Category Archives: light

Living optical fibers

The word ‘living’ isn’t usually associated with optical fibers and the addition had me thinking that this October 11, 2021 Nanowerk Spotlight story by Michael Berger would be a synthetic biology story. Well, not exactly. Do read on for a good introduction describing glass, fiber optics, and optogenetics,

Glass is one of the oldest manufactured materials used by humans and glass making dates back at least 6000 years, long before humans had discovered how to smelt iron. Glasses have been based on the chemical compound silica – silicon dioxide, or quartz – the primary constituent of sand. Soda-lime glass, containing around 70% silica, accounts for around 90% of manufactured glass.

Historically, we are familiar with glasses’ decorative use or as window panes, household items, and in optics such as eyeglasses, microscopes and telescopes. More recently, starting in the 1950s, glass has been used in the manufacture of fiber optic cables, a technology that has revolutionized the communications industry and helped ring in the digital revolution.

Fiber optic cables propagate a signal as a pulse of light along a transparent medium, usually glass. This is not only used to transmit information but, for instance in many healthcare and biomedical applications, scientists use optical fibers for sensing applications by shining light into a sample and evaluating the absorbed or transmitted light.

A recent development in this field is optogenetics, a neuromodulation method that uses activation or deactivation of brain cells by illumination with different colors of light in order to treat brain disorders.

Berger goes on to explain the latest work and reveals what ‘living’ means where this work is concerned,

This work represents a simple and low-cost approach to fabricating optical fibers made from biological materials. These fibers can be easily modified for specific applications and don’t require sophisticated equipment to generate relevant information. This method could be used for many practical sensing and biological modeling applications.

“We use a natural, ionic, and biologically compatible crosslinking approach, which enables us to produce flexible hydrogel fibers in continuous multi-layered architectures, meaning they are easy to produce and can be modified after fabrication,” explains Guimarães [Carlos Guimarães, the paper’s first author]. “Similarly to silica fibers, the core hydrogel of our structures can be exposed, fused to another fiber or reassembled if they break, and efficiently guide light through the established connection.”

These flexible hydrogel fibers are made from sugars and work just like solid-state optical fibers used to transmit data. However, they are biocompatible so they can be easily integrated with biological systems.

“We could even consider them to be alive [emphasis mine] since we can use them to grow living cells inside the fiber,” says Guimarães. “As these embedded cells grow over time, we can then use light to inform on living dynamic events, for example to track cancer invasive proliferation into optical information.” [emphasis mine]

As to what constitutes optical information in this context,

Another intriguing aspect of these hydrogel fibers is that their permeable mesh enables the inclusion of biological targets of interest for detection. For example, the scientists observed that fibers were able to soak SARS-CoV-2 viruses, and by integrating nanoparticles for their binding and detection, shifts in visible light could be observed for detecting the accumulation of viral particles within the fiber.

“When light moving through the fiber encounters living cells, it changes its characteristics depending on cellular density, invasive proliferation, expression of molecules, etc.” Guimarães notes. “This light-cell interaction can digitize complex biological events, converting responses such as cancer cell progression in 3D environments and susceptibility to drugs into numbers and data, very fast and without the need for sample destruction.”

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

Engineering Polysaccharide-Based Hydrogel Photonic Constructs: From Multiscale Detection to the Biofabrication of Living Optical Fibers by Carlos F. Guimarães, Rajib Ahmed, Amideddin Mataji-Kojouri, Fernando Soto, Jie Wang, Shiqin Liu, Tanya Stoyanova, Alexandra P. Marques, Rui L. Reis, Utkan Demirci. Advanced Materials DOI: https://doi.org/10.1002/adma.202105361 First published: 07 October 2021

This paper is behind a paywall.

Attosecond imaging technology with record high-harmonic generation

This July 21, 2021 news item on Nanowerk is all about laser pulses and tiny timescales.

Cornell researchers have developed nanostructures that enable record-breaking conversion of laser pulses into high-harmonic generation, paving the way for new scientific tools for high-resolution imaging and studying physical processes that occur at the scale of an attosecond – one quintillionth of a second [emphasis mine].

High-harmonic generation has long been used to merge photons from a pulsing laser into one, ultrashort photon with much higher energy, producing extreme ultraviolet light and X-rays used for a variety of scientific purposes. Traditionally, gases have been used as sources of harmonics, but a research team led by Gennady Shvets, professor of applied and engineering physics in the College of Engineering, has shown that engineered nanostructures have a bright future for this application.

llustration of an infrared laser hitting a gallium-phosphide metsurface, which efficiently produces even and odd high-harmonic generation. Credit: Daniil Shilkin/Provided

A July 21, 2021 Cornell University news release by Syl Kacapyr (also on EurekAlert), which originated the news item, provides more detail about the nanostructures,

The nanostructures created by the team make up an ultrathin resonant gallium-phosphide metasurface that overcomes many of the usual problems associated with high-harmonic generation in gases and other solids. The gallium-phosphide material permits harmonics of all orders without reabsorbing them, and the specialized structure can interact with the laser pulse’s entire light spectrum.

“Achieving this required engineering of the metasurface’s structure using full-wave simulations,” Shcherbakov [Maxim Shcherbakov] said. “We carefully selected the parameters of the gallium-phosphide particles to fulfill this condition, and then it took a custom nanofabrication flow to bring it to light.”

The result is nanostructures capable of generating both even and odd harmonics – a limitation of most other harmonic materials – covering a wide range of photon energies between 1.3 and 3 electron volts. The record-breaking conversion efficiency enables scientists to observe molecular and electronic dynamics within a material with just one laser shot, helping to preserve samples that may otherwise be degraded by multiple high-powered shots.

The study is the first to observe high-harmonic generated radiation from a single laser pulse, which allowed the metasurface to withstand high powers – five to 10 times higher than previously shown in other metasurfaces.

“It opens up new opportunities to study matter at ultrahigh fields, a regime not readily accessible before,” Shcherbakov said. “With our method, we envision that people can study materials beyond metasurfaces, including but not limited to crystals, 2D materials, single atoms, artificial atomic lattices and other quantum systems.”

Now that the research team has demonstrated the advantages of using nanostructures for high-harmonic generation, it hopes to improve high-harmonic devices and facilities by stacking the nanostructures together to replace a solid-state source, such as crystals.

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

Generation of even and odd high harmonics in resonant metasurfaces using single and multiple ultra-intense laser pulses by Maxim R. Shcherbakov, Haizhong Zhang, Michael Tripepi, Giovanni Sartorello, Noah Talisa, Abdallah AlShafey, Zhiyuan Fan, Justin Twardowski, Leonid A. Krivitsky, Arseniy I. Kuznetsov, Enam Chowdhury & Gennady Shvets. Nature Communications volume 12, Article number: 4185 DOI: https://doi.org/10.1038/s41467-021-24450-9 Published: 07 July 2021

This paper is open access.

Nano-photosynthesis in your brain as a stroke treatment?

A May 19, 2021 news item on phys.org sheds some light on a new approach to stroke treatments,

Blocked blood vessels in the brains of stroke patients prevent oxygen-rich blood from getting to cells, causing severe damage. Plants and some microbes produce oxygen through photosynthesis. What if there was a way to make photosynthesis happen in the brains of patients? Now, researchers reporting in ACS’ Nano Letters have done just that in cells and in mice, using blue-green algae and special nanoparticles, in a proof-of-concept demonstration.

A May 19, 2021 American Chemical Society (ACS) news release, which originated the news item, provides more information on strokes and how this new approach may prove useful,

Strokes result in the deaths of 5 million people worldwide every year, according to the World Health Organization. Millions more survive, but they often experience disabilities, such as difficulties with speech, swallowing or memory. The most common cause is a blood vessel blockage in the brain, and the best way to prevent permanent brain damage from this type of stroke is to dissolve or surgically remove the blockage as soon as possible. However, those options only work within a narrow time window after the stroke happens and can be risky. Blue-green algae, such as Synechococcus elongatus, have been studied previously to treat the lack of oxygen in heart tissue and tumors using photosynthesis. But the visible light needed to trigger the microbes can’t penetrate the skull, and although near-infrared light can pass through, it is insufficient to directly power photosynthesis. “Up-conversion” nanoparticles, often used for imaging, can absorb near-infrared photons and emit visible light. So, Lin Wang, Zheng Wang, Guobin Wang and colleagues at Huazhong University of Science and Technology wanted to see if they could develop a new approach that could someday be used for stroke patients by combining these parts — S. elongatus, nanoparticles and near-infrared light — in a new “nano-photosynthetic” system.

The researchers paired S. elongatus with neodymium up-conversion nanoparticles that transform tissue-penetrating near-infrared light to a visible wavelength that the microbes can use to photosynthesize. In a cell study, they found that the nano-photosynthesis approach reduced the number of neurons that died after oxygen and glucose deprivation. They then injected the microbes and nanoparticles into mice with blocked cerebral arteries and exposed the mice to near-infrared light. The therapy reduced the number of dying neurons, improved the animals’ motor function and even helped new blood vessels to start growing. Although this treatment is still in the animal testing stage, it has promise to advance someday toward human clinical trials, the researchers say.

The authors acknowledge funding from the National Key Basic Research Program of China, the National Natural Science Foundation of China, the Chinese Ministry of Education’s Science and Technology Program, the Major Scientific and Technological Innovation Projects in Hubei Province, and the Joint Fund of Ministry of Education for Equipment Pre-research.

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

Oxygen-Generating Cyanobacteria Powered by Upconversion-Nanoparticles-Converted Near-Infrared Light for Ischemic Stroke Treatment by Jian Wang, Qiangfei Su, Qiying Lv, Bo Cai, Xiakeerzhati Xiaohalati, Guobin Wang, Zheng Wang, and Lin Wang. Nano Lett. 2021, 21, 11, 4654–4665 DOI: https://doi.org/10.1021/acs.nanolett.1c00719 Publication Date:May 19, 2021 © 2021 American Chemical Society

This paper is behind a paywall.

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.

Will you be my friend? Yes, after we activate our ultraminiature, wireless, battery-free, fully implantable devices

Perhaps I’m the only one who’s disconcerted?

Here’s the research (in text form) as to why we’re watching these scampering, momentary mouse friends, from a May 10, 2021 Northwestern University news release (also on EurekAlert) by Amanda Morris,

Northwestern University researchers are building social bonds with beams of light.

For the first time ever, Northwestern engineers and neurobiologists have wirelessly programmed — and then deprogrammed — mice to socially interact with one another in real time. The advancement is thanks to a first-of-its-kind ultraminiature, wireless, battery-free and fully implantable device that uses light to activate neurons.

This study is the first optogenetics (a method for controlling neurons with light) paper exploring social interactions within groups of animals, which was previously impossible with current technologies.

The research was published May 10 [2021] in the journal Nature Neuroscience.

The thin, flexible, wireless nature of the implant allows the mice to look normal and behave normally in realistic environments, enabling researchers to observe them under natural conditions. Previous research using optogenetics required fiberoptic wires, which restrained mouse movements and caused them to become entangled during social interactions or in complex environments.

“With previous technologies, we were unable to observe multiple animals socially interacting in complex environments because they were tethered,” said Northwestern neurobiologist Yevgenia Kozorovitskiy, who designed the experiment. “The fibers would break or the animals would become entangled. In order to ask more complex questions about animal behavior in realistic environments, we needed this innovative wireless technology. It’s tremendous to get away from the tethers.”

“This paper represents the first time we’ve been able to achieve wireless, battery-free implants for optogenetics with full, independent digital control over multiple devices simultaneously in a given environment,” said Northwestern bioelectronics pioneer John A. Rogers, who led the technology development. “Brain activity in an isolated animal is interesting, but going beyond research on individuals to studies of complex, socially interacting groups is one of the most important and exciting frontiers in neuroscience. We now have the technology to investigate how bonds form and break between individuals in these groups and to examine how social hierarchies arise from these interactions.”

Kozorovitskiy is the Soretta and Henry Shapiro Research Professor of Molecular Biology and associate professor of neurobiology in Northwestern’s Weinberg College of Arts and Sciences. She also is a member of the Chemistry of Life Processes Institute. Rogers is the Louis Simpson and Kimberly Querrey Professor of Materials Science and Engineering, Biomedical Engineering and Neurological Surgery in the McCormick School of Engineering and Northwestern University Feinberg School of Medicine and the director of the Querrey Simpson Institute for Bioelectronics.

Kozorovitskiy and Rogers led the work with Yonggang Huang, the Jan and Marcia Achenbach Professor in Mechanical Engineering at McCormick, and Zhaoqian Xie, a professor of engineering mechanics at Dalian University of Technology in China. The paper’s co-first authors are Yiyuan Yang, Mingzheng Wu and Abraham Vázquez-Guardado — all at Northwestern.

Promise and problems of optogenetics

Because the human brain is a system of nearly 100 billion intertwined neurons, it’s extremely difficult to probe single — or even groups of — neurons. Introduced in animal models around 2005, optogenetics offers control of specific, genetically targeted neurons in order to probe them in unprecedented detail to study their connectivity or neurotransmitter release. Researchers first modify neurons in living mice to express a modified gene from light-sensitive algae. Then they can use external light to specifically control and monitor brain activity. Because of the genetic engineering involved, the method is not yet approved in humans.

“It sounds like sci-fi, but it’s an incredibly useful technique,” Kozorovitskiy said. “Optogenetics could someday soon be used to fix blindness or reverse paralysis.”

Previous optogenetics studies, however, were limited by the available technology to deliver light. Although researchers could easily probe one animal in isolation, it was challenging to simultaneously control neural activity in flexible patterns within groups of animals interacting socially. Fiberoptic wires typically emerged from an animal’s head, connecting to an external light source. Then a software program could be used to turn the light off and on, while monitoring the animal’s behavior.

“As they move around, the fibers tugged in different ways,” Rogers said. “As expected, these effects changed the animal’s patterns of motion. One, therefore, has to wonder: What behavior are you actually studying? Are you studying natural behaviors or behaviors associated with a physical constraint?”

Wireless control in real time

A world-renowned leader in wireless, wearable technology, Rogers and his team developed a tiny, wireless device that gently rests on the skull’s outer surface but beneath the skin and fur of a small animal. The half-millimeter-thick device connects to a fine, flexible filamentary probe with LEDs on the tip, which extend down into the brain through a tiny cranial defect.

The miniature device leverages near-field communication protocols, the same technology used in smartphones for electronic payments. Researchers wirelessly operate the light in real time with a user interface on a computer. An antenna surrounding the animals’ enclosure delivers power to the wireless device, thereby eliminating the need for a bulky, heavy battery.

Activating social connections

To establish proof of principle for Rogers’ technology, Kozorovitskiy and colleagues designed an experiment to explore an optogenetics approach to remote-control social interactions among pairs or groups of mice.

When mice were physically near one another in an enclosed environment, Kozorovitskiy’s team wirelessly synchronously activated a set of neurons in a brain region related to higher order executive function, causing them to increase the frequency and duration of social interactions. Desynchronizing the stimulation promptly decreased social interactions in the same pair of mice. In a group setting, researchers could bias an arbitrarily chosen pair to interact more than others.

“We didn’t actually think this would work,” Kozorovitskiy said. “To our knowledge, this is the first direct evaluation of a major long-standing hypothesis about neural synchrony in social behavior.”

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

Wireless multilateral devices for optogenetic studies of individual and social behaviors by Yiyuan Yang, Mingzheng Wu, Amy J. Wegener, Jose G. Grajales-Reyes, Yujun Deng, Taoyi Wang, Raudel Avila, Justin A. Moreno, Samuel Minkowicz, Vasin Dumrongprechachan, Jungyup Lee, Shuangyang Zhang, Alex A. Legaria, Yuhang Ma, Sunita Mehta, Daniel Franklin, Layne Hartman, Wubin Bai, Mengdi Han, Hangbo Zhao, Wei Lu, Yongjoon Yu, Xing Sheng, Anthony Banks, Xinge Yu, Zoe R. Donaldson, Robert W. Gereau IV, Cameron H. Good, Zhaoqian Xie, Yonggang Huang, Yevgenia Kozorovitskiy and John A. Rogers. Nature Neuroscience (2021)
DOI: https://doi.org/10.1038/s41593-021-00849-x Published 10 May 2021

This paper is behind a paywall.

This latest research seems to be the continuation of research featured here in a July 16, 2019 posting: “Controlling neurons with light: no batteries or wires needed.”

Nanosensors use AI to explore the biomolecular world

EPFL scientists have developed AI-powered nanosensors that let researchers track various kinds of biological molecules without disturbing them. Courtesy: École polytechnique fédérale de Lausanne (EPFL)

If you look at the big orange dot (representing the nanosensors?), you’ll see those purplish/fuschia objects resemble musical notes (biological molecules?). I think that brainlike object to the left and in light blue is the artificial intelligence (AI) component. (If anyone wants to correct my guesses or identify the bits I can’t, please feel free to add to the Comments for this blog.)

Getting back to my topic, keep the ‘musical notes’ in mind as you read about some of the latest research from l’École polytechnique fédérale de Lausanne (EPFL) in an April 7, 2021 news item on Nanowerk,

The tiny world of biomolecules is rich in fascinating interactions between a plethora of different agents such as intricate nanomachines (proteins), shape-shifting vessels (lipid complexes), chains of vital information (DNA) and energy fuel (carbohydrates). Yet the ways in which biomolecules meet and interact to define the symphony of life is exceedingly complex.

Scientists at the Bionanophotonic Systems Laboratory in EPFL’s School of Engineering have now developed a new biosensor that can be used to observe all major biomolecule classes of the nanoworld without disturbing them. Their innovative technique uses nanotechnology, metasurfaces, infrared light and artificial intelligence.

To each molecule its own melody

In this nano-sized symphony, perfect orchestration makes physiological wonders such as vision and taste possible, while slight dissonances can amplify into horrendous cacophonies leading to pathologies such as cancer and neurodegeneration.

An April 7, 2021 EPFL press release, which originated the news item, provides more detail,

“Tuning into this tiny world and being able to differentiate between proteins, lipids, nucleic acids and carbohydrates without disturbing their interactions is of fundamental importance for understanding life processes and disease mechanisms,” says Hatice Altug, the head of the Bionanophotonic Systems Laboratory. 

Light, and more specifically infrared light, is at the core of the biosensor developed by Altug’s team. Humans cannot see infrared light, which is beyond the visible light spectrum that ranges from blue to red. However, we can feel it in the form of heat in our bodies, as our molecules vibrate under the infrared light excitation.

Molecules consist of atoms bonded to each other and – depending on the mass of the atoms and the arrangement and stiffness of their bonds – vibrate at specific frequencies. This is similar to the strings on a musical instrument that vibrate at specific frequencies depending on their length. These resonant frequencies are molecule-specific, and they mostly occur in the infrared frequency range of the electromagnetic spectrum. 

“If you imagine audio frequencies instead of infrared frequencies, it’s as if each molecule has its own characteristic melody,” says Aurélian John-Herpin, a doctoral assistant at Altug’s lab and the first author of the publication. “However, tuning into these melodies is very challenging because without amplification, they are mere whispers in a sea of sounds. To make matters worse, their melodies can present very similar motifs making it hard to tell them apart.” 

Metasurfaces and artificial intelligence

The scientists solved these two issues using metasurfaces and AI. Metasurfaces are man-made materials with outstanding light manipulation capabilities at the nano scale, thereby enabling functions beyond what is otherwise seen in nature. Here, their precisely engineered meta-atoms made out of gold nanorods act like amplifiers of light-matter interactions by tapping into the plasmonic excitations resulting from the collective oscillations of free electrons in metals. “In our analogy, these enhanced interactions make the whispered molecule melodies more audible,” says John-Herpin.

AI is a powerful tool that can be fed with more data than humans can handle in the same amount of time and that can quickly develop the ability to recognize complex patterns from the data. John-Herpin explains, “AI can be imagined as a complete beginner musician who listens to the different amplified melodies and develops a perfect ear after just a few minutes and can tell the melodies apart, even when they are played together – like in an orchestra featuring many instruments simultaneously.” 

The first biosensor of its kind

When the scientists’ infrared metasurfaces are augmented with AI, the new sensor can be used to analyze biological assays featuring multiple analytes simultaneously from the major biomolecule classes and resolving their dynamic interactions. 

“We looked in particular at lipid vesicle-based nanoparticles and monitored their breakage through the insertion of a toxin peptide and the subsequent release of vesicle cargos of nucleotides and carbohydrates, as well as the formation of supported lipid bilayer patches on the metasurface,” says Altug.

This pioneering AI-powered, metasurface-based biosensor will open up exciting perspectives for studying and unraveling inherently complex biological processes, such as intercellular communication via exosomesand the interaction of nucleic acids and carbohydrates with proteins in gene regulation and neurodegeneration. 

“We imagine that our technology will have applications in the fields of biology, bioanalytics and pharmacology – from fundamental research and disease diagnostics to drug development,” says Altug. 

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

Infrared Metasurface Augmented by Deep Learning for Monitoring Dynamics between All Major Classes of Biomolecules by Aurelian John‐Herpin, Deepthy Kavungal. Lea von Mücke, Hatice Altug. Advanced Materials Volume 33, Issue 14 April 8, 2021 2006054 DOI: https://doi.org/10.1002/adma.202006054 First published: 22 February 2021

This paper is open access.

Metals useful in photonics?

Researchers at the University of Ottawa have debunked a myth, one involving metals and light according to a March 1i, 2021 news item on phys.org (Note: Links have been removed),

Researchers at the University of Ottawa have debunked the decade-old myth of metals being useless in photonics—the science and technology of light—with their findings, recently published in Nature Communications, expected to lead to many applications in the field of nanophotonics.

“We broke the record for the resonance quality factor (Q-factor) of a periodic array of metal nanoparticles by one order of magnitude compared to previous reports,” said senior author Dr. Ksenia Dolgaleva, Canada Research Chair in Integrated Photonics (Tier 2) and Associate Professor in the School of Electrical Engineering and Computer Science (EECS) at the University of Ottawa.

A March 18, 2021 University of Ottawa news release (also on EurekAlert), which originated the news item, introduced me to the word ‘lossy’ and discussed the decade-long myth in more detail,

“It is a well-known fact that metals are very lossy when they interact with light, which means they cause the dissipation of electrical energy. The high losses compromise their use in optics and photonics. We demonstrated ultra-high-Q resonances in a metasurface (an artificially structured surface) comprised of an array of metal nanoparticles embedded inside a flat glass substrate. These resonances can be used for efficient light manipulating and enhanced light-matter interaction, showing metals are useful in photonics.”

“In previous works, researchers attempted to mitigate the adverse effect of losses to access favorable properties of metal nanoparticle arrays,” observed the co-lead author of the study Md Saad Bin-Alam, a uOttawa doctoral student in EECS.

“However, their attempts did not provide a significant improvement in the quality factors of the resonances of the arrays. We implemented a combination of techniques rather than a single approach and obtained an order-of-magnitude improvement demonstrating a metal nanoparticle array (metasurface) with a record-high quality factor.”

According to the researchers, structured surfaces – also called metasurfaces – have very promising prospects in a variety of nanophotonic applications that can never be explored using traditional natural bulk materials. Sensors, nanolasers, light beam shaping and steering are just a few examples of the many applications.

“Metasurfaces made of noble metal nanoparticles – gold or silver for instance – possess some unique benefits over non-metallic nanoparticles. They can confine and control light in a nanoscale volume that is less than one quarter of the wavelength of light (less than 100 nm, while the width of a hair is over 10 000 nm),” explained Md Saad Bin-Alam.

“Interestingly, unlike in non-metallic nanoparticles, the light is not confined or trapped inside the metal nanoparticles but is concentrated close to their surface. This phenomenon is scientifically called ‘localized surface plasmon resonances (LSPRs)’. This feature gives a great superiority to metal nanoparticles compared to their dielectric counterparts, because one could exploit such surface resonances to detect bio-organisms or molecules in medicine or chemistry. Also, such surface resonances could be used as the feedback mechanism necessary for laser gain. In such a way, one can realize a nanoscale tiny laser that can be adopted in many future nanophotonic applications, like light detection and ranging (LiDAR) for the far-field object detection.”

According to the researchers, the efficiency of these applications depends on the resonant Q-factors.

“Unfortunately, due to the high ‘absorptive’ and ‘radiative’ loss in metal nanoparticles, the LSPRs Q-factors are very low,” said co-lead author Dr. Orad Reshef, a postdoctoral fellow in the Department of Physics at the University of Ottawa.

“More than a decade ago, researchers found a way to mitigate the dissipative loss by carefully arranging the nanoparticles in a lattice. From such ‘surface lattice’ manipulation, a new ‘surface lattice resonance (SLR)’ emerges with suppressed losses. Until our work, the maximum Q-factors reported in SLRs was around a few hundred. Although such early reported SLRs were better than the low-Q LSPRs, they were still not very impressive for efficient applications. It led to the myth that metals are not useful for practical applications.”

A myth that the group was able to deconstruct during its work at the University of Ottawa’s Advanced Research Complex between 2017 and 2020.

“At first, we performed numerical modelling of a gold nanoparticle metasurface and were surprised to obtain quality factors of several thousand,” said Md Saad Bin-Alam, who primarily designed the metasurface structure.

“This value has never been reported experimentally, and we decided to analyze why and to attempt an experimental demonstration of such a high Q. We observed a very high-Q SLR of value nearly 2400, that is at least 10 times larger than the largest SLRs Q reported earlier.”

A discovery that made them realize that there’s still a lot to learn about metals.

“Our research proved that we are still far from knowing all the hidden mysteries of metal (plasmonic) nanostructures,” concluded Dr. Orad Reshef, who fabricated the metasurface sample. “Our work has debunked a decade-long myth that such structures are not suitable for real-life optical applications due to the high losses. We demonstrated that, by properly engineering the nanostructure and carefully conducting an experiment, one can improve the result significantly.”

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

Ultra-high-Q resonances in plasmonic metasurfaces by M. Saad Bin-Alam, Orad Reshef, Yaryna Mamchur, M. Zahirul Alam, Graham Carlow, Jeremy Upham, Brian T. Sullivan, Jean-Michel Ménard, Mikko J. Huttunen, Robert W. Boyd & Ksenia Dolgaleva. Nature Communications volume 12, Article number: 974 (2021) DOI: https://doi.org/10.1038/s41467-021-21196-2 Published 12 February 2021

This paper is open access.

Put a ring on it: preventing clumps of gold nanoparticles

Caption: A comparison of how linear PEG (left) and cyclic PEG (right) attach to a gold nanoparticle Credit: Yubo Wang, Takuya Yamamoto

A January 20, 2021 news item on phys.org focuses on work designed to stop gold nanoparticles from clumping together (Note: A link has been removed),

Hokkaido University scientists have found a way to prevent gold nanoparticles from clumping, which could help towards their use as an anti-cancer therapy.

Attaching ring-shaped synthetic compounds to gold nanoparticles helps them retain their essential light-absorbing properties, Hokkaido University researchers report in the journal Nature Communications.

A January 20, 2021 Hokkaido University press release (also on EurekAlert but published Jan. 21, 2020), which originated the news item, elaborates on the work,

Metal nanoparticles have unique light-absorbing properties, making them interesting for a wide range of optical, electronic and biomedical applications. For example, if delivered to a tumour, they could react with applied light to kill cancerous tissue. A problem with this approach, though, is that they easily clump together in solution, losing their ability to absorb light. This clumping happens in response to a variety of factors, including temperature, salt concentration and acidity.

Scientists have been trying to find ways to ensure nanoparticles stay dispersed in their target environments. Covering them with polyethylene glycol, otherwise known as PEG, has been relatively successful at this in the case of gold nanoparticles. PEG is biocompatible and can prevent gold surfaces from clumping together in the laboratory and in living organisms, but improvements are still needed.

Applied chemist Takuya Yamamoto and colleagues at Hokkaido University, The University of Tokyo, and Tokyo Institute of Technology found that mixing gold nanoparticles with ring-shaped PEG, rather than the normally linear PEG, significantly improved dispersion. The ‘cyclic-PEG’ (c-PEG) attaches to the surfaces of the nanoparticles without forming chemical bonds with them, a process called physisorption. The coated nanoparticles remained dispersed when frozen, freeze-dried and heated.

The team tested the c-PEG-covered gold nanoparticles in mice and found that they cleared slowly from the blood and accumulated better in tumours compared to gold nanoparticles coated with linear PEG. However, accumulation was lower than desired levels, so the researchers recommend further investigations to fine-tune the nanoparticles for this purpose.

Associate Professor Takuya Yamamoto is part of the Laboratory of Chemistry of Molecular Assemblies at Hokkaido University, where he studies the properties and applications of various cyclic chemical compounds.

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

Enhanced dispersion stability of gold nanoparticles by the physisorption of cyclic poly(ethylene glycol) by Yubo Wang, Jose Enrico Q. Quinsaat, Tomoko Ono, Masatoshi Maeki, Manabu Tokeshi, Takuya Isono, Kenji Tajima, Toshifumi Satoh, Shin-ichiro Sato, Yutaka Miura & Takuya Yamamoto. Nature Communications volume 11, Article number: 6089 (2020) DOI: https://doi.org/10.1038/s41467-020-19947-8 Published: 30 November 2020

This paper is open access.

Spider web-like electronics with graphene

A spiderweb-inspired fractal design is used for hemispherical 3D photodetection to replicate the vision system of arthropods. (Sena Huh image)

This image is pretty and I’m pretty sure it’s an illustration and not a real photodetection system. Regardless, an Oct. 21, 2020 news item on Nanowerk describes the research into producing a real 3D hemispheric photodetector for biomedical imaging (Note: A link has been removed),

Purdue University innovators are taking cues from nature to develop 3D photodetectors for biomedical imaging.

The researchers used some architectural features from spider webs to develop the technology. Spider webs typically provide excellent mechanical adaptability and damage-tolerance against various mechanical loads such as storms.

“We employed the unique fractal design of a spider web for the development of deformable and reliable electronics that can seamlessly interface with any 3D curvilinear surface,” said Chi Hwan Lee, a Purdue assistant professor of biomedical engineering and mechanical engineering. “For example, we demonstrated a hemispherical, or dome-shaped, photodetector array that can detect both direction and intensity of incident light at the same time, like the vision system of arthropods such as insects and crustaceans.”

The Purdue technology uses the structural architecture of a spider web that exhibits a repeating pattern. This work is published in Advanced Materials (“Fractal Web Design of a Hemispherical Photodetector Array with Organic-Dye-Sensitized Graphene Hybrid Composites”).

An Oct. 21, 2020 Purdue University news release by Chris Adam, which originated the news item, delves further into the work,

Lee said this provides unique capabilities to distribute externally induced stress throughout the threads according to the effective ratio of spiral and radial dimensions and provides greater extensibility to better dissipate force under stretching. Lee said it also can tolerate minor cuts of the threads while maintaining overall strength and function of the entire web architecture.

“The resulting 3D optoelectronic architectures are particularly attractive for photodetection systems that require a large field of view and wide-angle antireflection, which will be useful for many biomedical and military imaging purposes,” said Muhammad Ashraful Alam, the Jai N. Gupta Professor of Electrical and Computer Engineering.

Alam said the work establishes a platform technology that can integrate a fractal web design with system-level hemispherical electronics and sensors, thereby offering several excellent mechanical adaptability and damage-tolerance against various mechanical loads.

“The assembly technique presented in this work enables deploying 2D deformable electronics in 3D architectures, which may foreshadow new opportunities to better advance the field of 3D electronic and optoelectronic devices,” Lee said.

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

Fractal Web Design of a Hemispherical Photodetector Array with Organic‐Dye‐Sensitized Graphene Hybrid Composites by Eun Kwang Lee, Ratul Kumar Baruah, Jung Woo Leem, Woohyun Park, Bong Hoon Kim, Augustine Urbas, Zahyun Ku, Young L. Kim, Muhammad Ashraful Alam, Chi Hwan Lee. Advanced Materials Volume 32, Issue 46 November 19, 2020 2004456 DOI: https://doi.org/10.1002/adma.202004456 First published online: 12 October 2020

This paper is behind a paywall.

Gold nanotubes for treating mesothelioma?

An October 26, 2020 news item on Nanowerk describes some new research that may lead the way to treatments for people with asbestos-related cancers (e.g., mesothelioma), Note: A link has been removed,

Gold nanotubes – tiny hollow cylinders one thousandth the width of a human hair – could be used to treat mesothelioma, a type of cancer caused by exposure to asbestos, according to a team of researchers at the Universities of Cambridge and Leeds.

In a study published in journal Small (“Exploring High Aspect Ratio Gold Nanotubes as Cytosolic Agents: Structural Engineering and Uptake into Mesothelioma Cells”), the researchers demonstrate that once inside the cancer cells, the nanotubes absorb light, causing them to heat up, thereby killing the cells.

Here`s an image illustrating the research,

Caption: Confocal fluorescence image of gold nanotures (green) in mesothelioma cells. Credit: Arsalan Azad

An October 27, 2020 University of Cambridge press release (also on EurekAlert but published on Oct. 26, 2020), which originated the news item, describes the context for the research and provides a few more technical details,

More than 2,600 people are diagnosed in the UK each year with mesothelioma, a malignant form of cancer caused by exposure to asbestos. Although the use of asbestos is outlawed in the UK now, the country has the world’s highest levels of mesothelioma because it imported vast amounts of asbestos in the post-war years. The global usage of asbestos remains high, particularly in low- and middle-income countries, which means mesothelioma will become a global problem.

“Mesothelioma is one of the ‘hard-to-treat’ cancers, and the best we can offer people with existing treatments is a few months of extra survival,” said Dr Arsalan Azad from the Cambridge Institute for Medical Research at the University of Cambridge. “There’s an important unmet need for new, effective treatments.”

In 2018, the University of Cambridge was awarded £10million from the Engineering and Physical Sciences Research Council to help develop engineering solutions, including nanotech, to find ways to address hard-to-treat cancers.

In a collaboration between the University of Cambridge and University of Leeds, researchers have developed a form of gold nanotubes whose physical properties are ‘tunable’ – in other words, the team can tailor the wall thickness, microstructure, composition, and ability to absorb particular wavelengths of light.

The researchers added the nanotubes to mesothelioma cells cultured in the lab and found that they were absorbed by the cells, residing close to the nucleus, where the cell’s DNA lies. When the team targeted the cells with a laser, the nanotubes absorbed the light and heated up, killing the mesothelioma cell.

Professor Stefan Marciniak, also from the Cambridge Institute for Medical Research, added: “The mesothelioma cells ‘eat’ the nanotubes, leaving them susceptible when we shine light on them. Laser light is able to penetrate deep into tissue without causing damage to surrounding tissue. It then gets absorbed by the nanotubes, which heat up and, we hope in the future, could be used to cause localised cancer-cell killing.”

The team will be developing the work further to ensure the nanotubes are targeted to cancer cells with less effect on normal tissue.

The nanotubes are made in a two-step process. First, solid silver nanorods are created of the desired diameter. Gold is then deposited from solution onto the surface of the silver. As the gold builds-up at the surface, the silver dissolves from the inside to leave a hollow nanotube.

The approach advanced by the Leeds team allows these nanotubes to be developed at room temperature, which should make their manufacture at scale more feasible.

Professor Stephen Evans from the School of Physics and Astronomy at the University of Leeds said: “Having control over the size and shape of the nanotubes allows us to tune them to absorb light where the tissue is transparent and will allow them to be used for both the imaging and treatment of cancers. The next stage will be to load these nanotubes with medicines for enhanced therapies.”

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

Exploring High Aspect Ratio Gold Nanotubes as Cytosolic Agents: Structural Engineering and Uptake into Mesothelioma Cells by Sunjie Ye, Arsalan A. Azad, Joseph E. Chambers, Alison J. Beckett, Lucien Roach, Samuel C. T. Moorcroft, Zabeada Aslam, Ian A. Prior, Alexander F. Markham, P. Louise Coletta, Stefan J. Marciniak, Stephen D. Evans. Small DOI: https://doi.org/10.1002/smll.202003793 First published: 25 October 2020

This paper is open access.