Tag Archives: Thor Balkhed

Growing electrodes in your brain?

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This isn’t for everybody. From a February 23, 2023 news item on Nanowerk, Note: A link has been removed,

The boundaries between biology and technology are becoming blurred. Researchers at Linköping, Lund, and Gothenburg universities in Sweden have successfully grown electrodes in living tissue using the body’s molecules as triggers. The result, published in the journal Science (“Metabolite-induced in vivo fabrication of substrate-free organic bioelectronics”), paves the way for the formation of fully integrated electronic circuits in living organisms.

Caption: The injectable gel being tested on a microfabricated circuit. Credit: Thor Balkhed

I have two news releases for this research. First, the February 23, 2023 American Association for the Advancement of Science (AAAS) news release on EurekAlert,

Researchers have developed a way to make bioelectronics directly inside living tissues, an approach they tested by making electrodes in the brain, heart, and fin tissue of living zebrafish, as well as in isolated mammalian muscle tissues. According to the authors, the new method paves the way for in vivo fabrication of fully integrated electronic circuits within the nervous system and other living tissue. “Safety and stability analyses over long periods will be essential to determining whether such technology is useful for chronic implantations,” writes Sahika Inal in a related Perspective. “However, the strategy … suggests that any living tissue can turn into electronic matter and brings the field closer to generating seamless biotic-abiotic interfaces with a potentially long lifetime and minimum harm to tissues.” Implantable electronic devices that can interface with soft biological neural tissues offer a valuable approach to studying the complex electrical signaling of the nervous system and enable the therapeutic modulation of neural circuitry to prevent or treat various diseases and disorders. However, conventional bioelectronic implants often require the use of rigid electronic substrates that are incompatible with delicate living tissues and can provoke injury and inflammation that can affect a device’s electrical properties and long-term performance. Overcoming the incompatibility between static, solid-state electronic materials and dynamic, soft biological tissues has proven challenging. Here, Xenofon Strakosas and colleagues present a method to fabricate polymer-based, substrate-free electronic conducting materials directly inside a tissue. Strakosas et al. developed a complex molecular precursor cocktail that, when injected into a tissue, uses endogenous metabolites (glucose and lactate) to induce polymerization of organic precursors to form conducting polymer gels. To demonstrate the approach, the authors “grew” gel electrodes in the brain, heart, and fin tissue of living zebrafish, with no signs of tissue damage, and in isolated mammalian muscle tissues, including beef, pork and chicken. In medicinal leeches, they showed how the conducting gel could interface nervous tissue with electrodes on a tiny flexible probe.

The second is the February 23, 2023 Linköping University press release on EurekAlert, which originated the news item, and it provides further insight,

“For several decades, we have tried to create electronics that mimic biology. Now we let biology create the electronics for us,” says Professor Magnus Berggren at the Laboratory for Organic Electronics, LOE, at Linköping University.

Linking electronics to biological tissue is important to understand complex biological functions, combat diseases in the brain, and develop future interfaces between man and machine. However, conventional bioelectronics, developed in parallel with the semiconductor industry, have a fixed and static design that is difficult, if not impossible, to combine with living biological signal systems.

To bridge this gap between biology and technology, researchers have developed a method for creating soft, substrate-free, electronically conductive materials in living tissue. By injecting a gel containing enzymes as the “assembly molecules”, the researchers were able to grow electrodes in the tissue of zebrafish and medicinal leeches.

“Contact with the body’s substances changes the structure of the gel and makes it electrically conductive, which it isn’t before injection. Depending on the tissue, we can also adjust the composition of the gel to get the electrical process going,” says Xenofon Strakosas, researcher at LOE and Lund University and one of the study’s main authors.

The body’s endogenous molecules are enough to trigger the formation of electrodes. There is no need for genetic modification or external signals, such as light or electrical energy, which has been necessary in previous experiments. The Swedish researchers are the first in the world to succeed in this.

Their study paves the way for a new paradigm in bioelectronics. Where it previously took implanted physical objects to start electronic processes in the body, injection of a viscous gel will be enough in the future.

In their study, the researchers further show that the method can target the electronically conducting material to specific biological substructures and thereby create suitable interfaces for nerve stimulation. In the long term, the fabrication of fully integrated electronic circuits in living organisms may be possible.

In experiments conducted at Lund University, the team successfully achieved electrode formation in the brain, heart, and tail fins of zebrafish and around the nervous tissue of medicinal leeches. The animals were not harmed by the injected gel and were otherwise not affected by the electrode formation. One of the many challenges in these trials was to take the animals’ immune system into account.

“By making smart changes to the chemistry, we were able to develop electrodes that were accepted by the brain tissue and immune system. The zebrafish is an excellent model for the study of organic electrodes in brains,” says Professor Roger Olsson at the Medical Faculty at Lund University, who also has a chemistry laboratory at the University of Gothenburg.

It was Professor Roger Olsson who took the initiative for the study, after he read about the electronic rose developed by researchers at Linköping University in 2015. One research problem, and an important difference between plants and animals, was the difference in cell structure. Whereas plants have rigid cell walls which allow for the formation of electrodes, animal cells are more like a soft mass. Creating a gel with enough structure and the right combination of substances to form electrodes in such surroundings was a challenge that took many years to solve.

“Our results open up for completely new ways of thinking about biology and electronics. We still have a range of problems to solve, but this study is a good starting point for future research,” says Hanne Biesmans, PhD student at LOE and one of the main authors.

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

Metabolite-induced in vivo fabrication of substrate-free organic bioelectronics by Xenofon Strakosas, Hanne Biesmans, Tobias Abrahamsson, Karin Hellman, Malin Silverå Ejneby, Mary J. Donahue, Peter Ekström, Fredrik Ek, Marios Savvakis, Martin Hjort, David Bliman, Mathieu Linares, Caroline Lindholm, Eleni Stavrinidou, Jennifer Y. Gerasimov, Daniel T. Simon, Roger Olsson, and Magnus Berggren. Science 23 Feb 2023 Vol 379, Issue 6634 pp. 795-802 DOI: 10.1126/science.adc9998

This paper is behind a paywall.

Mimicking the brain with an evolvable organic electrochemical transistor

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Simone Fabiano and Jennifer Gerasimov have developed a learning transistor that mimics the way synapses function. Credit: Thor Balkhed

At a guess, this was originally a photograph which has been passed through some sort of programme to give it a paintinglike quality.

Moving onto the research, I don’t see any reference to memristors (another of the ‘devices’ that mimics the human brain) so perhaps this is an entirely different way to mimic human brains? A February 5, 2019 news item on ScienceDaily announces the work from Linkoping University (Sweden),

A new transistor based on organic materials has been developed by scientists at Linköping University. It has the ability to learn, and is equipped with both short-term and long-term memory. The work is a major step on the way to creating technology that mimics the human brain.

…

A February 5, 2019 Linkoping University press release (also on EurekAlert), which originated the news item, describes this ‘nonmemristor’ research into brainlike computing in more detail,

Until now, brains have been unique in being able to create connections where there were none before. In a scientific article in Advanced Science, researchers from Linköping University describe a transistor that can create a new connection between an input and an output. They have incorporated the transistor into an electronic circuit that learns how to link a certain stimulus with an output signal, in the same way that a dog learns that the sound of a food bowl being prepared means that dinner is on the way.

A normal transistor acts as a valve that amplifies or dampens the output signal, depending on the characteristics of the input signal. In the organic electrochemical transistor that the researchers have developed, the channel in the transistor consists of an electropolymerised conducting polymer. The channel can be formed, grown or shrunk, or completely eliminated during operation. It can also be trained to react to a certain stimulus, a certain input signal, such that the transistor channel becomes more conductive and the output signal larger.

“It is the first time that real time formation of new electronic components is shown in neuromorphic devices”, says Simone Fabiano, principal investigator in organic nanoelectronics at the Laboratory of Organic Electronics, Campus Norrköping.

The channel is grown by increasing the degree of polymerisation of the material in the transistor channel, thereby increasing the number of polymer chains that conduct the signal. Alternatively, the material may be overoxidised (by applying a high voltage) and the channel becomes inactive. Temporary changes of the conductivity can also be achieved by doping or dedoping the material.

“We have shown that we can induce both short-term and permanent changes to how the transistor processes information, which is vital if one wants to mimic the ways that brain cells communicate with each other”, says Jennifer Gerasimov, postdoc in organic nanoelectronics and one of the authors of the article.

By changing the input signal, the strength of the transistor response can be modulated across a wide range, and connections can be created where none previously existed. This gives the transistor a behaviour that is comparable with that of the synapse, or the communication interface between two brain cells.

It is also a major step towards machine learning using organic electronics. Software-based artificial neural networks are currently used in machine learning to achieve what is known as “deep learning”. Software requires that the signals are transmitted between a huge number of nodes to simulate a single synapse, which takes considerable computing power and thus consumes considerable energy.

“We have developed hardware that does the same thing, using a single electronic component”, says Jennifer Gerasimov.

“Our organic electrochemical transistor can therefore carry out the work of thousands of normal transistors with an energy consumption that approaches the energy consumed when a human brain transmits signals between two cells”, confirms Simone Fabiano.

The transistor channel has not been constructed using the most common polymer used in organic electronics, PEDOT, but instead using a polymer of a newly-developed monomer, ETE-S, produced by Roger Gabrielsson, who also works at the Laboratory of Organic Electronics and is one of the authors of the article. ETE-S has several unique properties that make it perfectly suited for this application – it forms sufficiently long polymer chains, is water-soluble while the polymer form is not, and it produces polymers with an intermediate level of doping. The polymer PETE-S is produced in its doped form with an intrinsic negative charge to balance the positive charge carriers (it is p-doped).

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

An Evolvable Organic Electrochemical Transistor for Neuromorphic Applications by Jennifer Y. Gerasimov, Roger Gabrielsson, Robert Forchheimer, Eleni Stavrinidou, Daniel T. Simon, Magnus Berggren, Simone Fabiano. Advanced Science DOI: https://doi.org/10.1002/advs.201801339 First published: 04 February 2019

This paper is open access.

There’s one other image associated this work that I want to include here,

Synaptic transistor. Sketch of the organic electrochemical transistor, formed by electropolymerization of ETE‐S in the transistor channel. The electrolyte solution is confined by a PDMS well (not shown). In this work, we define the input at the gate as the presynaptic signal and the response at the drain as the postsynaptic terminal. During operation, the drain voltage is kept constant while the gate is pulsed. Synaptic weight is defined as the amplitude of the current response to a standard gate voltage characterization pulse of −0.1 V. Different memory functionalities are accessible by applying gate voltage Courtesy: Linkoping University Researchers

Soft things for your brain

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

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

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

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

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

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

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

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

New conductive material

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

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

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

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

Important future applications

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

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

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

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

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

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

This paper is open access.

Organic nanoelectronics in water

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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.