Tag Archives: bioelectronics

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.”

Synaptic transistor better then memristor when it comes to brainlike learning for computers

An April 30, 2021 news item on Nanowerk announced research from a joint team at Northwestern University (located in Chicago, Illinois, US) and University of Hong Kong of researchers in the field of neuromorphic (brainlike) computing,

Researchers have developed a brain-like computing device that is capable of learning by association.

Similar to how famed physiologist Ivan Pavlov conditioned dogs to associate a bell with food, researchers at Northwestern University and the University of Hong Kong successfully conditioned their circuit to associate light with pressure.

The device’s secret lies within its novel organic, electrochemical “synaptic transistors,” which simultaneously process and store information just like the human brain. The researchers demonstrated that the transistor can mimic the short-term and long-term plasticity of synapses in the human brain, building on memories to learn over time.

With its brain-like ability, the novel transistor and circuit could potentially overcome the limitations of traditional computing, including their energy-sapping hardware and limited ability to perform multiple tasks at the same time. The brain-like device also has higher fault tolerance, continuing to operate smoothly even when some components fail.

“Although the modern computer is outstanding, the human brain can easily outperform it in some complex and unstructured tasks, such as pattern recognition, motor control and multisensory integration,” said Northwestern’s Jonathan Rivnay, a senior author of the study. “This is thanks to the plasticity of the synapse, which is the basic building block of the brain’s computational power. These synapses enable the brain to work in a highly parallel, fault tolerant and energy-efficient manner. In our work, we demonstrate an organic, plastic transistor that mimics key functions of a biological synapse.”

Rivnay is an assistant professor of biomedical engineering at Northwestern’s McCormick School of Engineering. He co-led the study with Paddy Chan, an associate professor of mechanical engineering at the University of Hong Kong. Xudong Ji, a postdoctoral researcher in Rivnay’s group, is the paper’s first author.

Caption: By connecting single synaptic transistors into a neuromorphic circuit, researchers demonstrated that their device could simulate associative learning. Credit: Northwestern University

An April 30, 2021 Northwestern University news release (also on EurekAlert), which originated the news item, includes a good explanation about brainlike computing and information about how synaptic transistors work along with some suggestions for future applications,

Conventional, digital computing systems have separate processing and storage units, causing data-intensive tasks to consume large amounts of energy. Inspired by the combined computing and storage process in the human brain, researchers, in recent years, have sought to develop computers that operate more like the human brain, with arrays of devices that function like a network of neurons.

“The way our current computer systems work is that memory and logic are physically separated,” Ji said. “You perform computation and send that information to a memory unit. Then every time you want to retrieve that information, you have to recall it. If we can bring those two separate functions together, we can save space and save on energy costs.”

Currently, the memory resistor, or “memristor,” is the most well-developed technology that can perform combined processing and memory function, but memristors suffer from energy-costly switching and less biocompatibility. These drawbacks led researchers to the synaptic transistor — especially the organic electrochemical synaptic transistor, which operates with low voltages, continuously tunable memory and high compatibility for biological applications. Still, challenges exist.

“Even high-performing organic electrochemical synaptic transistors require the write operation to be decoupled from the read operation,” Rivnay said. “So if you want to retain memory, you have to disconnect it from the write process, which can further complicate integration into circuits or systems.”

How the synaptic transistor works

To overcome these challenges, the Northwestern and University of Hong Kong team optimized a conductive, plastic material within the organic, electrochemical transistor that can trap ions. In the brain, a synapse is a structure through which a neuron can transmit signals to another neuron, using small molecules called neurotransmitters. In the synaptic transistor, ions behave similarly to neurotransmitters, sending signals between terminals to form an artificial synapse. By retaining stored data from trapped ions, the transistor remembers previous activities, developing long-term plasticity.

The researchers demonstrated their device’s synaptic behavior by connecting single synaptic transistors into a neuromorphic circuit to simulate associative learning. They integrated pressure and light sensors into the circuit and trained the circuit to associate the two unrelated physical inputs (pressure and light) with one another.

Perhaps the most famous example of associative learning is Pavlov’s dog, which naturally drooled when it encountered food. After conditioning the dog to associate a bell ring with food, the dog also began drooling when it heard the sound of a bell. For the neuromorphic circuit, the researchers activated a voltage by applying pressure with a finger press. To condition the circuit to associate light with pressure, the researchers first applied pulsed light from an LED lightbulb and then immediately applied pressure. In this scenario, the pressure is the food and the light is the bell. The device’s corresponding sensors detected both inputs.

After one training cycle, the circuit made an initial connection between light and pressure. After five training cycles, the circuit significantly associated light with pressure. Light, alone, was able to trigger a signal, or “unconditioned response.”

Future applications

Because the synaptic circuit is made of soft polymers, like a plastic, it can be readily fabricated on flexible sheets and easily integrated into soft, wearable electronics, smart robotics and implantable devices that directly interface with living tissue and even the brain [emphasis mine].

“While our application is a proof of concept, our proposed circuit can be further extended to include more sensory inputs and integrated with other electronics to enable on-site, low-power computation,” Rivnay said. “Because it is compatible with biological environments, the device can directly interface with living tissue, which is critical for next-generation bioelectronics.”

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

Mimicking associative learning using an ion-trapping non-volatile synaptic organic electrochemical transistor by Xudong Ji, Bryan D. Paulsen, Gary K. K. Chik, Ruiheng Wu, Yuyang Yin, Paddy K. L. Chan & Jonathan Rivnay . Nature Communications volume 12, Article number: 2480 (2021) DOI: https://doi.org/10.1038/s41467-021-22680-5 Published: 30 April 2021

This paper is open access.

“… devices that directly interface with living tissue and even the brain,” would I be the only one thinking about cyborgs?

Cortical spheroids (like mini-brains) could unlock (larger) brain’s mysteries

A March 19, 2021 Northwestern University news release on EurekAlert announces the creation of a device designed to monitor brain organoids (for anyone unfamiliar with brain organoids there’s more information after the news),

A team of scientists, led by researchers at Northwestern University, Shirley Ryan AbilityLab and the University of Illinois at Chicago (UIC), has developed novel technology promising to increase understanding of how brains develop, and offer answers on repairing brains in the wake of neurotrauma and neurodegenerative diseases.

Their research is the first to combine the most sophisticated 3-D bioelectronic systems with highly advanced 3-D human neural cultures. The goal is to enable precise studies of how human brain circuits develop and repair themselves in vitro. The study is the cover story for the March 19 [March 17, 2021 according to the citation] issue of Science Advances.

The cortical spheroids used in the study, akin to “mini-brains,” were derived from human-induced pluripotent stem cells. Leveraging a 3-D neural interface system that the team developed, scientists were able to create a “mini laboratory in a dish” specifically tailored to study the mini-brains and collect different types of data simultaneously. Scientists incorporated electrodes to record electrical activity. They added tiny heating elements to either keep the brain cultures warm or, in some cases, intentionally overheated the cultures to stress them. They also incorporated tiny probes — such as oxygen sensors and small LED lights — to perform optogenetic experiments. For instance, they introduced genes into the cells that allowed them to control the neural activity using different-colored light pulses.

This platform then enabled scientists to perform complex studies of human tissue without directly involving humans or performing invasive testing. In theory, any person could donate a limited number of their cells (e.g., blood sample, skin biopsy). Scientists can then reprogram these cells to produce a tiny brain spheroid that shares the person’s genetic identity. The authors believe that, by combining this technology with a personalized medicine approach using human stem cell-derived brain cultures, they will be able to glean insights faster and generate better, novel interventions.

“The advances spurred by this research will offer a new frontier in the way we study and understand the brain,” said Shirley Ryan AbilityLab’s Dr. Colin Franz, co-lead author on the paper who led the testing of the cortical spheroids. “Now that the 3-D platform has been developed and validated, we will be able to perform more targeted studies on our patients recovering from neurological injury or battling a neurodegenerative disease.”

Yoonseok Park, postdoctoral fellow at Northwestern University and co-lead author, added, “This is just the beginning of an entirely new class of miniaturized, 3-D bioelectronic systems that we can construct to expand the capacity of the regenerative medicine field. For example, our next generation of device will support the formation of even more complex neural circuits from brain to muscle, and increasingly dynamic tissues like a beating heart.”

Current electrode arrays for tissue cultures are 2-D, flat and unable to match the complex structural designs found throughout nature, such as those found in the human brain. Moreover, even when a system is 3-D, it is extremely challenging to incorporate more than one type of material into a small 3-D structure. With this advance, however, an entire class of 3-D bioelectronics devices has been tailored for the field of regenerative medicine.

“Now, with our small, soft 3-D electronics, the capacity to build devices that mimic the complex biological shapes found in the human body is finally possible, providing a much more holistic understanding of a culture,” said Northwestern’s John Rogers, who led the technology development using technology similar to that found in phones and computers. “We no longer have to compromise function to achieve the optimal form for interfacing with our biology.”

As a next step, scientists will use the devices to better understand neurological disease, test drugs and therapies that have clinical potential, and compare different patient-derived cell models. This understanding will then enable a better grasp of individual differences that may account for the wide variation of outcomes seen in neurological rehabilitation.

“As scientists, our goal is to make laboratory research as clinically relevant as possible,” said Kristen Cotton, research assistant in Dr. Franz’s lab. “This 3-D platform opens the door to new experiments, discovery and scientific advances in regenerative neurorehabilitation medicine that have never been possible.”

Caption: Three dimensional multifunctional neural interfaces for cortical spheroids and engineered assembloids Credit: Northwestern University

As for what brain ogranoids might be, Carl Zimmer in an Aug. 29, 2019 article for the New York Times provides an explanation,

Organoids Are Not Brains. How Are They Making Brain Waves?

Two hundred and fifty miles over Alysson Muotri’s head, a thousand tiny spheres of brain cells were sailing through space.

The clusters, called brain organoids, had been grown a few weeks earlier in the biologist’s lab here at the University of California, San Diego. He and his colleagues altered human skin cells into stem cells, then coaxed them to develop as brain cells do in an embryo.

The organoids grew into balls about the size of a pinhead, each containing hundreds of thousands of cells in a variety of types, each type producing the same chemicals and electrical signals as those cells do in our own brains.

In July, NASA packed the organoids aboard a rocket and sent them to the International Space Station to see how they develop in zero gravity.

Now the organoids were stowed inside a metal box, fed by bags of nutritious broth. “I think they are replicating like crazy at this stage, and so we’re going to have bigger organoids,” Dr. Muotri said in a recent interview in his office overlooking the Pacific.

What, exactly, are they growing into? That’s a question that has scientists and philosophers alike scratching their heads.

On Thursday, Dr. Muotri and his colleagues reported that they  have recorded simple brain waves in these organoids. In mature human brains, such waves are produced by widespread networks of neurons firing in synchrony. Particular wave patterns are linked to particular forms of brain activity, like retrieving memories and dreaming.

As the organoids mature, the researchers also found, the waves change in ways that resemble the changes in the developing brains of premature babies.

“It’s pretty amazing,” said Giorgia Quadrato, a neurobiologist at the University of Southern California who was not involved in the new study. “No one really knew if that was possible.”

But Dr. Quadrato stressed it was important not to read too much into the parallels. What she, Dr. Muotri and other brain organoid experts build are clusters of replicating brain cells, not actual brains.

If you have the time, I recommend reading Zimmer’s article in its entirety. Perhaps not coincidentally, Zimmer has an excerpt titled “Lab-Grown Brain Organoids Aren’t Alive. But They’re Not Not Alive, Either.” published in Slate.com,

From Life’s Edge: The Search For What It Means To Be Alive by Carl Zimmer, published by Dutton, an imprint of Penguin Publishing Group, a division of Penguin Random House, LLC. Copyright © 2021 by Carl Zimmer.

Cleber Trujillo led me to a windowless room banked with refrigerators, incubators, and microscopes. He extended his blue-gloved hands to either side and nearly touched the walls. “This is where we spend half our day,” he said.

In that room Trujillo and a team of graduate students raised a special kind of life. He opened an incubator and picked out a clear plastic box. Raising it above his head, he had me look up at it through its base. Inside the box were six circular wells, each the width of a cookie and filled with what looked like watered-down grape juice. In each well 100 pale globes floated, each the size of a housefly head.

Getting back to the research about monitoring brain organoids, here’s a link to and a citation for the paper about cortical spheroids,

Three-dimensional, multifunctional neural interfaces for cortical spheroids and engineered assembloids by Yoonseok Park, Colin K. Franz, Hanjun Ryu, Haiwen Luan, Kristen Y. Cotton, Jong Uk Kim, Ted S. Chung, Shiwei Zhao, Abraham Vazquez-Guardado, Da Som Yang, Kan Li, Raudel Avila, Jack K. Phillips, Maria J. Quezada, Hokyung Jang, Sung Soo Kwak, Sang Min Won, Kyeongha Kwon, Hyoyoung Jeong, Amay J. Bandodkar, Mengdi Han, Hangbo Zhao, Gabrielle R. Osher, Heling Wang, KunHyuck Lee, Yihui Zhang, Yonggang Huang, John D. Finan and John A. Rogers. Science Advances 17 Mar 2021: Vol. 7, no. 12, eabf9153 DOI: 10.1126/sciadv.abf9153

This paper appears to be open access.

According to a March 22, 2021 posting on the Shirley Riley AbilityLab website, the paper is featured on the front cover of Science Advances (vol. 7 no. 12).

Cyborgs based on melanin circuits

Pigments for biocompatible electronics? According to a March 26, 2019 news item on Nanowerk this is a distinct possibility (Note: A link has been removed),

The dark brown melanin pigment, eumelanin, colors hair and eyes, and protects our skin from sun damage. It has also long been known to conduct electricity, but too little for any useful application – until now.

In a landmark study published in Frontiers in Chemistry (“Evidence of Unprecedented High Electronic Conductivity in Mammalian Pigment Based Eumelanin Thin Films After Thermal Annealing in Vacuum”), Italian researchers subtly modified the structure of eumelanin by heating it in a vacuum.

“Our process produced a billion-fold increase in the electrical conductivity of eumelanin,” say study senior authors Dr. Alessandro Pezzella of University of Naples Federico II and Dr. Paolo Tassini of Italian National Agency for New Technologies, Energy and Sustainable Economic Development. “This makes possible the long-anticipated design of melanin-based electronics, which can be used for implanted devices due to the pigment’s biocompatibility.”

This is a rather dreamy image to illustrate the point,

Despite extensive research on the structure of melanin, nobody has yet managed to harness its potential in implantable electronics. Image: Shutterstock. [downloaded from https://blog.frontiersin.org/2019/03/26/will-cyborgs-circuits-be-made-from-melanin/]

A March 26, 2019 Frontiers in Chemistry (journal) press release (also on EurekAlert), which originated the news item, expands on the theme,

A young Pezzella had not even begun school when scientists first discovered that a type of melanin can conduct electricity. Excitement quickly rose around the discovery because eumelanin – the dark brown pigment found in hair, skin and eyes – is fully biocompatible.

“Melanins occur naturally in virtually all forms of life. They are non-toxic and do not elicit an immune reaction,” explains Pezzella. “Out in the environment, they are also completely biodegradable.”

Decades later, and despite extensive research on the structure of melanin, nobody has managed to harness its potential in implantable electronics.

“To date, conductivity of synthetic as well as natural eumelanin has been far too low for valuable applications,” he adds.

Some researchers tried to increase the conductivity of eumelanin by combining it with metals, or super-heating it into a graphene-like material – but what they were left with was not truly the biocompatible conducting material promised.

Determined to find the real deal, the Neapolitan group considered the structure of eumelanin.

“All of the chemical and physical analyses of eumelanin paint the same picture – of electron-sharing molecular sheets, stacked messily together. The answer seemed obvious: neaten the stacks and align the sheets, so they can all share electrons – then the electricity will flow.”

This process, called annealing, is used already to increase electrical conductivity and other properties in materials such as metals.

For the first time, the researchers put films of synthetic eumelanin through an annealing process under high vacuum to neaten them up – a little like hair straightening, but with only the pigment.

“We heated these eumelanin films – no thicker than a bacterium – under vacuum conditions, from 30 min up to 6 hours,” describes Tassini. “We call the resulting material High Vacuum Annealed Eumelanin, HVAE.”

The annealing worked wonders for eumelanin: the films slimmed down by more than half, and picked up quite a tan.

“The HVAE films were now dark brown and about as thick as a virus,” Tassini reports.

Crucially, the films had not simply been burnt to a crisp.

“All our various analyses agree that these changes reflect reorganization of eumelanin molecules from a random orientation to a uniform, electron-sharing stack. The annealing temperatures were too low to break up the eumelanin, and we detected no combustion to elemental carbon.”

Having achieved the intended structural changes to eumelanin, the researchers proved their hypothesis in spectacular fashion.

“The conductivity of the films increased billion-fold to an unprecedented value of over 300 S/cm, after annealing at 600°C for 2 hours,” Pezzella confirms.

Although well short of most metal conductors – copper has a conductivity of around 6 x 107 S/cm – this finding launches eumelanin well into a useful range for bioelectronics.

What’s more, the conductivity of HVAE was tunable according to the annealing conditions.

“The conductivity of the films increased with increasing temperature, from 1000-fold at 200°C. This opens the possibility of tailoring eumelanin for a wide range of applications in organic electronics and bioelectronics. It also strongly supports the conclusion from structural analysis that annealing reorganized the films, rather than burning them.”

There is one potential dampener: immersion of the films in water results in a marked decrease in conductivity.

“This contrasts with untreated eumelanin which, albeit in a much lower range, becomes more conductive with hydration (humidity) because it conducts electricity via ions as well as electrons. Further research is needed to fully understand the ionic vs. electronic contributions in eumelanin conductivity, which could be key to how eumelanin is used practically in implantable electronics.” concludes Pezzella.

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

Evidence of Unprecedented High Electronic Conductivity in Mammalian Pigment Based Eumelanin Thin Films After Thermal Annealing in Vacuum by Ludovico Migliaccio, Paola Manini, Davide Altamura, Cinzia Giannini, Paolo Tassini, Maria Grazia Maglione, Carla Minarini, and Alessandro Pezzella. Front. Chem., 26 March 2019 DOI: https://doi.org/10.3389/fchem.2019.00162

This paper is open access.

Organic nanoelectronics in water

Researchers in Sweden have developed organic electronics that are stable in water according to a January 11, 2018 news item on ScienceDaily,

Researchers at the Laboratory of Organic Electronics, Linköping University [Sweden], have developed the world’s first complementary electrochemical logic circuits that can function stably for long periods in water. This is a highly significant breakthrough in the development of bioelectronics.

A January 11, 2018 Linköping University press release, which originated the news item, notes this latest advance is based on work that started in 2002,

Complementary logic circuitComplementary logic circuit Photo credit: Thor Balkhed

The first printable organic electrochemical transistors were presented by researchers at LiU as early as 2002, and research since then has progressed rapidly. Several organic electronic components, such as light-emitting diodes and electrochromic displays, are already commercially available.

The dominating material used until now has been PEDOT:PSS, which is a p-type material, in which the charge carriers are holes. In order to construct effective electron components, a complementary material, n-type, is required, in which the charge carriers are electrons.
It has been difficult to find a sufficiently stable polymer material, one that can operate in water media and in which the long polymer chains can sustain high current when the material is doped.

N-type material

In an article in the prestigious scientific journal Advanced Materials, Simone Fabiano, head of research in the Organic Nanoelectronics group at the Laboratory of Organic Electronics, presents, together with his colleagues, results from an n-type conducting material in which the ladder-type structure of the polymer backbone favours ambient stability and high current when doped. One example is BBL, poly(benzimidazobenzophenanthroline), a material often used in solar cell research.

Postdoctoral researcher Hengda Sun has found a method to create thick films of the material. The thicker the film, the greater the conductivity.

“We have used spray-coating to produce films up to 200 nm thick. These can reach extremely high conductivities,” says Simone Fabiano.

The method can also be successfully used together with printed electronics across large surfaces.

Hengda Sun has also shown that the circuits function for long periods, both in the presence of oxygen and water.

Moist surroundings

“This may appear at first glance to be a small advance in a specialised field, but what is great about it is that it has major consequences for many applications. We can now construct complementary logic circuits – inverters, sensors and other components – that function in moist surroundings,” says Simone Fabiano.

“Resistors are needed in logical circuits that are based solely on p-type electrochemical transistors. These are rather bulky, and this limits the applications that can be achieved. With an n-type material in our toolbox, we can produce complementary circuits that occupy the available space much more efficiently, since resistors are no longer required in the logical circuits,” says Magnus Berggren, professor of organic electronics and head of the Laboratory for Organic Electronics.

Applications of the organic components include logic circuits that can be printed on textile or paper, various types of cheap sensor, non-rigid and flexible displays, and – not least – the huge field of bioelectronics. Polymers that conduct both ions and electrons are the bridge needed between the ion-conducting systems in the body and the electronic components of, for example, sensors.

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

Complementary Logic Circuits Based on High-Performance n-Type Organic Electrochemical Transistors by Hengda Sun, Mikhail Vagin, Suhao Wang, Xavier Crispin, Robert Forchheimer, Magnus Berggren, and Simone Fabiano. Advanced Materials Vol. 30 Issue 3 Version of Record online: 10 JAN 2018 DOI: 10.1002/adma.201704916

© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.

Using melanin in bioelectronic devices

Brazilian researchers are working with melanin to make biosensors and other bioelectronic devices according to a Dec. 20, 2016 news item on phys.org,

Bioelectronics, sometimes called the next medical frontier, is a research field that combines electronics and biology to develop miniaturized implantable devices capable of altering and controlling electrical signals in the human body. Large corporations are increasingly interested: a joint venture in the field has recently been announced by Alphabet, Google’s parent company, and pharmaceutical giant GlaxoSmithKline (GSK).

One of the challenges that scientists face in developing bioelectronic devices is identifying and finding ways to use materials that conduct not only electrons but also ions, as most communication and other processes in the human organism use ionic biosignals (e.g., neurotransmitters). In addition, the materials must be biocompatible.

Resolving this challenge is one of the motivations for researchers at São Paulo State University’s School of Sciences (FC-UNESP) at Bauru in Brazil. They have succeeded in developing a novel route to more rapidly synthesize and to enable the use of melanin, a polymeric compound that pigments the skin, eyes and hair of mammals and is considered one of the most promising materials for use in miniaturized implantable devices such as biosensors.

A Dec. 14, 2016 FAPESP (São Paulo Research Foundation) press release, which originated the news item, further describes both the research and a recent meeting where the research was shared (Note: A link has been removed),

Some of the group’s research findings were presented at FAPESP Week Montevideo during a round-table session on materials science and engineering.

The symposium was organized by the Montevideo Group Association of Universities (AUGM), Uruguay’s University of the Republic (UdelaR) and FAPESP and took place on November 17-18 at UdelaR’s campus in Montevideo. Its purpose was to strengthen existing collaborations and establish new partnerships among South American scientists in a range of knowledge areas. Researchers and leaders of institutions in Uruguay, Brazil, Argentina, Chile and Paraguay attended the meeting.

“All the materials that have been tested to date for applications in bioelectronics are entirely synthetic,” said Carlos Frederico de Oliveira Graeff, a professor at UNESP Bauru and principal investigator for the project, in an interview given to Agência FAPESP.

“One of the great advantages of melanin is that it’s a totally natural compound and biocompatible with the human body: hence its potential use in electronic devices that interface with brain neurons, for example.”

Application challenges

According to Graeff, the challenges of using melanin as a material for the development of bioelectronic devices include the fact that like other carbon-based materials, such as graphene, melanin is not easily dispersible in an aqueous medium, a characteristic that hinders its application in thin-film production.

Furthermore, the conventional process for synthesizing melanin is complex: several steps are hard to control, it can last up to 56 days, and it can result in disorderly structures.

In a series of studies performed in recent years at the Center for Research and Development of Functional Materials (CDFM), where Graeff is a leading researcher and which is one of the Research, Innovation and Dissemination Centers (RIDCs) funded by FAPESP, he and his collaborators managed to obtain biosynthetic melanin with good dispersion in water and a strong resemblance to natural melanin using a novel synthesis route.

The process developed by the group at CDMF takes only a few hours and is based on changes in parameters such as temperature and the application of oxygen pressure to promote oxidation of the material.

By applying oxygen pressure, the researchers were able to increase the density of carboxyl groups, which are organic functional groups consisting of a carbon atom double bonded to an oxygen atom and single bonded to a hydroxyl group (oxygen + hydrogen). This enhances solubility and facilitates the suspension of biosynthetic melanin in water.

“The production of thin films of melanin with high homogeneity and quality is made far easier by these characteristics,” Graeff said.

By increasing the density of carboxyl groups, the researchers were also able to make biosynthetic melanin more similar to the biological compound.

In living organisms, an enzyme that participates in the synthesis of melanin facilitates the production of carboxylic acids. The new melanin synthesis route enabled the researchers to mimic the role of this enzyme chemically while increasing carboxyl group density.

“We’ve succeeded in obtaining a material that’s very close to biological melanin by chemical synthesis and in producing high-quality film for use in bioelectronic devices,” Graeff said.

Through collaboration with colleagues at research institutions in Canada [emphasis mine], the Brazilian researchers have begun using the material in a series of applications, including electrical contacts, pH sensors and photovoltaic cells.

More recently, they have embarked on an attempt to develop a transistor, a semiconductor device used to amplify or switch electronic signals and electrical power.

“Above all, we aim to produce transistors precisely in order to enhance this coupling of electronics with biological systems,” Graeff said.

I’m glad to have gotten some information about the work in South America. It’s one of FrogHeart’s shortcomings that I have so little about the research in that area of the world. I believe this is largely due to my lack of Spanish language skills. Perhaps one day there’ll be a universal translator that works well. In the meantime, it was a surprise to see Canada mentioned in this piece. I wonder which Canadian research institutions are involved with this research in South America.

‘Seamless’ bioeletronics made possible with protein bridge

For some years now I’ve been tagging certain posts with ‘machine/flesh’ as more bioelectronic devices are being invented for use as implants of various kinds.

Researchers at the University of Washington (state) have found a means of making bioelectronics implants a more comfortable fit in the body according to an Oct. 4, 2016 news item on phys.org,

Life has always played by its own set of molecular rules. From the biochemistry behind the first cells, evolution has constructed wonders like hard bone, rough bark and plant enzymes that harvest light to make food.

But our tools for manipulating life—to treat disease, repair damaged tissue and replace lost limbs—come from the nonliving realm: metals, plastics and the like. Though these save and preserve lives, our synthetic treatments are rooted in a chemical language ill-suited to our organic elegance. Implanted electrodes scar, wires overheat and our bodies struggle against ill-fitting pumps, pipes or valves.

A solution lies in bridging this gap where artificial meets biological—harnessing biological rules to exchange information between the biochemistry of our bodies and the chemistry of our devices. In a paper published Sept. 22 [2016] in Scientific Reports, engineers at the University of Washington unveiled peptides—small proteins which carry out countless essential tasks in our cells—that can provide just such a link.

An Oct. 3, 2016 University of Washington (state) news release (also on EurekAlert), which originated the news item, expands on the theme,

The team, led by UW professor Mehmet Sarikaya in the Departments of Materials Science & Engineering, shows how a genetically engineered peptide can assemble into nanowires atop 2-D, solid surfaces that are just a single layer of atoms thick. These nanowire assemblages are critical because the peptides relay information across the bio/nano interface through molecular recognition — the same principles that underlie biochemical interactions such as an antibody binding to its specific antigen or protein binding to DNA.

Since this communication is two-way, with peptides understanding the “language” of technology and vice versa, their approach essentially enables a coherent bioelectronic interface.

“Bridging this divide would be the key to building the genetically engineered biomolecular solid-state devices of the future,” said Sarikaya, who is also a professor of chemical engineering and oral health sciences.

His team in the UW Genetically Engineered Materials Science and Engineering Center studies how to coopt the chemistry of life to synthesize materials with technologically significant physical, electronic and photonic properties. To Sarikaya, the biochemical “language” of life is a logical emulation.

“Nature must constantly make materials to do many of the same tasks we seek,” he said.

The UW team wants to find genetically engineered peptides with specific chemical and structural properties. They sought out a peptide that could interact with materials such as gold, titanium and even a mineral in bone and teeth. These could all form the basis of future biomedical and electro-optical devices. Their ideal peptide should also change the physical properties of synthetic materials and respond to that change. That way, it would transmit “information” from the synthetic material to other biomolecules — bridging the chemical divide between biology and technology.

In exploring the properties of 80 genetically selected peptides — which are not found in nature but have the same chemical components of all proteins — they discovered that one, GrBP5, showed promising interactions with the semimetal graphene. They then tested GrBP5’s interactions with several 2-D nanomaterials which, Sarikaya said, “could serve as the metals or semiconductors of the future.”

“We needed to know the specific molecular interactions between this peptide and these inorganic solid surfaces,” he added.

Their experiments revealed that GrBP5 spontaneously organized into ordered nanowire patterns on graphene. With a few mutations, GrBP5 also altered the electrical conductivity of a graphene-based device, the first step toward transmitting electrical information from graphene to cells via peptides.

In parallel, Sarikaya’s team modified GrBP5 to produce similar results on a semiconductor material — molybdenum disulfide — by converting a chemical signal to an optical signal. They also computationally predicted how different arrangements of GrBP5 nanowires would affect the electrical conduction or optical signal of each material, showing additional potential within GrBP5’s physical properties.

“In a way, we’re at the flood gates,” said Sarikaya. “Now we need to explore the basic properties of this bridge and how we can modify it to permit the flow of ‘information’ from electronic and photonic devices to biological systems.”

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

Bioelectronic interfaces by spontaneously organized peptides on 2D atomic single layer materials by Yuhei Hayamizu, Christopher R. So, Sefa Dag, Tamon S. Page, David Starkebaum, & Mehmet Sarikaya. Scientific Reports 6, Article number: 33778 (2016) doi:10.1038/srep33778 Published online: 22 September 2016

This paper is open access.

This image illustrates the GrBP5 nanowires,

A top view image of GrBP5 nanowires on a 2-D surface of molybdenum disulfide.Mehmet Sarikaya/Scientific Reports

A top view image of GrBP5 nanowires on a 2-D surface of molybdenum disulfide.Mehmet Sarikaya/Scientific Reports

Man with world’s first implanted bionic arm participates in first Cybathlon (olympics for cyborgs)

The world’s first Cybathlon is being held on Oct. 8, 2016 in Zurich, Switzerland. One of the participants is an individual who took part in some groundbreaking research into implants which was featured in my Oct. 10, 2014 posting. There’s more about the Cybathlon and the participant in an Oct. 4, 2016 news item on phys.org,

A few years ago, a patient was implanted with a bionic arm for the first time in the world using control technology developed at Chalmers University of Technology. He is now taking part in Cybathlon, a new international competition in which 74 participants with physical disabilities will compete against each other, using the latest robotic prostheses and other assistive technologies – a sort of ‘Cyborg Olympics’.

The Paralympics will now be followed by the Cybathlon, which takes place in Zürich on October 8th [2016]. This is the first major competition to show that the boundaries between human and machine are becoming more and more blurred. The participants will compete in six different disciplines using the machines they are connected to as well as possible.

Cybathlon is intended to drive forward the development of prostheses and other types of assistive aids. Today, such technologies are often highly advanced technically, but provide limited value in everyday life.

An Oct. 4, 2016 Chalmers University of Technology press release by Johanna Wilde, which originated the news item, provides details about the competitor, his prosthetic device, and more,

Magnus, one of the participants, has now had his biomechatronically integrated arm prosthesis for almost four years. He says that his life has totally changed since the implantation, which was performed by Dr Rickard Brånemark, associate professor at Sahlgrenska University Hospital.

“I don’t feel handicapped since I got this arm”, says Magnus. “I can now work full time and can perform all the tasks in both my job and my family life. The prosthesis doesn’t feel like a machine, but more like my own arm.”

Magnus lives in northern Sweden and works as a lorry driver. He regularly visits Gothenburg in southern Sweden and carries out tests with researcher Max Ortiz Catalan, assistant professor at Chalmers University of Technology, who has been in charge of developing the technology and leads the team competing in the Cybathlon.

“This is a completely new research field in which we have managed to directly connect the artificial limb to the skeleton, nerves and muscles,” says Dr Max Ortiz Catalan. “In addition, we are including direct neural sensory feedback in the prosthetic arm so the patient can intuitively feel with it.”

Today Magnus can feel varying levels of pressure in his artificial hand, something which is necessary to instinctively grip an object firmly enough. He is unique in the world in having a permanent sensory connection between the prosthesis and his nervous system, working outside laboratory conditions. Work is now under way to add more types of sensations.

At the Cybathlon he will be competing for the Swedish team, which is formed by Chalmers University of Technology, Sahlgrenska University Hospital and the company Integrum AB.

The competition has a separate discipline for arm prostheses. In this discipline Magnus has to complete a course made up of six different stations at which the prosthesis will be put to the test. For example, he has to open a can with a can opener, load a tray with crockery and open a door with the tray in his hand. The events at the Cybathlon are designed to be spectator-friendly while being based on various operations that the participants have to cope with in their daily lives.

“However, the competition will not really show the unique advantages of our technology, such as the sense of touch and the bone-anchored attachment which makes the prosthesis comfortable enough to wear all day,” says Max Ortiz Catalan.

Magnus is the only participant with an amputation above the elbow. This naturally makes the competition more difficult for him than for the others, who have a natural elbow joint.

“From a competitive perspective Cybathlon is far from ideal to demonstrate clinically viable technology,” says Max Ortiz Catalan. “But it is a major and important event in the human-machine interface field in which we would like to showcase our technology. Unlike several of the other participants, Magnus will compete in the event using the same technology he uses in his everyday life.”

Facts about Cybathlon
•    The very first Cybathlon is being organised by the Swiss university ETH Zürich.
•    The €5 million event will take place in Zürich´s 7600 spectator ice hockey stadium, Swiss Arena.
•    74 participants are competing for 59 different teams from 25 countries around the world. In total, the teams consist of about 300 scientists, engineers, support staff and competitors.
•    The teams range from small ad hoc teams to the world’s largest manufacturers of advanced prostheses.
•    The majority of the teams are groups from research labs and many of the prostheses have come straight out of the lab.
•    Unlike the Olympics and Paralympics, the Cybathlon participants are not athletes but ordinary people with various disabilities. The aims of the competition are to establish a dialogue between academia and industry, to facilitate discussion between technology developers and people with disabilities and to promote the use of robotic assistive aids to the general public.
•    Cybathlon will return in 2020, as a seven-day event in Tokyo, to coincide with the Olympics.

Facts about the Swedish team
The Opra Osseointegration team is a multidisciplinary team comprising technical and medical partners. The team is led by Dr Max Ortiz Catalan, assistant professor at Chalmers University of Technology, who has been in charge of developing the technology in close collaboration with Dr Rickard Brånemark, who is a surgeon at Sahlgrenska University Hospital and an associate professor at Gothenburg University. Dr Brånemark led the team performing the implantation of the device. Integrum AB, a Swedish company, complements the team as the pioneering provider of bone-anchored limb prostheses.

This video gives you an idea of what it’s in store on Oct. 8, 2016,