Tag Archives: University of Groningen

A formal theory for neuromorphic (brainlike) computing hardware needed

This is one my older pieces as the information dates back to October 2023 but neuromorphic computing is one of my key interests and I’m particularly interested to see the upsurge in the discussion of hardware, here goes. From an October 17, 2023 news item on Nanowerk,

There is an intense, worldwide search for novel materials to build computer microchips with that are not based on classic transistors but on much more energy-saving, brain-like components. However, whereas the theoretical basis for classic transistor-based digital computers is solid, there are no real theoretical guidelines for the creation of brain-like computers.

Such a theory would be absolutely necessary to put the efforts that go into engineering new kinds of microchips on solid ground, argues Herbert Jaeger, Professor of Computing in Cognitive Materials at the University of Groningen [Netherlands].

Key Takeaways
Scientists worldwide are searching for new materials to build energy-saving, brain-like computer microchips as classic transistor miniaturization reaches its physical limit.

Theoretical guidelines for brain-like computers are lacking, making it crucial for advancements in the field.

The brain’s versatility and robustness serve as an inspiration, despite limited knowledge about its exact workings.

A recent paper suggests that a theory for non-digital computers should focus on continuous, analogue signals and consider the characteristics of new materials.

Bridging gaps between diverse scientific fields is vital for developing a foundational theory for neuromorphic computing..

An October 17, 2023 University of Groningen press release (also on EurekAlert), which originated the news item, provides more context for this proposal,

Computers have, so far, relied on stable switches that can be off or on, usually transistors. These digital computers are logical machines and their programming is also based on logical reasoning. For decades, computers have become more powerful by further miniaturization of the transistors, but this process is now approaching a physical limit. That is why scientists are working to find new materials to make more versatile switches, which could use more values than just the digitals 0 or 1.

Dangerous pitfall

Jaeger is part of the Groningen Cognitive Systems and Materials Center (CogniGron), which aims to develop neuromorphic (i.e. brain-like) computers. CogniGron is bringing together scientists who have very different approaches: experimental materials scientists and theoretical modelers from fields as diverse as mathematics, computer science, and AI. Working closely with materials scientists has given Jaeger a good idea of the challenges that they face when trying to come up with new computational materials, while it has also made him aware of a dangerous pitfall: there is no established theory for the use of non-digital physical effects in computing systems.

Our brain is not a logical system. We can reason logically, but that is only a small part of what our brain does. Most of the time, it must work out how to bring a hand to a teacup or wave to a colleague on passing them in a corridor. ‘A lot of the information-processing that our brain does is this non-logical stuff, which is continuous and dynamic. It is difficult to formalize this in a digital computer,’ explains Jaeger. Furthermore, our brains keep working despite fluctuations in blood pressure, external temperature, or hormone balance, and so on. How is it possible to create a computer that is as versatile and robust? Jaeger is optimistic: ‘The simple answer is: the brain is proof of principle that it can be done.’

Neurons

The brain is, therefore, an inspiration for materials scientists. Jaeger: ‘They might produce something that is made from a few hundred atoms and that will oscillate, or something that will show bursts of activity. And they will say: “That looks like how neurons work, so let’s build a neural network”.’ But they are missing a vital bit of knowledge here. ‘Even neuroscientists don’t know exactly how the brain works. This is where the lack of a theory for neuromorphic computers is problematic. Yet, the field doesn’t appear to see this.’

In a paper published in Nature Communications on 16 August, Jaeger and his colleagues Beatriz Noheda (scientific director of CogniGron) and Wilfred G. van der Wiel (University of Twente) present a sketch of what a theory for non-digital computers might look like. They propose that instead of stable 0/1 switches, the theory should work with continuous, analogue signals. It should also accommodate the wealth of non-standard nanoscale physical effects that the materials scientists are investigating.

Sub-theories

Something else that Jaeger has learned from listening to materials scientists is that devices from these new materials are difficult to construct. Jaeger: ‘If you make a hundred of them, they will not all be identical.’ This is actually very brain-like, as our neurons are not all exactly identical either. Another possible issue is that the devices are often brittle and temperature-sensitive, continues Jaeger. ‘Any theory for neuromorphic computing should take such characteristics into account.’

Importantly, a theory underpinning neuromorphic computing will not be a single theory but will be constructed from many sub-theories (see image below). Jaeger: ‘This is in fact how digital computer theory works as well, it is a layered system of connected sub-theories.’ Creating such a theoretical description of neuromorphic computers will require close collaboration of experimental materials scientists and formal theoretical modellers. Jaeger: ‘Computer scientists must be aware of the physics of all these new materials [emphasis mine] and materials scientists should be aware of the fundamental concepts in computing.’

Blind spots

Bridging this divide between materials science, neuroscience, computing science, and engineering is exactly why CogniGron was founded at the University of Groningen: it brings these different groups together. ‘We all have our blind spots,’ concludes Jaeger. ‘And the biggest gap in our knowledge is a foundational theory for neuromorphic computing. Our paper is a first attempt at pointing out how such a theory could be constructed and how we can create a common language.’

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

Toward a formal theory for computing machines made out of whatever physics offers by Herbert Jaeger, Beatriz Noheda & Wilfred G. van der Wiel. Nature Communications volume 14, Article number: 4911 (2023) DOI: https://doi.org/10.1038/s41467-023-40533-1 Published: 16 August 2023

This paper is open access and there’s a 76 pp. version, “Toward a formal theory for computing machines made out of whatever physics offers: extended version” (emphasis mine) available on arXchiv.

Caption: A general theory of physical computing systems would comprise existing theories as special cases. Figure taken from an extended version of the Nature Comm paper on arXiv. Credit: Jaeger et al. / University of Groningen

With regard to new materials for neuromorphic computing, my January 4, 2024 posting highlights a proposed quantum material for this purpose.

Memristors, it’s all about the oxides

I have one research announcement from China and another from the Netherlands, both of which concern memristors and oxides.

China

A May 17, 2021 news item on Nanowerk announces work, which suggests that memristors may not need to rely solely on oxides but could instead utilize light more gainfully,

Scientists are getting better at making neuron-like junctions for computers that mimic the human brain’s random information processing, storage and recall. Fei Zhuge of the Chinese Academy of Sciences and colleagues reviewed the latest developments in the design of these ‘memristors’ for the journal Science and Technology of Advanced Materials …

Computers apply artificial intelligence programs to recall previously learned information and make predictions. These programs are extremely energy- and time-intensive: typically, vast volumes of data must be transferred between separate memory and processing units. To solve this issue, researchers have been developing computer hardware that allows for more random and simultaneous information transfer and storage, much like the human brain.

Electronic circuits in these ‘neuromorphic’ computers include memristors that resemble the junctions between neurons called synapses. Energy flows through a material from one electrode to another, much like a neuron firing a signal across the synapse to the next neuron. Scientists are now finding ways to better tune this intermediate material so the information flow is more stable and reliable.

I had no success locating the original news release, which originated the news item, but have found this May 17, 2021 news item on eedesignit.com, which provides the remaining portion of the news release.

“Oxides are the most widely used materials in memristors,” said Zhuge. “But oxide memristors have unsatisfactory stability and reliability. Oxide-based hybrid structures can effectively improve this.”

Memristors are usually made of an oxide-based material sandwiched between two electrodes. Researchers are getting better results when they combine two or more layers of different oxide-based materials between the electrodes. When an electrical current flows through the network, it induces ions to drift within the layers. The ions’ movements ultimately change the memristor’s resistance, which is necessary to send or stop a signal through the junction.

Memristors can be tuned further by changing the compounds used for electrodes or by adjusting the intermediate oxide-based materials. Zhuge and his team are currently developing optoelectronic neuromorphic computers based on optically-controlled oxide memristors. Compared to electronic memristors, photonic ones are expected to have higher operation speeds and lower energy consumption. They could be used to construct next generation artificial visual systems with high computing efficiency.

Now for a picture that accompanied the news release, which follows,

Fig. The all-optically controlled memristor developed for optoelectronic neuromorphic computing (Image by NIMTE)

Here’s the February 7, 2021 Ningbo Institute of Materials Technology and Engineering (NIMTE) press release featuring this work and a more technical description,

A research group led by Prof. ZHUGE Fei at the Ningbo Institute of Materials Technology and Engineering (NIMTE) of the Chinese Academy of Sciences (CAS) developed an all-optically controlled (AOC) analog memristor, whose memconductance can be reversibly tuned by varying only the wavelength of the controlling light.

As the next generation of artificial intelligence (AI), neuromorphic computing (NC) emulates the neural structure and operation of the human brain at the physical level, and thus can efficiently perform multiple advanced computing tasks such as learning, recognition and cognition.

Memristors are promising candidates for NC thanks to the feasibility of high-density 3D integration and low energy consumption. Among them, the emerging optoelectronic memristors are competitive by virtue of combining the advantages of both photonics and electronics. However, the reversible tuning of memconductance depends highly on the electric excitation, which have severely limited the development and application of optoelectronic NC.

To address this issue, researchers at NIMTE proposed a bilayered oxide AOC memristor, based on the relatively mature semiconductor material InGaZnO and a memconductance tuning mechanism of light-induced electron trapping and detrapping.

The traditional electrical memristors require strong electrical stimuli to tune their memconductance, leading to high power consumption, a large amount of Joule heat, microstructural change triggered by the Joule heat, and even high crosstalk in memristor crossbars.

On the contrary, the developed AOC memristor does not involve microstructure changes, and can operate upon weak light irradiation with light power density of only 20 μW cm-2, which has provided a new approach to overcome the instability of the memristor.

Specifically, the AOC memristor can serve as an excellent synaptic emulator and thus mimic spike-timing-dependent plasticity (STDP) which is an important learning rule in the brain, indicating its potential applications in AOC spiking neural networks for high-efficiency optoelectronic NC.

Moreover, compared to purely optical computing, the optoelectronic computing using our AOC memristor showed higher practical feasibility, on account of the simple structure and fabrication process of the device.

The study may shed light on the in-depth research and practical application of optoelectronic NC, and thus promote the development of the new generation of AI.

This work was supported by the National Natural Science Foundation of China (No. 61674156 and 61874125), the Strategic Priority Research Program of Chinese Academy of Sciences (No. XDB32050204), and the Zhejiang Provincial Natural Science Foundation of China (No. LD19E020001).

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

Hybrid oxide brain-inspired neuromorphic devices for hardware implementation of artificial intelligence by Jingrui Wang, Xia Zhuge & Fei Zhuge. Science and Technology of Advanced Materials Volume 22, 2021 – Issue 1 Pages 326-344 DOI: https://doi.org/10.1080/14686996.2021.1911277 Published online:14 May 2021

This paper appears to be open access.

Netherlands

In this case, a May 18, 2021 news item on Nanowerk marries oxides to spintronics,

Classic computers use binary values (0/1) to perform. By contrast, our brain cells can use more values to operate, making them more energy-efficient than computers. This is why scientists are interested in neuromorphic (brain-like) computing.

Physicists from the University of Groningen (the Netherlands) have used a complex oxide to create elements comparable to the neurons and synapses in the brain using spins, a magnetic property of electrons.

The press release, which follows, was accompanied by this image illustrating the work,

Caption: Schematic of the proposed device structure for neuromorphic spintronic memristors. The write path is between the terminals through the top layer (black dotted line), the read path goes through the device stack (red dotted line). The right side of the figure indicates how the choice of substrate dictates whether the device will show deterministic or probabilistic behaviour. Credit: Banerjee group, University of Groningen

A May 18, 2021 University of Groningen press release (also on EurekAlert), which originated the news item, adds more ‘spin’ to the story,

Although computers can do straightforward calculations much faster than humans, our brains outperform silicon machines in tasks like object recognition. Furthermore, our brain uses less energy than computers. Part of this can be explained by the way our brain operates: whereas a computer uses a binary system (with values 0 or 1), brain cells can provide more analogue signals with a range of values.

Thin films

The operation of our brains can be simulated in computers, but the basic architecture still relies on a binary system. That is why scientist look for ways to expand this, creating hardware that is more brain-like, but will also interface with normal computers. ‘One idea is to create magnetic bits that can have intermediate states’, says Tamalika Banerjee, Professor of Spintronics of Functional Materials at the Zernike Institute for Advanced Materials, University of Groningen. She works on spintronics, which uses a magnetic property of electrons called ‘spin’ to transport, manipulate and store information.

In this study, her PhD student Anouk Goossens, first author of the paper, created thin films of a ferromagnetic metal (strontium-ruthenate oxide, SRO) grown on a substrate of strontium titanate oxide. The resulting thin film contained magnetic domains that were perpendicular to the plane of the film. ‘These can be switched more efficiently than in-plane magnetic domains’, explains Goossens. By adapting the growth conditions, it is possible to control the crystal orientation in the SRO. Previously, out-of-plane magnetic domains have been made using other techniques, but these typically require complex layer structures.

Magnetic anisotropy

The magnetic domains can be switched using a current through a platinum electrode on top of the SRO. Goossens: ‘When the magnetic domains are oriented perfectly perpendicular to the film, this switching is deterministic: the entire domain will switch.’ However, when the magnetic domains are slightly tilted, the response is probabilistic: not all the domains are the same, and intermediate values occur when only part of the crystals in the domain have switched.

By choosing variants of the substrate on which the SRO is grown, the scientists can control its magnetic anisotropy. This allows them to produce two different spintronic devices. ‘This magnetic anisotropy is exactly what we wanted’, says Goossens. ‘Probabilistic switching compares to how neurons function, while the deterministic switching is more like a synapse.’

The scientists expect that in the future, brain-like computer hardware can be created by combining these different domains in a spintronic device that can be connected to standard silicon-based circuits. Furthermore, probabilistic switching would also allow for stochastic computing, a promising technology which represents continuous values by streams of random bits. Banerjee: ‘We have found a way to control intermediate states, not just for memory but also for computing.’

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

Anisotropy and Current Control of Magnetization in SrRuO3/SrTiO3 Heterostructures for Spin-Memristors by A.S. Goossens, M.A.T. Leiviskä and T. Banerjee. Frontiers in Nanotechnology DOI: https://doi.org/10.3389/fnano.2021.680468 Published: 18 May 2021

This appears to be open access.

Australian peacock spiders, photonic nanostructures, and making money

Researcher Bor-Kai Hsiung’s work has graced this blog before but the topic was tarantulas and their structural colour. This time, it’s all about Australian peacock spiders and their structural colour according to a December 22, 2017 news item on ScienceDaily,

Even if you are arachnophobic, you probably have seen pictures or videos of Australian peacock spiders (Maratus spp.). These tiny spiders are only 1-5 mm long but are famous for their flamboyant courtship displays featuring diverse and intricate body colorations, patterns, and movements.

The spiders extremely large anterior median eyes have excellent color vision and combine with their bright colors to make peacock spiders cute enough to cure most people of their arachnophobia. But these displays aren’t just pretty to look at, they also inspire new ways for humans to produce color in technology.

One species of peacock spider — the rainbow peacock spider (Maratus robinsoni) is particularly neat, because it showcases an intense rainbow iridescent signal in males’ courtship displays to the females. This is the first known instance in nature of males using an entire rainbow of colors to entice females. Dr. Bor-Kai Hsiung led an international team of researchers from the US (UAkron, Cal Tech, UC San Diego, UNL [University of Nebraska-Lincoln]), Belgium (Ghent University), Netherlands (UGroningen), and Australia to discover how rainbow peacock spiders produce this unique multi-color iridescent signal.

A December 22, 2017 Ghent University (Belgium) press release on Alpha Galileo, which originated the news item, provides more technical detail,

Using a diverse array of research techniques, including light and electron microscopy, hyperspectral imaging, imaging scatterometry, nano 3D printing and optical modeling, the team found the origin of this intense rainbow iridescence emerged from specialized abdominal scales of the spiders. These scales have an airfoil-like microscopic 3D contour with nanoscale diffraction grating structures on the surface.

The interaction between the surface nano-diffraction grating and the microscopic curvature of the scales enables separation and isolation of light into its component wavelengths at finer angles and smaller distances than are possible with current manmade engineering technologies.

Inspiration from these super iridescent scales can be used to overcome current limitations in spectral manipulation, and to further reduce the size of optical spectrometers for applications where fine-scale spectral resolution is required in a very small package, notably instruments on space missions, or wearable chemical detection systems. And it could have a wide array of implications to fields ranging from life sciences and biotechnologies to material sciences and engineering.

Here’s a video of an Australian rainbow peacock spider,

Here’s more from the YouTube description published on April 13, 2017 by Peacockspiderman,

Scenes of Maratus robinsoni, a spider Peter Robinson discovered and David Hill and I named it after him in 2012. You can read our description on pages 36-41 in Peckhamia 103.2, which can be downloaded from the Peckhamia website http://peckhamia.com/peckhamia_number…. This is one of the two smallest species of peacock spider (2.5 mm long) and the only spider we know of in which colour changes occur every time it moves, this video was created to document this. Music: ‘Be Still’ by Johannes Bornlöf licensed through my MCN ‘Brave Bison’ from ‘Epidemic Sound’ For licensing inquiries please contact Brave Bison licensing@bravebison.io

The University of California at San Diego also published a December 22, 2017 news release about this work, which covers some of the same ground while providing a few new tidbits of information,

Brightly colored Australian peacock spiders (Maratus spp.) captivate even the most arachnophobic viewers with their flamboyant courtship displays featuring diverse and intricate body colorations, patterns, and movements – all packed into miniature bodies measuring less than five millimeters in size for many species. However, these displays are not just pretty to look at. They also inspire new ways for humans to produce color in technology.

One species of peacock spider – the rainbow peacock spider (Maratus robinsoni) – is particularly impressive, because it showcases an intense rainbow iridescent signal in males’ courtship displays to females. This is the first known instance in nature of males using an entire rainbow of colors to entice females to mate. But how do males make their rainbows? A new study published in Nature Communications looked to answer that question.

Figuring out the answers was inherently interdisciplinary so Bor-Kai Hsiung, a postdoctoral scholar at Scripps Institution of Oceanography at the University of California San Diego, assembled an international team that included biologists, physicists and engineers. Starting while he was a Ph.D. student at The University of Akron under the mentorship of Todd Blackledge and Matthew Shawkey, the team included researchers from UA, Scripps Oceanography, California Institute of Technology, and University of Nebraska-Lincoln, the University of Ghent in Belgium, University of Groningen in Netherlands, and Australia to discover how rainbow peacock spiders produce this unique iridescent signal.

The team investigated the spider’s photonic structures using techniques that included light and electron microscopy, hyperspectral imaging, imaging scatterometry and optical modeling to generate hypotheses about how the spider’s scale generate such intense rainbows. The team then used cutting-edge nano 3D printing to fabricate different prototypes to test and validate their hypotheses. In the end, they found that the intense rainbow iridescence emerged from specialized abdominal scales on the spiders. These scales combine an airfoil-like microscopic 3D contour with nanoscale diffraction grating structures on the surface. It is the interaction between the surface nano-diffraction grating and the microscopic curvature of the scales that enables separation and isolation of light into its component wavelengths at finer angles and smaller distances than are possible with current engineering technologies.

“Who knew that such a small critter would create such an intense iridescence using extremely sophisticated mechanisms that will inspire optical engineers,” said Dimitri Deheyn, Hsuing’s advisor at Scripps Oceanography and a coauthor of the study.

For Hsiung, the finding wasn’t quite so unexpected.

“One of the main questions that I wanted to address in my Ph.D. dissertation was ‘how does nature modulate iridescence?’ From a biomimicry perspective, to fully understand and address a question, one has to take extremes from both ends into consideration. I purposefully chose to study these tiny spiders with intense iridescence after having investigated the non-iridescent blue tarantulas,” said Hsiung.

The mechanism behind these tiny rainbows may inspire new color technology, but would not have been discovered without research combining basic natural history with physics and engineering, the researchers said.

“Nanoscale 3D printing allowed us to experimentally validate our models, which was really exciting,” said Shawkey. “We hope that these techniques will become common in the future.”

“As an engineer, what I found fascinating about these spider structural colors is how these long evolved complex structures can still outperform human engineering,” said Radwanul Hasan Siddique, a postdoctoral scholar at Caltech and study coauthor. “Even with high-end fabrication techniques, we could not replicate the exact structures. I wonder how the spiders assemble these fancy structural patterns in the first place!”

Inspiration from these super iridescent spider scales can be used to overcome current limitations in spectral manipulation, and to reduce the size of optical spectrometers for applications where fine-scale spectral resolution is required in a very small package, notably instruments on space missions, or wearable chemical detection systems.

In the end, peacock spiders don’t just produce nature’s smallest rainbows.They could also have implications for a wide array of fields ranging from life sciences and biotechnologies to material sciences and engineering.

Before citing the paper and providing a link, here’s a story by Robert F. Service for Science magazine about attempts to capitalize on ‘spider technology’, in this case spider silk,

The hype over spider silk has been building since 1710. That was the year François Xavier Bon de Saint Hilaire, president of the Royal Society of Sciences in Montpellier, France, wrote to his colleagues, “You will be surpriz’d to hear, that Spiders make a Silk, as beautiful, strong and glossy, as common Silk.” Modern pitches boast that spider silk is five times stronger than steel yet more flexible than rubber. If it could be made into ropes, a macroscale web would be able to snare a jetliner.

The key word is “if.” Researchers first cloned a spider silk gene in 1990, in hopes of incorporating it into other organisms to produce the silk. (Spiders can’t be farmed like silkworms because they are territorial and cannibalistic.) Today, Escherichia coli bacteria, yeasts, plants, silkworms, and even goats have been genetically engineered to churn out spider silk proteins, though the proteins are often shorter and simpler than the spiders’ own. Companies have managed to spin those proteins into enough high-strength thread to produce a few prototype garments, including a running shoe by Adidas and a lightweight parka by The North Face. But so far, companies have struggled to mass produce these supersilks.

Some executives say that may finally be about to change. One Emeryville, California-based startup, Bolt Threads, says it has perfected growing spider silk proteins in yeast and is poised to turn out tons of spider silk thread per year. In Lansing, Michigan, Kraig Biocraft Laboratories says it needs only to finalize negotiations with silkworm farms in Vietnam to produce mass quantities of a combination spider/silkworm silk, which the U.S. Army is now testing for ballistics protection. …

I encourage you to read Service’s article in its entirety if the commercialization prospects for spider silk interest you as it includes gems such as this,

Spider silk proteins are already making their retail debut—but in cosmetics and medical devices, not high-strength fibers. AMSilk grows spider silk proteins in E. coli and dries the purified protein into powders or mixes it into gels, for use as additives for personal care products, such as moisture-retaining skin lotions. The silk proteins supposedly help the lotions form a very smooth, but breathable, layer over the skin. Römer says the company now sells tons of its purified silk protein ingredients every year.

Finally, here’s a citation for and a link to the paper about Australian peacock spiders and nanophotonics,

Rainbow peacock spiders inspire miniature super-iridescent optics by Bor-Kai Hsiung, Radwanul Hasan Siddique, Doekele G. Stavenga, Jürgen C. Otto, Michael C. Allen, Ying Liu, Yong-Feng Lu, Dimitri D. Deheyn, Matthew D. Shawkey, & Todd A. Blackledge. Nature Communications 8, Article number: 2278 (2017) doi:10.1038/s41467-017-02451-x Published online: 22 December 2017

This paper is open access.

As for Bor-Kai Hsiung’s other mentions here:

How tarantulas get blue (December 7, 2015 posting)

Noniridescent photonics inspired by tarantulas (October 19, 2016 posting)

More on the blue tarantula noniridescent photonics (December 28, 2016 posting)

Predicting drug side effects with guts-on-a-chip

It’s been a while since I’ve featured a story about a technology that could drastically reduce (or even eliminate) animal testing. Researchers in the Netherlands have announced some guts-on-a-chip research that may do just that. From an Aug. 22, 2017 news item on ScienceDaily,

Research conducted at Leiden has established that guts-on-chips respond in the same way to aspirin as real human organs do. This is a sign that these model organs are good predictors of the effect of medical drugs on the human body.

A method to test medical drugs for efficacy and potential side-effects, but then much cheaper and using the fewest possible lab animals: this is likely to be possible in future thanks to organs-on-chips, miniature model organs on microchips. In these model organs, which are equipped with human organ cells and microfluidic channels, researchers and pharmacists can mimic the working of an organ.

An Aug. 17, 2017 University of Leiden (Universiteit Leiden) press release, which originated the news item, provides more detail,

Leiden researchers, their spin-off company Mimetas and pharmaceutical company Roche have now shown that one type of organ chip experiences the same side-effects from the drug aspirin as the same organ in the human body. This is good news, because it is a sign that these miniature model organs are good predictors of the effect of medical drugs in the human body.

Aspirin

The researchers exposed 357 guts-on-chips for a significant period to the substance acetylsalicylic acid, better known as the analgesic aspirin. It has been known for a long time already that this substance can lead to gastrointestinal perforation, a complication that can be fatal if untreated. ‘We saw exactly the same side-effects occur in our guts-on-chips,’ says Professor of Analytical Biosciences Thomas Hankemeier. ‘In our model guts the gut wall also became more permeable after the drug had been administered.’

Effectiveness of candidate drugs

According to Hankemeier, the research shows that organs-on-chips are suited to testing a medical drug for efficacy and side-effects. This is good news for pharmacists, because the model organs make it easier for them to evaluate whether candidate drugs are effective or harmful. Many substances would be excluded from futher research before a drug entered the lab animal phase. This would help reduce the cost of drug production and mean less animal testing.

Diagnosing diseases

Organs-on-chips have taken off in recent years. They will be increasingly important in the near future, not just in drug development but also in the diagnosis of disease. Leiden researchers are at the forefront of this development. Hankemeier and a number of other groups (Erasmus MC, VUmc, RU Groningen) have been awared a 1.5 million ZonMW grant to research the effect of the body’s micro-organisms in the gut on the development of dementia. Organ-on-a-chip technology will play an important role here. Mimetas is the first company in the world to produce and sell organ chips on a large scale.

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

Membrane-free culture and real-time barrier integrity assessment of perfused intestinal epithelium tubes by Sebastiaan J. Trietsch, Elena Naumovska, Dorota Kurek, Meily C. Setyawati, Marianne K. Vormann, Karlijn J. Wilschut, Henriëtte L. Lanz, Arnaud Nicolas, Chee Ping Ng, Jos Joore, Stefan Kustermann, Adrian Roth, Thomas Hankemeier, Annie Moisan, & Paul Vulto. Nature Communications 8, Article number: 262 (2017) doi:10.1038/s41467-017-00259-3 Published online: 15 August 2017

This paper is open access.

You can find Mimetas here.

High-performance, low-energy artificial synapse for neural network computing

This artificial synapse is apparently an improvement on the standard memristor-based artificial synapse but that doesn’t become clear until reading the abstract for the paper. First, there’s a Feb. 20, 2017 Stanford University news release by Taylor Kubota (dated Feb. 21, 2017 on EurekAlert), Note: Links have been removed,

For all the improvements in computer technology over the years, we still struggle to recreate the low-energy, elegant processing of the human brain. Now, researchers at Stanford University and Sandia National Laboratories have made an advance that could help computers mimic one piece of the brain’s efficient design – an artificial version of the space over which neurons communicate, called a synapse.

“It works like a real synapse but it’s an organic electronic device that can be engineered,” said Alberto Salleo, associate professor of materials science and engineering at Stanford and senior author of the paper. “It’s an entirely new family of devices because this type of architecture has not been shown before. For many key metrics, it also performs better than anything that’s been done before with inorganics.”

The new artificial synapse, reported in the Feb. 20 issue of Nature Materials, mimics the way synapses in the brain learn through the signals that cross them. This is a significant energy savings over traditional computing, which involves separately processing information and then storing it into memory. Here, the processing creates the memory.

This synapse may one day be part of a more brain-like computer, which could be especially beneficial for computing that works with visual and auditory signals. Examples of this are seen in voice-controlled interfaces and driverless cars. Past efforts in this field have produced high-performance neural networks supported by artificially intelligent algorithms but these are still distant imitators of the brain that depend on energy-consuming traditional computer hardware.

Building a brain

When we learn, electrical signals are sent between neurons in our brain. The most energy is needed the first time a synapse is traversed. Every time afterward, the connection requires less energy. This is how synapses efficiently facilitate both learning something new and remembering what we’ve learned. The artificial synapse, unlike most other versions of brain-like computing, also fulfills these two tasks simultaneously, and does so with substantial energy savings.

“Deep learning algorithms are very powerful but they rely on processors to calculate and simulate the electrical states and store them somewhere else, which is inefficient in terms of energy and time,” said Yoeri van de Burgt, former postdoctoral scholar in the Salleo lab and lead author of the paper. “Instead of simulating a neural network, our work is trying to make a neural network.”

The artificial synapse is based off a battery design. It consists of two thin, flexible films with three terminals, connected by an electrolyte of salty water. The device works as a transistor, with one of the terminals controlling the flow of electricity between the other two.

Like a neural path in a brain being reinforced through learning, the researchers program the artificial synapse by discharging and recharging it repeatedly. Through this training, they have been able to predict within 1 percent of uncertainly what voltage will be required to get the synapse to a specific electrical state and, once there, it remains at that state. In other words, unlike a common computer, where you save your work to the hard drive before you turn it off, the artificial synapse can recall its programming without any additional actions or parts.

Testing a network of artificial synapses

Only one artificial synapse has been produced but researchers at Sandia used 15,000 measurements from experiments on that synapse to simulate how an array of them would work in a neural network. They tested the simulated network’s ability to recognize handwriting of digits 0 through 9. Tested on three datasets, the simulated array was able to identify the handwritten digits with an accuracy between 93 to 97 percent.

Although this task would be relatively simple for a person, traditional computers have a difficult time interpreting visual and auditory signals.

“More and more, the kinds of tasks that we expect our computing devices to do require computing that mimics the brain because using traditional computing to perform these tasks is becoming really power hungry,” said A. Alec Talin, distinguished member of technical staff at Sandia National Laboratories in Livermore, California, and senior author of the paper. “We’ve demonstrated a device that’s ideal for running these type of algorithms and that consumes a lot less power.”

This device is extremely well suited for the kind of signal identification and classification that traditional computers struggle to perform. Whereas digital transistors can be in only two states, such as 0 and 1, the researchers successfully programmed 500 states in the artificial synapse, which is useful for neuron-type computation models. In switching from one state to another they used about one-tenth as much energy as a state-of-the-art computing system needs in order to move data from the processing unit to the memory.

This, however, means they are still using about 10,000 times as much energy as the minimum a biological synapse needs in order to fire. The researchers are hopeful that they can attain neuron-level energy efficiency once they test the artificial synapse in smaller devices.

Organic potential

Every part of the device is made of inexpensive organic materials. These aren’t found in nature but they are largely composed of hydrogen and carbon and are compatible with the brain’s chemistry. Cells have been grown on these materials and they have even been used to make artificial pumps for neural transmitters. The voltages applied to train the artificial synapse are also the same as those that move through human neurons.

All this means it’s possible that the artificial synapse could communicate with live neurons, leading to improved brain-machine interfaces. The softness and flexibility of the device also lends itself to being used in biological environments. Before any applications to biology, however, the team plans to build an actual array of artificial synapses for further research and testing.

Additional Stanford co-authors of this work include co-lead author Ewout Lubberman, also of the University of Groningen in the Netherlands, Scott T. Keene and Grégorio C. Faria, also of Universidade de São Paulo, in Brazil. Sandia National Laboratories co-authors include Elliot J. Fuller and Sapan Agarwal in Livermore and Matthew J. Marinella in Albuquerque, New Mexico. Salleo is an affiliate of the Stanford Precourt Institute for Energy and the Stanford Neurosciences Institute. Van de Burgt is now an assistant professor in microsystems and an affiliate of the Institute for Complex Molecular Studies (ICMS) at Eindhoven University of Technology in the Netherlands.

This research was funded by the National Science Foundation, the Keck Faculty Scholar Funds, the Neurofab at Stanford, the Stanford Graduate Fellowship, Sandia’s Laboratory-Directed Research and Development Program, the U.S. Department of Energy, the Holland Scholarship, the University of Groningen Scholarship for Excellent Students, the Hendrik Muller National Fund, the Schuurman Schimmel-van Outeren Foundation, the Foundation of Renswoude (The Hague and Delft), the Marco Polo Fund, the Instituto Nacional de Ciência e Tecnologia/Instituto Nacional de Eletrônica Orgânica in Brazil, the Fundação de Amparo à Pesquisa do Estado de São Paulo and the Brazilian National Council.

Here’s an abstract for the researchers’ paper (link to paper provided after abstract) and it’s where you’ll find the memristor connection explained,

The brain is capable of massively parallel information processing while consuming only ~1–100fJ per synaptic event1, 2. Inspired by the efficiency of the brain, CMOS-based neural architectures3 and memristors4, 5 are being developed for pattern recognition and machine learning. However, the volatility, design complexity and high supply voltages for CMOS architectures, and the stochastic and energy-costly switching of memristors complicate the path to achieve the interconnectivity, information density, and energy efficiency of the brain using either approach. Here we describe an electrochemical neuromorphic organic device (ENODe) operating with a fundamentally different mechanism from existing memristors. ENODe switches at low voltage and energy (<10pJ for 103μm2 devices), displays >500 distinct, non-volatile conductance states within a ~1V range, and achieves high classification accuracy when implemented in neural network simulations. Plastic ENODes are also fabricated on flexible substrates enabling the integration of neuromorphic functionality in stretchable electronic systems6, 7. Mechanical flexibility makes ENODes compatible with three-dimensional architectures, opening a path towards extreme interconnectivity comparable to the human brain.

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

A non-volatile organic electrochemical device as a low-voltage artificial synapse for neuromorphic computing by Yoeri van de Burgt, Ewout Lubberman, Elliot J. Fuller, Scott T. Keene, Grégorio C. Faria, Sapan Agarwal, Matthew J. Marinella, A. Alec Talin, & Alberto Salleo. Nature Materials (2017) doi:10.1038/nmat4856 Published online 20 February 2017

This paper is behind a paywall.

ETA March 8, 2017 10:28 PST: You may find this this piece on ferroelectricity and neuromorphic engineering of interest (March 7, 2017 posting titled: Ferroelectric roadmap to neuromorphic computing).

Nominations open for Kabiller Prizes in Nanoscience and Nanomedicine ($250,000 for visionary researcher and $10,000 for young investigator)

For a change I can publish something that doesn’t have a deadline in three days or less! Without more ado (from a Feb. 20, 2017 Northwestern University news release by Megan Fellman [h/t Nanowerk’s Feb. 20, 2017 news item]),

Northwestern University’s International Institute for Nanotechnology (IIN) is now accepting nominations for two prestigious international prizes: the $250,000 Kabiller Prize in Nanoscience and Nanomedicine and the $10,000 Kabiller Young Investigator Award in Nanoscience and Nanomedicine.

The deadline for nominations is May 15, 2017. Details are available on the IIN website.

“Our goal is to recognize the outstanding accomplishments in nanoscience and nanomedicine that have the potential to benefit all humankind,” said David G. Kabiller, a Northwestern trustee and alumnus. He is a co-founder of AQR Capital Management, a global investment management firm in Greenwich, Connecticut.

The two prizes, awarded every other year, were established in 2015 through a generous gift from Kabiller. Current Northwestern-affiliated researchers are not eligible for nomination until 2018 for the 2019 prizes.

The Kabiller Prize — the largest monetary award in the world for outstanding achievement in the field of nanomedicine — celebrates researchers who have made the most significant contributions to the field of nanotechnology and its application to medicine and biology.

The Kabiller Young Investigator Award recognizes young emerging researchers who have made recent groundbreaking discoveries with the potential to make a lasting impact in nanoscience and nanomedicine.

“The IIN at Northwestern University is a hub of excellence in the field of nanotechnology,” said Kabiller, chair of the IIN executive council and a graduate of Northwestern’s Weinberg College of Arts and Sciences and Kellogg School of Management. “As such, it is the ideal organization from which to launch these awards recognizing outstanding achievements that have the potential to substantially benefit society.”

Nanoparticles for medical use are typically no larger than 100 nanometers — comparable in size to the molecules in the body. At this scale, the essential properties (e.g., color, melting point, conductivity, etc.) of structures behave uniquely. Researchers are capitalizing on these unique properties in their quest to realize life-changing advances in the diagnosis, treatment and prevention of disease.

“Nanotechnology is one of the key areas of distinction at Northwestern,” said Chad A. Mirkin, IIN director and George B. Rathmann Professor of Chemistry in Weinberg. “We are very grateful for David’s ongoing support and are honored to be stewards of these prestigious awards.”

An international committee of experts in the field will select the winners of the 2017 Kabiller Prize and the 2017 Kabiller Young Investigator Award and announce them in September.

The recipients will be honored at an awards banquet Sept. 27 in Chicago. They also will be recognized at the 2017 IIN Symposium, which will include talks from prestigious speakers, including 2016 Nobel Laureate in Chemistry Ben Feringa, from the University of Groningen, the Netherlands.

2015 recipient of the Kabiller Prize

The winner of the inaugural Kabiller Prize, in 2015, was Joseph DeSimone the Chancellor’s Eminent Professor of Chemistry at the University of North Carolina at Chapel Hill and the William R. Kenan Jr. Distinguished Professor of Chemical Engineering at North Carolina State University and of Chemistry at UNC-Chapel Hill.

DeSimone was honored for his invention of particle replication in non-wetting templates (PRINT) technology that enables the fabrication of precisely defined, shape-specific nanoparticles for advances in disease treatment and prevention. Nanoparticles made with PRINT technology are being used to develop new cancer treatments, inhalable therapeutics for treating pulmonary diseases, such as cystic fibrosis and asthma, and next-generation vaccines for malaria, pneumonia and dengue.

2015 recipient of the Kabiller Young Investigator Award

Warren Chan, professor at the Institute of Biomaterials and Biomedical Engineering at the University of Toronto, was the recipient of the inaugural Kabiller Young Investigator Award, also in 2015. Chan and his research group have developed an infectious disease diagnostic device for a point-of-care use that can differentiate symptoms.

BTW, Warren Chan, winner of the ‘Young Investigator Award’, and/or his work have been featured here a few times, most recently in a Nov. 1, 2016 posting, which is mostly about another award he won but also includes links to some his work including my April 27, 2016 post about the discovery that fewer than 1% of nanoparticle-based drugs reach their destination.

2016 Nobel Chemistry Prize for molecular machines

Wednesday, Oct. 5, 2016 was the day three scientists received the Nobel Prize in Chemistry for their work on molecular machines, according to an Oct. 5, 2016 news item on phys.org,

Three scientists won the Nobel Prize in chemistry on Wednesday [Oct. 5, 2016] for developing the world’s smallest machines, 1,000 times thinner than a human hair but with the potential to revolutionize computer and energy systems.

Frenchman Jean-Pierre Sauvage, Scottish-born Fraser Stoddart and Dutch scientist Bernard “Ben” Feringa share the 8 million kronor ($930,000) prize for the “design and synthesis of molecular machines,” the Royal Swedish Academy of Sciences said.

Machines at the molecular level have taken chemistry to a new dimension and “will most likely be used in the development of things such as new materials, sensors and energy storage systems,” the academy said.

Practical applications are still far away—the academy said molecular motors are at the same stage that electrical motors were in the first half of the 19th century—but the potential is huge.

Dexter Johnson in an Oct. 5, 2016 posting on his Nanoclast blog (on the IEEE [Institute of Electrical and Electronics Engineers] website) provides some insight into the matter (Note: A link has been removed),

In what seems to have come both as a shock to some of the recipients and a confirmation to all those who envision molecular nanotechnology as the true future of nanotechnology, Bernard Feringa, Jean-Pierre Sauvage, and Sir J. Fraser Stoddart have been awarded the 2016 Nobel Prize in Chemistry for their development of molecular machines.

The Nobel Prize was awarded to all three of the scientists based on their complementary work over nearly three decades. First, in 1983, Sauvage (currently at Strasbourg University in France) was able to link two ring-shaped molecules to form a chain. Then, eight years later, Stoddart, a professor at Northwestern University in Evanston, Ill., demonstrated that a molecular ring could turn on a thin molecular axle. Then, eight years after that, Feringa, a professor at the University of Groningen, in the Netherlands, built on Stoddardt’s work and fabricated a molecular rotor blade that could spin continually in the same direction.

Speaking of the Nobel committee’s selection, Donna Nelson, a chemist and president of the American Chemical Society told Scientific American: “I think this topic is going to be fabulous for science. When the Nobel Prize is given, it inspires a lot of interest in the topic by other researchers. It will also increase funding.” Nelson added that this line of research will be fascinating for kids. “They can visualize it, and imagine a nanocar. This comes at a great time, when we need to inspire the next generation of scientists.”

The Economist, which appears to be previewing an article about the 2016 Nobel prizes ahead of the print version, has this to say in its Oct. 8, 2016 article,

BIGGER is not always better. Anyone who doubts that has only to look at the explosion of computing power which has marked the past half-century. This was made possible by continual shrinkage of the components computers are made from. That success has, in turn, inspired a search for other areas where shrinkage might also yield dividends.

One such, which has been poised delicately between hype and hope since the 1990s, is nanotechnology. What people mean by this term has varied over the years—to the extent that cynics might be forgiven for wondering if it is more than just a fancy rebranding of the word “chemistry”—but nanotechnology did originally have a fairly clear definition. It was the idea that machines with moving parts could be made on a molecular scale. And in recognition of this goal Sweden’s Royal Academy of Science this week decided to award this year’s Nobel prize for chemistry to three researchers, Jean-Pierre Sauvage, Sir Fraser Stoddart and Bernard Feringa, who have never lost sight of nanotechnology’s original objective.

Optimists talk of manufacturing molecule-sized machines ranging from drug-delivery devices to miniature computers. Pessimists recall that nanotechnology is a field that has been puffed up repeatedly by both researchers and investors, only to deflate in the face of practical difficulties.

There is, though, reason to hope it will work in the end. This is because, as is often the case with human inventions, Mother Nature has got there first. One way to think of living cells is as assemblies of nanotechnological machines. For example, the enzyme that produces adenosine triphosphate (ATP)—a molecule used in almost all living cells to fuel biochemical reactions—includes a spinning molecular machine rather like Dr Feringa’s invention. This works well. The ATP generators in a human body turn out so much of the stuff that over the course of a day they create almost a body-weight’s-worth of it. Do something equivalent commercially, and the hype around nanotechnology might prove itself justified.

Congratulations to the three winners!

With over 150 partners from over 20 countries, the European Union’s Graphene Flagship research initiative unveils its work package devoted to biomedical technologies

An April 11, 2016 news item on Nanowerk announces the Graphene Flagship’s latest work package,

With a budget of €1 billion, the Graphene Flagship represents a new form of joint, coordinated research on an unprecedented scale, forming Europe’s biggest ever research initiative. It was launched in 2013 to bring together academic and industrial researchers to take graphene from the realm of academic laboratories into European society in the timeframe of 10 years. The initiative currently involves over 150 partners from more than 20 European countries. The Graphene Flagship, coordinated by Chalmers University of Technology (Sweden), is implemented around 15 scientific Work Packages on specific science and technology topics, such as fundamental science, materials, health and environment, energy, sensors, flexible electronics and spintronics.

Today [April 11, 2016], the Graphene Flagship announced in Barcelona the creation of a new Work Package devoted to Biomedical Technologies, one emerging application area for graphene and other 2D materials. This initiative is led by Professor Kostas Kostarelos, from the University of Manchester (United Kingdom), and ICREA Professor Jose Antonio Garrido, from the Catalan Institute of Nanoscience and Nanotechnology (ICN2, Spain). The Kick-off event, held in the Casa Convalescència of the Universitat Autònoma de Barcelona (UAB), is co-organised by ICN2 (ICREA Prof Jose Antonio Garrido), Centro Nacional de Microelectrónica (CNM-IMB-CSIC, CIBER-BBN; CSIC Tenured Scientist Dr Rosa Villa), and Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS; ICREA Prof Mavi Sánchez-Vives).

An April 11, 2016 ICN2 press release, which originated the news item, provides more detail about the Biomedical Technologies work package and other work packages,

The new Work Package will focus on the development of implants based on graphene and 2D-materials that have therapeutic functionalities for specific clinical outcomes, in disciplines such as neurology, ophthalmology and surgery. It will include research in three main areas: Materials Engineering; Implant Technology & Engineering; and Functionality and Therapeutic Efficacy. The objective is to explore novel implants with therapeutic capacity that will be further developed in the next phases of the Graphene Flagship.

The Materials Engineering area will be devoted to the production, characterisation, chemical modification and optimisation of graphene materials that will be adopted for the design of implants and therapeutic element technologies. Its results will be applied by the Implant Technology and Engineering area on the design of implant technologies. Several teams will work in parallel on retinal, cortical, and deep brain implants, as well as devices to be applied in the periphery nerve system. Finally, The Functionality and Therapeutic Efficacy area activities will centre on development of devices that, in addition to interfacing the nerve system for recording and stimulation of electrical activity, also have therapeutic functionality.

Stimulation therapies will focus on the adoption of graphene materials in implants with stimulation capabilities in Parkinson’s, blindness and epilepsy disease models. On the other hand, biological therapies will focus on the development of graphene materials as transport devices of biological molecules (nucleic acids, protein fragments, peptides) for modulation of neurophysiological processes. Both approaches involve a transversal innovation environment that brings together the efforts of different Work Packages within the Graphene Flagship.

A leading role for Barcelona in Graphene and 2D-Materials

The kick-off meeting of the new Graphene Flagship Work Package takes place in Barcelona because of the strong involvement of local institutions and the high international profile of Catalonia in 2D-materials and biomedical research. Institutions such as the Catalan Institute of Nanoscience and Nanotechnology (ICN2) develop frontier research in a supportive environment which attracts talented researchers from abroad, such as ICREA Research Prof Jose Antonio Garrido, Group Leader of the ICN2 Advanced Electronic Materials and Devices Group and now also Deputy Leader of the Biomedical Technologies Work Package. Until summer 2015 he was leading a research group at the Technische Universität München (Germany).

Further Graphene Flagship events in Barcelona are planned; in May 2016 ICN2 will also host a meeting of the Spintronics Work Package. ICREA Prof Stephan Roche, Group Leader of the ICN2 Theoretical and Computational Nanoscience Group, is the deputy leader of this Work Package led by Prof Bart van Wees, from the University of Groningen (The Netherlands). Another Work Package, on optoelectronics, is led by Prof Frank Koppens from the Institute of Photonic Sciences (ICFO, Spain), with Prof Andrea Ferrari from the University of Cambridge (United Kingdom) as deputy. Thus a number of prominent research institutes in Barcelona are deeply involved in the coordination of this European research initiative.

Kostas Kostarelos, the leader of the Biomedical Technologies Graphene Flagship work package, has been mentioned here before in the context of his blog posts for The Guardian science blog network (see my Aug. 7, 2014 post for a link to his post on metaphors used in medicine).

Crowdfund nano spies for cancer

University of Groningen (Netherlands) researcher, Romana Schirhagl, is crowdfunding her development of a new technique (using nanodiamonds) for biomedical research which would allow observation of free radicals in cells. From a June 25, 2015 news item on Nanowerk,

Romana Schirhagl, a researcher at the University Medical Center Groningen, is hoping to garner public support for a new form of cancer research. Schirhagl wants to introduce miniscule diamonds into living cancer cells. Like spies, these nanodiamonds will be on a mission to reveal the secrets of the cell. Schirhagl applies a unique combination of knowledge and techniques from physics, chemistry and medicine in the research. This could form the basis of new and improved cancer drugs.

A June 16, 2015 University of Groningen press release, which originated the news item, provides background information for the research,

The research of Schirhagl and her research group in the department of Biomedical Engineering focuses on the behaviour of free radicals in a cell. These radicals have an important role in the body. They are sometimes extremely useful, as in the immune system, where they help fight bacteria and viruses, but sometimes very harmful, as when they actually harm healthy cells and can cause cancer. As the radicals only exist for a fraction of a second, it is difficult to tell them apart and study them.

New technique

Schirhagl wants to apply a new technique that currently is mainly used in fundamental physics but looks extremely promising for biomedical research. The technique is based on very small diamonds that can ‘sense’ the presence of magnetic fields from the radicals. The nanodiamonds are fluorescent and change in luminosity as a response to their environment. This makes it easier to determine which radicals occur when and how they work. This information should make it possible to improve cancer drugs – which themselves sometimes use free radicals – or even develop new ones.

Unexpectedly, the crowdfunding platform is the University of Groningen’s own. You can find out more about Nano spies here. To date the project has raised over 6,600 Euros towards a goal of 20,000 Euros.

Viewing a photosynthesis subsystem in a near-natural state

[downloaded from http://www.desy.de/infos__services/presse/pressemeldungen/@@news-view?id=9383]

Molecular structure of photosystem II, which arranges itself in rows. Credit: Martin Bommer/HU Berlin [downloaded from http://www.desy.de/infos__services/presse/pressemeldungen/@@news-view?id=9383]

Apparently, this image represents a near-natural state for a photosynthesis subsystem called, Photosynthesis II. Here’s more from a Nov. 4, 2014 news item on Nanowerk (Note: A link has been removed),

Photosynthesis is one of the most important processes in nature. The complex method with which all green plants harvest sunlight and thereby produce the oxygen in our air is, however, still not fully understood. Researchers using DESY’s X-ray light source PETRA III have examined a photosynthesis subsystem in a near-natural state. According to the scientists led by Privatdozentin Dr. Athina Zouni from the Humboldt University (HU) Berlin, the X-ray experiments on what is known as photosystem II reveal, for example, yet unknown structures. Their results are published in the scientific journal Structure (“Native-like Photosystem II Superstructure at 2.44 Å Resolution through Detergent Extraction from the Protein Crystal”). The technology utilised could also be of interest for analysing other biomolecules.

A Nov. 4, 2014 DESY (Deutsches Elektronen-Synchrotron) press release, which originated the news item, describes some of the issues with studying ‘photosynthetic machinery’,

Photosystem II forms part of the photosynthetic machinery where water, with the help of sunlight, is split into hydrogen and oxygen. As one of the membrane proteins, it sits in the cell membrane. Membrane proteins are a large and vital group of biomolecules that are, for example, important in addressing a variety of medical issues. In order to decode the protein structure and reveal details on how biomolecules function, researchers use the very bright and short-wave X-rays of PETRA III and other similar facilities. Small crystals, however, must initially be grown from these biomolecules.

“The structure of single molecules cannot be directly seen even with the brightest X-rays,” explains co-author and DESY researcher Dr. Anja Burkhardt of Measuring Station P11, where the experiments were carried out. “In a crystal, however, a multitude of these molecules are arranged in a highly symmetrical fashion. Thus the signal, resulting from X-ray diffraction of these molecules, is amplified. The molecular structure can then be calculated from the diffraction images.”

In addition to these difficulties the scientists were also grappling with this problem (from the press release),

Biomolecules – and especially membrane proteins – cannot easily be compelled into crystal form as it is contrary to their natural state. Preparing suitable samples is therefore a crucial step in the whole analysis process. For instance, photosystem II must be first separated from the membrane, where it is bound to numerous small fat molecules (lipids). Researchers use special detergents for this purpose, such as those also principally found in soap. The catch: instead of lipids, the biomolecules are now surrounded by detergents, which may make the crystals spongy under certain conditions, thus exacerbating the analysis.

“What we want is to come as close as possible to nature,” stresses Zouni. The closer the proteins in the crystal are to their natural state, the better the results.

The press release describes how the team solved the problem,

“The trick was to use a detergent that strongly differs from the lipids in composition and structure,” explains the researcher.

Before examining the biomolecular crystals using X-rays, a portion of the water is extracted and replaced by an anti-freeze. The crystals are usually frozen for the experiments because the high-energy X-ray doesn’t damage them so quickly in the frozen state. During this process, the researchers would like to avoid ice formation.

“The dehydration process removed not only the water in our samples, but also completely removed the detergent, something we didn’t expect,” says Zouni.“Our samples are closer to the natural state than what has been reported before.”

Consequently, the investigation’s spatial resolution increased from about 0.6 nanometres (a millionth of a millimetre) to 0.244 nanometres. This is not, in fact, the highest resolution ever achieved in a photosystem II study, but the analysis shows that the photosystem II proteins are arranged within the crystals as pairs of rows, something that also occurs in the natural environment.

This latest development builds on previous research according to the press release,

Electron microscope investigations by Professor Egbert Boekema’s group at the University of Groningen in the Netherlands had already shown the photosystems’ crystal like arrangement in the natural membrane — a kind of tiny solar cell. Electron microscopy could better recognize connections using direct observation of the native membrane while X-ray crystallography could reveal the smallest details.

The press release ends with how the latest work could have an impact on further research,

“We placed the structural data over the electron microscope images – they matched precisely,” says Zouni. The investigation also revealed structures that were invisible before. “We can see exactly where the bonds to the lipids are located,” the scientist explains. The more the researchers discover about photosystem II, the better they understand exactly how it functions.

The procedure of using a new detergent, however, is not only interesting in terms of photosystem II. “The method can potentially be applied to many membrane proteins,” stresses Zouni. In the future, many biomolecules could maybe examined in a more natural state than ever before.

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

Native-like Photosystem II Superstructure at 2.44 Å Resolution through Detergent Extraction from the Protein Crystal by Julia Hellmich, Martin Bommer, Anja Burkhardt, Mohamed Ibrahim, Jan Kern, Alke Meents, Frank Müh, Holger Dobbek, and Athina Zouni. Structure Volume 22, Issue 11, p1607–1615, 4 November 2014  DOI: http://dx.doi.org/10.1016/j.str.2014.09.007

This paper is open access.

ETA Nov. 6, 2014: On the off chance the links to the Nanowerk news item or DESY press release do not yield results, you may be able to find the DESY Nov. 5, 2014 news release here on EurekAlert.