damned if it doesn’t. No major corporation could undertake foreign operations on Bechtel’s scale without some cooperation from the U.S. government–and few companies could refuse a government request that, in return, they provide cover for intelligence agents. Given the enormous scope of Bechtel’s operations in global trouble spots–a $20-billion industrial development in Saudi Arabia, for example–it could only proceed with assurances that its relations with both Saudi and American governments were good. Where, exactly, is the line between right and wrong? [emphasis mine]
…
… The white elephants Bechtel scattered across the American landscape–particularly the nuclear power plants that threaten to bankrupt some of the country’s largest utility systems–are monuments to wasted talent and misdirected resources.
…

Finally, I get to the Roddenberry Foundation, which was founded by Gene Roddenberry’s (Star Trek) son. Here’s more from the About Us, Origin webpage,

Gene Roddenberry, creator of the Star Trek series, brought to his audiences meaningful and thought-provoking science fiction to “think, question, and challenge the status quo” with the intention of creating “a brighter future”. His work has touched countless lives and continues to entertain and inspire audiences worldwide. In 2010, Gene’s son Rod established the Roddenberry Foundation to build on his father’s legacy and philosophy of inclusion, diversity, and respect for life to drive social change and meaningfully improve the lives of people around the world.
…

While there are many criticisms of Mr. Roddenberry, there doesn’t seem to be anything that would be considered a serious scandal on the order of a Jeffrey Epstein or the whisper of scandal on the order of Sir Li Ka-shing or Bechtel.

Final comments

It’s a good thing when research is funded and being able to detect off-target effects from CRISPR is very good, assuming the research holds up to closer scrutiny.

As for vetting your donors, that’s tricky. Of course, Epstein was already a convicted sex offender when Ito accepted his funding for MIT but I cannot emphasize enough the amount of pressure these folks are under. Academia is always hungry for money. Hopefully this incident will introduce checks and balances in the donor process.

Better motor control for prosthetic hands (the illusion of feeling) and a discussion of superprostheses and reality

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I have two bits about prosthetics, one which focuses on how most of us think of them and another about science fiction fantasies.

Better motor control

This new technology comes via a collaboration between the University of Alberta, the University of New Brunswick (UNB) and Ohio’s Cleveland Clinic, from a March 18, 2018 article by Nicole Ireland for the Canadian Broadcasting Corporation’s (CBC) news online,

Rob Anderson was fighting wildfires in Alberta when the helicopter he was in crashed into the side of a mountain. He survived, but lost his left arm and left leg.

More than 10 years after that accident, Anderson, now 39, says prosthetic limb technology has come a long way, and he feels fortunate to be using “top of the line stuff” to help him function as normally as possible. In fact, he continues to work for the Alberta government’s wildfire fighting service.

His powered prosthetic hand can do basic functions like opening and closing, but he doesn’t feel connected to it — and has limited ability to perform more intricate movements with it, such as shaking hands or holding a glass.

Anderson, who lives in Grande Prairie, Alta., compares its function to “doing things with a long pair of pliers.”

“There’s a disconnect between what you’re physically touching and what your body is doing,” he told CBC News.

Anderson is one of four Canadian participants in a study that suggests there’s a way to change that. …

Six people, all of whom had arm amputations from below the elbow or higher, took part in the research. It found that strategically placed vibrating “robots” made them “feel” the movements of their prosthetic hands, allowing them to grasp and grip objects with much more control and accuracy.

All of the participants had all previously undergone a specialized surgical procedure called “targeted re-innervation.” The nerves that had connected to their hands before they were amputated were rewired to link instead to muscles (including the biceps and triceps) in their remaining upper arms and in their chests.

For the study, researchers placed the robotic devices on the skin over those re-innervated muscles and vibrated them as the participants opened, closed, grasped or pinched with their prosthetic hands.

While the vibration was turned on, the participants “felt” their artificial hands moving and could adjust their grip based on the sensation. …

I have an April 24, 2017 posting about a tetraplegic patient who had a number of electrodes implanted in his arms and hands linked to a brain-machine interface and which allowed him to move his hands and arms; the implants were later removed. It is a different problem with a correspondingly different technological solution but there does seem to be increased interest in implanting sensors and electrodes into the human body to increase mobility and/or sensation.

Anderson describes how it ‘feels,

“It was kind of surreal,” Anderson said. “I could visually see the hand go out, I would touch something, I would squeeze it and my phantom hand felt like it was being closed and squeezing on something and it was sending the message back to my brain.

“It was a very strange sensation to actually be able to feel that feedback because I hadn’t in 10 years.”

The feeling of movement in the prosthetic hand is an illusion, the researchers say, since the vibration is actually happening to a muscle elsewhere in the body. But the sensation appeared to have a real effect on the participants.

“They were able to control their grasp function and how much they were opening the hand, to the same degree that someone with an intact hand would,” said study co-author Dr. Jacqueline Hebert, an associate professor in the Faculty of Rehabilitation Medicine at the University of Alberta.

…

Although the researchers are encouraged by the study findings, they acknowledge that there was a small number of participants, who all had access to the specialized re-innervation surgery to redirect the nerves from their amputated hands to other parts of their body.

The next step, they say, is to see if they can also simulate the feeling of movement in a broader range of people who have had other types of amputations, including legs, and have not had the re-innervation surgery.

…

Here’s a March 15, 2018 CBC New Brunswick radio interview about the work,

This is a bit longer than most of the embedded audio pieces that I have here but it’s worth it. Sadly, I can’t identify the interviewer who did a very good job with Jon Sensinger, associate director of UNB’s Institute of Biomedical Engineering. One more thing, I noticed that the interviewer made no mention of the University of Alberta in her introduction or in the subsequent interview. I gather regionalism reigns supreme everywhere in Canada. Or, maybe she and Sensinger just forgot. It happens when you’re excited. Also, there were US institutions in Ohio and Virginia that participated in this work.

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

Illusory movement perception improves motor control for prosthetic hands by Paul D. Marasco, Jacqueline S. Hebert, Jon W. Sensinger, Courtney E. Shell, Jonathon S. Schofield, Zachary C. Thumser, Raviraj Nataraj, Dylan T. Beckler, Michael R. Dawson, Dan H. Blustein, Satinder Gill, Brett D. Mensh, Rafael Granja-Vazquez, Madeline D. Newcomb, Jason P. Carey, and Beth M. Orzell. Science Translational Medicine 14 Mar 2018: Vol. 10, Issue 432, eaao6990 DOI: 10.1126/scitranslmed.aao6990

This paper is open access.

Superprostheses and our science fiction future

A March 20, 2018 news item on phys.org features an essay on about superprostheses and/or assistive devices,

Assistive devices may soon allow people to perform virtually superhuman feats. According to Robert Riener, however, there are more pressing goals than developing superhumans.

What had until recently been described as a futuristic vision has become a reality: the first self-declared “cyborgs” have had chips implanted in their bodies so that they can open doors and make cashless payments. The latest robotic hand prostheses succeed in performing all kinds of grips and tasks requiring dexterity. Parathletes fitted with running and spring prostheses compete – and win – against the best, non-impaired athletes. Then there are robotic pets and talking humanoid robots adding a bit of excitement to nursing homes.

Some media are even predicting that these high-tech creations will bring about forms of physiological augmentation overshadowing humans’ physical capabilities in ways never seen before. For instance, hearing aids are eventually expected to offer the ultimate in hearing; retinal implants will enable vision with a sharpness rivalling that of any eagle; motorised exoskeletons will transform soldiers into tireless fighting machines.

Visions of the future: the video game Deus Ex: Human Revolution highlights the emergence of physiological augmentation. (Visualisations: Square Enix) Courtesy: ETH Zurich

Professor Robert Riener uses the image above to illustrate the notion of superprosthese in his March 20, 2018 essay on the ETH Zurich website,

All of these prophecies notwithstanding, our robotic transformation into superheroes will not be happening in the immediate future and can still be filed under Hollywood hero myths. Compared to the technology available today, our bodies are a true marvel whose complexity and performance allows us to perform an extremely wide spectrum of tasks. Hundreds of efficient muscles, thousands of independently operating motor units along with millions of sensory receptors and billions of nerve cells allow us to perform delicate and detailed tasks with tweezers or lift heavy loads. Added to this, our musculoskeletal system is highly adaptable, can partly repair itself and requires only minimal amounts of energy in the form of relatively small amounts of food consumed.

Machines will not be able to match this any time soon. Today’s assistive devices are still laboratory experiments or niche products designed for very specific tasks. Markus Rehm, an athlete with a disability, does not use his innovative spring prosthesis to go for walks or drive a car. Nor can today’s conventional arm prostheses help a person tie their shoes or button up their shirt. Lifting devices used for nursing care are not suitable for helping with personal hygiene tasks or in psychotherapy. And robotic pets quickly lose their charm the moment their batteries die.

Solving real problems

There is no denying that advances continue to be made. Since the scientific and industrial revolutions, we have become dependent on relentless progress and growth, and we can no longer separate today’s world from this development. There are, however, more pressing issues to be solved than creating superhumans.

On the one hand, engineers need to dedicate their efforts to solving the real problems of patients, the elderly and people with disabilities. Better technical solutions are needed to help them lead normal lives and assist them in their work. We need motorised prostheses that also work in the rain and wheelchairs that can manoeuvre even with snow on the ground. Talking robotic nurses also need to be understood by hard-of-hearing pensioners as well as offer simple and dependable interactivity. Their batteries need to last at least one full day to be recharged overnight.

In addition, financial resources need to be available so that all people have access to the latest technologies, such as a high-quality household prosthesis for the family man, an extra prosthesis for the avid athlete or a prosthesis for the pensioner. [emphasis mine]

Breaking down barriers

What is just as important as the ongoing development of prostheses and assistive devices is the ability to minimise or eliminate physical barriers. Where there are no stairs, there is no need for elaborate special solutions like stair lifts or stairclimbing wheelchairs – or, presumably, fully motorised exoskeletons.

Efforts also need to be made to transform the way society thinks about people with disabilities. More acknowledgement of the day-to-day challenges facing patients with disabilities is needed, which requires that people be confronted with the topic of disability when they are still children. Such projects must be promoted at home and in schools so that living with impairments can also attain a state of normality and all people can partake in society. It is therefore also necessary to break down mental barriers.

The road to a virtually superhuman existence is still far and long. Anyone reading this text will not live to see it. In the meantime, the task at hand is to tackle the mundane challenges in order to simplify people’s daily lives in ways that do not require technology, that allow people to be active participants and improve their quality of life – instead of wasting our time getting caught up in cyborg euphoria and digital mania.

I’m struck by Riener’s reference to financial resources and access. Sensinger mentions financial resources in his CBC radio interview although his concern is with convincing funders that prostheses that mimic ‘feeling’ are needed.

I’m also struck by Riener’s discussion about nontechnological solutions for including people with all kinds of abilities and disabilities.

There was no grand plan for combining these two news bits; I just thought they were interesting together.

Soft things for your brain

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A March 5, 2018 news item on Nanowerk describes the latest stretchable electrode (Note: A link has been removed),

Klas Tybrandt, principal investigator at the Laboratory of Organic Electronics at Linköping University [Sweden], has developed new technology for long-term stable neural recording. It is based on a novel elastic material composite, which is biocompatible and retains high electrical conductivity even when stretched to double its original length.

The result has been achieved in collaboration with colleagues in Zürich and New York. The breakthrough, which is crucial for many applications in biomedical engineering, is described in an article published in the prestigious scientific journal Advanced Materials (“High-Density Stretchable Electrode Grids for Chronic Neural Recording”).

A March 5, 2018 Linköping University press release, which originated the news item, gives more detail but does not mention that the nanowires are composed of titanium dioxide (you can find additional details in the abstract for the paper; link and citation will be provided later in this posting)),

The coupling between electronic components and nerve cells is crucial not only to collect information about cell signalling, but also to diagnose and treat neurological disorders and diseases, such as epilepsy.

It is very challenging to achieve long-term stable connections that do not damage neurons or tissue, since the two systems, the soft and elastic tissue of the body and the hard and rigid electronic components, have completely different mechanical properties.

The soft electrode stretched to twice its length Photo credit: Thor Balkhed

“As human tissue is elastic and mobile, damage and inflammation arise at the interface with rigid electronic components. It not only causes damage to tissue; it also attenuates neural signals,” says Klas Tybrandt, leader of the Soft Electronics group at the Laboratory of Organic Electronics, Linköping University, Campus Norrköping.

New conductive material

Klas Tybrandt has developed a new conductive material that is as soft as human tissue and can be stretched to twice its length. The material consists of gold coated titanium dioxide nanowires, embedded into silicone rubber. The material is biocompatible – which means it can be in contact with the body without adverse effects – and its conductivity remains stable over time.

“The microfabrication of soft electrically conductive composites involves several challenges. We have developed a process to manufacture small electrodes that also preserves the biocompatibility of the materials. The process uses very little material, and this means that we can work with a relatively expensive material such as gold, without the cost becoming prohibitive,” says Klas Tybrandt.

The electrodes are 50 µm [microns or micrometres] in size and are located at a distance of 200 µm from each other. The fabrication procedure allows 32 electrodes to be placed onto a very small surface. The final probe, shown in the photograph, has a width of 3.2 mm and a thickness of 80 µm.

The soft microelectrodes have been developed at Linköping University and ETH Zürich, and researchers at New York University and Columbia University have subsequently implanted them in the brain of rats. The researchers were able to collect high-quality neural signals from the freely moving rats for 3 months. The experiments have been subject to ethical review, and have followed the strict regulations that govern animal experiments.

Important future applications

Klas Tybrandt, researcher at Laboratory for Organic Electronics Photo credit: Thor Balkhed

“When the neurons in the brain transmit signals, a voltage is formed that the electrodes detect and transmit onwards through a tiny amplifier. We can also see which electrodes the signals came from, which means that we can estimate the location in the brain where the signals originated. This type of spatiotemporal information is important for future applications. We hope to be able to see, for example, where the signal that causes an epileptic seizure starts, a prerequisite for treating it. Another area of application is brain-machine interfaces, by which future technology and prostheses can be controlled with the aid of neural signals. There are also many interesting applications involving the peripheral nervous system in the body and the way it regulates various organs,” says Klas Tybrandt.

The breakthrough is the foundation of the research area Soft Electronics, currently being established at Linköping University, with Klas Tybrandt as principal investigator.
liu.se/soft-electronics

A video has been made available (Note: For those who find any notion of animal testing disturbing; don’t watch the video even though it is an animation and does not feature live animals),

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

High-Density Stretchable Electrode Grids for Chronic Neural Recording by Klas Tybrandt, Dion Khodagholy, Bernd Dielacher, Flurin Stauffer, Aline F. Renz, György Buzsáki, and János Vörös. Advanced Materials 2018. DOI: 10.1002/adma.201706520  First published 28 February 2018

This paper is open access.

World heritage music stored in DNA

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It seems a Swiss team from the École Polytechnique de Lausanne (EPFL) have collaborated with American companies Twist Bioscience and Microsoft, as well as, the University of Washington (state) to preserve two iconic jazz pieces on DNA (deoxyribonucleic acid) according to a Sept. 29, 2017 news item on phys.org,,

Thanks to an innovative technology for encoding data in DNA strands, two items of world heritage – songs recorded at the Montreux Jazz Festival [held in Switzerland] and digitized by EPFL – have been safeguarded for eternity. This marks the first time that cultural artifacts granted UNESCO heritage status have been saved in such a manner, ensuring they are preserved for thousands of years. The method was developed by US company Twist Bioscience and is being unveiled today in a demonstrator created at the EPFL+ECAL Lab.

“Tutu” by Miles Davis and “Smoke on the Water” by Deep Purple have already made their mark on music history. Now they have entered the annals of science, for eternity. Recordings of these two legendary songs were digitized by the Ecole Polytechnique Fédérale de Lausanne (EPFL) as part of the Montreux Jazz Digital Project, and they are the first to be stored in the form of a DNA sequence that can be subsequently decoded and listened to without any reduction in quality.

A Sept. 29, 2017 EPFL press release by Emmanuel Barraud, which originated the news item, provides more details,

This feat was achieved by US company Twist Bioscience working in association with Microsoft Research and the University of Washington. The pioneering technology is actually based on a mechanism that has been at work on Earth for billions of years: storing information in the form of DNA strands. This fundamental process is what has allowed all living species, plants and animals alike, to live on from generation to generation.

The entire world wide web in a shoe box

All electronic data storage involves encoding data in binary format – a series of zeros and ones – and then recording it on a physical medium. DNA works in a similar way, but is composed of long strands of series of four nucleotides (A, T, C and G) that make up a “code.” While the basic principle may be the same, the two methods differ greatly in terms of efficiency: if all the information currently on the internet was stored in the form of DNA, it would fit in a shoe box!

Recent advances in biotechnology now make it possible for humans to do what Mother Nature has always done. Today’s scientists can create artificial DNA strands, “record” any kind of genetic code on them and then analyze them using a sequencer to reconstruct the original data. What’s more, DNA is extraordinarily stable, as evidenced by prehistoric fragments that have been preserved in amber. Artificial strands created by scientists and carefully encapsulated should likewise last for millennia.

To help demonstrate the feasibility of this new method, EPFL’s Metamedia Center provided recordings of two famous songs played at the Montreux Jazz Festival: “Tutu” by Miles Davis, and “Smoke on the Water” by Deep Purple. Twist Bioscience and its research partners encoded the recordings, transformed them into DNA strands and then sequenced and decoded them and played them again – without any reduction in quality.

The amount of artificial DNA strands needed to record the two songs is invisible to the naked eye, and the amount needed to record all 50 years of the Festival’s archives, which have been included in UNESCO’s [United Nations Educational, Scientific and Cultural Organization] Memory of the World Register, would be equal in size to a grain of sand. “Our partnership with EPFL in digitizing our archives aims not only at their positive exploration, but also at their preservation for the next generations,” says Thierry Amsallem, president of the Claude Nobs Foundation. “By taking part in this pioneering experiment which writes the songs into DNA strands, we can be certain that they will be saved on a medium that will never become obsolete!”

A new concept of time

At EPFL’s first-ever ArtTech forum, attendees got to hear the two songs played after being stored in DNA, using a demonstrator developed at the EPFL+ECAL Lab. The system shows that being able to store data for thousands of years is a revolutionary breakthrough that can completely change our relationship with data, memory and time. “For us, it means looking into radically new ways of interacting with cultural heritage that can potentially cut across civilizations,” says Nicolas Henchoz, head of the EPFL+ECAL Lab.

Quincy Jones, a longstanding Festival supporter, is particularly enthusiastic about this technological breakthrough: “With advancements in nanotechnology, I believe we can expect to see people living prolonged lives, and with that, we can also expect to see more developments in the enhancement of how we live. For me, life is all about learning where you came from in order to get where you want to go, but in order to do so, you need access to history! And with the unreliability of how archives are often stored, I sometimes worry that our future generations will be left without such access… So, it absolutely makes my soul smile to know that EPFL, Twist Bioscience and their partners are coming together to preserve the beauty and history of the Montreux Jazz Festival for our future generations, on DNA! I’ve been a part of this festival for decades and it truly is a magnificent representation of what happens when different cultures unite for the sake of music. Absolute magic. And I’m proud to know that the memory of this special place will never be lost.

A Sept. 29, 2017 Twist Bioscience news release is repetitive in some ways but interesting nonetheless,

Twist Bioscience, a company accelerating science and innovation through rapid, high-quality DNA synthesis, today announced that, working with Microsoft and University of Washington researchers, they have successfully stored archival-quality audio recordings of two important music performances from the archives of the world-renowned Montreux Jazz Festival.

These selections are encoded and stored in nature’s preferred storage medium, DNA, for the first time. These tiny specks of DNA will preserve a part of UNESCO’s Memory of the World Archive, where valuable cultural heritage collections are recorded. This is the first time DNA has been used as a long-term archival-quality storage medium.

Quincy Jones, world-renowned Entertainment Executive, Music Composer and Arranger, Musician and Music Producer said, “With advancements in nanotechnology, I believe we can expect to see people living prolonged lives, and with that, we can also expect to see more developments in the enhancement of how we live. For me, life is all about learning where you came from in order to get where you want to go, but in order to do so, you need access to history! And with the unreliability of how archives are often stored, I sometimes worry that our future generations will be left without such access…So, it absolutely makes my soul smile to know that EPFL, Twist Bioscience and others are coming together to preserve the beauty and history of the Montreux Jazz Festival for our future generations, on DNA!…I’ve been a part of this festival for decades and it truly is a magnificent representation of what happens when different cultures unite for the sake of music. Absolute magic. And I’m proud to know that the memory of this special place will never be lost.”

“Our partnership with EPFL in digitizing our archives aims not only at their positive exploration, but also at their preservation for the next generations,” says Thierry Amsallem, president of the Claude Nobs Foundation. “By taking part in this pioneering experiment which writes the songs into DNA strands, we can be certain that they will be saved on a medium that will never become obsolete!”

The Montreux Jazz Digital Project is a collaboration between the Claude Nobs Foundation, curator of the Montreux Jazz Festival audio-visual collection and the École Polytechnique Fédérale de Lausanne (EPFL) to digitize, enrich, store, show, and preserve this notable legacy created by Claude Nobs, the Festival’s founder.

In this proof-of-principle project, two quintessential music performances from the Montreux Jazz Festival – Smoke on the Water, performed by Deep Purple and Tutu, performed by Miles Davis – have been encoded onto DNA and read back with 100 percent accuracy. After being decoded, the songs were played on September 29th [2017] at the ArtTech Forum (see below) in Lausanne, Switzerland. Smoke on the Water was selected as a tribute to Claude Nobs, the Montreux Jazz Festival’s founder. The song memorializes a fire and Funky Claude’s rescue efforts at the Casino Barrière de Montreux during a Frank Zappa concert promoted by Claude Nobs. Miles Davis’ Tutu was selected for the role he played in music history and the Montreux Jazz Festival’s success. Miles Davis died in 1991.

“We archived two magical musical pieces on DNA of this historic collection, equating to 140MB of stored data in DNA,” said Karin Strauss, Ph.D., a Senior Researcher at Microsoft, and one of the project’s leaders. “The amount of DNA used to store these songs is much smaller than one grain of sand. Amazingly, storing the entire six petabyte Montreux Jazz Festival’s collection would result in DNA smaller than one grain of rice.”

Luis Ceze, Ph.D., a professor in the Paul G. Allen School of Computer Science & Engineering at the University of Washington, said, “DNA, nature’s preferred information storage medium, is an ideal fit for digital archives because of its durability, density and eternal relevance. Storing items from the Montreux Jazz Festival is a perfect way to show how fast DNA digital data storage is becoming real.”

Nature’s Preferred Storage Medium

Nature selected DNA as its hard drive billions of years ago to encode all the genetic instructions necessary for life. These instructions include all the information necessary for survival. DNA molecules encode information with sequences of discrete units. In computers, these discrete units are the 0s and 1s of “binary code,” whereas in DNA molecules, the units are the four distinct nucleotide bases: adenine (A), cytosine (C), guanine (G) and thymine (T).

“DNA is a remarkably efficient molecule that can remain stable for millennia,” said Bill Peck, Ph.D., chief technology officer of Twist Bioscience. “This is a very exciting project: we are now in an age where we can use the remarkable efficiencies of nature to archive master copies of our cultural heritage in DNA. As we develop the economies of this process new performances can be added any time. Unlike current storage technologies, nature’s media will not change and will remain readable through time. There will be no new technology to replace DNA, nature has already optimized the format.”

DNA: Far More Efficient Than a Computer

Each cell within the human body contains approximately three billion base pairs of DNA. With 75 trillion cells in the human body, this equates to the storage of 150 zettabytes (1021) of information within each body. By comparison, the largest data centers can be hundreds of thousands to even millions of square feet to hold a comparable amount of stored data.

The Elegance of DNA as a Storage Medium

Like music, which can be widely varied with a finite number of notes, DNA encodes individuality with only four different letters in varied combinations. When using DNA as a storage medium, there are several advantages in addition to the universality of the format and incredible storage density. DNA can be stable for thousands of years when stored in a cool dry place and is easy to copy using polymerase chain reaction to create back-up copies of archived material. In addition, because of PCR, small data sets can be targeted and recovered quickly from a large dataset without needing to read the entire file.

How to Store Digital Data in DNA

To encode the music performances into archival storage copies in DNA, Twist Bioscience worked with Microsoft and University of Washington researchers to complete four steps: Coding, synthesis/storage, retrieval and decoding. First, the digital files were converted from the binary code using 0s and 1s into sequences of A, C, T and G. For purposes of the example, 00 represents A, 10 represents C, 01 represents G and 11 represents T. Twist Bioscience then synthesizes the DNA in short segments in the sequence order provided. The short DNA segments each contain about 12 bytes of data as well as a sequence number to indicate their place within the overall sequence. This is the process of storage. And finally, to ensure that the file is stored accurately, the sequence is read back to ensure 100 percent accuracy, and then decoded from A, C, T or G into a two-digit binary representation.

Importantly, to encapsulate and preserve encoded DNA, the collaborators are working with Professor Dr. Robert Grass of ETH Zurich. Grass has developed an innovative technology inspired by preservation of DNA within prehistoric fossils. With this technology, digital data encoded in DNA remains preserved for millennia.

About UNESCO’s Memory of the World Register

UNESCO established the Memory of the World Register in 1992 in response to a growing awareness of the perilous state of preservation of, and access to, documentary heritage in various parts of the world. Through its National Commissions, UNESCO prepared a list of endangered library and archive holdings and a world list of national cinematic heritage.

A range of pilot projects employing contemporary technology to reproduce original documentary heritage on other media began. These included, for example, a CD-ROM of the 13th Century Radzivill Chronicle, tracing the origins of the peoples of Europe, and Memoria de Iberoamerica, a joint newspaper microfilming project involving seven Latin American countries. These projects enhanced access to this documentary heritage and contributed to its preservation.

“We are incredibly proud to be a part of this momentous event, with the first archived songs placed into the UNESCO Memory of the World Register,” said Emily Leproust, Ph.D., CEO of Twist Bioscience.

About ArtTech

The ArtTech Foundation, created by renowned scientists and dignitaries from Crans-Montana, Switzerland, wishes to stimulate reflection and support pioneering and innovative projects beyond the known boundaries of culture and science.

Benefitting from the establishment of a favorable environment for the creation of technology companies, the Foundation aims to position itself as key promoter of ideas and innovative endeavors within a landscape of “Culture and Science” that is still being shaped.

Several initiatives, including our annual global platform launched in the spring of 2017, are helping to create a community that brings together researchers, celebrities in the world of culture and the arts, as well as investors and entrepreneurs from Switzerland and across the globe.

About EPFL

EPFL, one of the two Swiss Federal Institutes of Technology, based in Lausanne, is Europe’s most cosmopolitan technical university with students, professors and staff from over 120 nations. A dynamic environment, open to Switzerland and the world, EPFL is centered on its three missions: teaching, research and technology transfer. EPFL works together with an extensive network of partners including other universities and institutes of technology, developing and emerging countries, secondary schools and colleges, industry and economy, political circles and the general public, to bring about real impact for society.

About Twist Bioscience

At Twist Bioscience, our expertise is accelerating science and innovation by leveraging the power of scale. We have developed a proprietary semiconductor-based synthetic DNA manufacturing process featuring a high throughput silicon platform capable of producing synthetic biology tools, including genes, oligonucleotide pools and variant libraries. By synthesizing DNA on silicon instead of on traditional 96-well plastic plates, our platform overcomes the current inefficiencies of synthetic DNA production, and enables cost-effective, rapid, high-quality and high throughput synthetic gene production, which in turn, expedites the design, build and test cycle to enable personalized medicines, pharmaceuticals, sustainable chemical production, improved agriculture production, diagnostics and biodetection. We are also developing new technologies to address large scale data storage. For more information, please visit www.twistbioscience.com. Twist Bioscience is on Twitter. Sign up to follow our Twitter feed @TwistBioscience at https://twitter.com/TwistBioscience.

If you hadn’t read the EPFL press release first, it might have taken a minute to figure out why EPFL is being mentioned in the Twist Bioscience news release. Presumably someone was rushing to make a deadline. Ah well, I’ve seen and written worse.

I haven’t been able to find any video or audio recordings of the DNA-preserved performances but there is an informational video (originally published July 7, 2016) from Microsoft and the University of Washington describing the DNA-based technology,

I also found this description of listening to the DNA-preserved music in an Oct. 6, 2017 blog posting for the Canadian Broadcasting Corporation’s (CBC) Day 6 radio programme,

To listen to them, one must first suspend the DNA holding the songs in a solution. Next, one can use a DNA sequencer to read the letters of the bases forming the molecules. Then, algorithms can determine the digital code those letters form. From that code, comes the music.

It’s complicated but Ceze says his team performed this process without error.

You can find out more about UNESCO’s Memory of the World and its register here , more about the EPFL+ECAL Lab here, and more about Twist Bioscience here.

Bandage with a voice (sort of)

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Researchers at Empa (Swiss Federal Laboratories for Materials Testing and Research) have not developed a talking bandage despite the title (Bandage with a Voice) for a July 4, 2017 Empa press release (also a July 4, 2017 news item on Nanowerk),

A novel bandage alerts the nursing staff as soon as a wound starts healing badly. Sensors incorporated into the base material glow with a different intensity if the wound’s pH level changes. This way even chronic wounds could be monitored at home.

Using a UV lamp, the pH level in the wound can be verified without removing the bandage and the healing process can continue unimpeded. Image: Empa / CSEM

All too often, changing bandages is extremely unpleasant, even for smaller, everyday injuries. It stings and pulls, and sometimes a scab will even start bleeding again. And so we prefer to wait until the bandage drops off by itself.

It’s a different story with chronic wounds, though: normally, the nursing staff has to change the dressing regularly – not just for reasons of hygiene, but also to examine the wound, take swabs and clean it. Not only does this irritate the skin unnecessarily; bacteria can also get in, the risk of infection soars. It would be much better to leave the bandage on for longer and have the nursing staff “read” the condition of the wound from outside.

The idea of being able to see through a wound dressing gave rise to the project Flusitex (Fluorescence sensing integrated into medical textiles), which is being funded by the Swiss initiative Nano-Tera. Researchers from Empa teamed up with ETH Zurich, Centre Suisse d’Electronique et de Microtechnique (CSEM) and University Hospital Zurich to develop a high-tech system that is supposed to supply the nursing staff with relevant data about the condition of a wound. As Luciano Boesel from Empa’s Laboratory for Biomimetic Membranes and Textiles, who is coordinating the project at Empa, explains: “The idea of a smart wound dressing with integrated sensors is to provide continuous information on the state of the healing process without the bandages having to be changed any more frequently than necessary.” This would mean a gentler treatment for patients, less work for the nursing staff and, therefore, lower costs: globally, around 17 billion $ were spent on treating wounds last year.

When wounds heal, the body produces specific substances in a complex sequence of biochemical processes, which leads to a significant variation in a number of metabolic parameters. For instance, the amount of glucose and oxygen rises and falls depending on the phase of the healing process; likewise does the pH level change. All these variations can be detected with specialized sensors. With this in mind, Empa teamed up with project partner CSEM to develop a portable, cheap and easy-to-use device for measuring fluorescence that is capable of monitoring several parameters at once. It should enable nursing staff to keep tabs on the pH as well as on glucose and oxygen levels while the wound heals. If these change, conclusions about other key biochemical processes involved in wound healing can be drawn.

The bandage reveals ist measurings in UV light.

A high pH signals chronic wounds

The pH level is particularly useful for chronic wounds. If the wound heals normally, the pH rises to 8 before falling to 5 or 6. If a wound fails to close and becomes chronic, however, the pH level fluctuates between 7 and 8. Therefore, it would be helpful if a signal on the bandage could inform the nursing staff that the wound pH is permanently high. If the bandage does not need changing for reasons of hygiene and pH levels are low, on the other hand, they could afford to wait.

But how do the sensors work? The idea: if certain substances appear in the wound fluid, “customized” fluorescent sensor molecules respond with a physical signal. They start glowing and some even change color in the visible or ultra-violet (UV) range. Thanks to a color scale, weaker and stronger changes in color can be detected and the quantity of the emitted substance be deduced.

Empa chemist Guido Panzarasa from the Laboratory for Biomimetic Membranes and Textiles vividly demonstrates how a sample containing sensor molecules begins to fluoresce in the lab. He carefully drips a solution with a pH level of 7.5 into a dish. Under a UV light, the change is plain to see. He adds another solution and the luminescence fades. A glance at the little bottle confirms it: the pH level of the second solution is lower.

Luminous molecules under UV

The Empa team designed a molecule composed of benzalkonium chloride and pyranine. While benzalkonium chloride is a substance also used for conventional medical soap to combat bacteria, fungi and other microorganisms, pyranine is a dye found in highlighters that glows under UV light. “This biomarker works really well,” says Panzarasa; “especially at pH levels between 5.5 and 7.5. The colors can be visualized with simple UV lamps available in electronics stores.” The Empa team recently published their results in the journal “Sensors and Actuators”.

The designer molecule has another advantage: thanks to the benzalkonium chloride, it has an antimicrobial effect, as researchers from Empa’s Laboratory for Biointerfaces confirmed for the bacteria strain Staphylococcus aureus. Unwelcome bacteria might potentially also be combatted by selecting the right bandage material in future. As further investigations, such as on the chemical’s compatibility with cells and tissues, are currently lacking, however, the researchers do not yet know how their sensor works in a complex wound.

Keen interest from industry

In order to illustrate what a smart wound dressing might actually look like in future, Boesel places a prototype on the lab bench. “You don’t have to cover the entire surface of wound dressings with sensors,” he explains. “It’s enough for a few small areas to be impregnated with the pyranine benzalkonium molecules and integrated into the base material. This means the industrial wound dressings won’t be much pricier than they are now – only up to 20% more expensive.” Empa scientists are currently working on this in the follow-up project FlusiTex-Gateway in cooperation with industrial partners Flawa, Schöller, Kenzen and Theranoptics.
Panzarasa now drips various liquids with different pH levels onto all the little cylinders on the wound pad prototype. Sure enough, the lighter and darker dots are also clearly discernible as soon as the UV lamp is switched on. They are even visible to the naked eye and glow in bright yellow if liquids with a high pH come into contact with the sensor. The scientists are convinced: since the pH level is so easy to read and provides precise information about the acidic or alkaline state of the sample, this kind of wound dressing is just the ticket as a diagnostic tool. Using the fluorescence meter developed by CSEM, more accurate, quantitative measure-ments of the pH level can be accomplished for medical purposes.

According to Boesel, it might one day even be possible to read the signals with the aid of a smartphone camera. Combined with a simple app, nursing staff and doctors would have a tool that enables them to easily and conveniently read the wound status “from outside”, even without a UV lamp. And patients would then also have the possibility of detecting the early onset of a chronic wound at home.

I wonder how long or even if this innovation will ever make its way into medical practice. I’m guessing this stage would be described as ‘proof of concept’ and that clinical testing is still many years away.

The metaphor in the press release’s title helped to wake me up. Thank you to whoever wrote it.

Nanoparticle behaviour in the environment unpredictable

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These Swiss researchers took on a fairly massive project according to an April 19, 2017 news item on ScienceDaily,

The nanotech industry is booming. Every year, several thousands of tonnes of man-made nanoparticles are produced worldwide; sooner or later, a certain part of them will end up in bodies of water or soil. But even experts find it difficult to say exactly what happens to them there. It is a complex question, not only because there are many different types of man-made (engineered) nanoparticles, but also because the particles behave differently in the environment depending on the prevailing conditions.

Researchers led by Martin Scheringer, Senior Scientist at the Department of Chemistry and Applied Biosciences, wanted to bring some clarity to this issue. They reviewed 270 scientific studies, and the nearly 1,000 laboratory experiments described in them, looking for patterns in the behaviour of engineered nanoparticles. The goal was to make universal predictions about the behaviour of the particles.

An April 19, 2017ETH Zurich press release by Fabio Bergamin (also on EurekAlert), which originated the news item, elaborates,

Particles attach themselves to everything

However, the researchers found a very mixed picture when they looked at the data. “The situation is more complex than many scientists would previously have predicted,” says Scheringer. “We need to recognise that we can’t draw a uniform picture with the data available to us today.”

Nicole Sani-Kast, a doctoral student in Scheringer’s group and first author of the analysis published in the journal PNAS [Proceedings of the National Academy of Sciences], adds: “Engineered nanoparticles behave very dynamically and are highly reactive. They attach themselves to everything they find: to other nanoparticles in order to form agglomerates, or to other molecules present in the environment.”

Network analysis

To what exactly the particles react, and how quickly, depends on various factors such as the acidity of the water or soil, the concentration of the existing minerals and salts, and above all, the composition of the organic substances dissolved in the water or present in the soil. The fact that the engineered nanoparticles often have a surface coating makes things even more complicated. Depending on the environmental conditions, the particles retain or lose their coating, which in turn influences their reaction behaviour.

To evaluate the results available in the literature, Sani-Kast used a network analysis for the first time in this research field. It is a technique familiar in social research for measuring networks of social relations, and allowed her to show that the data available on engineered nanoparticles is inconsistent, insufficiently diverse and poorly structured.

More method for machine learning

“If more structured, consistent and sufficiently diverse data were available, it may be possible to discover universal patterns using machine learning methods,” says Scheringer, “but we’re not there yet.” Enough structured experimental data must first be available.

“In order for the scientific community to carry out such experiments in a systematic and standardised manner, some kind of coordination is necessary,” adds Sani-Kast, but she is aware that such work is difficult to coordinate. Scientists are generally well known for preferring to explore new methods and conditions rather than routinely performing standardized experiments.

[additional material]

Distinguishing man-made and natural nanoparticles

In addition to the lack of systematic research, there is also a second tangible problem in researching the behaviour of engineered nanoparticles: many engineered nanoparticles consist of chemical compounds that occur naturally in the soil. So far it has been difficult to measure the engineered particles in the environment since it is hard to distinguish them from naturally occurring particles with the same chemical composition.

However, researchers at ETH Zurich’s Department of Chemistry and Applied Biosciences, under the direction of ETH Professor Detlef Günther, have recently established an effective method that makes such a distinction possible in routine investigations. They used a state-of-the-art and highly sensitive mass spectrometry technique (called spICP-TOF mass spectrometry) to determine which chemical elements make up individual nanoparticles in a sample.

In collaboration with scientists from the University of Vienna, the ETH researchers applied the method to soil samples with natural cerium-containing particles, into which they mixed engineered cerium dioxide nanoparticles. Using machine learning methods, which were ideally suited to this particular issue, the researchers were able to identify differences in the chemical fingerprints of the two particle classes. “While artificially produced nanoparticles often consist of a single compound, natural nanoparticles usually still contain a number of additional chemical elements,” explains Alexander Gundlach-Graham, a postdoc in Günther’s group.

The new measuring method is very sensitive: the scientists were able to measure engineered particles in samples with up to one hundred times more natural particles.

The researchers have produced a visualization of their network analysis,

The researchers evaluated the experimental data published in the scientific literature using a network analysis. This analysis reveals which types of nanoparticles (blue) have been studied under which environmental conditions (red). (Visualisations: Thomas Kast)

Here are links and citation for two papers associated with this research,

A network perspective reveals decreasing material diversity in studies on nanoparticle interactions with dissolved organic matter by Nicole Sani-Kast, Jérôme Labille, Patrick Ollivier, Danielle Slomberg, Konrad Hungerbühler, and Martin Scheringer. PNAS 2017, 114: E1756-E1765, DOI: 10.1073/pnas.1608106114

Single-particle multi-element fingerprinting (spMEF) using inductively-coupled plasma time-of-flight mass spectrometry (ICP-TOFMS) to identify engineered nanoparticles against the elevated natural background in soils by Antonia Praetorius, Alexander Gundlach-Graham, Eli Goldberg, Willi Fabienke, Jana Navratilova, Andreas Gondikas, Ralf Kaegi, Detlef Günther, Thilo Hofmann, and Frank von der Kammer. Environonmental Science: Nano 2017, 4: 307-314, DOI: 10.1039/c6en00455e

Both papers are behind a paywall.

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Tag Archives: ETH Zurich

Graphene can be used in quantum components

Exotic magnetism: a quantum simulation from D-Wave Sytems

Quantum annealing and more

Graphene and its magnetism

University of Cambridge and superconductivity

Aalto University’s valleytronics

Citations and links

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

Detecting off-target effects of CRISPR gene-editing

Money

AstraZeneca

Innovative Genomics Institute (IGI)

Gladstone Institutes

Final comments

Better motor control for prosthetic hands (the illusion of feeling) and a discussion of superprostheses and reality

Better motor control

Superprostheses and our science fiction future

Solving real problems

Breaking down barriers

Soft things for your brain

New conductive material

Important future applications

World heritage music stored in DNA

Bandage with a voice (sort of)

A high pH signals chronic wounds

Luminous molecules under UV

Keen interest from industry

Nanoparticle behaviour in the environment unpredictable